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International Journal of Environmental... Jul 2020Ageing is associated with changes of physical and physiological parameters, but there is evidence that regular physical activity could minimize these effects....
BACKGROUND
Ageing is associated with changes of physical and physiological parameters, but there is evidence that regular physical activity could minimize these effects. Additionally, the older population presents a great risk of suboptimal nutrition. Therefore, the purpose of this study was to review the evidence of nutritional strategies and endurance exercises in the older population.
METHODS
A systematic review was performed based on the preferred reporting items for systematic reviews and meta-analysis (PRISMA) statement. The search was carried out in three different databases: PubMed, Web of Science, and SPORTDiscus.
RESULTS
Eight studies were included in the present review. The use of caffeine and beta-alanine supplementation with proteins have been found to be beneficial in both sexes. In older women, a balanced diet, an increase in protein, supplementation with beta hydroxy methyl butyrate, and supplementation with sodium bicarbonate have been favorable. However, no benefit has been seen in older men with sodium bicarbonate or ubiquinone supplementation. Nevertheless, the use of supplements should be prescribed according to individual characteristics and physical activity.
CONCLUSIONS
Caffeine and high protein supplement with beta-alanine may provide positive effects in the older population. In addition, in older women, bicarbonate supplementation and beta-hydroxyethyl butyrate (HMB), lysine, and arginine supplementation have shown positive effects on exercise performance.
Topics: Aged; Aging; Caffeine; Dietary Supplements; Exercise; Exercise Therapy; Female; Humans; Male; Physical Endurance
PubMed: 32698345
DOI: 10.3390/ijerph17145224 -
Frontiers in Cardiovascular Medicine 2020MicroRNAs are highly investigated for their role in the pathogenesis of cardiovascular diseases. Nevertheless, evidence for clinical implementation is still lacking. In...
MicroRNAs are highly investigated for their role in the pathogenesis of cardiovascular diseases. Nevertheless, evidence for clinical implementation is still lacking. In our systematic review, we evaluated the potential of microRNAs as pathophysiological and diagnostic biomarkers of heart failure. We identified 72 differentially expressed microRNA molecules among groups of heart failure patients and control groups by searching the PubMed database. We did not identify a substantial overlap of differentially expressed microRNAs among different studies; only five microRNAs (miR-1228, miR-122, miR-423-5p, miR-142-3p, and exosomal miR-92b-5p) were differentially expressed in more than one included study. Gene set enrichment analysis, based on the gene targets of microRNAs presented in the included studies, showed that gene targets of differentially expressed microRNAs were enriched in the MAPK, TGFβ, PI3K-Akt, and IL-2 signaling pathways, as well as apoptosis pathway, p53 activity regulation, and angiogenesis pathway. Results of our systematic review show that there is currently insufficient support for the use of any of the presented microRNAs as pathophysiological or prognostic biomarkers in the clinical setting.
PubMed: 33195446
DOI: 10.3389/fcvm.2020.00161 -
JCPP Advances Jul 2021Non-shared environment (NSE) effects account for around one-third of the etiology of autism spectrum disorder (ASD). However, the knowledge of mechanisms and phenotypic...
BACKGROUND
Non-shared environment (NSE) effects account for around one-third of the etiology of autism spectrum disorder (ASD). However, the knowledge of mechanisms and phenotypic profiles associated with NSE in ASD is scarce.
METHODS
A systematic search was conducted using Embase, MEDLINE, and PsycINFO for studies published in English between 1990 and August 2020 using co-twin control design to compare behavioral and biological phenotypes among monozygotic (MZ) twin pairs concordant/discordant for ASD, clinical autism symptoms, or autistic traits. Risk of bias was assessed through a modified Newcastle-Ottawa Scale.
