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Drug Safety Mar 2017Thienopyridines are a class of antiplatelet drugs widely used in cardiovascular disease prevention and treatment. A recent concern has come to light regarding the safety... (Comparative Study)
Comparative Study Meta-Analysis Review
INTRODUCTION
Thienopyridines are a class of antiplatelet drugs widely used in cardiovascular disease prevention and treatment. A recent concern has come to light regarding the safety of thienopyridines because of the possible risk of malignancy. We therefore performed a systematic review and meta-analysis to evaluate the association between thienopyridine exposure and malignancy.
METHODS
We searched the MEDLINE and EMBASE databases in March 2016 for studies that evaluated incident cancer and cancer mortality with and without exposure to thienopyridines. Relevant studies were identified, and data were extracted and analysed using random-effects meta-analysis.
RESULTS
A total of nine studies (six randomised controlled trials and three cohort studies) that included 282,084 participants were included. The cancer event rate with clopidogrel and prasugrel was 3.25% and 1.58% respectively. When compared with standard aspirin or placebo, thienopyridines are not significantly associated with cancer mortality and event rate (odds ratio [OR] 1.12, 95% confidence interval [CI] 0.80-1.56, n = 3; and OR 0.92, 95% CI 0.52-1.64, n = 2, respectively. Further analyses examining clopidogrel showed no significant association with cancer event rate or malignancy-related death. When comparing prasugrel with clopidogrel, no significant association was noted for cancer event rate (OR 1.10, 95% CI 0.89-1.37, n = 2]. Subanalyses according to cancer location showed that thienopyridines are not significantly associated with malignancy mortality and/or incidence.
CONCLUSIONS
Our results suggest that there is currently insufficient evidence to suggest that thienopyridine exposure is associated with an increased risk of cancer event rate or mortality.
Topics: Aspirin; Clopidogrel; Humans; Incidence; Neoplasms; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Randomized Controlled Trials as Topic; Risk; Thienopyridines; Ticlopidine
PubMed: 28035491
DOI: 10.1007/s40264-016-0481-2 -
Journal of Hazardous Materials Aug 2022Increasing usage of antimicrobials is a significant contributor to the emergence and dissemination of antimicrobial resistance. Wastewater-based epidemiology is a useful...
Increasing usage of antimicrobials is a significant contributor to the emergence and dissemination of antimicrobial resistance. Wastewater-based epidemiology is a useful tool for evaluating public health, via the monitoring of chemical and biological markers in wastewater influent, such as antibiotics. Sixteen antimicrobials and their metabolites were studied: sulfonamides, trimethoprim, metronidazole, quinolones, nitrofurantoin, cyclines, and antiretrovirals. Correction factors (CFs) for human drug excretion, for various drug forms, were determined via a systematic literature review of pharmacokinetic research. Analyte stability was examined over a 24 h study. The estimation of community-wide drug intake was evaluated using the corresponding catchment prescription data. Overall, antimicrobials excreted in an unchanged form were often observed to over-estimate daily intake. This could be attributed to biotransformation, e.g., via glucuronide cleavage, or direct disposal of unused drugs. Acetyl-sulfonamides, trimethoprim, hydroxy-metronidazole, clarithromycin, ciprofloxacin, ofloxacin, tetracycline, and oxytetracycline generally performed well in the estimation of drug intake, relative to prescription records. The low prevalence of quinolone and trimethoprim metabolites, and the low stability of nitrofurantoin, limited the ability to evaluate these metabolites and their respective CFs.
