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European Journal of Cancer (Oxford,... Jun 2023The faecal immunochemical test (FIT) suffers from suboptimal performance and participation in colorectal cancer (CRC) screening. Urinary volatile organic compounds... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The faecal immunochemical test (FIT) suffers from suboptimal performance and participation in colorectal cancer (CRC) screening. Urinary volatile organic compounds (VOCs) may be a useful alternative. We aimed to determine the diagnostic potential of urinary VOCs for CRC/adenomas. By relating VOCs to known pathways, we aimed to gain insight into the pathophysiology of colorectal neoplasia.
METHODS
A systematic search was performed in PubMed, EMBASE and Web of Science. Original studies on urinary VOCs for CRC/adenoma detection with a control group were included. QUADAS-2 tool was used for quality assessment. Meta-analysis was performed by adopting a bivariate model for sensitivity/specificity. Fagan's nomogram estimated the performance of combined FIT-VOC. Neoplasm-associated VOCs were linked to pathways using the KEGG database.
RESULTS
Sixteen studies-involving 837 CRC patients and 1618 controls-were included; 11 performed chemical identification and 7 chemical fingerprinting. In all studies, urinary VOCs discriminated CRC from controls. Pooled sensitivity and specificity for CRC based on chemical fingerprinting were 84% (95% CI 73-91%) and 70% (95% CI 63-77%), respectively. The most distinctive individual VOC was butanal (AUC 0.98). The estimated probability of having CRC following negative FIT was 0.38%, whereas 0.09% following negative FIT-VOC. Combined FIT-VOC would detect 33% more CRCs. In total 100 CRC-associated urinary VOCs were identified; particularly hydrocarbons, carboxylic acids, aldehydes/ketones and amino acids, and predominantly involved in TCA-cycle or alanine/aspartate/glutamine/glutamate/phenylalanine/tyrosine/tryptophan metabolism, which is supported by previous research on (colorectal)cancer biology. The potential of urinary VOCs to detect precancerous adenomas or gain insight into their pathophysiology appeared understudied.
CONCLUSION
Urinary VOCs hold potential for non-invasive CRC screening. Multicentre validation studies are needed, especially focusing on adenoma detection. Urinary VOCs elucidate underlying pathophysiologic processes.
Topics: Humans; Volatile Organic Compounds; Biomarkers, Tumor; Early Detection of Cancer; Colorectal Neoplasms; Adenoma; Colonic Neoplasms
PubMed: 37030079
DOI: 10.1016/j.ejca.2023.03.002 -
Drug Metabolism Reviews Nov 2023Nebivolol is a beta-1 receptor blocker used to treat hypertension, heart failure, erectile dysfunction, vascular disease, and diabetes mellitus. This review investigated... (Review)
Review
Nebivolol is a beta-1 receptor blocker used to treat hypertension, heart failure, erectile dysfunction, vascular disease, and diabetes mellitus. This review investigated the data regarding pharmacokinetic (PK) parameters, drug-drug interactions, dextrorotatory (D), and levorotatory (L) stereoisomers of nebivolol. The articles related to the PK of nebivolol were retrieved by searching the five databases; Google Scholar, PubMed, Cochrane Library, ScienceDirect, and EBSCO. A total of 20 studies comprising plasma concentration-time profile data following the nebivolol's oral and intravenous (IV) administration were included. The area under the concentration-time curve from zero to infinity (AUC) was 15 times greater in poor metabolizers (PMs) than in extensive metabolizers (EMs). In hypertensive patients, L-nebivolol expressed a higher maximum plasma concentration (C) than D-nebivolol, i.e. 2.5 ng/ml vs 1.2 ng/ml. The AUC of nebivolol was 3-fold greater in chronic kidney disease (CKD). The clearance (CL) was increased in obese than in controls from 51.6 ± 11.6 L/h to 71.6 ± 17.4 L/h when 0.5 mg/ml IV solution was infused. Nebivolol showed higher C, AUC and half-life (t) when co-administered with bupropion, duloxetine, fluvoxamine, paroxetine, lansoprazole, and fluoxetine. This concise review of nebivolol would be advantageous in assessing all PK parameters, which may be crucial for clinicians to avoid drug-drug interactions, prevent adverse drug events and optimize the dosage regimen in diseased patients diagnosed with hypertension and cardiovascular disorders.
