ABSTRACT
BACKGROUND: Alpha-synucleinopathies are incurable neurodegenerative diseases. Abelson tyrosine kinase inhibitors (Abl TKIs) may be disease-modifying therapies. This systematic review, meta-analysis, and meta-regression evaluated the use of Abl TKIs in their treatment. METHODS: We searched PubMed, Embase, and Cochrane databases for trials using Abl TKIs in patients with Parkinson's disease and Lewy body dementia published until July 2023. The outcome was the change in the MDS-UPDRS-III (Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale III). DerSimonian-Laird random-effects model was used to calculate the pooled effect estimates. Leave-one-out forest plots were used for the sensitivity analysis, and meta-regression (restricted maximum likelihood) was performed. RESULTS: Five studies (197 patients) were included. Nilotinib 300 mg had an effect size of -1.154 (95% confidence interval [CI], -3.000 to 0.692). Nilotinib 150 mg and bosutinib 100 mg versus placebo yielded 0.82 (95% CI, -3.76 to 5.41). Sensitivity analysis showed that 1 trial changed the significance of the nilotinib 300 mg single-arm analysis (MD = -1.723; 95% CI, -2.178 to -1.268). Meta-regression revealed that lower age (EC = -0.9103, SE = 0.2286, P < 0.0001) and higher baseline MDS-UPDRS-III scores (EC = 0.1210, SE = 0.0168, P < 0.0001) could explain the inefficacy of nilotinib 300 mg. CONCLUSIONS: Nilotinib (300 mg) proved effective postsensitivity analysis, unlike lower doses and bosutinib in Parkinson's disease/Lewy body dementia. Abl TKIs showed reduced efficacy in younger, more impaired patients, indicating the need for further testing with higher-potency drugs in patients who have diseases that are in the early stage but with a later onset.
Subject(s)
Lewy Body Disease , Parkinson Disease , Protein Kinase Inhibitors , Humans , Parkinson Disease/drug therapy , Lewy Body Disease/drug therapy , Protein Kinase Inhibitors/therapeutic use , Pyrimidines/therapeutic use , Aniline Compounds/therapeutic use , Nitriles/therapeutic use , Proto-Oncogene Proteins c-abl/antagonists & inhibitors , Quinolines/therapeutic useABSTRACT
BACKGROUND: Alpha-synucleinopathies are incurable neurodegenerative diseases. Abelson tyrosine kinase inhibitors (Abl TKIs) may be disease-modifying therapies. This systematic review, meta-analysis, and meta-regression evaluated the use of Abl TKIs in their treatment. METHODS: We searched PubMed, Embase, and Cochrane databases for trials using Abl TKIs in patients with Parkinson's disease and Lewy body dementia published until July 2023. The outcome was the change in the MDS-UPDRS-III (Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale III). DerSimonian-Laird random-effects model was used to calculate the pooled effect estimates. Leave-one-out forest plots were used for the sensitivity analysis, and meta-regression (restricted maximum likelihood) was performed. RESULTS: Five studies (197 patients) were included. Nilotinib 300 mg had an effect size of -1.154 (95% confidence interval [CI], -3.000 to 0.692). Nilotinib 150 mg and bosutinib 100 mg versus placebo yielded 0.82 (95% CI, -3.76 to 5.41). Sensitivity analysis showed that 1 trial changed the significance of the nilotinib 300 mg single-arm analysis (MD = -1.723; 95% CI, -2.178 to -1.268). Meta-regression revealed that lower age (EC = -0.9103, SE = 0.2286, P < 0.0001) and higher baseline MDS-UPDRS-III scores (EC = 0.1210, SE = 0.0168, P < 0.0001) could explain the inefficacy of nilotinib 300 mg. CONCLUSIONS: Nilotinib (300 mg) proved effective postsensitivity analysis, unlike lower doses and bosutinib in Parkinson's disease/Lewy body dementia. Abl TKIs showed reduced efficacy in younger, more impaired patients, indicating the need for further testing with higher-potency drugs in patients who have diseases that are in the early stage but with a later onset.
ABSTRACT
INTRODUCTION: The Selective Functional Movement Assessment (SFMA) is a functional movement assessment method to observe movement restrictions in individuals with known musculoskeletal disorders, although it has also been used to evaluate healthy athletes of different sports. AIM: The present paper aimed to evaluate the applicability of SFMA in a clinical setting and to verify whether a student can correctly perform it. METHODS: An introductory and explanatory email was sent to the subjects, containing the instructions needed to produce a video with SFMA evaluation movements. SFMA methodology was then used to analyze the received videos. The results between interobserver and intraobserver agreement were compared to the literature, considered the gold standard methods. RESULTS: Twenty-eight subjects (17.71 ± 1.96 years aged) were rated. The functional non-painful scenario (FN) has been assigned more frequently by all raters. The student's intra-rater reliability proved to be moderate (Kappa coefficient 0.49). Results for inter-rater reliability showed that the reliability degree between the senior physiotherapist and student before and after their educational path is good (Kappa coefficient 0.60 and 0.62, respectively). CONCLUSIONS: The results of this study showed SFMA intra-rater reliability to be moderate, while inter-rater reliability can be considered good. These characteristics make it a valuable tool for sport's needs, even when used by students.
