-
CNS & Neurological Disorders Drug... 2016Coenzyme Q10 (CoQ10) is an antioxidant that enhances the activity of complex I and II in the Electron Transport Chain. Many preclinical and clinical studies evaluated... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Coenzyme Q10 (CoQ10) is an antioxidant that enhances the activity of complex I and II in the Electron Transport Chain. Many preclinical and clinical studies evaluated CoQ10 for neuroprotection against Parkinson's disease (PD). The aim of this study is to synthesize evidence from published randomized controlled trials (RCTs) about the benefit of CoQ10 supplementation for patients with Parkinson's disease.
METHODS
We followed the PRISMA statement guidelines during the preparation of this systematic review and metaanalysis. A computer literature search for (PubMed, EBSCO, Web of science and Ovid Midline) was carried out. We included RCTs comparing CoQ10 with placebo in terms of motor functions and quality of life. Outcomes of total Unified Parkinson's Disease Rating Scale (UPDRS), UPDRS I, UPDRS II, UPDRS III and Schwab and England scores were pooled as standardized mean difference (SMD) between two groups from baseline to the endpoint.
RESULTS
Five RCTs (981 patients) were included in this study. The overall effect did not favor either of the two groups in terms of: total UPDRS score (SMD -0.05, 95%CI [-0.10, 0.15]), UPDRS I (SMD -0.03, 95% CI [-0.23, 0.17]), UPDRS II (SMD -0.10, 95%CI [-0.35, 0.15]), UPDRS III (SMD -0.05, 95%CI [-0.07, 0.17]) or Schwab and England score (SMD 0.08, 95%CI [-0.13, 0.29]).
CONCLUSION
CoQ10 supplementation does not slow functional decline nor provide any symptomatic benefit for patients with Parkinson's disease.
Topics: Antioxidants; Clinical Trials as Topic; Humans; Oxidative Stress; Parkinson Disease; Treatment Outcome; Ubiquinone
PubMed: 26553164
DOI: 10.2174/1871527314666150821103306 -
World Journal of Gastroenterology Aug 2017To performed a systematic review and meta-analysis to determine any possible differences in terms of effectiveness, safety and tolerability between existing... (Meta-Analysis)
Meta-Analysis Review
AIM
To performed a systematic review and meta-analysis to determine any possible differences in terms of effectiveness, safety and tolerability between existing colon-cleansing products in patients with inflammatory bowel disease.
METHODS
Systematic searches were performed (January 1980-September 2016) using MEDLINE, EMBASE, Scopus, CENTRAL and ISI Web of knowledge for randomized trials assessing preparations with or without adjuvants, given in split and non-split dosing, and in high (> 3 L) or low-volume (2 L or less) regimens. Bowel cleansing quality was the primary outcome. Secondary outcomes included patient willingness-to-repeat the procedure and side effects/complications.
RESULTS
Out of 439 citations, 4 trials fulfilled our inclusion criteria ( = 449 patients). One trial assessed the impact of adding simethicone to polyethylene glycol (PEG) 4 L with no effect on bowel cleansing quality, but a better tolerance. Another trial compared senna to castor oil, again without any differences in term of bowel cleansing. Two trials compared the efficacy of PEG high-volume PEG low-volume associated to an adjuvant in split-dose regimens: PEG low-dose efficacy was not different to PEG high-dose; OR = 0.84 (0.37-1.92). A higher proportion of patients were willing to repeat low-volume preparations high-volume; OR = 5.11 (1.31-20.0).
CONCLUSION
In inflammatory bowel disease population, PEG low-volume regimen seems not inferior to PEG high-volume to clean the colon, and yields improved willingness-to-repeat. Further additional research is urgently required to compare contemporary products in this population.
