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Sports Health 2021Energy drinks are the fastest growing product in the beverage industry. However, there is concern regarding potential for adverse effects with use. (Meta-Analysis)
Meta-Analysis
CONTEXT
Energy drinks are the fastest growing product in the beverage industry. However, there is concern regarding potential for adverse effects with use.
OBJECTIVE
To evaluate the reported adverse effects of energy drink consumption.
DATA SOURCES
The electronic databases MEDLINE, EMBASE, and PubMed were searched for relevant studies from inception to November 2019, and pertinent data were abstracted.
STUDY SELECTION
Only clinical studies reporting adverse events after energy drink consumption were included.
STUDY DESIGN
Systematic review.
LEVEL OF EVIDENCE
Level 4.
DATA EXTRACTION
Data regarding sample size characteristics, energy drink characteristics, comparators, and all adverse events were extracted in duplicate and recorded.
RESULTS
A total of 32 studies and 96,549 individuals were included. Frequently reported adverse events in the pediatric population were insomnia (35.4%), stress (35.4%), and depressive mood (23.1%). Frequently reported adverse events in the adult population were insomnia (24.7%), jitteriness/restlessness/shaking hands (29.8%), and gastrointestinal upset (21.6%). Alcohol mixed with energy drinks significantly reduced the likelihood of sedation effects but increased the likelihood of stimulatory effects. Energy drink consumption significantly increased the odds of insomnia (OR, 5.02; 95% CI, 1.72-14.63) and jitteriness/activeness (OR, 3.52; 95% CI, 1.28-9.67) compared with the control group.
CONCLUSION
The authors recommend that individuals avoid frequent energy drink consumption (5-7 energy drinks/week) and avoid co-consumption with alcohol; increased regulatory standards should be placed in the sale of energy drinks, particularly with regard to the pediatric population.
Topics: Alcohol Drinking; Caffeine; Depression; Energy Drinks; Gastrointestinal Diseases; Humans; Sleep Initiation and Maintenance Disorders; Stress, Psychological
PubMed: 33211984
DOI: 10.1177/1941738120949181 -
BMJ (Clinical Research Ed.) Oct 2021To assess the effectiveness and safety of different preparations and doses of non-steroidal anti-inflammatory drugs (NSAIDs), opioids, and paracetamol for knee and hip...
OBJECTIVE
To assess the effectiveness and safety of different preparations and doses of non-steroidal anti-inflammatory drugs (NSAIDs), opioids, and paracetamol for knee and hip osteoarthritis pain and physical function to enable effective and safe use of these drugs at their lowest possible dose.
DESIGN
Systematic review and network meta-analysis of randomised trials.
DATA SOURCES
Cochrane Central Register of Controlled Trials (CENTRAL), Medline, Embase, regulatory agency websites, and ClinicalTrials.gov from inception to 28 June 2021.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
Randomised trials published in English with ≥100 patients per group that evaluated NSAIDs, opioids, or paracetamol (acetaminophen) to treat osteoarthritis.
OUTCOMES AND MEASURES
The prespecified primary outcome was pain. Physical function and safety outcomes were also assessed.
REVIEW METHODS
Two reviewers independently extracted outcomes data and evaluated the risk of bias of included trials. Bayesian random effects models were used for network meta-analysis of all analyses. Effect estimates are comparisons between active treatments and oral placebo.
RESULTS
192 trials comprising 102 829 participants examined 90 different active preparations or doses (68 for NSAIDs, 19 for opioids, and three for paracetamol). Five oral preparations (diclofenac 150 mg/day, etoricoxib 60 and 90 mg/day, and rofecoxib 25 and 50 mg/day) had ≥99% probability of more pronounced treatment effects than the minimal clinically relevant reduction in pain. Topical diclofenac (70-81 and 140-160 mg/day) had ≥92.3% probability, and all opioids had ≤53% probability of more pronounced treatment effects than the minimal clinically relevant reduction in pain. 18.5%, 0%, and 83.3% of the oral NSAIDs, topical NSAIDs, and opioids, respectively, had an increased risk of dropouts due to adverse events. 29.8%, 0%, and 89.5% of oral NSAIDs, topical NSAIDs, and opioids, respectively, had an increased risk of any adverse event. Oxymorphone 80 mg/day had the highest risk of dropouts due to adverse events (51%) and any adverse event (88%).
