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Behavioural Neurology 2022Aromatic L-amino acid decarboxylase (AADC) deficiency is a rare congenital autosomal recessive metabolic disorder caused by pathogenic homozygous or compound... (Review)
Review
Aromatic L-amino acid decarboxylase (AADC) deficiency is a rare congenital autosomal recessive metabolic disorder caused by pathogenic homozygous or compound heterozygous variants in the dopa decarboxylase (DDC) gene. Adeno-associated viral vector-mediated gene transfer of the human AADC gene into the putamina has become available. This systematic review on PubMed, Scopus databases, and other sources is aimed at describing the AADC whole phenotypic spectrum in order to facilitate its early diagnosis. Literature reviews, original articles, retrospective and comparative studies, large case series, case reports, and short communications were considered. A database was set up using Microsoft Excel to collect clinical, molecular, biochemical, and therapeutic data. By analysing 261 patients from 41 papers with molecular and/or biochemical diagnosis of AADC deficiency for which individuality could be determined with certainty, we found symptom onset to occur in the first 6 months of life in 93% of cases. Hypotonia and developmental delay are cardinal signs, reported as present in 73.9% and 72% of cases, respectively. Oculogyric crises were seen in 67% of patients while hypokinesia in 42% and ptosis in 26%. Dysautonomic features have been revealed in 53% and gastrointestinal symptoms in 19% of cases. With 37% and 30% of patients reported being affected by sleep and behavioural disorders, it seems to be commoner than previously acknowledged. Although reporting bias cannot be excluded, there is still a need for comprehensive clinical descriptions of symptoms at onset and during follow-up. In fact, our review suggests that most of the neurological and extraneurological symptoms and signs reported, although quite frequent in this condition, are not pathognomonic, and therefore, ADCC deficiency can remain an underdiscovered disorder.
Topics: Humans; Dopa Decarboxylase; Retrospective Studies; Amino Acid Metabolism, Inborn Errors; Amino Acids
PubMed: 36268467
DOI: 10.1155/2022/2210555 -
Current Problems in Cardiology Feb 2023Heart failure (HF) is one of the leading causes of maternal mortality and morbidity in the United States. Peripartum cardiomyopathy (PPCM) constitutes up to 70% of all... (Meta-Analysis)
Meta-Analysis Review
Heart failure (HF) is one of the leading causes of maternal mortality and morbidity in the United States. Peripartum cardiomyopathy (PPCM) constitutes up to 70% of all HF in pregnancy. Cardiac angiogenic imbalance caused by cleaved 16kDa prolactin has been hypothesized to contribute to the development of PPCM, fueling investigation of prolactin inhibitors for the management of PPCM. We conducted a systematic review and meta-analysis to assess the impact of prolactin inhibition on left ventricular (LV) function and mortality in patients with PPCM. We included English language articles from PubMed and EMBASE published upto March 2022. We pooled the mean difference (MD) for left ventricular ejection fraction (LVEF) at follow-up, odds ratio (OR) for LV recovery and risk ratio (RR) for all-cause mortality using random-effects meta-analysis. Among 548 studies screened, 10 studies (3 randomized control trials (RCTs), 2 retrospective and 5 prospective cohorts) were included in the systematic review. Patients in the Bromocriptine + standard guideline directed medical therapy (GDMT) group had higher LVEF% (pMD 12.56 (95% CI 5.84-19.28, I2=0%) from two cohorts and pMD 14.25 (95% CI 0.61-27.89, I2=88%) from two RCTs) at follow-up compared to standard GDMT alone group. Bromocriptine group also had higher odds of LV recovery (pOR 3.55 (95% CI 1.39-9.1, I2=62)). We did not find any difference in all-cause mortality between the groups. Our analysis demonstrates that the addition of Bromocriptine to standard GDMT was associated with a significant improvement in LVEF% and greater odds of LV recovery, without significant reduction in all-cause mortality.
