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Brain & Spine 2024TBIs contribute in over one-third of injury-related deaths with mortality rates as high as 50% in trauma centers serving the most severe TBI. The effect of TBI on... (Review)
Review
INTRODUCTION
TBIs contribute in over one-third of injury-related deaths with mortality rates as high as 50% in trauma centers serving the most severe TBI. The effect of TBI on mortality is about 10% across all ages. Amantadine hydrochloride is one of the most commonly prescribed medications for patients undergoing inpatient neurorehabilitation who have disorders of consciousness. It is a dopamine (DA) receptor agonist and a N-Methyl-D-aspartate (NMDA) receptor antagonist via dopamine release and dopamine reuptake inhibition. The current study will synthesize the current available evidence and show the effect of Amantadine in functional improvement after TBI.
RESEARCH QUESTION
Does Amantadine have an effect on functional improvement of TBI patients?
MATERIAL AND METHODS
This systematic review included all randomized placebo-controlled trials that compare the use of Amantadine versus placebo for functional improvement of patients after TBI. Outcome measures included DRS, GCS and/or GOS scores.
RESULTS
Three studies with a total of 281 patients were included in the quantitative analyses. GRADE assessments show that there was a high certainty of evidence for functional improvement in terms of DRS scores.
DISCUSSION AND CONCLUSION
Evidence of this review show that the use of Amantadine may have a beneficial effect on functional outcome in moderate to severe traumatic brain injuries among adult patients. Given the still-limited body of knowledge, more relevant studies must be made exploring the impact of Amantadine therapies on promoting functional recovery within the brain injury rehabilitation care continuum, with the goals of achieving larger sample sizes and establishing the early- or later-treatment beneficial effects.
PubMed: 38465280
DOI: 10.1016/j.bas.2024.102773 -
European Journal of Pain (London,... Aug 2019N-methyl-D-aspartate (NMDA) receptors are involved in pain signalling and neuroplasticity. Memantine has been shown to have analgesic properties in pre-clinical and... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND OBJECTIVE
N-methyl-D-aspartate (NMDA) receptors are involved in pain signalling and neuroplasticity. Memantine has been shown to have analgesic properties in pre-clinical and small clinical studies. We conducted a systematic review and meta-analysis to assess the efficacy of memantine to prevent or reduce chronic pain.
DATABASES AND DATA TREATMENT
MEDLINE, EMBASE and CENTRAL databases were searched for comparative trials using memantine, either against placebo or active medications, for chronic pain in adults. Pain relief was considered our primary outcome. Meta-analyses were conducted if outcomes were reported in two or more studies. Outcomes were reported as mean differences (MD) or risk ratios (RR) with 95% confidence intervals (CI). Quality was assessed using the GRADE approach.
RESULTS
Among 454 citations, 15 studies were included with populations predominantly consisting of neuropathic conditions and fibromyalgia. Overall, we observed unclear reporting of randomization and allocation methods, apart from potential for publication bias. Among the 11 studies looking at chronic pain treatment, the difference in end pain score with memantine was not significant: MD = -0.58 units (95% CI -1.31, 0.14); I = 82% (low quality). In two surgical studies using memantine for pain prevention, memantine decreased pain intensity: MD = -1.02 units (95% CI -1.38, -0.66); I = 0%. Dizziness was significantly more common with memantine: RR = 4.90 (95% CI 1.26, 18.99); I = 52% (moderate quality).
CONCLUSION
The current evidence regarding the use of memantine for chronic pain is limited and uncertain. Despite its potential, pain relief achieved in clinical studies is small and is associated with an increase in dizziness.
SIGNIFICANCE
Despite a sound rationale, the benefit of using memantine for chronic pain is unclear. Our systematic review and meta-analysis show that memantine may have the potential to decrease pain. However, it can also increase common adverse effects. Considering the small number of studies with potential for bias and inconclusive evidence, there was low to very low certainty. Hence, no clear recommendations can be made about its routine clinical use until larger and more definitive studies are conducted.