CONCLUSIONS
Etoricoxib 60 mg/day and diclofenac 150 mg/day seem to be the most effective oral NSAIDs for pain and function in patients with osteoarthritis. However, these treatments are probably not appropriate for patients with comorbidities or for long term use because of the slight increase in the risk of adverse events. Additionally, an increased risk of dropping out due to adverse events was found for diclofenac 150 mg/day. Topical diclofenac 70-81 mg/day seems to be effective and generally safer because of reduced systemic exposure and lower dose, and should be considered as first line pharmacological treatment for knee osteoarthritis. The clinical benefit of opioid treatment, regardless of preparation or dose, does not outweigh the harm it might cause in patients with osteoarthritis.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO number CRD42020213656.
Topics: Acetaminophen; Administration, Oral; Administration, Topical; Aged; Analgesics, Opioid; Anti-Inflammatory Agents, Non-Steroidal; Female; Humans; Male; Middle Aged; Minimal Clinically Important Difference; Network Meta-Analysis; Osteoarthritis, Hip; Osteoarthritis, Knee; Pain Management
PubMed: 34642179
DOI: 10.1136/bmj.n2321 -
Diabetes, Obesity & Metabolism May 2019The use of sodium glucose co-transporter 2 (SGLT2) inhibitors in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) has been limited,... (Meta-Analysis)
Meta-Analysis
Effect of SGLT2 inhibitors on cardiovascular, renal and safety outcomes in patients with type 2 diabetes mellitus and chronic kidney disease: A systematic review and meta-analysis.
AIM
The use of sodium glucose co-transporter 2 (SGLT2) inhibitors in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) has been limited, primarily because glycaemic efficacy is dependent on kidney function. We performed a systematic review and meta-analysis to assess the efficacy and safety of SGLT2 inhibitors in patients with T2DM and CKD, defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m .
MATERIALS AND METHODS
We searched MEDLINE, EMBASE and the Cochrane Library until 7 August 2018 and websites of the US, European and Japanese regulatory authorities until 27 July 2018 for data from randomized controlled trials of SGLT2 inhibitors that included reporting of effects on biomarkers, cardiovascular, renal or safety outcomes in individuals with T2DM and CKD. Random effects models and inverse variance weighting were used to calculate relative risks with 95% confidence intervals.
RESULTS
Data were obtained from 27 studies with up to 7363 participants involved. In patients with T2DM and CKD, SGLT2 inhibitors lowered glycated haemoglobin (-0.29%; 95% CI, -0.39 to -0.19) as well as blood pressure, body weight and albuminuria. SGLT2 inhibition reduced the risk of cardiovascular death, nonfatal myocardial infarction or nonfatal stroke (RR, 0.81; 95% CI, 0.70-0.94) and heart failure (RR, 0.61; 95% CI, 0.48-0.78), without a clear effect on all-cause mortality (HR, 0.86; 95% CI, 0.73-1.01). These agents also attenuated the annual decline in eGFR slope (placebo-subtracted difference of 1.35 mL/1.73 m /y; 95% CI, 0.78-1.93) and reduced the risk of the composite renal outcome (HR, 0.71; 95% CI, 0.53-0.95). There was no evidence of additional risks with SGLT2 inhibition in CKD beyond those already known for the class, although heterogeneity was observed across individual agents for some safety outcomes.
CONCLUSION
Currently available data suggest that, despite only modest reductions in glycated haemoglobin, SGLT2 inhibitors reduce the risk of cardiovascular and renal outcomes in patients with T2DM and CKD, without clear evidence of additional safety concerns.