RESULTS
Twenty six articles were included. Differential DNA methylation and gene expression were found among ASD discordant twins; however, genetic results were inconsistent. Neurological disorders and early medical events were associated with ASD and autistic traits, while no within pair differences were found for minor physical anomalies or head circumference. Structural and functional brain imaging studies and research on social and other cognitive/behavioral functions were inconclusive. Risk of bias assessment found that all studies used the same exposure (or outcome) measures to collect data for participants and most used either secure health-related records or structured interviews for ascertainment of exposure; however, only a handful of studies representative of the population from which they were drawn. Formal assessment of risk of publication bias (i.e., funnel plot) was not possible.
CONCLUSIONS
Our results suggest that NSE in ASD could be associated with heterogeneous postzygotic genetic mechanisms and manifest as a range of biological and behavioral phenotypes. Extant findings were limited by relatively few studies, small sample sizes, and methodological diversity. More research is needed on co-occurring biological and behavioral phenotypes using a consistent format for designing, analyzing, and reporting MZ ASD discordant twin studies in order to further examine the role of NSE in the etiology of ASD.
PubMed: 37431470
DOI: 10.1111/jcv2.12017 -
Journal of Neuro-oncology Nov 2022Shorter hypofractionated radiation therapy (HF-RT) schedules may have radiobiological, patient convenience and healthcare resource advantages over conventionally... (Meta-Analysis)
Meta-Analysis
Moderately hypofractionated versus conventionally fractionated radiation therapy with temozolomide for young and fit patients with glioblastoma: an institutional experience and meta-analysis of literature.
PURPOSE
Shorter hypofractionated radiation therapy (HF-RT) schedules may have radiobiological, patient convenience and healthcare resource advantages over conventionally fractionated radiation therapy (CF-RT) in glioblastoma (GBM). We report outcomes of young, fit GBM patients treated with HF-RT and CF-RT during the COVID-19 pandemic, and a meta-analysis of HF-RT literature in this patient subgroup.
METHODS
Hospital records of patients with IDH-wildtype GBM treated with HF-RT (50 Gy/20 fractions) and CF-RT (60 Gy/30 fractions) between January 2020 and September 2021 were reviewed. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method. Univariable analysis was performed using Cox regression analysis. A systematic search and meta-analysis of studies from January 2000 to January 2022 was performed.
RESULTS
41 patients were treated (HF-RT:15, CF-RT:26). For both HF-RT and CF-RT groups, median age was 58 years and 80-90% were ECOG 0-1. There were more methylated tumours in the HF-RT group. All patients received concurrent/adjuvant temozolomide. At 19.2 months median follow-up, median OS was 19.8 months and not-reached for HF-RT and CF-RT (p = 0.5), and median PFS was 7.7 and 5.8 months, respectively (p = 0.8). HF-RT or CF-RT did not influence OS/PFS on univariable analysis. Grade 3 radionecrosis rate was 6.7% and 7.7%, respectively. 15 of 1135 studies screened from a systematic search were eligible for meta-analysis. For studies involving temozolomide, pooled median OS and PFS with HF-RT were 17.5 and 9.9 months (927 and 862 patients). Studies using shortened HF-RT schedules reported 0-2% Grade 3 radionecrosis rates.
CONCLUSION
HF-RT may offer equivalent outcomes and reduce treatment burden compared to CF-RT in young, fit GBM patients.
Topics: Humans; Middle Aged; Antineoplastic Agents, Alkylating; Brain Neoplasms; COVID-19; Glioblastoma; Pandemics; Temozolomide
PubMed: 36355260
DOI: 10.1007/s11060-022-04151-z -
JAMA Dermatology Sep 2021Multiple interventions are available for the treatment of actinic keratosis (AK). However, most randomized clinical trials and meta-analyses focus on short-term efficacy... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Multiple interventions are available for the treatment of actinic keratosis (AK). However, most randomized clinical trials and meta-analyses focus on short-term efficacy outcomes.
OBJECTIVE
To investigate and synthesize the long-term efficacy (≥12 months) of interventions for AK from parallel-arm randomized clinical trials.
DATA SOURCES
Searches in MEDLINE, Embase, and Central were conducted from inception until April 6, 2020. The reference lists of the included studies and pertinent trial registers were hand searched. The study was completed February 27, 2021.