Topics: Male; Humans; Nebivolol; Hypertension; Fluvoxamine; Lansoprazole; Drug Interactions
PubMed: 37849071
DOI: 10.1080/03602532.2023.2271195 -
Nanotechnology Mar 2023Metal-organic frameworks (MOFs), as a class of promising material with adjustable function and controllable structure, have been widely used in the food industry,... (Review)
Review
Metal-organic frameworks (MOFs), as a class of promising material with adjustable function and controllable structure, have been widely used in the food industry, chemical industry, biological medicine, and sensors. Biomacromolecules and living systems play a critical role in the world. However, the insufficiency in stability, recyclability, and efficiency, significantly impedes their further utilization in slightly harsh conditions. MOF-bio-interface engineering effectively address the above-mentioned shortages of biomacromolecules and living systems, and thereby attracting considerable attentions. Herein, we systematically review the achievements in the area of MOF-bio-interface. In particular, we summarize the interface between MOFs and proteins (enzymes and non-enzymatic proteins), polysaccharides, DNA, cells, microbes, and viruses. Meanwhile, we discuss the limitations of this approach and propose future research directions. We expect that this review could provide new insights and inspire new research efforts towards life science and material science.
Topics: Metal-Organic Frameworks
PubMed: 36796094
DOI: 10.1088/1361-6528/acbc81 -
Neuroscience and Biobehavioral Reviews Dec 2022Cannabidiol's (CBD) safety profile and broad action has made it a popular treatment option for anxiety and co-occurring sleep disturbance. However, its efficacy in... (Review)
Review
Cannabidiol's (CBD) safety profile and broad action has made it a popular treatment option for anxiety and co-occurring sleep disturbance. However, its efficacy in healthy and clinical populations, treatment duration, formulation and doses for optimal therapeutic benefits remains unclear. Selected databases were examined from inception to October 2022. Study selection, data extraction and Cochrane Risk of Bias assessments were conducted according to PRISMA guidelines and registered on the PROSPERO database (CRD42021247476) with 58 full-text studies meeting the eligibility criteria and administered CBD only or with Δ-9-tetrahydrocannabinol (THC) across healthy and clinical populations. In healthy populations and certain non-cannabis using clinical populations, CBD had greater anxiolytic effects without prominent effects on sleep. An inverted U-shaped dose relationship, and CBD ratio to THC in combined treatments likely moderated these effects. Mechanistically, observed CBD effects occurred via primary modulation of the endocannabinoid system and secondary regulation of neuroendocrine function. Additional research is needed to understand CBD mechanisms of action across diverse groups.
Topics: Humans; Cannabinoids; Dronabinol; Cannabidiol; Anxiety; Sleep Wake Disorders; Sleep
PubMed: 36370842
DOI: 10.1016/j.neubiorev.2022.104941 -
Digestion 2023Vonoprazan, a novel potassium-competitive acid blocker, has a strong acid suppression effect and potent efficacy in acid-associated diseases, including Helicobacter... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Vonoprazan, a novel potassium-competitive acid blocker, has a strong acid suppression effect and potent efficacy in acid-associated diseases, including Helicobacter pylori eradication. We performed a systematic review and meta-analysis to investigate the efficacy and safety of vonoprazan/amoxicillin dual therapy for H. pylori eradication.
METHODS
We conducted a systematic literature search through PubMed, Web of Science, EMBASE, and the Cochrane Library up to June 2022, to identify randomized controlled trials and cohort studies comparing vonoprazan/amoxicillin dual therapy and triple therapies for H. pylori eradication. Primary outcomes were cure rates and relative efficacy. Secondary outcomes included adverse events, dropout rate, and subgroup analysis.