Topics: Adult; Analgesics; Chronic Pain; Fibromyalgia; Humans; Memantine; Receptors, N-Methyl-D-Aspartate
PubMed: 30848504
DOI: 10.1002/ejp.1393 -
Drugs & Aging Jun 2015There is no cure for dementia, and no treatments exist to halt or reverse the course of the disease. Treatments are aimed at improving cognitive and functional outcomes. (Review)
Review
BACKGROUND
There is no cure for dementia, and no treatments exist to halt or reverse the course of the disease. Treatments are aimed at improving cognitive and functional outcomes.
OBJECTIVE
Our objective was to review the basis of pharmacological treatments for dementia and to summarize the benefits and risks of dementia treatments.
METHODS
We performed a systematic literature search of MEDLINE through November 2014, for English-language trials and observational studies on treatment of dementia and mild cognitive impairment. Additional references were identified by searching bibliographies of relevant publications. Whenever possible, pooled data from meta-analyses or systematic reviews were obtained. Studies were included for review if they were randomized trials or observational studies on dementia or mild cognitive impairment that evaluated efficacy outcomes or adverse outcomes associated with treatment. Studies were excluded if they evaluated non-FDA approved treatments, or if they evaluated treatment in disorders other than dementia and mild cognitive impairment.
RESULTS
The literature search found 540 potentially relevant studies, of which 257 were included in the systematic review. In pooled trial data, cholinesterase inhibitors (ChEIs) produce small improvements in cognitive, functional, and global benefits in patients with mild to moderate Alzheimer's and Lewy body dementia, but the clinical significance of these effects are unclear. There is no significant benefit seen for vascular dementia. The efficacy of ChEI treatment appears to wane over time, with minimal benefit seen after 1 year. There is no evidence for benefit for those with advanced disease or those aged over 85 years. Adverse effects are significantly increased with ChEIs, in a dose-dependent manner. A two- to fivefold increased risk for gastrointestinal, neurological, and cardiovascular side effects is related to cholinergic stimulation, the most serious being weight loss, debility, and syncope. Those aged over 85 years have double the risk of adverse events compared with younger patients. Memantine monotherapy may provide some cognitive benefit for patients with moderate to severe Alzheimer's and vascular dementia, but the benefit is small and may wane over the course of several months. Memantine exhibits no significant benefit in mild dementia or Lewy body dementia or as an add-on treatment with ChEIs. Memantine has a relatively favorable side-effect profile, at least under controlled trial conditions.
CONCLUSIONS
ChEIs produce small, short-lived improvements in cognitive function in mild to moderate dementia, which may not translate into clinically meaningful effects. Marginal benefits are seen with severe disease, long-term treatment, and advanced age. Cholinergic side effects, including weight loss, debility, and syncope, are clinically significant and could be especially detrimental in the frail elderly population, in which the risks of treatment outweigh the benefits. Memantine monotherapy may have minimal benefits in moderate to severe dementia, balanced by minimal adverse effects.
Topics: Aged; Aged, 80 and over; Cholinesterase Inhibitors; Dementia; Female; Humans; Male; Memantine; Middle Aged; Observational Studies as Topic; Randomized Controlled Trials as Topic; Risk Assessment
PubMed: 25941104
DOI: 10.1007/s40266-015-0266-9 -
Neurodegenerative Disease Management Dec 2020Fatigue is a debilitating symptom of multiple sclerosis (MS) affecting at least 75% of patients. Amantadine has been tested for MS-related fatigue treatment but... (Meta-Analysis)
Meta-Analysis
Fatigue is a debilitating symptom of multiple sclerosis (MS) affecting at least 75% of patients. Amantadine has been tested for MS-related fatigue treatment but efficacy and safety remain unclear. We performed a systematic review and meta-analysis of qualified literatures searched until 30 April 2020. A total of 11 clinical trials were included. The meta-analysis revealed improvement of MS-related fatigue with amantadine treatment using the patients' subjective responses and validated fatigue scales. Amantadine is the most studied drug that has shown improvement of MS-related fatigue, with mild side effects and good tolerability. Larger studies using a standard measurement for MS-related fatigue are recommended to improve the quality of evidence. Safety and efficacy on long-term use needs further investigation.