Topics: Cardiovascular Diseases; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Nephropathies; Humans; Hypoglycemic Agents; Renal Insufficiency, Chronic; Sodium-Glucose Transporter 2 Inhibitors; Treatment Outcome
PubMed: 30697905
DOI: 10.1111/dom.13648 -
Frontiers in Endocrinology 2022Ferroptosis is a newly discovered form of cell death that differs from other forms of regulated cell death at morphological, biochemical, and genetic levels, and is... (Review)
Review
Ferroptosis is a newly discovered form of cell death that differs from other forms of regulated cell death at morphological, biochemical, and genetic levels, and is characterized by iron-dependent accumulation of lipid peroxides. Ferroptosis is closely related to intracellular metabolism of amino acids, lipids, and iron. Hence, its regulation may facilitate disease intervention and treatment. Diabetic kidney disease is one of the most serious complications of diabetes, which leads to serious psychological and economic burdens to patients and society when it progresses to end-stage renal disease. At present, there is no effective treatment for diabetic kidney disease. Ferroptosis has been recently identified in animal models of diabetic kidney disease. Herein, we systematically reviewed the regulatory mechanism of ferroptosis, its association with different forms of cell death, summarized its relationship with diabetic kidney disease, and explored its regulation to intervene with the progression of diabetic kidney disease or as a treatment.
Topics: Amino Acids; Animals; Diabetes Mellitus; Diabetic Nephropathies; Ferroptosis; Iron; Lipid Peroxides
PubMed: 36246888
DOI: 10.3389/fendo.2022.945976 -
Signal Transduction and Targeted Therapy Feb 2021The abnormal regulation of alternative splicing is usually accompanied by the occurrence and development of tumors, which would produce multiple different isoforms and...
The abnormal regulation of alternative splicing is usually accompanied by the occurrence and development of tumors, which would produce multiple different isoforms and diversify protein expression. The aim of the present study was to conduct a systematic review in order to describe the regulatory mechanisms of alternative splicing, as well as its functions in tumor cells, from proliferation and apoptosis to invasion and metastasis, and from angiogenesis to metabolism. The abnormal splicing events contributed to tumor progression as oncogenic drivers and/or bystander factors. The alterations in splicing factors detected in tumors and other mis-splicing events (i.e., long non-coding and circular RNAs) in tumorigenesis were also included. The findings of recent therapeutic approaches targeting splicing catalysis and splicing regulatory proteins to modulate pathogenically spliced events (including tumor-specific neo-antigens for cancer immunotherapy) were introduced. The emerging RNA-based strategies for the treatment of cancer with abnormally alternative splicing isoforms were also discussed. However, further studies are still required to address the association between alternative splicing and cancer in more detail.
Topics: Alternative Splicing; Carcinogenesis; Gene Expression Regulation, Neoplastic; Humans; Neoplasms; RNA Splicing; RNA Splicing Factors; RNA, Circular
PubMed: 33623018
DOI: 10.1038/s41392-021-00486-7 -
BMJ (Clinical Research Ed.) Apr 2023To investigate the role of air pollutants in risk of dementia, considering differences by study factors that could influence findings. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To investigate the role of air pollutants in risk of dementia, considering differences by study factors that could influence findings.
DESIGN
Systematic review and meta-analysis.
DATA SOURCES
EMBASE, PubMed, Web of Science, Psycinfo, and OVID Medline from database inception through July 2022.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
Studies that included adults (≥18 years), a longitudinal follow-up, considered US Environmental Protection Agency criteria air pollutants and proxies of traffic pollution, averaged exposure over a year or more, and reported associations between ambient pollutants and clinical dementia. Two authors independently extracted data using a predefined data extraction form and assessed risk of bias using the Risk of Bias In Non-randomised Studies of Exposures (ROBINS-E) tool. A meta-analysis with Knapp-Hartung standard errors was done when at least three studies for a given pollutant used comparable approaches.
RESULTS
2080 records identified 51 studies for inclusion. Most studies were at high risk of bias, although in many cases bias was towards the null. 14 studies could be meta-analysed for particulate matter <2.5 µm in diameter (PM). The overall hazard ratio per 2 μg/m PM was 1.04 (95% confidence interval 0.99 to 1.09). The hazard ratio among seven studies that used active case ascertainment was 1.42 (1.00 to 2.02) and among seven studies that used passive case ascertainment was 1.03 (0.98 to 1.07). The overall hazard ratio per 10 μg/m nitrogen dioxide was 1.02 ((0.98 to 1.06); nine studies) and per 10 μg/m nitrogen oxide was 1.05 ((0.98 to 1.13); five studies). Ozone had no clear association with dementia (hazard ratio per 5 μg/m was 1.00 (0.98 to 1.05); four studies).