RESULTS
Five studies with 1,852 patients were included in the analysis. The cure rates of vonoprazan/amoxicillin dual therapy were 85.6% with 95% confidence interval (CI) of 79.7-91.5% and 88.5% (95% CI: 83.2-93.8%) in the intention-to-treat and per-protocol analyses. The efficacy of vonoprazan/amoxicillin dual therapy was not inferior to that of triple therapy with pooled risk ratio (RR) of 1.03 (95% CI: 0.97-1.10) and 1.02 (95% CI: 0.98-1.08) in intention-to-treat and per-protocol analyses; while it was significantly superior to the omeprazole or lansoprazole-based triple therapy (RR = 1.15, 95% CI: 1.05-1.25, p = 0.001). For clarithromycin-resistant strains, vonoprazan/amoxicillin dual therapy showed superiority to vonoprazan-based triple therapy (86.7% vs. 71.4%, RR = 1.20, 95% CI: 1.03-1.39, p = 0.02); however, vonoprazan/amoxicillin dual therapy was significant inferior to vonoprazan-based triple therapy for clarithromycin-sensitive strains (83.0% vs. 92.8%, RR = 0.90, 95% CI: 0.85-0.95, p = 0.0002). The adverse effects of vonoprazan/amoxicillin dual therapy were lower than those of triple therapy (21.2% vs. 26.5%, RR = 0.86, 95% CI: 0.73-1.01, p = 0.06), especially the incidence of diarrhea (p = 0.01).
CONCLUSIONS
The efficacy of vonoprazan/amoxicillin dual therapy is noninferior to vonoprazan-based triple therapy but superior to the omeprazole or lansoprazole-based triple therapy and has less side effects. Patients with clarithromycin-resistant strains are particularly expected to benefit from vonoprazan/amoxicillin dual therapy.
Topics: Humans; Amoxicillin; Clarithromycin; Helicobacter pylori; Anti-Bacterial Agents; Helicobacter Infections; Proton Pump Inhibitors; Drug Therapy, Combination; Pyrroles; Lansoprazole; Omeprazole; Treatment Outcome
PubMed: 37015201
DOI: 10.1159/000529622 -
The Cochrane Database of Systematic... Aug 2023Carotid artery stenosis is narrowing of the carotid arteries. Asymptomatic carotid stenosis is when this narrowing occurs in people without a history or symptoms of this... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Carotid artery stenosis is narrowing of the carotid arteries. Asymptomatic carotid stenosis is when this narrowing occurs in people without a history or symptoms of this disease. It is caused by atherosclerosis; that is, the build-up of fats, cholesterol, and other substances in and on the artery walls. Atherosclerosis is more likely to occur in people with several risk factors, such as diabetes, hypertension, hyperlipidaemia, and smoking. As this damage can develop without symptoms, the first symptom can be a fatal or disabling stroke, known as ischaemic stroke. Carotid stenosis leading to ischaemic stroke is most common in men older than 70 years. Ischaemic stroke is a worldwide public health problem.
OBJECTIVES
To assess the effects of pharmacological interventions for the treatment of asymptomatic carotid stenosis in preventing neurological impairment, ipsilateral major or disabling stroke, death, major bleeding, and other outcomes.
SEARCH METHODS
We searched the Cochrane Stroke Group trials register, CENTRAL, MEDLINE, Embase, two other databases, and three trials registers from their inception to 9 August 2022. We also checked the reference lists of any relevant systematic reviews identified and contacted specialists in the field for additional references to trials.
SELECTION CRITERIA
We included all randomised controlled trials (RCTs), irrespective of publication status and language, comparing a pharmacological intervention to placebo, no treatment, or another pharmacological intervention for asymptomatic carotid stenosis.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methodological procedures. Two review authors independently extracted the data and assessed the risk of bias of the trials. A third author resolved disagreements when necessary. We assessed the evidence certainty for key outcomes using GRADE.