Topics: Amantadine; Fatigue; Female; Humans; Male; Multiple Sclerosis
PubMed: 33012266
DOI: 10.2217/nmt-2020-0030 -
The Cochrane Database of Systematic... Sep 2020Antisocial personality disorder (AsPD) is associated with rule-breaking, criminality, substance use, unemployment, relationship difficulties, and premature death.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Antisocial personality disorder (AsPD) is associated with rule-breaking, criminality, substance use, unemployment, relationship difficulties, and premature death. Certain types of medication (drugs) may help people with AsPD. This review updates a previous Cochrane review, published in 2010.
OBJECTIVES
To assess the benefits and adverse effects of pharmacological interventions for adults with AsPD.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, 13 other databases and two trials registers up to 5 September 2019. We also checked reference lists and contacted study authors to identify studies.
SELECTION CRITERIA
Randomised controlled trials in which adults (age 18 years and over) with a diagnosis of AsPD or dissocial personality disorder were allocated to a pharmacological intervention or placebo control condition.
DATA COLLECTION AND ANALYSIS
Four authors independently selected studies and extracted data. We assessed risk of bias and created 'Summary of findings tables' and assessed the certainty of the evidence using the GRADE framework. The primary outcomes were: aggression; reconviction; global state/global functioning; social functioning; and adverse events.
MAIN RESULTS
We included 11 studies (three new to this update), involving 416 participants with AsPD. Most studies (10/11) were conducted in North America. Seven studies were conducted exclusively in an outpatient setting, one in an inpatient setting, and one in prison; two studies used multiple settings. The average age of participants ranged from 28.6 years to 45.1 years (overall mean age 39.6 years). Participants were predominantly (90%) male. Study duration ranged from 6 to 24 weeks, with no follow-up period. Data were available from only four studies involving 274 participants with AsPD. All the available data came from unreplicated, single reports, and did not allow independent statistical analysis to be conducted. Many review findings were limited to descriptive summaries based on analyses carried out and reported by the trial investigators. No study set out to recruit participants on the basis of having AsPD; many participants presented primarily with substance abuse problems. The studies reported on four primary outcomes and six secondary outcomes. Primary outcomes were aggression (six studies) global/state functioning (three studies), social functioning (one study), and adverse events (seven studies). Secondary outcomes were leaving the study early (eight studies), substance misuse (five studies), employment status (one study), impulsivity (one study), anger (three studies), and mental state (three studies). No study reported data on the primary outcome of reconviction or the secondary outcomes of quality of life, engagement with services, satisfaction with treatment, housing/accommodation status, economic outcomes or prison/service outcomes. Eleven different drugs were compared with placebo, but data for AsPD participants were only available for five comparisons. Three classes of drug were represented: antiepileptic; antidepressant; and dopamine agonist (anti-Parkinsonian) drugs. We considered selection bias to be unclear in 8/11 studies, attrition bias to be high in 7/11 studies, and performance bias to be low in 7/11 studies. Using GRADE, we rated the certainty of evidence for each outcome in this review as very low, meaning that we have very little confidence in the effect estimates reported. Phenytoin (antiepileptic) versus placebo One study (60 participants) reported very low-certainty evidence that phenytoin (300 mg/day), compared to placebo, may reduce the mean frequency of aggressive acts per week (phenytoin mean = 0.33, no standard deviation (SD) reported; placebo mean = 0.51, no SD reported) in male prisoners with aggression (skewed data) at endpoint (six weeks). The same study (60 participants) reported no evidence of difference between phenytoin and placebo in the number of participants reporting the adverse event of nausea during week one (odds ratio (OR) 1.00, 95% confidence interval (CI) 0.06 to 16.76; very low-certainty evidence). The study authors also reported that no important side effects were detectable via blood cell counts or liver enzyme tests (very low-certainty evidence). The study did not measure reconviction, global/state functioning or social functioning. Desipramine (antidepressant) versus placebo One study (29 participants) reported no evidence of a difference between desipramine (250 to 300 mg/day) and placebo on mean social functioning scores (desipramine = 0.19; placebo = 0.21), assessed with the family-social domain of the Addiction Severity Index (scores range from zero to one, with higher values indicating worse social functioning), at endpoint (12 weeks) (very low-certainty evidence). Neither of the studies included in this comparison measured the other primary outcomes: aggression; reconviction; global/state functioning; or adverse events. Nortriptyline (antidepressant) versus placebo One study (20 participants) reported no evidence of a difference between nortriptyline (25 to 75 mg/day) and placebo on mean global state/functioning scores (nortriptyline = 0.3; placebo = 0.7), assessed with the Symptom Check List-90 (SCL-90) Global Severity Index (GSI; mean of subscale scores, ranging from zero to four, with higher scores indicating greater severity of symptoms), at endpoint (six months) in men with alcohol dependency (very low-certainty evidence). The study measured side effects but did not report data on adverse events for the AsPD subgroup. The study did not measure aggression, reconviction or social functioning. Bromocriptine (dopamine agonist) versus placebo One study (18 participants) reported no evidence of difference between bromocriptine (15 mg/day) and placebo on mean global state/functioning scores (bromocriptine = 0.4; placebo = 0.7), measured with the GSI of the SCL-90 at endpoint (six months) (very low-certainty evidence). The study did not provide data on adverse effects, but reported that 12 patients randomised to the bromocriptine group experienced severe side effects, five of whom dropped out of the study in the first two days due to nausea and severe flu-like symptoms (very low-certainty evidence). The study did not measure aggression, reconviction and social functioning. Amantadine (dopamine agonist) versus placebo The study in this comparison did not measure any of the primary outcomes.
