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Cureus Sep 2022Parkinson's disease (PD) is a chronic neurodegenerative disease that is challenging to treat due to its progressive nature and its weaning response to therapy.... (Review)
Review
Parkinson's disease (PD) is a chronic neurodegenerative disease that is challenging to treat due to its progressive nature and its weaning response to therapy. Safinamide, a monoamine oxidase type-B inhibitor (MAOB-I), has shown promise in managing dyskinesias caused by levodopa (L-dopa), carbidopa, and PD features such as pain and depression. This systematic review aimed to evaluate safinamide's efficacy as a monotherapy and an add-on in tackling these issues. We composed this systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Our group searched the following databases: Manchester University Library, ScienceDirect, Google Scholar, PubMed, PubMed Central, and MedLine for articles produced in the last ten years using various search terms and criteria, which we outlined in the search strategy and eligibility criteria sections. We excluded 722 out of the initially screened 730 records for multiple reasons, such as titles and abstracts being irrelevant to the topic, articles without free full access, articles originally not in the English language, and articles that did not score 70% or above on their respective quality assessment tools. The studies explored supported safinamide's use in managing motor fluctuations, pain, depression, and improving patients' quality of life.
PubMed: 36259026
DOI: 10.7759/cureus.29118 -
Frontiers in Neurology 2022Parkinson's disease (PD) causes movement disorders [called motor symptoms (MS)], and motor dysfunction poses a great barrier to the quality of life. Although...
BACKGROUND
Parkinson's disease (PD) causes movement disorders [called motor symptoms (MS)], and motor dysfunction poses a great barrier to the quality of life. Although pharmacological therapy like levodopa can relieve the symptoms, it can also cause complications, such as psychosis, nausea, and dyskinesia. A therapy with more minor side effects is needed for PD. Therapeutic massages are the most commonly used forms of complementary and alternative medicine (CAM), but no systematic review and meta-analysis have focused on the efficacy of massage on PD.
OBJECTIVE
To evaluate the quality of evidence and efficacy of therapeutic massage for improving MS in PD.
METHODS
We independently searched four electronic databases, including Chinese National Knowledge Infrastructure (CNKI), MEDLINE/PubMed, Embase, and Cochrane Library, for randomized controlled trials (RCTs) about therapeutic massage and other available manual therapies improving MS in PD from January 1, 2012, to December 31, 2021 (recent 10 years). The main outcome measures were total effectiveness and the Unified Parkinson's Disease Rating Scale (UPDRS), including UPDRS total, II, and III. For the statistical analysis, the risk ratio, standard mean difference, and 95% confidence interval (CI) were used to calculate effect sizes between groups. To determine heterogeneity, statistical index was used.
RESULTS
A total of 363 PD participants in seven RCTs and one randomized pilot-control study were included in this meta-analysis. The total effectiveness showed that therapeutic massage was more effective than the intervention of the control group for improving MS [ratio risk (RR): 1.33, 95% CI (1.14-1.55), = 0.0002]. The UPDRS-III scores showed that massage improves motor function more than the control group [SMD = -0.46, 95% CI (-0.67, -0.24), < 0.00001]. But we found that massage performed no better than the control group in improving daily life activities [SMD = -0.15, 95% CI (-0.40, 0.10), = 0.23].
CONCLUSION
Therapeutic massage was effective in improving MS in PD. It is suggested to be an appropriate form of CAM in treating PD.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=323182, identifier: CRD42022323182.
PubMed: 36133798
DOI: 10.3389/fneur.2022.915232 -
European Journal of Clinical... Nov 2022Antihypertensive drugs are among the most prescribed drugs during pregnancy. Methyldopa, labetalol, and nifedipine have been perceived safe to use during pregnancy and... (Review)
Review
PURPOSE
Antihypertensive drugs are among the most prescribed drugs during pregnancy. Methyldopa, labetalol, and nifedipine have been perceived safe to use during pregnancy and are therefore recommended in international guidelines for treatment of hypertension. In this review, we provide a complete overview of what is known on the pharmacokinetics (PK) of the antihypertensive drugs methyldopa, labetalol, and nifedipine throughout pregnancy.
METHODS
A systematic search was performed to retrieve studies on the PK of methyldopa, labetalol, and nifedipine used throughout pregnancy. The search was restricted to English and original studies. The systematic search was conducted on July 27, 2021, in Embase, Medline Ovid, Web of Science, Cochrane Library, and Google Scholar. Keywords were methyldopa, labetalol, nifedipine, pharmacokinetics, pregnancy, and placenta.