Topics: Cathartics; Clinical Trials as Topic; Colon; Colonoscopy; Drug Administration Schedule; Humans; Inflammatory Bowel Diseases; Patient Satisfaction; Treatment Outcome
PubMed: 28932092
DOI: 10.3748/wjg.v23.i32.5994 -
Journal of Cachexia, Sarcopenia and... Jun 2024Significant variation exists in the outcomes used in cancer cachexia trials, including measures of body composition, which are often selected as primary or secondary... (Review)
Review
Significant variation exists in the outcomes used in cancer cachexia trials, including measures of body composition, which are often selected as primary or secondary endpoints. To date, there has been no review of the most commonly selected measures or their potential sensitivity to detect changes resulting from the interventions being examined. The aim of this systematic review is to assess the frequency and diversity of body composition measures that have been used in cancer cachexia trials. MEDLINE, Embase and Cochrane Library databases were systematically searched between January 1990 and June 2021. Eligible trials examined adults (≥18 years) who had received an intervention aiming to treat or attenuate the effects of cancer cachexia for >14 days. Trials were also of a prospective controlled design and included body weight or at least one anthropometric, bioelectrical or radiological endpoint pertaining to body composition, irrespective of the modality of intervention (e.g., pharmacological, nutritional, physical exercise and behavioural) or comparator. Trials with a sample size of <40 patients were excluded. Data extraction used Covidence software, and reporting followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidance. This review was prospectively registered (PROSPERO: CRD42022276710). A total of 84 clinical trials, comprising 13 016 patients, were eligible for inclusion. Non-small-cell lung cancer and pancreatic cancer were studied most frequently. The majority of trial interventions were pharmacological (52%) or nutritional (34%) in nature. The most frequently reported endpoints were assessments of body weight (68 trials, n = 11 561) followed by bioimpedance analysis (BIA)-based estimates (23 trials, n = 3140). Sixteen trials (n = 3052) included dual-energy X-ray absorptiometry (DEXA)-based endpoints, and computed tomography (CT) body composition was included in eight trials (n = 841). Discrepancies were evident when comparing the efficacy of interventions using BIA-based estimates of lean tissue mass against radiological assessment modalities. Body weight, BIA and DEXA-based endpoints have been most frequently used in cancer cachexia trials. Although the optimal endpoints cannot be determined from this review, body weight, alongside measurements from radiological body composition analysis, would seem appropriate. The choice of radiological modality is likely to be dependent on the trial setting, population and intervention in question. CT and magnetic resonance imaging, which have the ability to accurately discriminate tissue types, are likely to be more sensitive and provide greater detail. Endpoints are of particular importance when aligned with the intervention's mechanism of action and/or intended patient benefit.
Topics: Humans; Cachexia; Neoplasms; Body Composition; Body Weight; Clinical Trials as Topic
PubMed: 38738581
DOI: 10.1002/jcsm.13478 -
Clinical Breast Cancer Dec 2019Optimal treatment of breast cancer brain metastases (BCBM) is often hampered by limitations in diagnostic abilities. Developing innovative tools for BCBM diagnosis is...
Optimal treatment of breast cancer brain metastases (BCBM) is often hampered by limitations in diagnostic abilities. Developing innovative tools for BCBM diagnosis is vital for early detection and effective treatment. In this study we explored the advances in trial for the diagnosis of BCBM, with review of the literature. On May 8, 2019, we searched ClinicalTrials.gov for interventional and diagnostic clinical trials involving BCBM, without limiting for date or location. Information on trial characteristics, experimental interventions, results, and publications were collected and analyzed. In addition, a systematic review of the literature was conducted to explore published studies related to BCBM diagnosis. Only 9 diagnostic trials explored BCBM. Of these, 1 trial was withdrawn because of low accrual numbers. Three trials were completed; however, none had published results. Modalities in trial for BCBM diagnosis entailed magnetic resonance imaging (MRI), computed tomography (CT), positron emission tomography (PET), PET-CT, nanobodies, and circulating tumor cells (CTCs), along with a collection of novel tracers and imaging biomarkers. MRI continues to be the diagnostic modality of choice, whereas CT is best suited for acute settings. Advances in PET and PET-CT allow the collection of metabolic and functional information related to BCBM. CTC characterization can help reflect on the molecular foundations of BCBM, whereas cell-free DNA offers new genetic material for further exploration in trials. The integration of machine learning in BCBM diagnosis seems inevitable as we continue to aim for rapid and accurate detection and better patient outcomes.
