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Heliyon Mar 2024Despite existing evidence linking dyskinesia to levodopa, the primary treatment for Parkinson's, the dose-response relationship and risk factors remain uncertain. In... (Review)
Review
Despite existing evidence linking dyskinesia to levodopa, the primary treatment for Parkinson's, the dose-response relationship and risk factors remain uncertain. In this study, the risk for dyskinesia in patients with Parkinson's disease receiving levodopa was evaluated via meta-analysis and meta-regression approaches to examine dyskinesia risk factors more reliably and improve treatment strategies and patient care. The PubMed and Embase databases were searched to identify randomized controlled trials comparing levodopa with other anti-Parkinson's drugs published in English before June 31, 2023. The primary outcome was dyskinesia, and a risk of bias assessment was performed. In total, 24 studies met the inclusion criteria; 21 had a low risk of bias, and 3 had a high risk of bias. These studies included 4698 patients with Hoehn and Yahr Grade I-III Parkinson's disease. Our meta-analysis showed that the risk of dyskinesia was higher for levodopa than for other anti-Parkinson's drugs (odds ratio: 2.52 [95% confidence interval: 1.84-3.46]). Dyskinesia was not related to age (slope coefficient: 0.185 [0.095]; = 0.061), disease duration (slope coefficient: 0.011 [0.018]; = 0.566), or treatment duration (slope coefficient: 0.008 [0.007]; = 0.216). The mean levodopa equivalent dose (slope coefficient: 0.004 [0.001]; = 0.001) in the experimental group and the differences in drug doses between the experimental and control groups were correlated with the risk of dyskinesia. Results of randomized controlled trials supported an association between the levodopa dose and dyskinesia in patients with Parkinson's disease. Compared with levodopa users, users of other anti-Parkinson's drugs had a lower incidence of dyskinesia. Age, disease duration, and treatment duration were not correlated with dyskinesia. These findings suggest that anti-Parkinson's drugs other than levodopa, particularly in cases of early-stage Parkinson's disease, should be considered to reduce the risk of dyskinesia.
PubMed: 38515703
DOI: 10.1016/j.heliyon.2024.e27956 -
Tremor and Other Hyperkinetic Movements... 2024Tardive Dyskinesia (TD) is a neurological disorder characterized by involuntary movements, often caused by dopamine receptor antagonists. Vesicular Monoamine Transporter... (Comparative Study)
Comparative Study Review
BACKGROUND
Tardive Dyskinesia (TD) is a neurological disorder characterized by involuntary movements, often caused by dopamine receptor antagonists. Vesicular Monoamine Transporter 2 (VMAT2) inhibitors, such as valbenazine and deutetrabenazine, have emerged as promising therapies for TD and several clinical trials have shown their efficacy. This study aims to compare the efficacy and safety profile of VMAT2 inhibitors, focusing on a recent trial conducted in the Asian population.
METHODS
We reviewed the PubMed, Cochrane Library, Embase database, and clinicaltrials.gov between January 2017 and October 2023, using the keywords "tardive dyskinesia" AND ("valbenazine" [all fields] OR " deutetrabenazine " [all fields]) AND "clinical trial". The reviewed articles were studied for efficacy and side effects.
RESULTS
An initial search yielded 230 articles, of which 104 were duplicates. Following the title and abstract screening, 25 additional articles were excluded. A full-text review resulted in the exclusion of 96 more articles. Ultimately, four double-blind clinical trials met the inclusion criteria. The deutetrabenazine studies demonstrated significant improvements in Abnormal Involuntary Movement Scale (AIMS) scores compared to placebo, with no difference in adverse events. The valbenazine studies showed favorable results in reducing TD symptoms and were well-tolerated.