Topics: Pregnancy; Female; Humans; Bromocriptine; Prolactin; Peripartum Period; Cardiomyopathies; Ventricular Function, Left; Heart Failure; Stroke Volume; Pregnancy Complications, Cardiovascular
PubMed: 36261102
DOI: 10.1016/j.cpcardiol.2022.101461 -
Ageing Research Reviews Dec 2022Dementia is a progressive neurodegenerative syndrome that has no cure. Although a significant proportion of people with dementia progress into the severe stages of the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Dementia is a progressive neurodegenerative syndrome that has no cure. Although a significant proportion of people with dementia progress into the severe stages of the disease, evidence on the clinical effectiveness of treatments for people with severe dementia remains limited.
AIMS
To systematically review the effectiveness of pharmacological and non-pharmacological treatments for people living with severe dementia and assess the quality of the evidence.
METHOD
We searched MEDLINE, EMBASE, PsycINFO, CINAHL and online clinical trial registers up to January 2022, for Randomised Controlled Trials (RCT) in people living with severe dementia. Quality and risk of bias were assessed independently by two authors.
RESULTS
A total of 30 trials met our inclusion criteria of which 14 evaluated the effectiveness of pharmacological treatments, and 16 evaluated a non-pharmacological intervention. Pharmacological treatments: Meta-analyses indicated that pharmacological treatments (donepezil: 10 mg, 5 mg; galantamine: 24 mg; memantine: 10 mg) are associated with better outcomes compared to placebo for: severity of symptoms (standardized mean difference (SMD) 0.37, 95% CI 0.26-0.48; 4 studies; moderate-certainty evidence), activities of daily living (SMD 0.15, 95% CI 0.04-0.26; 5 studies; moderate-certainty evidence), and clinical impression of change (Relative Risk (RR) 1.34, 95% CI 1.14-1.57; 4 studies; low-certainty evidence). Pharmacological treatments were also more likely to reduce mortality compared to placebo (RR 0.60, 95% CI 0.40-0.89; 6 studies; low-certainty evidence). Non-pharmacological treatments: Five trials were included in the meta-analyses of non-pharmacological interventions (multi-sensory stimulation, needs assessment, and activities-based interventions); results showed that non-pharmacological interventions may reduce neuropsychiatric symptoms of dementia compared to usual care (SMD -0.33, 95% CI -0.59 to -0.06; low certainty evidence).
CONCLUSIONS
There is moderate-certainty evidence that pharmacological treatments may decrease disease severity and improve function for people with severe dementia. Non-pharmacological treatments are probably effective in reducing neuropsychiatric symptoms but the quality of evidence remains low. There is an urgent need for high-quality evidence for other outcomes and for developing service-user informed interventions for this under-served group.
Topics: Humans; Dementia; Activities of Daily Living; Memantine; Treatment Outcome
PubMed: 36243355
DOI: 10.1016/j.arr.2022.101758 -
Pharmacology Research & Perspectives Oct 2022The misattribution of an adverse drug reaction (ADR) as a symptom or illness can lead to the prescribing of additional medication, referred to as a prescribing cascade....
The misattribution of an adverse drug reaction (ADR) as a symptom or illness can lead to the prescribing of additional medication, referred to as a prescribing cascade. The aim of this systematic review is to identify published prescribing cascades in community-dwelling adults. A systematic review was reported in line with the PRISMA guidelines and pre-registered with PROSPERO. Electronic databases (Medline [Ovid], EMBASE, PsycINFO, CINAHL, Cochrane Library) and grey literature sources were searched. Inclusion criteria: community-dwelling adults; risk-prescription medication; outcomes-initiation of new medicine to "treat" or reduce ADR risk; study type-cohort, cross-sectional, case-control, and case-series studies. Title/abstract screening, full-text screening, data extraction, and methodological quality assessment were conducted independently in duplicate. A narrative synthesis was conducted. A total of 101 studies (reported in 103 publications) were included. Study sample sizes ranged from 126 to 11 593 989 participants and 15 studies examined older adults specifically (≥60 years). Seventy-eight of 101 studies reported a potential prescribing cascade including calcium channel blockers to loop diuretic (n = 5), amiodarone to levothyroxine (n = 5), inhaled corticosteroid to topical antifungal (n = 4), antipsychotic to anti-Parkinson drug (n = 4), and acetylcholinesterase inhibitor to urinary incontinence drugs (n = 4). Identified prescribing cascades occurred within three months to one year following initial medication. Methodological quality varied across included studies. Prescribing cascades occur for a broad range of medications. ADRs should be included in the differential diagnosis for patients presenting with new symptoms, particularly older adults and those who started a new medication in the preceding 12 months.