Topics: Brain Neoplasms; Breast Neoplasms; Clinical Trials as Topic; Female; Humans; Magnetic Resonance Imaging; Neoplastic Cells, Circulating; Positron Emission Tomography Computed Tomography; Prognosis
PubMed: 31262686
DOI: 10.1016/j.clbc.2019.05.018 -
Sleep & Breathing = Schlaf & Atmung Sep 2015Snoring is the sound produced by the vibration of the soft tissues caused by the air passing through a narrow upper airway during sleep. It is usually associated with... (Comparative Study)
Comparative Study Review
BACKGROUND
Snoring is the sound produced by the vibration of the soft tissues caused by the air passing through a narrow upper airway during sleep. It is usually associated with the conditions that increase upper airway resistance, but can occur in their absence too (primary snoring). Considering its sheer prevalence, the associated comorbidities, like carotid atherosclerosis and the social disorder that it can represent, treatment for snoring must be considered even in the absence of any other medical condition. Treatment options include conservative approaches like weight reduction, smoking and alcohol cessation, sleep positioning, mechanical nasal dilators, and continuous positive airway pressure (CPAP) to more radical approaches like surgery. Till date, we have no drugs for treating the primary pathology of snoring.
METHODS
A systematic literature search was carried out in PUBMED and EMBASE, and we found only nine randomized control trial's and one interventional study focusing on the pharmacotherapy of snoring per se, even as the literature is replete with studies evaluating drug therapy for obstructive sleep apnea.
RESULT
Drugs evaluated include protriptyline, pseudoephedrine and domperidone, mometasone, nasal surfactant, Botulinum toxin type A, and some homeopathic and oil-based nasal sprays. The selected studies showed no strength in data and had a great methodological heterogeneity, so it is impossible to compare the analyzed studies.
DISCUSSION
Even though there are no consistent data to support pharmacologic treatment for primary snoring, through the critical analysis of these studies, we have discussed about the future directions for clinical trials in this area to arrive at a clinically meaningful decision.
Topics: Humans; Randomized Controlled Trials as Topic; Sleep Apnea, Obstructive; Snoring; Treatment Outcome
PubMed: 25680547
DOI: 10.1007/s11325-015-1123-0 -
BMC Geriatrics May 2016Risks and prevalence of malnutrition and dehydration are high in older people but even higher in older people with dementia. In the EDWINA (Eating and Drinking Well IN... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Risks and prevalence of malnutrition and dehydration are high in older people but even higher in older people with dementia. In the EDWINA (Eating and Drinking Well IN dementiA) systematic review we aimed to assess effectiveness of interventions aiming to improve, maintain or facilitate food/drink intake indirectly, through food service or dining environment modification, education, exercise or behavioural interventions in people with cognitive impairment or dementia (across all settings, levels of care and support, types and degrees of dementia).
METHODS
We comprehensively searched Medline and twelve further databases, plus bibliographies, for intervention studies with ≥3 cognitively impaired adult participants (any type/stage). The review was conducted with service user input in accordance with Cochrane Collaboration's guidelines. We duplicated assessment of inclusion, data extraction, and validity assessment, tabulating data. Meta-analysis (statistical pooling) was not appropriate so data were tabulated and synthesised narratively.
RESULTS
We included 56 interventions (reported in 51 studies). Studies were small and there were no clearly effective, or clearly ineffective, interventions. Promising interventions included: eating meals with care-givers, family style meals, soothing mealtime music, constantly accessible snacks and longer mealtimes, education and support for formal and informal care-givers, spaced retrieval and Montessori activities, facilitated breakfast clubs, multisensory exercise and multicomponent interventions.
CONCLUSIONS
We found no definitive evidence on effectiveness, or lack of effectiveness, of specific interventions but studies were small and short term. A variety of promising indirect interventions need to be tested in large, high-quality RCTs, and may be approaches that people with dementia and their formal or informal care-givers would wish to try.
TRIAL REGISTRATION
The systematic review protocol was registered (CRD42014007611) and is published, with the full MEDLINE search strategy, on Prospero (http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42014007611).