DISCUSSION
The studies reviewed in this analysis underscore the potential of deutetrabenazine and valbenazine as valuable treatment options for TD in diverse populations. Both medications demonstrated significant improvements in AIMS scores, suggesting their effectiveness in managing TD symptoms. Additionally, they exhibited favorable safety profiles, with low rates of serious adverse events and no significant increase in QT prolongation, parkinsonism, suicidal ideation, or mortality.
CONCLUSION
The studies reviewed highlight the promising efficacy and tolerability of deutetrabenazine and valbenazine as treatments for Tardive Dyskinesia, providing new hope for individuals affected by this challenging condition.
Topics: Humans; Randomized Controlled Trials as Topic; Tardive Dyskinesia; Tetrabenazine; Valine; Vesicular Monoamine Transport Proteins
PubMed: 38497033
DOI: 10.5334/tohm.842 -
Frontiers in Neuroscience 2024This study used network Meta-analysis to compare the effects of different transcranial magnetic stimulation (TMS) modalities on the effectiveness and long-term validity...
Effect of different modalities of transcranial magnetic stimulation on Parkinson's patients cognitive impairment and long-term effectiveness: a systematic review and network meta-analysis.
OBJECTIVE
This study used network Meta-analysis to compare the effects of different transcranial magnetic stimulation (TMS) modalities on the effectiveness and long-term validity of improving cognitive function in Parkinson's patients.
METHODS
Computer searches of the Cochrane Library, PubMed, Web of Science, Embass, CNKI and Wanfang Data were conducted to collect randomized controlled clinical studies on TMS to improve cognitive function in Parkinson's patients published from the time of library construction to December 2023.
RESULTS
A total of 22 studies and 1,473 patients were included, comprising 5 interventions: high frequency repetitive transcranial magnetic stimulation (HF-rTMS), low frequency repetitive transcranial magnetic stimulation (LF-rTMS), intermittent theta burst stimulation (iTBS), sham stimulation and conventional rehabilitation therapy (CRT). Network Meta-analysis showed that the ranking results of different TMS intervention modalities in terms of MoCA scores were: HF-rTMS > LF-rTMS > iTBS > sham > CRT, the ranking results of different TMS intervention modalities in terms of MMSE scores were: HF-rTMS > LF-rTMS > sham > CRT. The effect of TMS on improving Parkinsonian cognitive function lasted for 1 month compared to the no-stimulation group.
CONCLUSION
TMS has some long-term sustained effects on improving cognitive function in Parkinson's patients. HF-rTMS is more effective in improving cognitive function in Parkinson's patients.: https://www.crd.york.ac.uk/PROSPERO, identifier: CRD42023463958.
PubMed: 38495111
DOI: 10.3389/fnins.2024.1354864 -
International Journal of Molecular... Mar 2024This systematic review addresses the use of ( in the symptomatological intervention of neurodegenerative disease. The existence of gut microbiota dysbiosis has been... (Review)
Review
This systematic review addresses the use of ( in the symptomatological intervention of neurodegenerative disease. The existence of gut microbiota dysbiosis has been associated with systemic inflammatory processes present in neurodegenerative disease, creating the opportunity for new treatment strategies. This involves modifying the strains that constitute the gut microbiota to enhance synaptic function through the gut-brain axis. Recent studies have evaluated the beneficial effects of the use of on motor and cognitive symptomatology, alone or in combination. This systematic review includes 20 research articles ( = 3 in human and = 17 in animal models). The main result of this research was that the use of alone or in combination produced improvements in symptomatology related to neurodegenerative disease. However, one of the studies included reported negative effects after the administration of . This systematic review provides current and relevant information about the use of this probiotic in pathologies that present neurodegenerative processes such as Alzheimer's disease, Parkinson's disease and Multiple Sclerosis.
Topics: Animals; Humans; Neurodegenerative Diseases; Access to Information; Alzheimer Disease; Parkinson Disease; Lactobacillus plantarum; Probiotics
PubMed: 38474254
DOI: 10.3390/ijms25053010 -
The Patient Jul 2024Compared with early stages (eBC) metastatic BC (mBC) is incurable. In mBC, aggressive treatment may increase the duration of survival but may also cause severe treatment...