STUDY SELECTION
Two reviewers screened the titles and abstracts of 2741 records. Finally, 17 published reports (original studies and follow-up reports) referring to 15 independent randomized clinical trials with an overall sample size of 4252 patients were included.
DATA EXTRACTION AND SYNTHESIS
Two reviewers independently extracted data on study, patient, and intervention characteristics. Network meta-analysis (NMA) of each outcome was conducted with a frequentist approach. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) guidance for NMA was used to assess the certainty of evidence. The revised Cochrane risk-of-bias tool for randomized clinical trials was used to evaluate the methodologic quality.
MAIN OUTCOMES AND MEASURES
Participant complete clearance, participant partial clearance, and lesion-specific clearance were the outcomes, with each assessed at least 12 months after the end of treatment.
RESULTS
Data from 15 independent randomized clinical trials including 4252 patients were extracted and synthesized. Ten studies were included in an NMA for the outcome of participant complete clearance, with photodynamic therapy with aminolevulinate (ALA-PDT) showing the most favorable risk ratio (RR) compared with placebo (RR, 8.06; 95% CI, 2.07-31.37; GRADE, moderate), followed by imiquimod, 5% (RR, 5.98; 95% CI, 2.26-15.84; GRADE, very low), photodynamic therapy with methyl aminolevulinate (MAL-PDT) (RR, 5.95; 95% CI, 1.21-29.41; GRADE, low), and cryosurgery (RR, 4.67; 95% CI, 1.36-16.66; GRADE, very low). Similarly, ALA-PDT had the highest RR in the NMA for lesion-specific clearance (RR, 5.08; 95% CI, 2.49-10.33; GRADE, moderate). No NMA was possible for participant partial clearance owing to poor reporting of this outcome.
CONCLUSIONS AND RELEVANCE
This systematic review and network meta-analysis found that therapy including ALA-PDT, imiquimod, 5%, MAL-PDT, and cryosurgery was associated with significant long-term efficacy in the NMA. This study provides data for a possible use in an evidence-based framework for selecting interventions with sustained lesion clearance.
Topics: Cryosurgery; Humans; Imiquimod; Keratosis, Actinic; Network Meta-Analysis; Photochemotherapy; Randomized Controlled Trials as Topic
PubMed: 34347015
DOI: 10.1001/jamadermatol.2021.2779 -
Saudi Journal of Anaesthesia 2024Many premedication agents with opioid-sparing properties have been used in patients undergoing various elective surgeries. Memantine is an N-methyl-D-aspartate (NMDA)... (Review)
Review
Many premedication agents with opioid-sparing properties have been used in patients undergoing various elective surgeries. Memantine is an N-methyl-D-aspartate (NMDA) receptor antagonist that has been used by many researchers as an opioid-sparing strategy. Various databases like PubMed, Scopus, Cochrane Library, and clinicaltrials.gov were searched after registering the review protocol in PROSPERO for randomized-controlled trials (RCTs) that investigated the efficacy and safety of memantine premedication in adult patients undergoing various elective surgeries. The risk of bias (RoB-2) scale was used to assess the quality of evidence. From the 225 articles that were identified after a database search, 3 studies were included for a qualitative systematic review and a quantitative meta-analysis. The pooled analysis revealed that the use of memantine provided better pain scores at 2nd (mean difference: -0.82, 95% CI: -1.60, -0.05, = 0.04) with significant heterogeneity ( = 0.06; I² =71%), and 6 hours postoperatively (mean difference: -1.80, 95% CI: -2.23, -1.37, < 0.00001), but not at 1 hour. The sedation scores at 1 hour were higher in the memantine group but comparable in the 2nd hour. The number of doses of rescue analgesia and nausea/vomiting in the postoperative period was comparable in both groups. The results of this review suggest that memantine premedication could provide better pain scores in the immediate postoperative period with acceptable adverse effects. However, the current evidence is insufficient to suggest the routine use of memantine as a premedication before elective surgeries.