Topics: Anti-Bacterial Agents; Anti-Infective Agents; Humans; Metronidazole; Nitrofurantoin; Quinolones; Sulfonamides; Trimethoprim; Wastewater-Based Epidemiological Monitoring; Water Pollutants, Chemical
PubMed: 35594673
DOI: 10.1016/j.jhazmat.2022.129001 -
Cutaneous and Ocular Toxicology Jun 2017Diphoterine, developed by the French company Prevor, is a polyvalent, chelating, amphoteric and slightly hypertonic solution used in the management of chemical cutaneous... (Review)
Review
CONTEXT
Diphoterine, developed by the French company Prevor, is a polyvalent, chelating, amphoteric and slightly hypertonic solution used in the management of chemical cutaneous and ocular burns. While used extensively in Europe and Canada, it is has not been approved by the United States Occupational Safety and Health Administration (OSHA) as an alternative to the water-rinse method due to a lack of evidence of its safety and efficacy on human subjects. An unbiased and extensive systematic review was undertaken in order to better understand Diphoterine's safety and efficaciousness on humans.
OBJECTIVE
Review the safety and efficacy of Diphoterine for treating chemical burns of the skin and eyes in humans.
METHODS
Data sources: Information sources included Pubmed, the National Library of Medicine's Medline Database and the "Publications" sections of the Prevor website. Search terms included Diphoterine, chemical burn, ocular burn and cutaneous burn.
STUDY SELECTION
Any study type published through a peer-reviewed journal up to May 2016 was considered eligible. Published data must have included Diphoterine in the treatment of chemical burns on the skin or eyes as well as meet other specified criteria. Acceptable studies had to use either a quantitative (e.g. number of work days lost) or qualitative (e.g. level of erythema) approach when measuring cutaneous or ocular lesion outcomes.
DATA EXTRACTION
Independent assessment of article inclusion by two authors using predefined criteria.
RESULTS AND CONCLUSION
Diphoterine is safe and highly effective in improving healing time, healing sequelae and pain management of chemical burns on the skin and eyes of humans. Outcomes are significantly improved when compared to water or a physiologic solution equivalent. We recommend that this product be readily available to emergency responders and companies that expose their employees to hazardous chemical substances in order to improve healing sequelae, pain management and lost work days from these types of burns.
Topics: Burns, Chemical; Dermatologic Agents; Eye Burns; Humans; Occupational Injuries; Ophthalmic Solutions; Organic Chemicals; Pain Management; Treatment Outcome; Wound Healing
PubMed: 27486965
DOI: 10.1080/15569527.2016.1217423 -
Cells Aug 2023There is an increasing interest in biomarkers of nitric oxide dysregulation and oxidative stress to guide management and identify new therapeutic targets in patients... (Meta-Analysis)
Meta-Analysis Review
There is an increasing interest in biomarkers of nitric oxide dysregulation and oxidative stress to guide management and identify new therapeutic targets in patients with chronic obstructive pulmonary disease (COPD). We conducted a systematic review and meta-analysis of the association between circulating metabolites within the arginine (arginine, citrulline, ornithine, asymmetric, ADMA, and symmetric, SDMA dimethylarginine), transsulfuration (methionine, homocysteine, and cysteine) and folic acid (folic acid, vitamin B, and vitamin B) metabolic pathways and COPD. We searched electronic databases from inception to 30 June 2023 and assessed the risk of bias and the certainty of evidence. In 21 eligible studies, compared to healthy controls, patients with stable COPD had significantly lower methionine (standardized mean difference, SMD = -0.50, 95% CI -0.95 to -0.05, = 0.029) and folic acid (SMD = -0.37, 95% CI -0.65 to -0.09, = 0.009), and higher homocysteine (SMD = 0.78, 95% CI 0.48 to 1.07, < 0.001) and cysteine concentrations (SMD = 0.34, 95% CI 0.02 to 0.66, = 0.038). Additionally, COPD was associated with significantly higher ADMA (SMD = 1.27, 95% CI 0.08 to 2.46, = 0.037), SDMA (SMD = 3.94, 95% CI 0.79 to 7.08, = 0.014), and ornithine concentrations (SMD = 0.67, 95% CI 0.13 to 1.22, = 0.015). In subgroup analysis, the SMD of homocysteine was significantly associated with the biological matrix assessed and the forced expiratory volume in the first second to forced vital capacity ratio, but not with age, study location, or analytical method used. Our study suggests that the presence of significant alterations in metabolites within the arginine, transsulfuration, and folic acid pathways can be useful for assessing nitric oxide dysregulation and oxidative stress and identifying novel treatment targets in COPD. (PROSPERO registration number: CRD42023448036.).
