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EClinicalMedicine Feb 2024-related myopathies (-RM) are caused by pathogenic variants in the gene which encodes the type 1 ryanodine receptor (RyR1). RyR1 is the sarcoplasmic reticulum (SR)...
BACKGROUND
-related myopathies (-RM) are caused by pathogenic variants in the gene which encodes the type 1 ryanodine receptor (RyR1). RyR1 is the sarcoplasmic reticulum (SR) calcium release channel that mediates excitation-contraction coupling in skeletal muscle. RyR1 sub-conductance, SR calcium leak, reduced RyR1 expression, and oxidative stress often contribute to -RM pathogenesis. Loss of RyR1-calstabin1 association, SR calcium leak, and increased RyR1 open probability were observed in 17 -RM patient skeletal muscle biopsies and improved following treatment with Rycal compounds. Thus, we initiated a first-in-patient trial of Rycal S48168 (ARM210) in ambulatory adults with genetically confirmed -RM.
METHODS
Participants received 120 mg (n = 3) or 200 mg (n = 4) S48168 (ARM210) daily for 29 days. The primary endpoint was safety and tolerability. Exploratory endpoints included S48168 (ARM210) pharmacokinetics (PK), target engagement, motor function measure (MFM)-32, hand grip and pinch strength, timed functional tests, PROMIS fatigue scale, semi-quantitative physical exam strength measurements, and oxidative stress biomarkers. The trial was registered with clinicaltrials.gov (NCT04141670) and was conducted at the National Institutes of Health Clinical Center between October 28, 2019 and December 12, 2021.
FINDINGS
S48168 (ARM210) was well-tolerated, did not cause any serious adverse events, and exhibited a dose-dependent PK profile. Three of four participants who received the 200 mg/day dose reported improvements in PROMIS-fatigue at 28 days post-dosing, and also demonstrated improved proximal muscle strength on physical examination.
INTERPRETATION
S48168 (ARM210) demonstrated favorable safety, tolerability, and PK, in -RM affected individuals. Most participants who received 200 mg/day S48168 (ARM210) reported decreased fatigue, a key symptom of -RM. These results set the foundation for a randomized, double-blind, placebo-controlled proof of concept trial to determine efficacy of S48168 (ARM210) in -RM.
FUNDING
NINDS and NINR Intramural Research Programs, NIH Clinical Center Bench to Bedside Award (2017-551673), ARMGO Pharma Inc., and its development partner Les Laboratoires Servier.
PubMed: 38318125
DOI: 10.1016/j.eclinm.2024.102433 -
Hong Kong Journal of Occupational... Dec 2022The study aimed to describe the finger dexterity in office workers of an Asian population.
AIM
The study aimed to describe the finger dexterity in office workers of an Asian population.
METHODS
One hundred twenty-seven right-handed office workers, aged 21-50 with a similar split of male and female, were recruited with finger dexterity measured by the O'Connor Finger Dexterity Test. The grip strength, tip and lateral pinch strength of both hands were also measured.
RESULTS
This study provided the percentile score of the O'Connor Finger Dexterity Test of both males and females in the Asian population. Raw scores of below 218 and 213 seconds in male and female participants respectively reach the 90th percentile, and above 237 and 235 seconds in male and female below the 10th percentile. Results showed no significant difference in local mean scores across different age groups, between male and female and with varying hours of working in typing, filing, and writing. A significant difference was only found in finger dexterity and years of working as office workers. No significant correlation was found between the finger dexterity with grip strength, tip and lateral pinch of the dominant right hand. The results were similar to the original normative score with similar work skills and demands.
CONCLUSION
The mean scores could be used as a valid reference for local occupational therapists to evaluate the finger dexterity of office workers. However, caution has to be taken that conclusions drawn can be biased because of the relatively small sample size, and the results cannot be generalized to represent a wider Asian population.
PubMed: 36467522
DOI: 10.1177/15691861221114258 -
Journal of Wrist Surgery Jun 2020A common notion is that more complex techniques for treating trapeziometacarpal arthritis such as ligament reconstruction and tendon interposition (LRTI) better...