Topics: Behavior Therapy; Clinical Trials as Topic; Dehydration; Dementia; Drinking; Early Medical Intervention; Eating; Exercise; Humans; Treatment Outcome
PubMed: 27142469
DOI: 10.1186/s12877-016-0256-8 -
BMC Musculoskeletal Disorders Sep 2017The objectives are to compare the efficacy of intra-articular hyaluronic acid (IA-HA) alone and in combination with anti-inflammatory drugs (IA-HA + AI),... (Comparative Study)
Comparative Study Meta-Analysis Review
Effects of hyaluronic acid combined with anti-inflammatory drugs compared with hyaluronic acid alone, in clinical trials and experiments in osteoarthritis: a systematic review and meta-analysis.
BACKGROUND
The objectives are to compare the efficacy of intra-articular hyaluronic acid (IA-HA) alone and in combination with anti-inflammatory drugs (IA-HA + AI), corticosteroids (CS) or non-steroidal anti-inflammatory drugs (NSAIDs) in clinical trials and in vivo and in vitro studies of osteoarthritis (OA).
METHODS
Data in the BIOSIS, CINAHL, Cochrane Library, EMBASE and Medline databases were collected and analyzed. Random effects models were used to compute the effect size (ES) of the mean difference in pain reduction scores from baseline and the relative risk (RR) of adverse events. The ES of histological scores in vivo and cartilage metabolism in vitro were also calculated. We conducted sensitivity analysis of blinding and intention-to-treat (ITT), compared IA-HA combined with CS vs. IA-HA alone in trials, and compared the effects of HA + AI vs. AI alone in vitro, including anabolic and catabolic gene expression.
RESULTS
Thirteen out of 382 papers were included for data analysis. In clinical trials, the ES of pain reduction scores within the 1st month was -4.24 (-6.19, -2.29); 2nd-12th month, -1.39 (-1.95, -0.82); and within one year, -1.63 (-2.19, -1.08), favoring IA-HA + AI (P < 0.001). The ES of RR was 1.08 (0.59, 1.98), and histological scores was 1.38 (-0.55, 3.31). The ES of anabolic gene expression was 1.22 (0.18, 2.25), favoring HA alone (P < 0.05); catabolic gene expression was 0.74 (-0.44, 1.53), favoring HA alone; and glycosaminoglycans remaining was -2.45 (-5.94, 1.03).
CONCLUSIONS
IA-HA + AI had greater efficacy for pain relief than IA-HA alone within a one-year period. However, HA + AI down-regulated the ACAN gene when compared with HA alone in vitro.
Topics: Anti-Inflammatory Agents; Clinical Trials as Topic; Drug Therapy, Combination; Humans; Hyaluronic Acid; Osteoarthritis; Treatment Outcome
PubMed: 28877688
DOI: 10.1186/s12891-017-1743-6 -
Clinical and Experimental Dermatology Jul 2017Human scabies (infestation with the mite Sarcoptes scabiei var hominis) causes a significant disease burden worldwide, yet there are no agreed diagnostic guidelines. We... (Review)
Review
Human scabies (infestation with the mite Sarcoptes scabiei var hominis) causes a significant disease burden worldwide, yet there are no agreed diagnostic guidelines. We aimed to determine whether a consistent approach to diagnosing scabies has been used for published scabies therapeutic trials. The data sources used were the MEDLINE, Embase and Cochrane databases, from 1946 to 29 August 2013. Eligible studies were trials of therapeutic interventions against scabies in human subjects, published in English, enrolling patients with scabies, and using various therapeutic interventions. Language was a limitation of this study as some relevant trials published in languages other than English may have been excluded. Each study was reviewed by two independent authors, who assessed the clinical examination and testing approaches used for scabies diagnosis in the included studies. We found that of 71 included trials, 40 (56%) specified which clinical findings were used for diagnosis, which were predominantly rash, rash distribution, pruritus and mite burrows. Parasitological testing was used in 63% of trials (n = 45) and was used more frequently in clinic-based than in field studies. Nearly one-quarter of trials (24%, n = 17) did not define the diagnostic method used. Overall, the diagnostic approaches were poorly described, prohibiting accurate comparison of existing studies. This review further supports the need for consensus diagnostic guidelines for scabies.
Topics: Clinical Trials as Topic; Diagnosis, Differential; Humans; Scabies
PubMed: 28556185
DOI: 10.1111/ced.13152 -
Trials Feb 2019Inter-observer variability in stroke aetiological classification may have an effect on trial power and estimation of treatment effect. We modelled the effect of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Inter-observer variability in stroke aetiological classification may have an effect on trial power and estimation of treatment effect. We modelled the effect of misclassification on required sample size in a hypothetical cardioembolic (CE) stroke trial.