Topics: Humans; Cysteine; Nitric Oxide; Metabolomics; Arginine; Methionine; Racemethionine; Folic Acid; Homocysteine; Vitamins
PubMed: 37681911
DOI: 10.3390/cells12172180 -
Addiction (Abingdon, England) Jul 2016Since its market release, gabapentin has been presumed to have no abuse potential and subsequently has been prescribed widely off-label, despite increasing reports of... (Review)
Review
BACKGROUND AND AIMS
Since its market release, gabapentin has been presumed to have no abuse potential and subsequently has been prescribed widely off-label, despite increasing reports of gabapentin misuse. This review estimates and describes the prevalence and effects of, motivations behind and risk factors for gabapentin misuse, abuse and diversion.
METHODS
Databases were searched for peer-reviewed papers demonstrating gabapentin misuse, characterized by taking a larger dosage than prescribed or taking gabapentin without a prescription, and diversion. All types of studies were considered; grey literature was excluded. Thirty-three papers met inclusion criteria, consisting of 23 case studies and 11 epidemiological reports. Published reports came from the United States, the United Kingdom, Germany, Finland, India, South Africa and France, and two analyzed websites not specific to a particular country.
RESULTS
Prevalence of gabapentin misuse in the general population was reported to be 1%, 40-65% among individuals with prescriptions and between 15 and 22% within populations of people who abuse opioids. An array of subjective experiences reminiscent of opioids, benzodiazepines and psychedelics were reported over a range of doses, including those within clinical recommendations. Gabapentin was misused primarily for recreational purposes, self-medication or intentional self-harm and was misused alone or in combination with other substances, especially opioids, benzodiazepines and/or alcohol. Individuals with histories of drug abuse were most often involved in its misuse.
CONCLUSIONS
Epidemiological and case report evidence suggests that the anti-epileptic and analgesic medication gabapentin is being misused internationally, with substance abuse populations at special risk for misuse/abuse.
Topics: Amines; Analgesics; Cyclohexanecarboxylic Acids; Gabapentin; Humans; Prescription Drug Diversion; Prescription Drug Misuse; Prevalence; Substance-Related Disorders; gamma-Aminobutyric Acid
PubMed: 27265421
DOI: 10.1111/add.13324 -
The Cochrane Database of Systematic... Jan 2017This review replaces part of an earlier review that evaluated gabapentin for both neuropathic pain and fibromyalgia, now split into separate reviews for the two... (Review)
Review
BACKGROUND
This review replaces part of an earlier review that evaluated gabapentin for both neuropathic pain and fibromyalgia, now split into separate reviews for the two conditions. This review will consider pain in fibromyalgia only.Fibromyalgia is associated with widespread pain lasting longer than three months, and is frequently associated with symptoms such as poor sleep, fatigue, depression, and reduced quality of life. Fibromyalgia is more common in women.Gabapentin is an antiepileptic drug widely licensed for treatment of neuropathic pain. It is not licensed for the treatment of fibromyalgia, but is commonly used because fibromyalgia can respond to the same medicines as neuropathic pain.
OBJECTIVES
To assess the analgesic efficacy of gabapentin for fibromyalgia pain in adults and the adverse events associated with its use in clinical trials.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Register of Studies Online, MEDLINE via Ovid and Embase via Ovid from inception to 24 May 2016. We also searched the reference lists of retrieved studies and reviews, and searched online clinical trial registries.
SELECTION CRITERIA
Randomised, double-blind trials of eight weeks' duration or longer for treating fibromyalgia pain in adults, comparing gabapentin with placebo or an active comparator.