A common notion is that more complex techniques for treating trapeziometacarpal arthritis such as ligament reconstruction and tendon interposition (LRTI) better preserve the scaphometacarpal (SMC) space compared to a simple trapeziectomy and that this leads to superior functional outcomes. The purpose of this systematic review is to evaluate the relationship between scaphometacarpal space and objective outcomes such as grip and pinch strength as well as subjective patient-reported outcomes. A systematic review of the literature was conducted according to PRISMA guidelines. Inclusion criteria were studies reporting SMC space and outcomes after surgery for carpometacarpal arthritis. The primary outcomes of these studies included any measure of postoperative scaphometacarpal space (trapezial height/trapezial index) as well as key pinch strength, grip strength, or lateral pinch strength. Studies that did not assess for association between SMC space and outcomes were excluded. Fourteen studies were included in this systematic review. Three (21.4%) studies found a statistically significant correlation between postoperative SMC space and postoperative pinch or grip strength. The correlation was weakly positive in one study (key pinch vs. scaphometacarpal space, = 0.13), positive but unlisted in another (lateral pinch vs. trapezial ratio), and negative in the third study (key pinch vs. trapezial space ratio, = -0.47). Preservation of the SMC space postoperatively is not associated with postoperative outcomes. Further research is necessary to better characterize the importance of maintaining the SMC space in patients undergoing LRTI in order to substantiate claims by proponents of the procedure.
PubMed: 32509434
DOI: 10.1055/s-0039-1692477 -
IEEE Transactions on Bio-medical... May 2023The purpose of this work was to develop an open-source musculoskeletal model of the hand and wrist and to evaluate its performance during simulations of functional tasks.
OBJECTIVE
The purpose of this work was to develop an open-source musculoskeletal model of the hand and wrist and to evaluate its performance during simulations of functional tasks.
METHODS
The current model was developed by adapting and expanding upon existing models. An optimal control theory framework that combines forward-dynamics simulations with a simulated-annealing optimization was used to simulate maximum grip and pinch force. Active and passive hand opening were simulated to evaluate coordinated kinematic hand movements.
RESULTS
The model's maximum grip force production matched experimental measures of grip force, force distribution amongst the digits, and displayed sensitivity to wrist flexion. Simulated lateral pinch strength replicated in vivo palmar pinch strength data. Additionally, predicted activations for 7 of 8 muscles fell within variability of EMG data during palmar pinch. The active and passive hand opening simulations predicted reasonable activations and demonstrated passive motion mimicking tenodesis, respectively.
CONCLUSION
This work advances simulation capabilities of hand and wrist models and provides a foundation for future work to build upon.
SIGNIFICANCE
This is the first open-source musculoskeletal model of the hand and wrist to be implemented during both functional kinetic and kinematic tasks. We provide a novel simulation framework to predict maximal grip and pinch force which can be used to evaluate how potential surgical and rehabilitation interventions influence these functional outcomes while requiring minimal experimental data.
Topics: Wrist; Hand; Wrist Joint; Hand Strength; Muscles
PubMed: 36301780
DOI: 10.1109/TBME.2022.3217722 -
Behavioral Sciences (Basel, Switzerland) May 2023The COVID-19 lockdown restrictions affected physical performance and cognitive function in older people as they were confined to their homes. There is an association...
The COVID-19 lockdown restrictions affected physical performance and cognitive function in older people as they were confined to their homes. There is an association between physical and cognitive functions. Mild Cognitive Impairment (MCI) is a condition that risks progressing to dementia. This study aimed to identify the relationship between handgrip strength (HGS), Timed Up-and-Go (TUG), and MCI in older people during the COVID-19 pandemic restrictions. The cross-sectional study recruited 464 eligible participants for an interview and anthropometric measurement. The Montreal Cognitive Assessment-Basic (MoCA-B), HGS, and TUG were measured in addition to demographic and health characteristics. A total of 398 participants (85.8%) were found to have MCI when screened with the MoCA-B. Their mean age was 71.09 ± 5.81 years. Forward multiple regression analysis demonstrated that HGS (β = 0.032, < 0.001), education level (β = 2.801, < 0.001), TUG (β = -0.022, = 0.013), Thai Geriatric Depression Score, TGDS (β = -0.248, = 0.011), and age (β = -1.677, = 0.019) were associated with MCI. A decrease in HGS and an increased TUG might allow for the early detection of MCI and promote physical training in order to reduce the risk of MCI. Further studies can investigate multidomain indicators for MCI, for example, fine motor skills and pinch strength as components of the motor abilities.
PubMed: 37232647
DOI: 10.3390/bs13050410 -
Turkish Journal of Physical Medicine... Mar 2021In this study, we aimed to investigate the availability of the Timed Up and Go (TUG) test in daily practice instead of the Tampa Scale for Kinesiophobia (TSK) test for...
OBJECTIVES
In this study, we aimed to investigate the availability of the Timed Up and Go (TUG) test in daily practice instead of the Tampa Scale for Kinesiophobia (TSK) test for the evaluation of fear of movement and to assess the functionality of the upper extremity in postmastectomy lymphedema patients.