MAIN RESULTS
We included 34 RCTs with 11,571 participants. Data for meta-analysis were available from only 22 studies with 6887 participants. The mean follow-up period was 2.5 years. None of the 34 included studies assessed neurological impairment and quality of life. Antiplatelet agent (acetylsalicylic acid) versus placebo Acetylsalicylic acid (1 study, 372 participants) may result in little to no difference in ipsilateral major or disabling stroke (risk ratio (RR) 1.08, 95% confidence interval (CI) 0.47 to 2.47), stroke-related mortality (RR 1.40, 95% CI 0.54 to 3.59), progression of carotid stenosis (RR 1.16, 95% CI 0.79 to 1.71), and adverse events (RR 0.81, 95% CI 0.41 to 1.59), compared to placebo (all low-certainty evidence). The effect of acetylsalicylic acid on major bleeding is very uncertain (RR 0.98, 95% CI 0.06 to 15.53; very low-certainty evidence). The study did not measure neurological impairment or quality of life. Antihypertensive agents (metoprolol and chlorthalidone) versus placebo The antihypertensive agent, metoprolol, may result in no difference in ipsilateral major or disabling stroke (RR 0.14, 95% CI 0.02 to1.16; 1 study, 793 participants) and stroke-related mortality (RR 0.57, 95% CI 0.17 to 1.94; 1 study, 793 participants) compared to placebo (both low-certainty evidence). However, chlorthalidone may slow the progression of carotid stenosis (RR 0.45, 95% CI 0.23 to 0.91; 1 study, 129 participants; low-certainty evidence) compared to placebo. Neither study measured neurological impairment, major bleeding, adverse events, or quality of life. Anticoagulant agent (warfarin) versus placebo The evidence is very uncertain about the effects of warfarin (1 study, 919 participants) on major bleeding (RR 1.19, 95% CI 0.97 to 1.46; very low-certainty evidence), but it may reduce adverse events (RR 0.89, 95% CI 0.81 to 0.99; low-certainty evidence) compared to placebo. The study did not measure neurological impairment, ipsilateral major or disabling stroke, stroke-related mortality, progression of carotid stenosis, or quality of life. Lipid-lowering agents (atorvastatin, fluvastatin, lovastatin, pravastatin, probucol, and rosuvastatin) versus placebo or no treatment Lipid-lowering agents may result in little to no difference in ipsilateral major or disabling stroke (atorvastatin, lovastatin, pravastatin, and rosuvastatin; RR 0.36, 95% CI 0.09 to 1.53; 5 studies, 2235 participants) stroke-related mortality (lovastatin and pravastatin; RR 0.25, 95% CI 0.03 to 2.29; 2 studies, 1366 participants), and adverse events (fluvastatin, lovastatin, pravastatin, probucol, and rosuvastatin; RR 0.76, 95% CI 0.53 to1.10; 7 studies, 3726 participants) compared to placebo or no treatment (all low-certainty evidence). The studies did not measure neurological impairment, major bleeding, progression of carotid stenosis, or quality of life.
AUTHORS' CONCLUSIONS
Although there is no high-certainty evidence to support pharmacological intervention, this does not mean that pharmacological treatments are ineffective in preventing ischaemic cerebral events, morbidity, and mortality. High-quality RCTs are needed to better inform the best medical treatment that may reduce the burden of carotid stenosis. In the interim, clinicians will have to use other sources of information.
Topics: Humans; Warfarin; Carotid Stenosis; Metoprolol; Atorvastatin; Chlorthalidone; Fluvastatin; Pravastatin; Probucol; Rosuvastatin Calcium; Stroke; Hemorrhage; Aspirin; Ischemic Stroke; Atherosclerosis
PubMed: 37565307
DOI: 10.1002/14651858.CD013573.pub2 -
Metabolism: Clinical and Experimental Jul 2023Thiamine (vitamin B1) is an essential cofactor in glucose metabolism, but it remains unclear whether thiamine status is lower in individuals with diabetes compared to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Thiamine (vitamin B1) is an essential cofactor in glucose metabolism, but it remains unclear whether thiamine status is lower in individuals with diabetes compared to individuals with normal glucose metabolism.
AIMS
We conducted a systematic review and meta-analysis to study whether the circulating concentrations of various thiamine analytes differ between people with and those without diabetes.
METHODS
PubMed and the Cochrane Central Register of Controlled Trials were searched according to the study protocol. The standardized mean difference (SMD) and 95 % confidence intervals (CI) of thiamine markers between individuals with and without diabetes were used as effect size (random effects model). Subgroup analysis considered albuminuria as an additional variable.