CONCLUSION
PM might be a risk factor for dementia, as well as nitrogen dioxide and nitrogen oxide, although with more limited data. The meta-analysed hazard ratios are subject to limitations that require interpretation with caution. Outcome ascertainment approaches differ across studies and each exposure assessment approach likely is only a proxy for causally relevant exposure in relation to clinical dementia outcomes. Studies that evaluate critical periods of exposure and pollutants other than PM, and studies that actively assess all participants for outcomes are needed. Nonetheless, our results can provide current best estimates for use in burden of disease and regulatory setting efforts.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42021277083.
Topics: Humans; Air Pollutants; Air Pollution; Dementia; Environmental Exposure
PubMed: 37019461
DOI: 10.1136/bmj-2022-071620 -
International Journal of Molecular... Sep 2022Immune checkpoint inhibitors (ICIs) are an important advancement in the field of cancer treatment, significantly improving the survival of patients with a series of... (Review)
Review
Immune checkpoint inhibitors (ICIs) are an important advancement in the field of cancer treatment, significantly improving the survival of patients with a series of advanced malignancies, like melanoma, non-small cell lung cancer (NSCLC), hepatocellular carcinoma (HCC), renal cell carcinoma (RCC), and Hodgkin lymphoma. ICIs act upon T lymphocytes and antigen-presenting cells, targeting programmed cell death protein 1 (PD1), programmed cell death protein ligand 1 (PD-L1), and cytotoxic T-lymphocyte antigen 4 (CTLA-4), breaking the immune tolerance of the T cells against malignant cells and enhancing the body's own immune response. A variety of cardiac-adverse effects are associated with ICI-based treatment, including pericarditis, arrhythmias, cardiomyopathy, and acute coronary syndrome, with myocarditis being the most studied due to its often-unexpected onset and severity. Overall, Myocarditis is rare but presents an immune-related adverse event (irAE) that has a high fatality rate. Considering the rising number of oncological patients treated with ICIs and the severity of their potential adverse effects, a good understanding and continuous investigation of cardiac irAEs is of the utmost importance. This systematic review aimed to revise recent publications (between 2016-2022) on ICI-induced cardiac toxicities and highlight the therapeutical approach and evolution in the selected cases.
Topics: Antineoplastic Agents, Immunological; Apoptosis Regulatory Proteins; B7-H1 Antigen; CTLA-4 Antigen; Carcinoma, Hepatocellular; Carcinoma, Non-Small-Cell Lung; Cardiotoxicity; Drug-Related Side Effects and Adverse Reactions; Humans; Immune Checkpoint Inhibitors; Ligands; Liver Neoplasms; Lung Neoplasms; Myocarditis; Programmed Cell Death 1 Receptor
PubMed: 36142866
DOI: 10.3390/ijms231810948 -
International Journal of Environmental... Mar 2020Following the recent electronic cigarette (e-cigarette) illness outbreak, the current review aimed to collect all related clinical cases for study and analysis and...
Following the recent electronic cigarette (e-cigarette) illness outbreak, the current review aimed to collect all related clinical cases for study and analysis and provide a critical synopsis of the proposed injury mechanism. Adhering to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analysis) guidelines, e-cigarette-related clinical cases were identified via Google Scholar and PubMed databases. Additionally, references of published case reports and previous review papers were manually searched, revealing 159 publications presenting e-cigarette-related case reports and 19 reports by the Centers for Disease Control and Prevention. 238 individual cases were identified; 53% traumatic injuries due to e-cigarette explosion or self-combustion, 24% respiratory cases, and 12% poisonings. Additional cases pertained to oral, cardiovascular, immunologic, hematologic, allergic reactions, infant complications, and altered medication levels. Case reports were mainly published between 2016-2019 (78%). The oldest case, a lipoid pneumonia, was published in 2012. The current review showed that e-cigarette-related health effects extend beyond the acute lung injury syndrome, including traumatic, thermal injuries and acute intoxications. Physicians should be aware of the distinct clinical presentations and be trained to respond and treat effectively. Regulators and public health authorities should address the regulatory gap regarding electronic nicotine delivery systems (ENDS) and novel tobacco products.