PubMed: 38313717
DOI: 10.4103/sja.sja_398_23 -
The Journal of Pain 2020Accumulating evidence suggests that epigenetic mechanisms may hold great potential in the field of pain. We systematically reviewed the literature exploring epigenetic...
Accumulating evidence suggests that epigenetic mechanisms may hold great potential in the field of pain. We systematically reviewed the literature exploring epigenetic mechanisms in people with pain. Four databases have been interrogated: MEDLINE, The Cochrane Central Register of Controlled Trial, Scopus, and Web of Science, following PRISMA guidelines in conducting study selection and assessment. Thirty-seven studies were included. Studies explored epigenetics in conditions such as fibromyalgia, CRPS, neuropathies, or osteoarthritis. Research focussed on genome-wide and gene-specific DNA methylation, and miRNA expression. Bioinformatics analyses exploring miRNA-associated molecular pathways were also performed. Several genes already known for their role in pain (BDNF, HDAC4, PRKG1, IL-17, TNFRSF13B, etc.), and several miRNAs linked to inflammatory regulation, nociceptive signalling and protein kinases functions have been found to differ significantly between people with chronic pain and healthy controls. Although the studies included were cross-sectional in nature, and no conclusion on causal links between epigenetic changes and pain could be drawn, we summarised the large amount of data available in literature on the topic, highlighting results that have been replicated by independent investigations. The field of pain epigenetics appears very exciting and has all the potential to lead to remarkable scientific advances. However, high-quality, well-powered, longitudinal studies are warranted. PERSPECTIVE: Though more high-quality research is needed, available research exploring epigenetic mechanisms or miRNAs in people with pain shows that genes regulating synaptic plasticity and excitability, protein kinases, and elements of the immune system might hold great potential in understanding the pathophysiology of different conditions.
Topics: DNA Methylation; Epigenesis, Genetic; Humans; MicroRNAs; Pain
PubMed: 31837447
DOI: 10.1016/j.jpain.2019.12.002 -
Frontiers in Oncology 2022Capsaicin (8-methyl-N-vanillyl-6-nonenamide) is one of the most important natural products in the genus Due to its numerous biological effects, there has been extensive...
Capsaicin (8-methyl-N-vanillyl-6-nonenamide) is one of the most important natural products in the genus Due to its numerous biological effects, there has been extensive and increasing research interest in capsaicin, resulting in increased scientific publications in recent years. Therefore, an in-depth bibliometric analysis of published literature on capsaicin from 2001 to 2021 was performed to assess the global research status, thematic and emerging areas, and potential insights into future research. Furthermore, recent research advances of capsaicin and its combination therapy on human cancer as well as their potential mechanisms of action were described. In the last two decades, research outputs on capsaicin have increased by an estimated 18% per year and were dominated by research articles at 93% of the 3753 assessed literature. In addition, anti-cancer/pharmacokinetics, cytotoxicity, neurological and pain research studies were the keyword clusters generated and designated as thematic domains for capsaicin research. It was evident that the United States, China, and Japan accounted for about 42% of 3753 publications that met the inclusion criteria. Also, visibly dominant collaboration nodes and networks with most of the other identified countries were established. Assessment of the eligible literature revealed that the potential of capsaicin for mitigating cancer mainly entailed its chemo-preventive effects, which were often linked to its ability to exert multi-biological effects such as anti-mutagenic, antioxidant and anti-inflammatory activities. However, clinical studies were limited, which may be related to some of the inherent challenges associated with capsaicin in the limited clinical trials. This review presents a novel approach to visualizing information about capsaicin research and a comprehensive perspective on the therapeutic significance and applications of capsaicin in the treatment of human cancer.