AUTHORS' CONCLUSIONS
The evidence summarised in this review is insufficient to draw any conclusion about the use of pharmacological interventions in the treatment of antisocial personality disorder. The evidence comes from single, unreplicated studies of mostly older medications. The studies also have methodological issues that severely limit the confidence we can draw from their results. Future studies should recruit participants on the basis of having AsPD, and use relevant outcome measures, including reconviction.
Topics: Adult; Aggression; Alcohol-Related Disorders; Amantadine; Antisocial Personality Disorder; Anxiety; Bromocriptine; Desipramine; Female; Humans; Male; Middle Aged; Nortriptyline; Phenytoin; Placebos; Psychotropic Drugs; Randomized Controlled Trials as Topic
PubMed: 32880105
DOI: 10.1002/14651858.CD007667.pub3 -
BMJ Open Apr 2016To summarise existing systematic reviews that assess the effects of non-pharmacological, pharmacological and alternative therapies on activities of daily living (ADL)... (Review)
Review
OBJECTIVE
To summarise existing systematic reviews that assess the effects of non-pharmacological, pharmacological and alternative therapies on activities of daily living (ADL) function in people with dementia.
DESIGN
Overview of systematic reviews.
METHODS
A systematic search in the Cochrane Database of Systematic Reviews, DARE, Medline, EMBASE and PsycInfo in April 2015. Systematic reviews of randomised controlled trials conducted in people with Alzheimer's disease or dementia measuring the impact on ADL function were included. Methodological quality of the systematic reviews was independently assessed by two authors using the AMSTAR tool. The quality of evidence of the primary studies for each intervention was assessed using GRADE.
RESULTS
A total of 23 systematic reviews were included in the overview. The quality of the reviews varied; however most (65%) scored 8/11 or more on the AMSTAR tool, indicating high quality. Interventions that were reported to be effective in minimising decline in ADL function were: exercise (6 studies, 289 participants, standardised mean difference (SMD) 0.68, 95% CI 0.08 to 1.27; GRADE: low), dyadic interventions (8 studies, 988 participants, SMD 0.37, 95% CI 0.05 to 0.69; GRADE: low) acetylcholinesterase inhibitors and memantine (12 studies, 4661 participants, donepezil 10 mg SMD 0.18, 95% CI 0.03 to 0.32; GRADE: moderate), selegiline (7 studies, 810 participants, SMD 0.27, 95% CI 0.13 to 0.41; GRADE: low), huperzine A (2 studies, 70 participants, SMD 1.48, 95% CI 0.95 to 2.02; GRADE: very low) and Ginkgo biloba (7 studies, 2530 participants, SMD 0.36, 95% CI 0.28 to 0.44; GRADE: very low).
CONCLUSIONS
Healthcare professionals should ensure that people with dementia are encouraged to exercise and that primary carers are trained and supported to provide safe and effective care for the person with dementia. Acetylcholinesterase inhibitors or memantine should be trialled unless contraindicated.
TRIAL REGISTRATION NUMBER
CRD42015020179.