RESULTS
Out of the 459 articles identified, 24 full-texts were eligible for the study, 20 of which qualified for the data analysis and four were evaluated for coherence. Compared to controls, individuals with diabetes showed lower concentrations of thiamine (pooled estimate SMD [95 % CI]: -0.97 [-1.89, -0.06]), thiamine monophosphate (-1.16 [-1.82, -0.50]), and total thiamine compounds (-1.01 [-1.48, -0.54]). Thiamine diphosphate (-0.72 [-1.54, 0.11] and erythrocyte transketolase activity (-0.42 [-0.90, 0.05]) tended to be lower in persons with diabetes than in controls without reaching statistical significance. Subgroup analysis showed that individuals with diabetes and albuminuria had lower thiamine levels than the controls (-2.68 [-5.34, -0.02]).
CONCLUSIONS
Diabetes is associated with lower levels of various thiamine markers, suggesting that individuals with diabetes may have higher thiamine requirements than those without diabetes, but well-designed studies are required to confirm these findings.
Topics: Humans; Thiamine; Albuminuria; Diabetes Mellitus; Thiamine Pyrophosphate; Glucose
PubMed: 37094704
DOI: 10.1016/j.metabol.2023.155565 -
Forensic Science International Sep 2022Suicide remains a global public health concern and the increased supply and use of synthetic stimulants globally may have implications for the burden of suicides... (Review)
Review
Suicide remains a global public health concern and the increased supply and use of synthetic stimulants globally may have implications for the burden of suicides attributable to substance use. This systematic review investigated any potential associations of stimulant use detected in post-mortem biological specimens and suicides. We conducted a systematic review and narrative synthesis (CRD42021237966). Medline, EMBASE, TOXLINE, and Scopus databases were searched for terms related to forensic toxicology, post-mortem toxicology, suicide and stimulants. The primary outcome was to estimate the prevalence of stimulant use in suicides. There were 26 studies whichcontributed to prevalence measures; in studies reporting at the individual compound level, suicides involved cocaine (0.1-23%), caffeine (3.2-22%), 3,4-methylenedioxymethamphetamine (0.1-17%), amphetamine (0.2-9.3%), methamphetamine (3.1-7%), and phentermine (0.9-1%). Overall, stimulant use in suicides was over-represented compared to estimates of stimulant use in the general population and has increased over time. Thirteen case reports used to contextualise suicides involving stimulants found no examples of cocaine or methamphetamine mono-intoxication of suicidal intent. This suggests mechanisms other than acute toxicity involved in stimulant-associated suicide. Future research by in-depth psychological autopsies of suicides involving stimulants, in combination with segmental hair analysis to determine the chronicity of stimulant exposure, may contribute to a better understanding of the burden of suicide attributable to stimulant use.
Topics: Amphetamine; Central Nervous System Stimulants; Cocaine; Humans; Methamphetamine; Suicide
PubMed: 35908335
DOI: 10.1016/j.forsciint.2022.111391 -
Human Reproduction Update Feb 2021Despite increasing regulation, exposure to persistent organic pollutants (POPs) remains a serious public health concern due to their accumulation in the environment and...
BACKGROUND
Despite increasing regulation, exposure to persistent organic pollutants (POPs) remains a serious public health concern due to their accumulation in the environment and ability to biomagnify up the food chain. POPs are associated with endocrine-disrupting effects including adverse reproductive outcomes that could affect fecundability, i.e. the capacity to conceive a pregnancy, quantified as time to pregnancy (TTP).
OBJECTIVE AND RATIONALE
Results of epidemiologic studies that examine the impact of various chemical classes of POPs on TTP have not been synthesised. We undertook a systematic review to summarise the strength of evidence for associations of four common groups of POPs with couple fecundability and to identify gaps and limitations in the literature in order to inform policy decisions and future research.