DATA COLLECTION AND ANALYSIS
Two independent review authors extracted data and assessed trial quality and risk of bias. We planned to use dichotomous data to calculate risk ratio and number needed to treat for one additional event, using standard methods. We assessed the evidence using GRADE (Grading of Recommendations Assessment, Development and Evaluation) and created a 'Summary of findings' table.
MAIN RESULTS
Two studies tested gabapentin to treat fibromyalgia pain. One was identified in previous versions of the review and is included here. We identified another study as a conference abstract, with insufficient detail to determine eligibility for inclusion; it is awaiting assessment. The one included study of 150 participants was a 12-week, multi-centre, randomised, double-blind, placebo-controlled, parallel-group study using last-observation-carried-forward imputation for withdrawals. The maximum dose was 2400 mg daily. The overall risk of bias was low, except for attrition bias.At the end of the trial, the outcome of 50% reduction in pain over baseline was not reported. The outcome of 30% or greater reduction in pain over baseline was achieved by 38/75 participants (49%) with gabapentin compared with 23/75 (31%) with placebo (very low quality). A patient global impression of change any category of "better" was achieved by 68/75 (91%) with gabapentin and 35/75 (47%) with placebo (very low quality).Nineteen participants discontinued the study because of adverse events: 12 in the gabapentin group (16%) and 7 in the placebo group (9%) (very low quality). The number of serious adverse events were not reported, and no deaths were reported (very low quality).
AUTHORS' CONCLUSIONS
We have only very low quality evidence and are very uncertain about estimates of benefit and harm because of a small amount of data from a single trial. There is insufficient evidence to support or refute the suggestion that gabapentin reduces pain in fibromyalgia.
Topics: Adult; Amines; Analgesics; Cyclohexanecarboxylic Acids; Female; Fibromyalgia; Gabapentin; Humans; Male; Middle Aged; Randomized Controlled Trials as Topic; gamma-Aminobutyric Acid
PubMed: 28045473
DOI: 10.1002/14651858.CD012188.pub2 -
Antiviral Research Jan 2024Remdesivir, molnupiravir, and nirmatrelvir/ritonavir are three antiviral agents approved by FDA emergency authorization for treating mild to moderate symptomatic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Remdesivir, molnupiravir, and nirmatrelvir/ritonavir are three antiviral agents approved by FDA emergency authorization for treating mild to moderate symptomatic COVID-19 adult outpatients at high risk for hospitalization and death.
OBJECTIVES
To compare the efficacy and safety of these antivirals based on updated published RCT and real-world data.
STUDY DESIGN
This systematic review followed the preferred reporting items for systematic reviews and meta-analysis framework guidelines. We searched all publications up to January 2023. RRs and 95% CIs for death, hospitalization, and adverse events were calculated.
RESULTS
Six RCTs and seven cohort studies were included, with 1,456,523 participants, of whom 50,979 were treated with antivirals. Remdesivir was associated with the lowest probability of hospitalization and death compared to nirmatrelvir/ritonavir and molnupiravir (P-scores 0.99 and 0.90, respectively, for remdesivir, 0.64 and 0.55, respectively for nirmatrelvir/ritonavir, and 0.26 and 0.49, respectively for molnupiravir). Based on indirect comparisons, remdesivir was associated with a statistically significant decreased risk for hospitalization compared to molnupiravir (RR 0.09; 95% CI 0.02-0.40) and to nirmatrelvir/ritonavir (RR 0.11; 95% CI 0.03-0.73). No statistically significant difference was found between antivirals in the mortality risk reduction and the risk for side effects.
CONCLUSIONS
This is the most comprehensive network meta-analysis integrating RCTs and real-world data. In our indirect comparison, remdesivir was associated with the highest efficacy in preventing hospitalization among high risk symptomatic COVID-19 outpatients, compared to nirmatrelvir/ritonavir and molnupiravir. This finding supports current guidelines, and may have importance when deciding which antiviral to use, together with other important factors.