RESULTS
A total of 1459 unique references were identified of which title and abstract were screened. Based on this screening, 67 full-text papers were assessed, to retain 30 PK studies of which 2 described methyldopa, 12 labetalol, and 16 nifedipine. No fetal accumulation is found for any of the antihypertensive drugs studied.
CONCLUSION
We conclude that despite decades of prescribing methyldopa, labetalol, and nifedipine throughout pregnancy, descriptions of their PK during pregnancy are hampered by a large heterogeneity in the low number of available studies. Aiming for evidence-based and personalized dosing of antihypertensive medication in the future, further studies on the relationship of both PK and pharmacodynamics (including the optimal blood pressure targeting) during pregnancy and pregnancy-related pathology are urgently needed to prevent undertreatment, overtreatment, and side effects.
Topics: Antihypertensive Agents; Female; Humans; Hypertension; Hypertension, Pregnancy-Induced; Labetalol; Methyldopa; Nifedipine; Pregnancy; Pregnancy Complications, Cardiovascular
PubMed: 36104450
DOI: 10.1007/s00228-022-03382-3 -
Parkinson's Disease 2022Rasagiline is a selective, irreversible monoamine oxidase type B inhibitor used as monotherapy in early Parkinson's disease and as an adjunct therapy to levodopa in...
BACKGROUND
Rasagiline is a selective, irreversible monoamine oxidase type B inhibitor used as monotherapy in early Parkinson's disease and as an adjunct therapy to levodopa in Parkinson's disease with motor fluctuations.
OBJECTIVES
This meta-analysis aimed to provide updated evidence on the efficacy for motor and nonmotor symptoms and the safety of rasagiline/levodopa versus levodopa in patients with Parkinson's disease experiencing motor fluctuations.
METHODS
A systematic literature search was conducted (January 18-19, 2021) using PubMed, Cochrane Library, EMBASE, Web of Science, and Google Scholar to identify randomized controlled trials comparing rasagiline/levodopa versus placebo/levodopa in patients with Parkinson's disease experiencing motor fluctuations. Outcomes included change in wearing-off time, Unified Parkinson's Disease Rating Scale (UPDRS)/Movement Disorder Society-UPDRS (MDS-UPDRS) II and III scores, treatment-emergent adverse events (TEAEs), and Parkinson's Disease Questionnaire (PDQ-39) summary index score. A random effect model was used to estimate the treatment effects.
RESULTS
Six studies were included (1912 patients). Significant improvements in wearing-off time (standardized mean difference [SMD]: -0.50, 95% confidence interval [CI]: -0.92 to -0.09, = 0.002), levodopa dosage (SMD: -0.18, 95% CI: -0.35 to -0.01, = 0.041), UPDRS/MDS-UPDRS II (SMD: -0.39, 95% CI: -0.52 to -0.25, < 0.0001), UPDRS/MDS-UPDRS III (SMD: -0.30, 95% CI: -0.44 to -0.16, < 0.0001), and PDQ-39 summary index score (SMD: -0.21, 95% CI: -0.37 to -0.04, = 0.013) were observed with rasagiline/levodopa versus placebo/levodopa. The incidence of TEAEs did not differ between treatments (risk ratio: 1.13, 95% CI: 0.98-1.30, = 0.093).
CONCLUSIONS
This meta-analysis further indicated the superiority of rasagiline/levodopa in improving motor and nonmotor symptoms of Parkinson's disease, with a similar safety profile to that of levodopa in Parkinson's disease with motor fluctuations.
PubMed: 36081594
DOI: 10.1155/2022/4216452 -
Annals of Medicine and Surgery (2012) Aug 2022There remains a scarcity of literature regarding COVID-19 and its neurological sequelae. This study highlights Parkinsonism as a post-COVID-19 sequela and helps us... (Review)
Review
BACKGROUND
There remains a scarcity of literature regarding COVID-19 and its neurological sequelae. This study highlights Parkinsonism as a post-COVID-19 sequela and helps us understand a possible link between the two.
METHODS
A literature search covering relevant databases was conducted for studies reporting the development of Parkinsonism in patients recovering from COVID-19 infection. A quality assessment tool developed by The Joanna Briggs Institute Critical Appraisal tools for the assessment of case reports was utilized. Fisher's exact test was used to explore the factors associated with COVID-19 and Parkinsonism as its complication.
