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Disease-a-month : DM Jul 2024Parkinson's disease (PD) is a neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the brain. Despite existing treatments, there...
BACKGROUND
Parkinson's disease (PD) is a neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the brain. Despite existing treatments, there remains an unmet need for therapies that can halt or reverse disease progression. Gene therapy has been tried and tested for a variety of illnesses, including PD. The goal of this systematic review is to assess gene therapy techniques' safety and effectiveness in PD clinical trials.
METHODS
Online databases PubMed/Medline, and Cochrane were used to screen the studies for this systematic review. The risk of bias of the included studies was assessed using standard tools.
RESULTS
Gene therapy can repair damaged dopaminergic neurons from the illness or deal with circuit anomalies in the basal ganglia connected to Parkinson's disease symptoms. Rather than only treating symptoms, this neuroprotective approach alters the illness itself. Medication for gene therapy is currently administered at the patient's bedside. It can hyperactivate specific brain circuits associated with motor dysfunction. PD therapies are developing quickly, and there aren't enough head-to-head trials evaluating the safety and effectiveness of available treatments. When choosing an advanced therapy, patient-specific factors should be considered in addition to the effectiveness and safety of each treatment option.
CONCLUSION
In comparison to conventional therapies, gene therapy may be advantageous for PD. It may minimize side effects, relieve symptoms, and offer dependable dopamine replacement.
Topics: Humans; Parkinson Disease; Genetic Therapy; Treatment Outcome
PubMed: 38849290
DOI: 10.1016/j.disamonth.2024.101754 -
Annals of Medicine and Surgery (2012) Jun 2024Recent studies have tried to establish an association between the use of alpha-1-adrenergic receptor antagonists (A1ARAs) used in benign prostatic hyperplasia (BPH) and...
BACKGROUND
Recent studies have tried to establish an association between the use of alpha-1-adrenergic receptor antagonists (A1ARAs) used in benign prostatic hyperplasia (BPH) and the risk of PD. The objective of the study is to compare the risk of Parkinson's disease (PD) between terazosin/alfuzosin/doxazosin (TZ/AZ/DZ) users and tamsulosin users.
METHODS
PubMed, Google Scholar, and Embase were systematically searched from inception to April 2023. Observational studies comparing the risk of PD among patients using different types of A1ARAs were included in the meta-analysis. The primary outcome was the hazard ratio (HR) with a 95% CI for the risk of occurrence of PD among A1ARAs users of two different classes.
RESULTS
This study was based on a total of 678 433 BPH patients, out of which 287 080 patients belonged to the TZ/AZ/DZ cohort and 391 353 patients belonged to the tamsulosin cohort. The pooled incidence of PD was higher in tamsulosin users (1.28%, 95% CI: 1.04-1.55%) than in TZ/AZ/DZ drug users (1.11%, 95% CI: 0.83-1.42%). The risk of occurrence of PD was significantly lower in patients taking TZ/AZ/DZ than tamsulosin (= 610,363, HR = 0.82, 95% CI = 0.71-0.94, = 0.01; I = 87.4%).
CONCLUSION
This meta-analysis demonstrated that patients with BPH who take TZ/AZ/DZ have a lower risk for developing PD than those who take tamsulosin.
PubMed: 38846867
DOI: 10.1097/MS9.0000000000002117 -
European Journal of Pharmacology Aug 2024Astaxanthin is a potent lipid-soluble carotenoid produced by several different freshwater and marine microorganisms, including microalgae, bacteria, fungi, and yeast.... (Review)
Review
Astaxanthin is a potent lipid-soluble carotenoid produced by several different freshwater and marine microorganisms, including microalgae, bacteria, fungi, and yeast. The proven therapeutic effects of astaxanthin against different diseases have made this carotenoid popular in the nutraceutical market and among consumers. Recently, astaxanthin is also receiving attention for its effects in the co-adjuvant treatment or prevention of neurological pathologies. In this systematic review, studies evaluating the efficacy of astaxanthin against different neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, cerebrovascular diseases, and spinal cord injury are analyzed. Based on the current literature, astaxanthin shows potential biological activity in both in vitro and in vivo models. In addition, its preventive and therapeutic activities against the above-mentioned diseases have been emphasized in studies with different experimental designs. In contrast, none of the 59 studies reviewed reported any safety concerns or adverse health effects as a result of astaxanthin supplementation. The preventive or therapeutic role of astaxanthin may vary depending on the dosage and route of administration. Although there is a consensus in the literature regarding its effectiveness against the specified diseases, it is important to determine the safe intake levels of synthetic and natural forms and to determine the most effective forms for oral intake.