SEARCH METHODS
We performed an electronic search of literature published between 1 January 2007 and 6 August 2019 in MEDLINE, EMBASE.com, Global Health, DART/TOXLINE and POPLINE. We included empirical research papers that examined human exposure to organochlorine (OC) pesticides, brominated flame retardants, polychlorinated organic compounds and/or per- and polyfluoroalkyl substances (PFAS) and considered TTP or fecundability as an outcome. Standardised forms for screening, data extraction and study quality were developed using DistillerSR software, and all reviews were completed in duplicate. We used the Newcastle-Ottawa Scale to assess risk of bias and devised additional quality metrics based on specific methodological features of fecundability studies.
OUTCOMES
The search returned 4573 articles, and 28 papers from 19 different studies met inclusion criteria. Among them, four studies measured TTP prospectively, three had data on participants' prenatal exposure, three examined associations in both male and female partners and one focused exclusively on males. Analyses varied widely in terms of exposure characterisation, precluding a meta-analytic approach. Evidence was strongest for adverse associations of female exposure to polychlorinated biphenyls with TTP, with some additional support for associations of female exposure to polybrominated diphenyl ethers and PFAS with longer TTP. Our review provided little or no support for associations between female exposure to OC pesticides or male exposure to any of the POP groups and TTP.
WIDER IMPLICATIONS
Evidence suggests that female exposure to at least some POPs may reduce fecundability. Although many of these chemicals are no longer in production, they are still detectable in human biosamples because of their persistence in the environment. Replacement chemicals that are being introduced as older ones are restricted may have similar reproductive consequences. Future studies should examine these newer POPs, assess interactions between POPs and other chemical and non-chemical exposures, investigate how POPs are distributed in and metabolised by the human body and focus on populations that may be disproportionately exposed.
Topics: Environmental Pollutants; Female; Halogenated Diphenyl Ethers; Humans; Male; Persistent Organic Pollutants; Pesticides; Polychlorinated Biphenyls; Pregnancy; Time-to-Pregnancy
PubMed: 33147335
DOI: 10.1093/humupd/dmaa037 -
Environmental Pollution (Barking, Essex... Jul 2022The relation between pesticides exposure and metabolic syndrome (MetS) has not been clearly identified. Performing a systematic review and meta-analysis, PubMed,... (Meta-Analysis)
Meta-Analysis Review
The relation between pesticides exposure and metabolic syndrome (MetS) has not been clearly identified. Performing a systematic review and meta-analysis, PubMed, Cochrane Library, Embase, and ScienceDirect were searched for studies reporting the risk of MetS following pesticides exposure and their contaminants. We included 12 studies for a total of 6789 participants, in which 1981 (29.1%) had a MetS. Overall exposure to pesticides and their contaminants increased the risk of MetS by 30% (95CI 22%-37%). Overall organochlorine increased the risk of MetS by 23% (14-32%), as well as for most types of organochlorines: hexachlorocyclohexane increased the risk by 53% (28-78%), hexachlorobenzene by 40% (0.01-80%), dichlorodiphenyldichloroethylene by 22% (9-34%), dichlorodiphenyltrichloroethane by 28% (5-50%), oxychlordane by 24% (1-47%), and transnonchlor by 35% (19-52%). Sensitivity analyses confirmed that overall exposure to pesticides and their contaminants increased the risk by 46% (35-56%) using crude data or by 19% (10-29%) using fully-adjusted model. The risk for overall pesticides and types of pesticides was also significant with crude data but only for hexachlorocyclohexane (36% risk increase, 17-55%) and transnonchlor (25% risk increase, 3-48%) with fully-adjusted models. Metaregressions demonstrated that hexachlorocyclohexane increased the risk of MetS in comparison to most other pesticides. The risk increased for more recent periods (Coefficient = 0.28, 95CI 0.20 to 0.37, by year). We demonstrated an inverse relationship with body mass index and male gender. In conclusion, pesticides exposure is a major risk factor for MetS. Besides organochlorine exposure, data are lacking for other types of pesticides. The risk increased with time, reflecting a probable increase of the use of pesticides worldwide. The inverse relationship with body mass index may signify a stockage of pesticides and contaminants in fat tissue.
Topics: DDT; Hexachlorocyclohexane; Humans; Hydrocarbons, Chlorinated; Male; Metabolic Syndrome; Pesticides
PubMed: 35439599
DOI: 10.1016/j.envpol.2022.119288