RESULTS
Ten studies were included in our study. The median age of patients was 60.0, with an interquartile range of 42.5-72.0. There were 8 males (61.5%) patients, and 53.8% of cases were reported to have at least one comorbidity. Cogwheel rigidity was the most common symptom of Parkinsonism in 11 patients. While the most standard treatment modality used was Levodopa in 76.9% of cases. Using the Fisher's Exact test, it was identified that 10 patients (76.9%) with bradykinesia made a full recovery.
CONCLUSION
Despite presumed "recovery" from COVID-19, patients still face a wide range of neurological complications. One of these complications presenting as Parkinsonism requires health care professionals to be on the lookout for the long-term effects of COVID-19. Hence, our study provides information on the possible likely hood of a link between COVID-19 and the development of Parkinsonism as post-COVID neurological sequelae.
PubMed: 35971509
DOI: 10.1016/j.amsu.2022.104281 -
Journal of Parkinson's Disease 2022STN-DBS is a cornerstone in the treatment of advanced Parkinson's disease (PD). The traditional approach is to use an awake operative technique with microelectrode... (Meta-Analysis)
Meta-Analysis
BACKGROUND
STN-DBS is a cornerstone in the treatment of advanced Parkinson's disease (PD). The traditional approach is to use an awake operative technique with microelectrode recording (MER). However, more centers start using an asleep MRI-guided technique without MER.
OBJECTIVE
We systematically reviewed the literature to compare STN-DBS surgery with and without MER for differences in clinical outcome.
METHODS
We systematically searched PubMed, Embase, MEDLINE, and Web of Science databases for randomized clinical trials and consecutive cohort studies published between 01-01-2000 and 26-08-2021, that included at least 10 PD patients who had received bilateral STN-DBS.
RESULTS
2,129 articles were identified. After abstract screening and full-text review, 26 studies were included in the final analysis, comprising a total of 34 study groups (29 MER and 5 non-MER). The standardized mean difference (SMD) in change in motor symptoms between baseline (OFF medication) and 6-24 months follow-up (OFF medication and ON stimulation) was 1.64 for the MER group and 1.87 for non-MER group (p = 0.59). SMD in change in levodopa equivalent daily dose (LEDD) was 1.14 for the MER group and 0.65 for non-MER group (p < 0.01). Insufficient data were available for comparative analysis of PDQ-39 and complications.
CONCLUSION
The change in motor symptoms from baseline to follow-up did not differ between studies that used MER and those that did not. The postoperative reduction in LEDD from baseline to follow-up was greater in the MER-group. In the absence of high-quality studies comparing both methods, there is a clear need for a well-designed comparative trial.
Topics: Deep Brain Stimulation; Humans; Levodopa; Microelectrodes; Parkinson Disease; Subthalamic Nucleus; Treatment Outcome
PubMed: 35912752
DOI: 10.3233/JPD-223333 -
Journal of Comparative Effectiveness... Aug 2022To assess the clinical efficacy and safety profile of opicapone (25 and 50 mg once daily) versus placebo. Levodopa-treated adults with Parkinson's disease. A... (Meta-Analysis)
Meta-Analysis Review
To assess the clinical efficacy and safety profile of opicapone (25 and 50 mg once daily) versus placebo. Levodopa-treated adults with Parkinson's disease. A systematic review and meta-analysis were conducted. Opicapone provided a greater reduction in the absolute OFF-time, increased the chances of ≥1-h reduction in the OFF-time and ≥1-h increase in the ON-time compared with placebo. Receiving opicapone more often facilitated levodopa dose reduction versus placebo. There were no differences in the occurrence of adverse events (severe and leading to drug discontinuation), but receiving opicapone increased the frequency of dyskinesia. Opicapone demonstrated superior clinical efficacy to placebo, with a comparable general safety profile.
Topics: Adult; Antiparkinson Agents; Catechol O-Methyltransferase Inhibitors; Double-Blind Method; Humans; Levodopa; Oxadiazoles; Parkinson Disease
PubMed: 35758044
DOI: 10.2217/cer-2022-0031 -
Neurology. Clinical Practice Apr 2022To investigate the efficacy and safety of CVT-301 in treating motor fluctuation in patients with Parkinson disease (PD). (Review)
Review
PURPOSE OF REVIEW
To investigate the efficacy and safety of CVT-301 in treating motor fluctuation in patients with Parkinson disease (PD).