Topics: Adult; Electronic Nicotine Delivery Systems; Female; Humans; Lung Injury; Male; Tobacco Products; United States; Vaping; Young Adult
PubMed: 32230711
DOI: 10.3390/ijerph17072248 -
EClinicalMedicine Jan 2023The aim of this study was to systematically synthesise the global evidence on the prevalence of persistent symptoms in a general post COVID-19 population.
BACKGROUND
The aim of this study was to systematically synthesise the global evidence on the prevalence of persistent symptoms in a general post COVID-19 population.
METHODS
A systematic literature search was conducted using multiple electronic databases (MEDLINE and The Cochrane Library, Scopus, CINAHL, and medRxiv) until January 2022. Studies with at least 100 people with confirmed or self-reported COVID-19 symptoms at ≥28 days following infection onset were included. Patient-reported outcome measures and clinical investigations were both assessed. Results were analysed descriptively, and meta-analyses were conducted to derive prevalence estimates. This study was pre-registered (PROSPERO-ID: CRD42021238247).
FINDINGS
194 studies totalling 735,006 participants were included, with five studies conducted in those <18 years of age. Most studies were conducted in Europe (n = 106) or Asia (n = 49), and the time to follow-up ranged from ≥28 days to 387 days. 122 studies reported data on hospitalised patients, 18 on non-hospitalised, and 54 on hospitalised and non-hospitalised combined (mixed). On average, at least 45% of COVID-19 survivors, regardless of hospitalisation status, went on to experience at least one unresolved symptom (mean follow-up 126 days). Fatigue was frequently reported across hospitalised (28.4%; 95% CI 24.7%-32.5%), non-hospitalised (34.8%; 95% CI 17.6%-57.2%), and mixed (25.2%; 95% CI 17.7%-34.6%) cohorts. Amongst the hospitalised cohort, abnormal CT patterns/x-rays were frequently reported (45.3%; 95% CI 35.3%-55.7%), alongside ground glass opacification (41.1%; 95% CI 25.7%-58.5%), and impaired diffusion capacity for carbon monoxide (31.7%; 95% CI 25.8%-3.2%).
INTERPRETATION
Our work shows that 45% of COVID-19 survivors, regardless of hospitalisation status, were experiencing a range of unresolved symptoms at ∼ 4 months. Current understanding is limited by heterogeneous study design, follow-up durations, and measurement methods. Definition of subtypes of Long Covid is unclear, subsequently hampering effective treatment/management strategies.
FUNDING
No funding.
PubMed: 36474804
DOI: 10.1016/j.eclinm.2022.101762 -
International Journal of Molecular... Apr 2022Glyphosate, a non-selective systemic biocide with broad-spectrum activity, is the most widely used herbicide in the world. It can persist in the environment for days or... (Review)
Review
Glyphosate, a non-selective systemic biocide with broad-spectrum activity, is the most widely used herbicide in the world. It can persist in the environment for days or months, and its intensive and large-scale use can constitute a major environmental and health problem. In this systematic review, we investigate the current state of our knowledge related to the effects of this pesticide on the nervous system of various animal species and humans. The information provided indicates that exposure to glyphosate or its commercial formulations induces several neurotoxic effects. It has been shown that exposure to this pesticide during the early stages of life can seriously affect normal cell development by deregulating some of the signaling pathways involved in this process, leading to alterations in differentiation, neuronal growth, and myelination. Glyphosate also seems to exert a significant toxic effect on neurotransmission and to induce oxidative stress, neuroinflammation and mitochondrial dysfunction, processes that lead to neuronal death due to autophagy, necrosis, or apoptosis, as well as the appearance of behavioral and motor disorders. The doses of glyphosate that produce these neurotoxic effects vary widely but are lower than the limits set by regulatory agencies. Although there are important discrepancies between the analyzed findings, it is unequivocal that exposure to glyphosate produces important alterations in the structure and function of the nervous system of humans, rodents, fish, and invertebrates.
Topics: Animals; Central Nervous System Depressants; Glycine; Herbicides; Neurotoxicity Syndromes; Glyphosate
PubMed: 35562999
DOI: 10.3390/ijms23094605