Topics: Activities of Daily Living; Alzheimer Disease; Caregivers; Cholinesterase Inhibitors; Complementary Therapies; Dementia; Dopamine Agents; Exercise; Humans; Memantine; Quality of Life
PubMed: 27121704
DOI: 10.1136/bmjopen-2015-010767 -
The International Journal of... Dec 2014We performed an updated meta-analysis of randomized controlled trials of combination therapy with cholinesterase inhibitors and memantine in patients with Alzheimer's... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
We performed an updated meta-analysis of randomized controlled trials of combination therapy with cholinesterase inhibitors and memantine in patients with Alzheimer's disease.
METHODS
We reviewed cognitive function, activities of daily living, behavioral disturbance, global assessment, discontinuation rate, and individual side effects.
RESULTS
Seven studies (total n=2182) were identified. Combination therapy significantly affected behavioral disturbance scores (standardized mean difference=-0.13), activity of daily living scores (standardized mean difference=-0.10), and global assessment scores (standardized mean difference=-0.15). In addition, cognitive function scores (standardized mean difference=-0.13, P=.06) exhibited favorable trends with combination therapy. The effects of combination therapy were more significant in the moderate-to-severe Alzheimer's disease subgroup in terms of all efficacy outcome scores. The discontinuation rate was similar in both groups, and there were no significant differences in individual side effects.
CONCLUSIONS
Combination therapy was beneficial for the treatment of moderate-to-severe Alzheimer's disease in terms of cognition, behavioral disturbances, activities of daily living, and global assessment was well tolerated.
Topics: Activities of Daily Living; Aged; Aged, 80 and over; Alzheimer Disease; Antiparkinson Agents; Cholinesterase Inhibitors; Cognition; Combined Modality Therapy; Female; Humans; Male; Memantine; Treatment Outcome
PubMed: 25548104
DOI: 10.1093/ijnp/pyu115 -
PloS One 2015We performed an updated meta-analysis of randomized placebo-controlled trials testing memantine monotherapy for patients with Alzheimer's disease (AD). (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
We performed an updated meta-analysis of randomized placebo-controlled trials testing memantine monotherapy for patients with Alzheimer's disease (AD).
METHODS
The meta-analysis included randomized controlled trials of memantine monotherapy for AD, omitting those in which patients were also administered a cholinesterase inhibitor. Cognitive function, activities of daily living, behavioral disturbances, global function, stage of dementia, drug discontinuation rate, and individual side effects were compared between memantine monotherapy and placebo groups. The primary outcomes were cognitive function and behavioral disturbances; the others were secondary outcomes.
RESULTS
Nine studies including 2433 patients that met the study's inclusion criteria were identified. Memantine monotherapy significantly improved cognitive function [standardized mean difference (SMD)=-0.27, 95% confidence interval (CI)=-0.39 to -0.14, p=0.0001], behavioral disturbances (SMD=-0.12, 95% CI=-0.22 to -0.01, p=0.03), activities of daily living (SMD=-0.09, 95% CI=-0.19 to -0.00, p=0.05), global function assessment (SMD=-0.18, 95% CI=-0.27 to -0.09, p=0.0001), and stage of dementia (SMD=-0.23, 95% CI=-0.33 to -0.12, p=0.0001) scores. Memantine was superior to placebo in terms of discontinuation because of inefficacy [risk ratio (RR)=0.36, 95% CI=0.17¬ to 0.74, p=0.006, number needed to harm (NNH)=non significant]. Moreover, memantine was associated with less agitation compared with placebo (RR=0.68, 95% CI=0.49 to 0.94, p=0.02, NNH=non significant). There were no significant differences in the rate of discontinuation because of all causes, all adverse events, and individual side effects other than agitation between the memantine monotherapy and placebo groups.
CONCLUSIONS
Memantine monotherapy improved cognition, behavior, activities of daily living, global function, and stage of dementia and was well-tolerated by AD patients. However, the effect size in terms of efficacy outcomes was small and thus there is limited evidence of clinical benefit.
Topics: Activities of Daily Living; Alzheimer Disease; Humans; Memantine; Publication Bias; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 25860130
DOI: 10.1371/journal.pone.0123289 -
Journal of Neurology, Neurosurgery, and... Feb 2015Recently, several large randomised controlled trials about the treatments of cognitive impairment or dementia due to Parkinson's disease (CIND-PD or PDD) and dementia... (Meta-Analysis)
Meta-Analysis Review
Efficacy and safety of cholinesterase inhibitors and memantine in cognitive impairment in Parkinson's disease, Parkinson's disease dementia, and dementia with Lewy bodies: systematic review with meta-analysis and trial sequential analysis.