PATIENTS AND METHODS
Between March 2018 and July 2018, a total of 30 female patients (mean age 53.8±12.3 years; range, 35 to 80 years) with postmastectomy lymphedema were included in this study. The severity of lymphedema of the patients was measured circumferentially at 5-cm intervals. All patients were evaluated for upper extremity functionality using the Timed Functional Arm and Shoulder Test, hand grip strength using a hand dynamometer, and pinch strength using a pinchmeter. The TSK test was used for the evaluation of fear of movement and TUG test was used for the evaluation of functional status of lower extremity.
RESULTS
There was a significant difference in functionality between the affected and unaffected side of upper extremity (p<0.05). According to the TSK results, all patients described themselves as kinesiophobic, and advanced fear of movement was found in 66.67% of the patients. However, according to the TUG scores, lower extremity functionality of all patients was normal.
CONCLUSION
Our study results showed that, independently of the severity of lymphedema, fear of movement was seen in every patient and functionality of upper extremity decreased on the affected side. On the other hand, the TUG test may not be useful to asses fear of movement in daily practice regarding to functional scores of these patients.
PubMed: 33948544
DOI: 10.5606/tftrd.2021.4616 -
Journal of Wrist Surgery Dec 2022There is a myriad of available surgical options for thumb carpometacarpal joint (CMCJ) arthritis and no robust evidence exists to guide the decisions of treating...
There is a myriad of available surgical options for thumb carpometacarpal joint (CMCJ) arthritis and no robust evidence exists to guide the decisions of treating surgeons. Our aim was to assess the comparative effectiveness of different surgical interventions available for the treatment of thumb CMCJ arthritis. We performed a systematic review, pairwise, and network meta-analysis of all randomized studies comparing surgical interventions for thumb CMCJ arthritis. Our primary outcomes were pain, function, and key pinch strength at long-term follow-up (> 6 months). Risk of bias and certainty of evidence were assessed for each outcome measure of compared interventions separately. Clinical recommendations were based on evidence of strong or moderate certainty. A total of 17 randomized studies were included in the systematic review. Where possible, pairwise and network meta-analyses were performed. Based on evidence of moderate certainty, trapeziectomy with a concomitant ligament reconstruction and tendon interposition (LRTI) does not appear to be associated with any long-term clinical benefits compared with simple trapeziectomy (function: mean difference [MD] -3.72 [-9.15, 1.71], = 0.64 favoring simple trapeziectomy; key pinch strength: MD 0.07 kg [-0.28, 0.43], = 0.68 favoring trapeziectomy with LRTI). Treatment rankings from the network meta-analysis favored trapeziectomy with and without LRTI, joint replacement, and arthrodesis. Trapeziectomy with LRTI appears to be associated with fewer major complications compared with joint replacement and arthrodesis, and more minor complications compared with simple trapeziectomy. Until further high-quality research indicates otherwise, simple trapeziectomy should be the preferred surgical modality for base of the thumb arthritis. This is a Level 1 study.
PubMed: 36504527
DOI: 10.1055/s-0042-1743117 -
Journal of Orthopaedics and... Aug 2022Distal ulna head or neck fracture is commonly associated with distal radius fracture. Treatment of these fractures remains controversial. Plate osteosynthesis is...
BACKGROUND
Distal ulna head or neck fracture is commonly associated with distal radius fracture. Treatment of these fractures remains controversial. Plate osteosynthesis is commonly performed. The purpose of this study was to observe clinical and radiological outcomes in ulna hook plate osteosynthesis for distal ulna fracture associated with distal radius fracture.
MATERIALS AND METHODS
This retrospective study between 2010 and 2018 included patients presenting combined displaced distal ulna fracture and distal radius fracture who were treated with ulna hook plate osteosynthesis. Patient evaluation included pain measurement with the visual analog scale, wrist range of motion, grip and pinch strengths, Quick Disabilities of the Arm, Shoulder and Hand (Q-DASH) score, and Mayo wrist score. Preoperative radiographs were reviewed to classify the distal ulna fracture according to Biyani. Bone union was evaluated on postoperative X-rays. At final follow-up, the usual radiographic parameters were measured and distal radioulnar joint (DRUJ) osteoarthritis was assessed.
RESULTS
A total of 48 patients were included. Mean age was 63 years old and mean follow-up was 28 months. According to the Biyani classification, there were 12 type I, 4 type II, 8 type III, and 24 type IV distal ulna fractures. Wrist flexion was 60°, extension 57°, pronation 85°, and supination 80°. Grip strength was 21 kg (86% of the uninjured opposite side). Pinch strength was 6.6 kg (92% of the uninjured opposite side). Clinical scores were very good to excellent, with a mean Q-DASH of 12 and a Mayo wrist score of 90. Discomfort or pain due to the implant that required implant removal was reported in 29%, and was higher in younger patients. Nonunion was observed in two cases and secondary implant displacement in one case. These three cases required secondary intervention with ulna head resection, which was higher in Biyani type IV. DRUJ osteoarthritis was observed in 12 patients (31%) and was higher in older patients.