Topics: Xanthophylls; Neuroprotective Agents; Humans; Animals; Neurodegenerative Diseases; Antioxidants; Aquatic Organisms
PubMed: 38843946
DOI: 10.1016/j.ejphar.2024.176706 -
Neurological Sciences : Official... Jun 2024To systematically review and conduct a meta-analysis to evaluate the safety and efficacy of the unilateral focused ultrasound (FUS) pallidotomy on motor complications in... (Review)
Review
To systematically review and conduct a meta-analysis to evaluate the safety and efficacy of the unilateral focused ultrasound (FUS) pallidotomy on motor complications in Parkinson's disease (PD) patients. A comprehensive search strategy was implemented through August 15, 2023, and updated on February 13, 2024, across six databases, identifying studies relevant to unilateral focused ultrasound pallidotomy and PD. Eligibility criteria included observational studies, clinical trials, and case series reporting on the impact of the intervention on motor complications in PD patients. The screening and data extraction were done by two independent reviewers. Risk of bias assessment utilized appropriate tools for different study designs. Statistical analysis involved narrative synthesis and meta-analysis. Subgroup analyses and leave-one-out analyses were performed. Five studies were included in our study, involving 112 PD patients undergoing FUS pallidotomy. UPDRS-II analysis revealed a significant improvement from baseline (mean difference (MD): -3.205, 95% CI: -4.501, -1.909, P < 0.001). UPDRS-III overall change was significant (MD: -10.177, 95% CI: [-12.748, -7.606], P < 0.001). UPDRS-IV showed a significant change from baseline (MD: -5.069, 95% CI: [-5.915, -4.224], P < 0.001). UDysRS demonstrated a significant overall improvement (MD: -18.895, 95% CI: [-26.973, -10.818], P < 0.001). The effect of FUS pallidotomy on motor complications in PD patients was effective, with a significant decrease in the UPDRS and UDysRS, reflecting improvement. The incidence of adverse events (headaches, pin-site pain, difficulty walking, and sonication-related head pain) of the FUS pallidotomy was not statistically significant, indicating its safety.
PubMed: 38842771
DOI: 10.1007/s10072-024-07617-2 -
Clinical Rehabilitation Jun 2024To systematically evaluate the efficacy and safety of acupuncture therapy for neuropsychiatric symptoms in patients with Parkinson's disease.
OBJECTIVE
To systematically evaluate the efficacy and safety of acupuncture therapy for neuropsychiatric symptoms in patients with Parkinson's disease.
METHODS
We searched eight databases from their inception until 14 April 2024, including PubMed, Cochrane Library, Embase, Web of Science, SinoMed, China National Knowledge Infrastructure, China Science and Technology Periodical Database, and Wanfang Database. The search aimed to find randomized controlled trials assessing the effectiveness of acupuncture for neuropsychiatric symptoms in patients with Parkinson's disease. Literature screening and data extraction were performed independently by the authors. Meta-analysis was conducted using RevMan V.5.3 software, and Stata 17.0 software was used for detecting publication bias and performing sensitivity analysis.
RESULTS
Twenty-eight studies, involving 2148 participants, met the inclusion criteria. The meta-analysis revealed that acupuncture therapy improved depression-related scale scores (standardized mean difference (SMD) = -0.70, 95%CI [-0.98, -0.42], < 0.00001), anxiety-related scale scores (SMD = -0.78, 95% CI [-1.43, -0.14], = 0.02), Montreal Cognitive Assessment scores (weighted mean difference (WMD) = 2.74, 95% CI [2.43, 3.05], < 0.00001), Mini Mental State Examination scores (WMD = 2.36, 95% CI [0.78, 3.94], = 0.003), Yale-Brown Obsessive Compulsive Scale scores, and Parkinson's Disease Questionnaire-39 scores (WMD = -2.66, 95% CI [-4.83, -0.49], = 0.02) compared to controls.
CONCLUSION
This review supports the application of acupuncture to reduce the severity of neuropsychiatric symptoms including depression, anxiety, and impulse control disorders, and to improve cognition and quality of life in patients with Parkinson's disease. The adverse effects associated with acupuncture, either alone or as adjunctive therapy, were relatively minor.
PubMed: 38840478
DOI: 10.1177/02692155241258278 -
Journal of Stroke May 2024Possible differences in the prevalence of cerebral amyloid angiopathy (CAA) in East-Asian compared to Western populations have received little attention, and results so... (Review)
Review
BACKGROUND AND PURPOSE
Possible differences in the prevalence of cerebral amyloid angiopathy (CAA) in East-Asian compared to Western populations have received little attention, and results so far have been ambiguous. Our aim is to compare the prevalence of CAA neuropathology and magnetic resonance imaging markers of CAA in East-Asian and Western cohorts reflecting the general population, cognitively normal elderly, patients with Alzheimer's disease (AD), and patients with (lobar) intracerebral hemorrhage (ICH).