RECENT FINDINGS
This study demonstrated that the CVT-301 group had a higher proportion of patients achieving an ON state than the placebo group (odds ratio [OR] = 2.68; 95% confidence interval [CI]: 1.86-3.86; < 0.00001). Moreover, CVT-301 had also shown to improve motor function by Unified Parkinson Disease Rating Scale part III score (standardized mean difference = 3.83; 95% CI: 2.44-5.23; < 0.00001) and promote an overall improvement of PD by Patient Global Impression of Change self-rating (OR = 2.95; 95% CI: 1.78-4.9; < 0.00001). The most common adverse events encountered were respiratory symptoms (OR = 12.18; 95% CI: 5.01-29.62; < 0.00001) and nausea (OR = 3.95; 95% CI: 1.01-15.41; = 0.05).
SUMMARY
CVT-301 had the potential to be an alternative or even a preferred treatment for motor fluctuation in patients with PD.
PubMed: 35747892
DOI: 10.1212/CPJ.0000000000001143 -
Cureus Apr 2022Stroke is a leading cause of death and disability, especially in certain ethnic groups. Impaired consciousness is a common outcome in stroke patients, serving as a... (Review)
Review
Stroke is a leading cause of death and disability, especially in certain ethnic groups. Impaired consciousness is a common outcome in stroke patients, serving as a predictor of prognosis and mortality. Lately, there has been increased interest in drugs such as Levodopa (LD), which have been found to promote wakefulness. To further appreciate this association, we gathered updated evidence of this novel therapeutic approach and compared it, evaluating its clinical use in an acute stroke setting. We carried out a systematic review of clinical trials conducted exclusively on stroke patients who received levodopa. Four clinical trials were reviewed and analyzed after applying the inclusion/exclusion criteria. The use of levodopa showed positive results in four of the clinical trials, and statistically significant results in 3/4 of the studies; however, more studies need to be conducted to corroborate these results.
PubMed: 35651458
DOI: 10.7759/cureus.24529 -
Frontiers in Aging Neuroscience 2022Non-ergot dopamine agonist (NEDA) are recommended as the first-line treatment for patients with early Parkinson's disease (PD) because of their efficacy in treating PD...
The Comparative Efficacy of Non-ergot Dopamine Agonist and Potential Risk Factors for Motor Complications and Side Effects From NEDA Use in Early Parkinson's Disease: Evidence From Clinical Trials.
BACKGROUND/OBJECTIVES
Non-ergot dopamine agonist (NEDA) are recommended as the first-line treatment for patients with early Parkinson's disease (PD) because of their efficacy in treating PD motor symptoms. However, systematic evaluations of the risk of motor complications induced by NEDA and risk factors potentially associated with motor complications are still lacking.
METHODS
Medline, Embase, the Cochrane Central Register of Controlled Trials, and Web of Science were searched for potentially eligible randomized controlled trials. The incidence of motor complications (dyskinesia, motor fluctuations), impulsive-compulsive behaviors and adverse events and clinical disability rating scale (UPDRS) scores were evaluated using standard meta-analytic methods. Metaregression was conducted on the incidence of motor complications (dyskinesia) with treatment duration and NEDA dose as covariates.
RESULTS
Patients treated with NEDA had significantly lower UPDRS total scores, motor scores and activity of daily living (ADL) scores than those receiving a placebo (weighted mean difference (WMD) -4.81, 95% CI -6.57 to -3.05; WMD -4.901, 95% CI -7.03 to -2.77; WMD -1.52, 95% CI -2.19 to -0.84, respectively). Patients in the NEDA and NEDA+open Levodopa (LD) groups had lower odds for dyskinesia than patients in the LD group (OR = 0.21, 95% CI: 0.15-0.29; OR = 0.31, 95% CI 0.24-0.42, respectively). Metaregressions indicated that the mean LD dose of the NEDA group increased, and the odds of developing dyskinesia increased ( = 0.012). However, the odds of developing dyskinesia in the NEDA group were not related to treatment duration ( = 0.308). PD patients treated with NEDA or NEDA+open LD had a lower risk of wearing-off implications than those treated with LD (all < 0.05). No significant difference was found between the NEDA and placebo groups in impulsive-compulsive behavior development ( > 0.05). Patients in the NEDA group were more likely to suffer somnolence, edema, constipation, dizziness, hallucinations, nausea and vomiting than those in the placebo or LD group.
CONCLUSION
NEDA therapy reduces motor symptoms and improves ADLs in early PD. The odds of developing motor complications were lower with NEDA than with LD, and dyskinesia increased with increasing LD equivalent dose and was not influenced by NEDA treatment duration. Therefore, long-term treatment with an appropriate dosage of NEDA might be more suitable than LD for early PD patients.
REGISTRATION
PROSPERO CRD42021287172.
PubMed: 35527736
DOI: 10.3389/fnagi.2022.831884