Topics: Acetylcholinesterase; Aged; Antifungal Agents; Antipsychotic Agents; Calcium Channel Blockers; Cholinesterase Inhibitors; Cross-Sectional Studies; Drug-Related Side Effects and Adverse Reactions; Humans; Independent Living; Sodium Potassium Chloride Symporter Inhibitors; Thyroxine
PubMed: 36123967
DOI: 10.1002/prp2.1008 -
BMC Neurology Aug 2022Quality of life (QoL) in patients with Parkinson's disease (PD) is increasingly used as an efficacy outcome in clinical studies of PD to evaluate the impact of treatment... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Quality of life (QoL) in patients with Parkinson's disease (PD) is increasingly used as an efficacy outcome in clinical studies of PD to evaluate the impact of treatment from the patient's perspective. Studies demonstrating the treatment effect of pramipexole on QoL remain inconclusive. This study aims to evaluate the effect of pramipexole on QoL in patients with PD by conducting a systematic review and meta-analysis of existing clinical trials.
METHODS
A systematic literature search of PubMed, Embase and the Cochrane Library was performed from inception to 30 April 2022 to identify randomised, placebo-controlled trials of patients with idiopathic PD receiving pramipexole, who reported a change from baseline in their QoL as measured by the 39-item Parkinson's Disease Questionnaire (PDQ-39). Risk of bias was independently assessed by two reviewers using the Cochrane Collaboration's tool for bias assessment.
RESULTS
Of 80 eligible articles screened, six trials consisting of at least 2000 patients with early or advanced PD were included. From the synthesis of all six selected trials, a significant mean change from baseline in the PDQ-39 total score of -2.49 (95% CI, -3.43 to -1.54; p < 0.0001) was observed with pramipexole compared with placebo. A trend toward improvement in QoL was consistently observed among patients who received optimal doses of pramipexole (≥ 80% of the study population on 1.5 mg dosage), regardless of disease severity (advanced versus early) or baseline QoL levels.
CONCLUSION
This meta-analysis provides evidence for the potential treatment benefit of pramipexole in improving QoL in patients with PD.
Topics: Antiparkinson Agents; Humans; Parkinson Disease; Pramipexole; Quality of Life; Severity of Illness Index
PubMed: 36008796
DOI: 10.1186/s12883-022-02830-y -
The Cochrane Database of Systematic... Aug 2022Autism spectrum disorder (ASD; also known as autism) is a developmental disability that begins in childhood and is typically seen in around 1% to 2% of children. It is... (Review)
Review
BACKGROUND
Autism spectrum disorder (ASD; also known as autism) is a developmental disability that begins in childhood and is typically seen in around 1% to 2% of children. It is characterised by social communication difficulties and repetitive and restricted behaviours and routines that can have a negative impact on a child's quality of life, achievement at school, and social interactions with others. It has been hypothesised that memantine, which is traditionally used to treat dementia, may be effective in reducing the core symptoms of autism as well as some co-occurring symptoms such as hyperactivity and language difficulties. If memantine is being used to treat the core symptoms of autism, it is important to review the evidence of its effectiveness.
OBJECTIVES
To assess the effects of memantine on the core symptoms of autism, including, but not limited to, social communication and stereotypical behaviours.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, nine other databases and three trials registers up to February 2022. We also checked reference lists of key studies and checked with experts in the field for any additional papers. We searched for retractions of the included studies in MEDLINE, Embase, and the Retraction Watch Database. No retractions or corrections were found.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) of any dose of memantine compared with placebo in autistic people. We also included RCTs in which only one group received memantine, but both groups received the same additional therapy (e.g. a behaviour intervention).