METHODS
We performed a systematic review to quantify the reliability (inter-observer variability) of various stroke aetiological classification systems. We then modelled the effect of this misclassification in a hypothetical trial of anticoagulant in CE stroke contaminated by patients with non-cardioembolic (non-CE) stroke aetiology. Rates of misclassification were based on the summary reliability estimates from our systematic review. We randomly sampled data from previous acute trials in CE and non-CE participants, using the Virtual International Stroke Trials Archive. We used bootstrapping to model the effect of varying misclassification rates on sample size required to detect a between-group treatment effect across 5000 permutations. We described outcomes in terms of survival and stroke recurrence censored at 90 days.
RESULTS
From 4655 titles, we found 14 articles describing three stroke classification systems. The inter-observer reliability of the classification systems varied from 'fair' to 'very good' and suggested misclassification rates of 5% and 20% for our modelling. The hypothetical trial, with 80% power and alpha 0.05, was able to show a difference in survival between anticoagulant and antiplatelet in CE with a sample size of 198 in both trial arms. Contamination of both arms with 5% misclassified participants inflated the required sample size to 237 and with 20% misclassification inflated the required sample size to 352, for equivalent trial power. For an outcome of stroke recurrence using the same data, base-case estimated sample size for 80% power and alpha 0.05 was n = 502 in each arm, increasing to 605 at 5% contamination and 973 at 20% contamination.
CONCLUSIONS
Stroke aetiological classification systems suffer from inter-observer variability, and the resulting misclassification may limit trial power.
TRIAL REGISTRATION
Protocol available at reviewregistry540 .
Topics: Anticoagulants; Clinical Trials as Topic; Data Interpretation, Statistical; Embolism; Heart Diseases; Humans; Models, Statistical; Observer Variation; Platelet Aggregation Inhibitors; Risk Factors; Sample Size; Stroke; Terminology as Topic; Time Factors; Treatment Outcome
PubMed: 30736833
DOI: 10.1186/s13063-019-3222-x -
Movement Disorders : Official Journal... Oct 2017Multiple system atrophy (MSA) is a rare neurodegenerative disease of undetermined cause. Although many clinical trials have been conducted, there is still no treatment... (Review)
Review
Multiple system atrophy (MSA) is a rare neurodegenerative disease of undetermined cause. Although many clinical trials have been conducted, there is still no treatment that cures the disease or slows its progression. We sought to assess the clinical trials, methodology, and quality of reporting of clinical trails conducted in MSA patients. We conducted a systematic review of all trials with at least 1 MSA patient subject to any pharmacological/nonpharmacological interventions. Two independent reviewers evaluated the methodological characteristics and quality of reporting of trials. A total of 60 clinical trials were identified, including 1375 MSA patients. Of the trials, 51% (n = 31) were single-arm studies. A total of 28% (n = 17) had a parallel design, half of which (n = 13) were placebo controlled. Of the studies, 8 (13.3%) were conducted in a multicenter setting, 3 of which were responsible for 49.3% (n = 678) of the total included MSA patients. The description of primary outcomes was unclear in 60% (n = 40) of trials. Only 10 (16.7%) clinical trials clearly described the randomization process. Blinding of the participants, personnel, and outcome assessments were at high risk of bias in the majority of studies. The number of dropouts/withdrawals was high (n = 326, 23.4% among the included patients). Overall, the design and quality of reporting of the reviewed studies is unsatisfactory. The most frequent clinical trials were small and single centered. Inadequate reporting was related to the information on the randomization process, sequence generation, allocation concealment, blinding of participants, and sample size calculations. Although improved during the recent years, methodological quality and trial design need to be optimized to generate more informative results. © 2017 International Parkinson and Movement Disorder Society.
Topics: Adult; Aged; Clinical Trials as Topic; Databases, Factual; Female; Humans; Male; Middle Aged; Multiple System Atrophy; Outcome Assessment, Health Care; Treatment Outcome
PubMed: 28782838
DOI: 10.1002/mds.27080