OBJECTIVE
Recently, several large randomised controlled trials about the treatments of cognitive impairment or dementia due to Parkinson's disease (CIND-PD or PDD) and dementia with Lewy bodies (DLB) were completed. Here, we systematically reviewed the studies (including the recent reports) to provide updated evidence for the treatments of CIND-PD, PDD and DLB.
METHODS
We searched Cochrane Dementia and Cognitive Improvement Group Specialised Register, Pubmed, Embase, and other sources for eligible trials. We selected global impression and cognitive function as primary efficacy outcomes, and dropouts and adverse events as safety outcomes. Furthermore, Meta-analysis and trial sequential analysis (TSA) were used here.
RESULTS
Ten trials were included in this study. Cholinesterase inhibitors and memantine produced small global efficacy on clinicians' global impression of change (CGIC), from a weighted mean difference of -0.40 (95% CI -0.77 to -0.03) to -0.65 (95% CI -1.28 to -0.01); however, cholinesterase inhibitors but not memantine significantly improved cognition on Mini-Mental State Examination (MMSE), from 1.04 (95% CI 0.43 to 1.65) to 2.57 (95% CI 0.90 to 4.23). Additionally, both of them had good safety outcomes, although rivastigmine showed an increased risk on adverse events than placebo (risk ratio, RR 1.19, TSA adjusted 95% CI 1.04 to 1.36), these events were usually mild or moderate, and the risk disappeared on serious adverse events.
CONCLUSIONS
Cholinesterase inhibitors and memantine slightly improve global impression; however, only cholinesterase inhibitors enhance cognitive function. Besides, all the drugs have good safety outcomes. But the limited trials precluded the generalisation of these outcomes.
Topics: Antiparkinson Agents; Cholinesterase Inhibitors; Cognition Disorders; Humans; Lewy Body Disease; Memantine; Parkinson Disease
PubMed: 24828899
DOI: 10.1136/jnnp-2014-307659 -
Journal of Parkinson's Disease 2021Many studies on Parkinson's disease (PD) patients affected by Coronavirus-disease-2019 (COVID-19) were recently published. However, the small sample size of infected...
BACKGROUND
Many studies on Parkinson's disease (PD) patients affected by Coronavirus-disease-2019 (COVID-19) were recently published. However, the small sample size of infected patients enrolled in most studies did not allow to draw robust conclusions on the COVID-19 impact in PD.
OBJECTIVE
We aimed to assess whether the prevalence and outcome of COVID-19 in PD patients are different from those observed in the general population.
METHODS
We conducted a systematic review of studies reporting data on PD patients with a diagnosis of COVID-19 (PD-COVID+). We extracted prevalence, clinical-demographic data, outcome, and mortality. We also analyzed risk or protective factors based on comparisons between PD-COVID+ and control populations with PD without COVID-19 or without PD with COVID-19.
RESULTS
We included 16 studies reporting on a total of 11,325 PD patients, 1,061 with a confirmed diagnosis of COVID-19. The median infection prevalence ranged from 0.6% to 8.5%. PD-COVID+ patients had a median age of 74 and a disease duration of 9.4 years. Pooling all PD-COVID+ patients from included studies, 28.6% required hospitalization, 37.1% required levodopa dose increasing, and 18.9% died. The case fatality was higher in PD-COVID+ patients than the general population, with longer PD duration as a possible risk factor for worse outcome. Amantadine and vitamin D were proposed as potential protective factors.
CONCLUSION
Available studies indicate a higher case fatality in PD patients affected by COVID-19 than the general population. Conversely, current literature does not definitively clarify whether PD patients are more susceptible to get infected. The potential protective role of vitamin D and amantadine is intriguing but deserves further investigation.
Topics: Antiparkinson Agents; COVID-19; Case-Control Studies; Humans; Levodopa; Parkinson Disease; Vitamin D; COVID-19 Drug Treatment
PubMed: 33749619
DOI: 10.3233/JPD-202463