INTRODUCTION
Compared with early stages (eBC) metastatic BC (mBC) is incurable. In mBC, aggressive treatment may increase the duration of survival but may also cause severe treatment side effects. A better understanding how patients with BC value different aspects of drug therapy might improve treatment effectiveness, satisfaction and adherence. This systematic review aims to identify and summarise studies evaluating patient preferences for drug therapy of BC and to compare preferences of patients with eBC and mBC.
METHODS
The systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The electronic databases PubMed and Web of Science were searched on 22 June 2023. All studies published to this point were considered. Original studies reporting patient preferences on BC drug therapy determined by any type of choice experiment were eligible. A narrative synthesis of the effect measures presented as relative importance ratings, trade-offs (required benefit to make a therapy worthwhile) or monetary values of the treatment attributes was reported for each study. Risk of bias assessment for individual studies was performed using the checklist for observational studies from the STROBE Statement and the checklist from 'Conducting Discrete Choice Experiments to Inform Healthcare Decision Making: A User's Guide'. The study protocol was registered at the PROSPERO database (CRD42022377031).
RESULTS
A total of 34 studies met the inclusion criteria were included in the analysis evaluating the preferences of patients with eBC (n = 18), mBC (n = 10) or any stage BC (n = 6) on, for example, chemotherapy, endocrine therapy, hormonal therapy or CKD4/6-inhibitors using different types of choice experiments. Regardless of the stage, most patients valued treatment effectiveness in terms of survival gains higher than potential adverse drug reactions (ADRs). Treatment cost, mode of administration, treatment regimen and monitoring aspects were considered as least important treatment attributes. In addition, preferences concerning 16 different types of ADRs were described, showing high heterogeneity within BC stages. Yet, comparable results across BC stages were observed.
CONCLUSIONS
Regardless of the stage, patients with BC consistently valued survival gains as the most important attribute and were willing to accept the risk of potential ADRs. Incorporating patient preferences in shared decision making may improve the effectiveness of interventions by enhancing adherence to drug therapy in patients suffering from BC.
Topics: Humans; Patient Preference; Breast Neoplasms; Female; Neoplasm Staging; Antineoplastic Agents; Neoplasm Metastasis
PubMed: 38451419
DOI: 10.1007/s40271-024-00679-6 -
Aging Clinical and Experimental Research Mar 2024Mild cognitive impairment (MCI) may evolve into dementia. Early recognition of possible evolution to Alzheimer's disease (AD) and dementia with Lewy Bodies (DLB) is of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Mild cognitive impairment (MCI) may evolve into dementia. Early recognition of possible evolution to Alzheimer's disease (AD) and dementia with Lewy Bodies (DLB) is of importance, but actual diagnostic criteria have some limitations. In this systematic review and meta-analysis, we aimed to find the most accurate markers that can discriminate patients with DLB versus AD, in MCI stage.
METHODS
We searched several databases up to 17 August 2023 including studies comparing markers that may distinguish DLB-MCI from AD-MCI. We reported data regarding sensitivity, specificity, and the area under the curves (AUCs) with their 95% confidence intervals (CIs).
RESULTS
Among 2219 articles initially screened, eight case-control studies and one cohort study were included for a total of 832 outpatients with MCI. The accuracy of cerebrospinal fluid (CSF) markers was the highest among the markers considered (AUC > 0.90 for the CSF markers), with the AUC of CSF Aβ42/Aβ40 of 0.94. The accuracy for clinical symptom scales was very good (AUC = 0.93), as evaluated in three studies. Although limited to one study, the accuracy of FDG-PET (cingulate island sign ratio) was very good (AUC = 0.95) in discriminating DLB from AD in MCI, while the accuracy of SPECT markers and EEG frequencies was variable.