PubMed: 35912207
DOI: 10.3389/fonc.2022.908487 -
Molecular Psychiatry Sep 2020To review the success rate and efficiency of industry-sponsored phase 2/3 clinical trials for adjunctive therapies for antidepressant partial- and non-responders with... (Review)
Review
To review the success rate and efficiency of industry-sponsored phase 2/3 clinical trials for adjunctive therapies for antidepressant partial- and non-responders with major depressive disorder (MDD), a systematic search of Pubmed/Medline was conducted, in addition to abstracts of major psychiatric meeting held since 2010, of randomized, placebo-controlled adjunct oral pharmacotherapy trials in this patient population. Forty-six (n = 33,900; 70 drug compactor arms) trials were pooled, yielding only three approved drugs. Twenty-two (31.4%) drug-placebo comparisons were successful. Numerically, success rates for treatment arms from studies with one versus more than one drug-placebo comparison were higher (39.3% versus 26.2%). The antidepressant lead-in employing single-blind placebo and the sequential-parallel comparison design (SPCD) were successful in 50% and 40% of cases, respectively. The direct randomization (no lead-in) design yielded positive results in one third of cases. The success rate of open-label antidepressant lead-ins without placebo or using double-blind placebo was very poor (<15%). There was also a pronounced discrepancy in terms of efficiency across study designs. Accounting for sample size requirements, a phase 3 program using SPCD would have a higher cumulative chance of yielding two positive trials (50%) than a phase 3 program using a single-blind placebo lead-in (40%). Future programs should carefully weigh the need for a lead-in, which is time-consuming, expensive and, in some cases (i.e., open-label antidepressant without placebo or with double-blind placebo) nearly futile. Instead, more effort should involve the use of studies where patients are directly randomized, such as the SPCD, with more investment shifted towards the accurate and independent vetting of subject eligibility.
Topics: Antidepressive Agents; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Depressive Disorder, Major; Double-Blind Method; Humans; Randomized Controlled Trials as Topic; Sample Size; Single-Blind Method; Treatment Outcome
PubMed: 31988433
DOI: 10.1038/s41380-020-0646-3 -
Journal of Neurology Oct 2022A variety of psychiatric syndromes are associated with NMDAR autoantibodies; however, their clinical relevance when only present in the serum is unclear. We explored... (Meta-Analysis)
Meta-Analysis Review
The clinical relevance of serum versus CSF NMDAR autoantibodies associated exclusively with psychiatric features: a systematic review and meta-analysis of individual patient data.
BACKGROUND
A variety of psychiatric syndromes are associated with NMDAR autoantibodies; however, their clinical relevance when only present in the serum is unclear. We explored whether patients with CSF NMDAR autoantibodies could be distinguished from patients with serum-only NMDAR autoantibodies.
METHODS
The electronic databases MEDLINE, EMBASE, PubMed, and PsycINFO were searched. Articles reporting adult patients with isolated psychiatric features and positive for NMDAR autoantibodies with relevant investigations were included. Patient level meta-analysis compared patients positive for CSF NMDAR autoantibodies with patients positive for serum NMDAR autoantibodies, but negative for CSF NMDAR autoantibodies. Dichotomous data were analysed using crude odds ratios (OR), whilst continuous data were analysed using Mann-Whitney Test (U). The protocol was prospectively registered (CRD42018082210).
RESULTS
Of 4413 publications, 42 were included, reporting 79 patients. Median age was 34 years (IQR 19 years); 56% (45/79) were female and 24% (16/68) had a tumour. In total, 41 patients were positive for CSF autoantibodies and 20 were positive for serum-only autoantibodies. Patients with CSF autoantibodies were significantly more likely to be female (p < 0.001) and have a rapid (< 3 month) onset of symptoms (p = 0.02) than patients with serum-only autoantibodies. They were also more likely to present with psychosis (p < 0.001), exhibit EEG (p = 0.006), MRI (p = 0.002), and CSF (p = 0.001) abnormalities, but less likely to present with insomnia (p = 0.04).
CONCLUSIONS
Patients with an isolated psychiatric syndrome with CSF NMDAR autoantibodies can potentially be distinguished from those with serum-only NMDAR autoantibodies based on clinicodemographic and investigation findings.
Topics: Adult; Anti-N-Methyl-D-Aspartate Receptor Encephalitis; Autoantibodies; Female; Humans; Male; Psychotic Disorders; Receptors, N-Methyl-D-Aspartate
PubMed: 35790561
DOI: 10.1007/s00415-022-11224-6