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. Our primary outcomes were core autism symptoms and adverse effects. Secondary outcomes were language, intelligence, memory, adaptive behaviour, hyperactivity, and irritability. We used GRADE to assess certainty of evidence.
MAIN RESULTS
We included three RCTs (two double-blind and one single-blind) with 204 participants that examined the short-term effect (immediately postintervention) of memantine in autistic people. Two studies took place in the USA and the other in Iran. All three studies focused on children and adolescents, with a mean age of 9.40 (standard deviation (SD) 2.26) years. Most participants were male (range across studies 73% to 87%). The diagnosis of ASD was based on the Diagnostic and Statistical Manual of Mental Disorders (4th edition; 4th edition, text revision; or 5th edition). To confirm the diagnosis, one study used the Autism Diagnostic Observation Schedule (ADOS) and the Autism Diagnostic Interview-Revised (ADI-R); one used ADOS, ADI-R or the Autism Diagnostic Interview Screener; and one used the Gilliam Autism Rating Scale. Dosage of memantine was based on the child's weight and ranged from 3 mg to 15 mg per day. Comparisons Two studies examined memantine compared with placebo; in the other study, both groups had a behavioural intervention while only one group was given memantine. Risk of bias All studies were rated at high risk of bias overall, as they were at high or unclear risk of bias across all but four domains in one study, and all but two domains in the other two studies. One study was funded by Forest Laboratories, LLC, (Jersey City, New Jersey), Allergan. The study sponsor was involved in the study design, data collection (via contracted clinical investigator sites), analysis and interpretation of data, and the decision to present these results. The other two studies reported no financial support or sponsorship; though in one of the two, the study medication was an in-kind contribution from Forest Pharmaceuticals. Primary outcomes There was no clear evidence of a difference between memantine and placebo with respect to severity of core symptoms of autism, although we are very uncertain about the evidence. The standardised mean difference in autism symptoms score in the intervention group versus the control group was -0.74 standard deviations (95% confidence interval (CI) -2.07 to 0.58; 2 studies, 181 participants; very low-certainty evidence; medium effect size); lower scores indicate less severe autistic symptoms. Two studies (144 participants) recorded adverse effects that the authors deemed related to the study and found there may be no difference between memantine and placebo (odds ratio (OR) 0.64, 95% CI 0.17 to 2.39; low-certainty evidence). Secondary outcomes There may be no difference between memantine and placebo on language (2 studies, 144 participants; low-certainty evidence); memory or adaptive behaviour (1 study, 23 participants; both low-certainty evidence); or hyperactivity or irritability (1 study, 121 participants; both low-certainty evidence).
AUTHORS' CONCLUSIONS
It is unclear whether memantine is an effective treatment for autistic children. None of the three included trials reported on the effectiveness of memantine in adults. Further studies using rigorous designs, larger samples, longer follow-up and clinically meaningful outcome measures that are important to autistic people and their families will strengthen our knowledge of the effects of memantine in autism.
Topics: Adolescent; Adult; Autism Spectrum Disorder; Child; Female; Humans; Male; Memantine; Odds Ratio; Outcome Assessment, Health Care; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 36006807
DOI: 10.1002/14651858.CD013845.pub2 -
Computational and Mathematical Methods... 2022Long-term physical therapy helps to improve the motor symptoms of patients with Parkinson's disease, but the effectiveness is not clear. The purpose of this study was to... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Long-term physical therapy helps to improve the motor symptoms of patients with Parkinson's disease, but the effectiveness is not clear. The purpose of this study was to evaluate the effect of long-term physical therapy on improving motor symptoms or daily activities in Parkinson's patients with drug use or discontinuation, as well as its impact on drug treatment dose. A subgroup analysis was conducted on different treatment methods to determine the most effective treatment method.