CONCLUSIONS
Few studies have assessed the accuracy of biomarkers and clinical tools to distinguish DLB from AD at the MCI stage. While results are promising for CSF markers, FDG-PET and clinical symptoms scales, more studies, particularly with a prospective design, are needed to evaluate their accuracy and clinical usefulness.
CLINICAL TRIAL REGISTRATION
Prospero (CRD42023422600).
Topics: Humans; Alzheimer Disease; Cohort Studies; Fluorodeoxyglucose F18; Lewy Body Disease; Cognitive Dysfunction
PubMed: 38451331
DOI: 10.1007/s40520-024-02704-y -
Frontiers in Neuroscience 2024Sleep disorders are one of the most common non-motor symptoms in PD. It can cause a notable decrease in quality of life and functioning in PD patients, as well as place...
BACKGROUND
Sleep disorders are one of the most common non-motor symptoms in PD. It can cause a notable decrease in quality of life and functioning in PD patients, as well as place a huge burden on both patients and caregivers. Currently, there are numerous non-pharmacological interventions available to improve sleep quality in PD, with disagreement as to which intervention is most effective. This network meta-analysis was performed to compare and rank non-pharmacological interventions to explore their efficacy in improving sleep quality in PD and to select the best interventions, with a view to providing references and bases for the development of clinical treatments and care programs.
METHODS
The PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, China National Knowledge Infrastructure (CNKI), and Wanfang databases were searched from inception to December 6, 2023. Two authors independently screened all studies, extracted the data, and evaluated risk of bias of included studies. STATA software version 17.0 was used to conduct the network meta-analysis.
RESULTS
Our network meta-analysis included 29 studies involving 1,477 participants and 16 non-pharmacological interventions. Although most nonpharmacological interventions showed non-significant effects, the surface under the cumulative ranking curve (SUCRA) values indicated that the best non-pharmacological intervention for sleep disorders was massage therapy (97.3%), followed by music therapy (94.2%), and Treadmill training (85.7%).
CONCLUSION
Massage therapy can be considered as an effective therapy for improving sleep quality in patients with PD. Due to limited quantity and quality of the included studies, more high quality studies are required to verify the conclusions of this network meta-analysis.
SYSTEMATIC REVIEW REGISTRATION
identifier CRD42023429339, PROSPERO (york.ac.uk).
PubMed: 38449730
DOI: 10.3389/fnins.2024.1337616 -
Frontiers in Physiology 2024Brain-Derived Neurotrophic Factor (BDNF) serum levels are reduced in patients with Parkinson's Disease (PD). This study aimed to assess the effect of exercise...
Brain-Derived Neurotrophic Factor (BDNF) serum levels are reduced in patients with Parkinson's Disease (PD). This study aimed to assess the effect of exercise intensity, volume and type on BDNF levels in patients with PD. We searched clinicaltrials.gov, CINAHL, Embase, PubMed, Scopus, Web of Science for both controlled and non-controlled studies in patients with PD, published between 2003 and 2022, which assessed Brain-Derived Neurotrophic Factor before and after different exercise protocols. Exercise intensity was estimated using a time-weighted average of Metabolic Equivalent of Task (MET), while exercise volume was estimated by multiplying MET for the duration of exercise. Exercise types were classified as aerobic, resistance, balance and others. We computed two distinct standardized measures of effects: Hedges' g to estimate differences between experimental and control group in pre-post intervention BDNF changes, and Cohen's d to measure pre-post intervention changes in BDNF values for each study arm. Meta-regression and linear regression were used to assess whether these effect measures were associated with intensity, volume and type. PROSPERO registration number: CRD42023418629. Sixteen studies (8 two-arm trials and 8 single-arm trials) including 370 patients with PD were eligible for the systematic review. Selected studies had a large variability in terms of population and intervention characteristics. The meta-analysis showed a significant improvement in BDNF levels in the exercise group compared to the control group, Hedges' g = 0.70 (95% CI: 0.03, 1.38), with substantial heterogeneity (I = 76.0%). Between-group differences in intensity were positively associated with change in BDNF in a subset of 5 controlled studies. In the analysis which included non-controlled studies, intensity and total exercise volume were both positively associated with BDNF change. No difference was found according to exercise type. Exercises of greater intensity may increase BDNF levels in patients with PD, while the role of volume of exercise needs to be further explored.