Topics: Adult; Humans; COVID-19; Network Meta-Analysis; Outpatients; Ritonavir; Antiviral Agents; Hydroxylamines; Cytidine; Nitriles; Lactams; Proline; Leucine
PubMed: 38056602
DOI: 10.1016/j.antiviral.2023.105768 -
The Cochrane Database of Systematic... Feb 2018Fibromyalgia is a chronic widespread pain condition affecting millions of people worldwide. Current pharmacotherapies are often ineffective and poorly tolerated.... (Review)
Review
BACKGROUND
Fibromyalgia is a chronic widespread pain condition affecting millions of people worldwide. Current pharmacotherapies are often ineffective and poorly tolerated. Combining different agents could provide superior pain relief and possibly also fewer side effects.
OBJECTIVES
To assess the efficacy, safety, and tolerability of combination pharmacotherapy compared to monotherapy or placebo, or both, for the treatment of fibromyalgia pain in adults.
SEARCH METHODS
We searched CENTRAL, MEDLINE, and Embase to September 2017. We also searched reference lists of other reviews and trials registries.
SELECTION CRITERIA
Double-blind, randomised controlled trials comparing combinations of two or more drugs to placebo or other comparators, or both, for the treatment of fibromyalgia pain.
DATA COLLECTION AND ANALYSIS
From all studies, we extracted data on: participant-reported pain relief of 30% or 50% or greater; patient global impression of clinical change (PGIC) much or very much improved or very much improved; any other pain-related outcome of improvement; withdrawals (lack of efficacy, adverse events), participants experiencing any adverse event, serious adverse events, and specific adverse events (e.g. somnolence and dizziness). The primary comparison was between combination and one or all single-agent comparators. We also assessed the evidence using GRADE and created a 'Summary of findings' table.
MAIN RESULTS
We identified 16 studies with 1474 participants. Three studies combined a non-steroidal anti-inflammatory drug (NSAID) with a benzodiazepine (306 participants); two combined amitriptyline with fluoxetine (89 participants); two combined amitriptyline with a different agent (92 participants); two combined melatonin with an antidepressant (164 participants); one combined carisoprodol, paracetamol (acetaminophen), and caffeine (58 participants); one combined tramadol and paracetamol (acetaminophen) (315 participants); one combined malic acid and magnesium (24 participants); one combined a monoamine oxidase inhibitor with 5-hydroxytryptophan (200 participants); and one combined pregabalin with duloxetine (41 participants). Six studies compared the combination of multiple agents with each component alone and with inactive placebo; three studies compared combination pharmacotherapy with each individual component but did not include an inactive placebo group; two studies compared the combination of two agents with only one of the agents alone; and three studies compared the combination of two or more agents only with inactive placebo.Heterogeneity among studies in terms of class of agents evaluated, specific combinations used, outcomes reported, and doses given prevented any meta-analysis. None of the combinations of drugs found provided sufficient data for analysis compared with placebo or other comparators for our preferred outcomes. We therefore provide a narrative description of results. There was no or inadequate evidence in any comparison for primary and secondary outcomes. Two studies only reported any primary outcomes of interest (patient-reported pain relief of 30%, or 50%, or greater). For each 'Risk of bias' item, only half or fewer of studies had unequivocal low risk of bias. Small size and selective reporting were common as high risk of bias.Our GRADE assessment was therefore very low for primary outcomes of pain relief of 30% or 50% or greater, PGIC much or very much improved or very much improved, any pain-related outcome, participants experiencing any adverse event, any serious adverse event, or withdrawing because of an adverse event.Three studies found some evidence that combination pharmacotherapy reduced pain compared to monotherapy; these trials tested three different combinations: melatonin and amitriptyline, fluoxetine and amitriptyline, and pregabalin and duloxetine. Adverse events experienced by participants were not serious, and where they were reported (in 12 out of 16 studies), all participants experienced them, regardless of treatment. Common adverse events were nausea, dizziness, somnolence, and headache.