METHODS
The researchers independently searched databases, including PubMed, Medline, Embase, Ovid, Cochrane Library, and ISI Web of science. The search deadline was June 2022. A randomized controlled trial was conducted on Parkinson's disease patients with HY stages 1-3 who received continuous physical therapy for 6 months or more. Systematic evaluation and meta-analysis were carried out by using common clinical evaluation indicators, namely, MDS-UPDRS exercise score, daily activity (ADL) score, or LED dose. The quality of the literature was assessed using the modified Jadad scale of Cochrane's bias risk tool.
RESULTS
A total of 523 Parkinson's disease patients with HY stages of 1-3 were included in the study. The results showed that long-term physical therapy could improve patients' motor symptoms with combined antiparkinsonian drugs ( = 2.61 and = 0.009) and had a significant positive effect on the motor symptoms of patients with discontinued antiparkinsonian drugs ( = 2.73 and = 0.006). Meanwhile, it could reduce the LED dose of patients with Parkinson's disease. The difference was statistically significant ( = 2.58 and = 0.010).
CONCLUSION
The results of this study indicated that physical therapy for at least 6 months or longer for patients with mild to moderate Parkinson's HY could effectively improve the motor symptoms of Parkinson's patients, whether or not combined with antiparkinson drugs. Meanwhile, long-term physical therapy reduced the LED dose of patients treated with drugs compared with patients in the control group who received short-term physical therapy, other types of intervention group, or no treatment.
Topics: Activities of Daily Living; Antiparkinson Agents; Humans; Parkinson Disease; Physical Therapy Modalities; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 35959355
DOI: 10.1155/2022/3393191 -
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 -
European Journal of Heart Failure Sep 2022Peripartum cardiomyopathy (PPCM) remains a major contributor to maternal morbidity and mortality worldwide. The disease is associated with various complications... (Meta-Analysis)
Meta-Analysis
AIMS
Peripartum cardiomyopathy (PPCM) remains a major contributor to maternal morbidity and mortality worldwide. The disease is associated with various complications occurring mainly early during its course. Reported adverse outcomes include decompensated heart failure, thromboembolic complications, arrhythmias and death. We sought to systematically and comprehensively review published literature on the management and outcome of women with PPCM across different geographical regions and to identify possible predictors of adverse outcomes.
METHODS AND RESULTS
We performed a comprehensive search of relevant literature (2000 to June 2021) across a number of electronic databases. Cohort, case-control and cross-sectional studies, as well as control arms of randomized controlled trials reporting on 6- and/or 12-month outcomes of PPCM were considered eligible (PROSPERO registration: CRD42021255654). Forty-seven studies (4875 patients across 60 countries) met the inclusion criteria. Haemodynamic and echocardiographic parameters were similar across all continents. All-cause mortality was 8.0% (95% confidence interval [CI] 5.5-10.8, I = 79.1%) at 6 months and 9.8% (95% CI 6.2-14.0, I = 80.5%) at 12 months. All-cause mortality was highest in Africa and Asia/Pacific. Overall, 44.1% (95% CI 36.1-52.2, I = 91.7%) of patients recovered their left ventricular (LV) function within 6 months and 58.7% (95% CI 48.1-68.9, I = 75.8%) within 12 months. Europe and North America reported the highest prevalence of LV recovery. Frequent prescription of beta-blocker, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker and bromocriptine/cabergoline were associated with significantly lower all-cause mortality and better LV recovery.
CONCLUSION
We identified significant global differences in 6- and 12-month outcomes in women with PPCM. Frequent prescription of guideline-directed heart failure therapy was associated with better LV recovery and lower all-cause mortality. Timely initiation and up-titration of heart failure therapy should therefore be strongly encouraged to improve outcome in PPCM.
Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Bromocriptine; Cabergoline; Cardiomyopathies; Cardiotonic Agents; Cross-Sectional Studies; Female; Heart Failure; Humans; Peripartum Period; Pregnancy; Pregnancy Complications, Cardiovascular; Puerperal Disorders
PubMed: 35778990
DOI: 10.1002/ejhf.2603 -
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