METHODS
We performed a systematic literature search in PubMed and Embase for original research papers on the prevalence of CAA and imaging markers of CAA published up until February 17th 2022. Records were screened by two independent reviewers. Pooled estimates were determined using random-effects models. We compared studies from Japan, China, Taiwan, South Korea (East-Asian cohorts) to studies from Europe or North America (Western cohorts) by meta-regression models.
RESULTS
We identified 12,257 unique records, and we included 143 studies on Western study populations and 53 studies on East-Asian study populations. Prevalence of CAA neuropathology did not differ between East-Asian and Western cohorts in any of the investigated patient domains. The prevalence of strictly lobar microbleeds was lower in East-Asian cohorts of population-based individuals (5.6% vs. 11.4%, P=0.020), cognitively normal elderly (2.6% vs. 11.4%, P=0.001), and patients with ICH (10.2% vs. 24.6%, P<0.0001). However, age was in general lower in the East-Asian cohorts.
CONCLUSION
The prevalence of CAA neuropathology in the general population, cognitively normal elderly, patients with AD, and patients with (lobar) ICH is similar in East-Asian and Western countries. In East-Asian cohorts reflecting the general population, cognitively normal elderly, and patients with ICH, strictly lobar microbleeds were less prevalent, likely due to their younger age. Consideration of potential presence of CAA is warranted in decisions regarding antithrombotic treatment and potential new anti-amyloid-β immunotherapy as treatment for AD in East-Asian and Western countries alike.
PubMed: 38836267
DOI: 10.5853/jos.2023.04287 -
Neurology Jul 2024Clinical trials in neurodegenerative diseases often encounter selective enrollment and under-representation of certain patient populations. This delays drug development... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND OBJECTIVES
Clinical trials in neurodegenerative diseases often encounter selective enrollment and under-representation of certain patient populations. This delays drug development and substantially limits the generalizability of clinical trial results. To inform recruitment and retention strategies, and to better understand the generalizability of clinical trial populations, we investigated which factors drive participation.
METHODS
We reviewed the literature systematically to identify barriers to and facilitators of trial participation in 4 major neurodegenerative disease areas: Alzheimer disease, Parkinson disease, amyotrophic lateral sclerosis, and Huntington disease. Inclusion criteria included original research articles published in a peer-reviewed journal and evaluating barriers to and/or facilitators of participation in a clinical trial with a drug therapy (either symptomatic or disease-modifying). The Critical Appraisal Skills Program checklist for qualitative studies was used to assess and ensure the quality of the studies. Qualitative thematic analyses were employed to identify key enablers of trial participation. Subsequently, we pooled quantitative data of each enabler using meta-analytical models.
RESULTS
Overall, we identified 36 studies, enrolling a cumulative sample size of 5,269 patients, caregivers, and health care professionals. In total, the thematic analysis resulted in 31 unique enablers of trial participation; the key factors were patient-related (own health benefit and altruism), study-related (treatment and study burden), and health care professional-related (information availability and patient-physician relationship). When meta-analyzed across studies, responders reported that the reason to participate was mainly driven by (1) the relationship with clinical staff (70% of the respondents; 95% CI 53%-83%), (2) the availability of study information (67%, 95% CI 38%-87%), and (3) the use or absence of a placebo or sham-control arm (53% 95% CI 32%-72%). There was, however, significant heterogeneity between studies (all < 0.001).
DISCUSSION
We have provided a comprehensive list of reasons why patients participate in clinical trials for neurodegenerative diseases. These results may help to increase participation rates, better inform patients, and facilitate patient-centric approaches, thereby potentially reducing selection mechanisms and improving generalizability of trial results.