AUTHORS' CONCLUSIONS
There are few, large, high-quality trials comparing combination pharmacotherapy with monotherapy for fibromyalgia, consequently limiting evidence to support or refute the use of combination pharmacotherapy for fibromyalgia.
Topics: 5-Hydroxytryptophan; Acetaminophen; Adult; Amitriptyline; Anti-Inflammatory Agents, Non-Steroidal; Antidepressive Agents; Benzodiazepines; Carisoprodol; Drug Therapy, Combination; Duloxetine Hydrochloride; Fibromyalgia; Fluoxetine; Humans; Magnesium; Malates; Melatonin; Monoamine Oxidase Inhibitors; Muscle Relaxants, Central; Pregabalin; Randomized Controlled Trials as Topic
PubMed: 29457627
DOI: 10.1002/14651858.CD010585.pub2 -
BJOG : An International Journal of... Apr 2024From menarche until menopause, the average menstruator will use over 11 000 tampons or sanitary pads. Vaginal and vulvar tissue is highly permeable, and chemicals are... (Review)
Review
BACKGROUND
From menarche until menopause, the average menstruator will use over 11 000 tampons or sanitary pads. Vaginal and vulvar tissue is highly permeable, and chemicals are absorbed without undergoing first-pass metabolism.
OBJECTIVES
To conduct a review of the literature to determine exposure to environmental chemicals in menstrual products.
SEARCH STRATEGY
This review identified 15 papers over the past 10 years.
SELECTION CRITERIA
Papers that measured chemicals in menstrual products and that measured human biomarkers of chemical exposure were included. Papers had to also be available in English.
DATA COLLECTION AND ANALYSIS
Reviewers assessed the articles and data provided. Multiple chemical groups were found.
MAIN RESULTS
Phthalates, volatile organic compounds, parabens, environmental phenols, fragrance chemicals, dioxins and dioxin-like compounds were detected in menstrual products. Research gaps were identified, including the lack of studies on newer products such as menstrual underwear and cups/discs. In addition to measuring chemicals in these products, future research should focus on clarifying the exposure per menstrual cycle to these chemicals to understand how menorrhagia and cycle length influence exposure from menstrual products.
CONCLUSION
Menstrual products contained measurable levels of a range of endocrine disrupting chemicals including phthalates, phenols and parabens. This reflects a potentially important route of exposure to chemicals that can impact women's reproductive health.
Topics: Humans; Female; Menstrual Hygiene Products; Parabens; Reproduction; Phthalic Acids; Phenols
PubMed: 37743685
DOI: 10.1111/1471-0528.17668 -
Environmental Science and Pollution... Nov 2016Persistent organic pollutants (POPs) are a group of heterogeneous compounds of both natural and anthropogenic origin with highly persistent and bioaccumulative... (Review)
Review
Persistent organic pollutants (POPs) are a group of heterogeneous compounds of both natural and anthropogenic origin with highly persistent and bioaccumulative properties. They cause a range of adverse effects to human health and the environment around the world. There is growing concern that POPs may increase breast cancer risk due to their xenoestrogenic properties. The aim of this systematic literature review is to summarize and integrate the risks of breast cancer following environmental exposure to POPs (other than DDT) from primary epidemiological studies published between 2006 and 2015. After searching various databases, 14 case-control studies and one cohort study were included. Evidence of an association between increased breast cancer risk and environmental exposure to these chemicals is inconsistent and inadequate to conclude with certainty. However, most of the studies have examined exposure to the pollutants after diagnosis of breast cancer, overlooking exposure during critical windows of vulnerability. They have also largely focused on individual chemicals but ignored the combined effects of different chemicals. Therefore, major data gaps remain in examining exposure during critical windows of vulnerability and assessing combined effects of multiple chemicals. Development of better exposure assessment methods addressing these gaps is required for future research.
Topics: Breast Neoplasms; Environmental Exposure; Environmental Pollutants; Female; Humans; Organic Chemicals
PubMed: 27628920
DOI: 10.1007/s11356-016-7577-1