PubMed: 38444767
DOI: 10.3389/fphys.2024.1352305 -
Journal of Frailty, Sarcopenia and Falls Mar 2024Physical activity and exercise can limit the development of sarcopenia in Parkinson's Disease. This review aims to evaluate the potential effects of behavioural change... (Review)
Review
A systematic review of Behaviour Change Interventions to improve exercise self-efficacy and adherence in people with Parkinson's disease using the Theoretical Domains Framework.
Physical activity and exercise can limit the development of sarcopenia in Parkinson's Disease. This review aims to evaluate the potential effects of behavioural change (BC) interventions on exercise self-efficacy and adherence in people with Parkinson's. We searched nine databases and included randomised and non-randomised studies reporting exercise self-efficacy, quality of life (QoL), physical function and/or exercise adherence. Two reviewers independently screened, data extracted, and assessed risk of bias and certainty of evidence. The interventions were mapped to the Theoretical Domains Framework. Eleven studies (n=901) were included. Four were randomised trials and risk of bias was mixed. Most interventions were multi-component, including education, behavioural techniques, and support groups. The most effective domains appear to be . Future research should examine multi-component BC interventions encompassing the five most effective TDF domains.
PubMed: 38444546
DOI: 10.22540/JFSF-09-066 -
Heliyon Mar 2024Minimum clinically important difference MCID) is the smallest change in an outcome measure that is considered clinically meaningful. Using validated MCID thresholds for...
Bridging the gap between statistical significance and clinical relevance: A systematic review of minimum clinically important difference (MCID) thresholds of scales reported in movement disorders research.
BACKGROUND
Minimum clinically important difference MCID) is the smallest change in an outcome measure that is considered clinically meaningful. Using validated MCID thresholds for outcomes powers trials adequately to detect meaningful treatment effects, aids in their interpretation and guides development of new outcome measures.
OBJECTIVES
To provide a comprehensive summary of MCID thresholds of various symptom severity scales reported in movement disorder.
METHODS
We conducted systematic review of the literature and included studies of one or more movement disorders, and reporting MCID scales.
RESULTS
2763 reports were screened. Final review included 32 studies. Risk of bias (RoB) assessment showed most studies were of good quality. Most commonly evaluated scale was Unified Parkinson's Disease Rating Scale (UPDRS) (11 out of 32). Four studies assessing MDS-UPDRS had assessed its different sub-parts, reporting a change of 2.64,3.05,3.25 and 0.9 points to detect clinically meaningful improvement and 2.45,2.51,4.63 and 0.8 points to detect clinically meaningful worsening, for the Part I, II, III and IV, respectively. For Parts II + III, I + II + III and I + II + III + IV, MCID thresholds reported for clinically meaningful improvement were 5.73, 4.9, 6.7 and 7.1 points respectively; while those for clinically meaningful worsening were 4.7, 4.2, 5.2 and 6.3 points, respectively. MCID thresholds reported for other scales included Abnormal Involuntary Movement Scale (AIMS), Toronto Western Spasmodic Torticollis Rating Scale (TWSRS), and Burke-Fahn-Marsden Dystonia Scale (BFMD).
CONCLUSION
This review summarizes all the MCID thresholds currently reported in Movement disorders research and provides a comprehensive resource for future trials, highlighting the need for standardized and validated MCID scales in movement disorder research.
PubMed: 38439837
DOI: 10.1016/j.heliyon.2024.e26479