Topics: Humans; Neurodegenerative Diseases; Clinical Trials as Topic; Patient Participation; Patient Selection
PubMed: 38830181
DOI: 10.1212/WNL.0000000000209503 -
Environmental Pollution (Barking, Essex... May 2024Prior reviews have highlighted that nature exposure was a valuable coping strategy enhancing mental health during the COVID-19 pandemic. However, no existing reviews... (Review)
Review
Prior reviews have highlighted that nature exposure was a valuable coping strategy enhancing mental health during the COVID-19 pandemic. However, no existing reviews have determined the quality of evidence and risk of bias of the empirical studies supporting this claim. To address this gap, we employed a Navigation Guide systematic review and meta-analysis approach to investigate associations between nature exposure and mental health during the pandemic. Searches in PubMed, Web of Science, Scopus, CINAHL, and PsycInfo retrieved relevant articles published between January 1, 2020, and March 4, 2024. We used the Navigation Guide methodology to assess the risk of bias and Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) assessments to evaluate the overall quality of evidence. Our search retrieved 113 studies that met the inclusion criteria and reported diverse types of exposure, including nature availability, nature visit frequency, green space accessibility, and green space type, alongside associations with 12 mental health outcomes. Meta-analyses found access to gardens was associated with lower odds of depression [(Pooled odds ratio [OR] = 0.71, 95%CI = 0.61, 0.82), I = 0%, n = 3] and anxiety [(Pooled OR = 0.73, 95%CI = 0.63, 0.84), I = 0%, n = 3]. Increased time in green spaces was associated with lower level of stress [(Pooled Corr = -0.11, 95%CI = -0.17, -0.05), I = 0%, n = 2]. Higher frequency of visits to nature was associated with improved mental well-being [(Pooled standardized beta = 0.10, 95%CI = 0.07, 0.14), I = 0%, n = 2] and general mental health [(Pooled standardized beta = 0.11, 95%CI = 0.03-0.38), I = 82%, n = 2]. However, the number of pooled studies was small and the overall quality of evidence was "very low" for all outcomes, and high levels of bias were observed (26% of studies had high, 71% probably high). Nonetheless, given the trends in the results, nature-based solutions emphasizing exposure to gardens and green spaces near the home may have promoted psychological resilience during this public health crisis.
PubMed: 38821342
DOI: 10.1016/j.envpol.2024.124284 -
Frontiers in Molecular Neuroscience 2024This study aims to visualize the trends and hotspots in the research of "ferroptosis in PD" and "pyroptosis in PD" through bibliometric analysis from the past to 2024.
OBJECTIVE
This study aims to visualize the trends and hotspots in the research of "ferroptosis in PD" and "pyroptosis in PD" through bibliometric analysis from the past to 2024.
METHODS
Literature was retrieved from the Web of Science Core Collection (WoSCC) from the past to February 16, 2024, and bibliometric analysis was conducted using Vosviewer and Citespace.
RESULTS
283 and 542 papers were collected in the field of "ferroptosis in PD" and "pyroptosis in PD." The number of publications in both fields has increased yearly, especially in "ferroptosis in PD," which will become the focus of PD research. China, the United States and England had extensive exchanges and collaborations in both fields, and more than 60% of the top 10 institutions were from China. In the fields of "ferroptosis in PD" and "pyroptosis in PD," the University of Melbourne and Nanjing Medical University stood out in terms of publication numbers, citation frequency, and centrality, and the most influential journals were Cell and Nature, respectively. The keyword time zone map showed that molecular mechanisms and neurons were the research hotspots of "ferroptosis in PD" in 2023, while memory and receptor 2 were the research hotspots of "pyroptosis in PD" in 2023, which may predict the future research direction.
CONCLUSION
This study provides insights into the development, collaborations, research themes, hotspots, and tendencies of "ferroptosis in PD" and "pyroptosis in PD." Overall situation of these fields is available for researchers to further explore the underlying mechanisms and potential treatments.
PubMed: 38817551
DOI: 10.3389/fnmol.2024.1400668 -
The Canadian Journal of Neurological... May 2024This systematic review primarily aims to identify the optimal physiotherapeutic intervention to improve hand dexterity in Parkinson's Disease (PD) patients. The... (Review)
Review
Evidence-Based Physiotherapeutic Interventions Enhancing Hand Dexterity, Activities of Daily Living and Quality of Life of Parkinson's Disease Patients: A Systematic Review.
OBJECTIVES
This systematic review primarily aims to identify the optimal physiotherapeutic intervention to improve hand dexterity in Parkinson's Disease (PD) patients. The secondary objectives were to identify the hand dexterity physiotherapeutic interventions available for PD patients, and to determine the quality of these interventions.
REVIEW METHODS
Eight electronic databases were systematically searched to identify relevant randomized controlled trial full-text articles using the established search strategy. The primary outcomes of interest were measurements for hand dexterity and activities of daily living (ADL).
RESULTS
A total of 11 studies comprising 647 participants with PD were included. Most studies had a high risk of performance bias and an unclear risk of selection bias. The intervention training period ranged from a single session to 12 weeks. Compared to their respective control group, eight out of 11 studies revealed significant results in hand dexterity, two out of three studies reported positive effects on ADL, four of seven studies showed significant improvements in upper limb motor performance, and two studies perceived positive benefits in terms of overall quality of life. Five out of 11 studies that recorded the occurrence of adverse events reported no adverse events post-intervention.
CONCLUSION
The dearth of evidence made it difficult to support any one intervention as the best intervention when compared to the other PD treatments in upper limb rehabilitation. Regardless, a home-based dexterity rehabilitation programme is still a promising approach to enhance dexterity-related functional abilities.
PubMed: 38812333
DOI: 10.1017/cjn.2024.53