CONCLUSIONS
Ulna hook plate fixation gives good clinical results and a high rate of fracture union, but complications are common. Implant irritation is a frequent complication, especially in young patients, and often requires implant removal.
LEVEL OF EVIDENCE
IV.
Topics: Aged; Bone Plates; Fracture Fixation, Internal; Humans; Middle Aged; Osteoarthritis; Radius Fractures; Range of Motion, Articular; Retrospective Studies; Treatment Outcome; Ulna; Ulna Fractures; Wrist
PubMed: 35972706
DOI: 10.1186/s10195-022-00658-3 -
Joint Diseases and Related Surgery 2021This study aims to evaluate the mid-term functional and radiological outcomes of magnesium-based screws in the treatment of scaphoid fractures.
OBJECTIVES
This study aims to evaluate the mid-term functional and radiological outcomes of magnesium-based screws in the treatment of scaphoid fractures.
PATIENTS AND METHODS
Between February 2015 and February 2018, a total of 21 patients (18 males, 3 females; mean age: 28.5±5.8 years; range, 19 to 39 years) with acute scaphoid waist fractures who underwent fracture fixation with biologically degradable magnesium-based compression screws were retrospectively analyzed. Fractures were classified according to the Herbert and Fisher classification. The absence of pain on palpation and painless active range of motion were accepted as the signs of union.
RESULTS
The mean follow-up was 43.3±5.3 (range, 36 to 52) months. According to the Herbert and Fisher classification, nine patients had type B1 and 12 patients had type B2 scaphoid fractures. Union was achieved in all cases. The mean time to union was 11.2±1.5 (range, 9 to 14) weeks. The mean grip strength, flexion, and extension were 43.57°, 73.57°, and 76.43°, respectively. The grip strength, pinch strength, and range of motion of the operated side were evaluated at the final follow-up visit and compared with the contralateral side (control group). No complication occurred. Any screw was not removed.
CONCLUSION
Magnesium-based compression screws can be safely used for acute scaphoid fractures considering their favorable functional and radiological results.
Topics: Adult; Bone Screws; Female; Fracture Fixation, Internal; Fractures, Bone; Humans; Magnesium; Male; Retrospective Studies; Scaphoid Bone; Treatment Outcome; Young Adult
PubMed: 34842105
DOI: 10.52312/jdrs.2021.298 -
Medicine Dec 2023We aimed to investigate the validity, reliability, and clinical relevance of Amadeo hand-finger robotic rehabilitation system measurements for evaluating spasticity and...
We aimed to investigate the validity, reliability, and clinical relevance of Amadeo hand-finger robotic rehabilitation system measurements for evaluating spasticity and strength in hemiplegic patients. In total, 161 participants (107 hemiplegic patients and 54 sex- and age-matched healthy controls) were included in this study. Spasticity was evaluated using the Modified Ashworth Scale, hand motor functions were evaluated using the Fugl-Meyer Assessment Hand Subscale, and hand grip and pinch strength were evaluated using the Jamar hand grip and pinch dynamometer. The Amadeo (Tyromotion) hand-finger robotic rehabilitation system was used to evaluate finger spasticity and strength of the participants. A statistically significant difference was found between the median values of the Modified Ashworth Scale (both clinical and robotic evaluation results) and the mean values of hand flexor and extensor strength measured with the robotic device in patients compared to healthy subjects (P < .01). Statistically, excellent agreement was obtained between the clinical and robotic test-retest results of the scale (P < .01) (intra-class correlation coefficient, ICC = .98-.99; ICC = .98-.99, respectively). There was a statistically significant positive correlation between the clinical and robotic device results of the Modified Ashworth Scale (r = .72; P < .01). There was a statistically significant positive correlation between the hand strength values measured with the robotic device, Jamar grip, pinch, and Fugl-Meyer Assessment Hand Subscale scores (P < .01) in the patient group. Hand finger spasticity and strength measurements of the Amadeo hand-finger robotic rehabilitation system were valid, reliable, and clinically correlated in stroke patients.
Topics: Humans; Hand Strength; Reproducibility of Results; Hemiplegia; Robotic Surgical Procedures; Fingers; Stroke; Muscle Spasticity; Stroke Rehabilitation
PubMed: 38065919
DOI: 10.1097/MD.0000000000036479