-
The Lancet. Gastroenterology &... Dec 2021Data are needed to inform the positioning of biologic therapy in the treatment of moderate-to-severe Crohn's disease, both first line and after previous biologic... (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND
Data are needed to inform the positioning of biologic therapy in the treatment of moderate-to-severe Crohn's disease, both first line and after previous biologic exposure. We aimed to assess the comparative efficacy and safety of biologics in patients with Crohn's disease.
METHODS
We did a systematic review and network meta-analysis of phase 2 and phase 3 randomised controlled trials done in adults (≥18 years) with moderate-to-severe Crohn's disease (Crohn's Disease Activity Index [CDAI] 220-450) treated with tumour necrosis factor (TNF) antagonists, anti-integrin, anti-interleukin (IL)-12 and IL-23p40, or anti-IL23p19 agents, either alone or in combination with immunosuppressants, as their first-line biologic or after previous biologic exposure, compared with placebo or an active comparator. The minimum duration of therapy was 14 days for trials reporting induction of remission in active disease and 22 weeks in trials reporting maintenance of remission. We searched Medline, EMBASE, the Cochrane CENTRAL Register of Controlled Trials, conference proceedings, trial registries, and unpublished data from inception to June 3, 2021, without any language restrictions. Summary estimates of the primary and secondary outcomes were extracted from the published reports; individual patient-level data were not sought. The primary endpoint was induction of clinical remission in patients with active disease (CDAI <150) and maintenance of remission in patients with response to induction therapy, with data extracted from published reports. A network meta-analysis with multivariate consistency model random-effects meta-regression was done, with rankings based on surface under the cumulative ranking curve (SUCRA) values.
FINDINGS
The search strategy yielded 18 382 citations, of which 31 trials were eligible for inclusion. On the basis of 15 randomised controlled trials including 2931 biologic-naive patients, infliximab monotherapy (odds ratio [OR] 4·53 [95% CI 1·49-13·79]), infliximab combined with azathioprine (7·49 [2·04-27·49]), adalimumab (3·01 [1·25-7·27]), and ustekinumab (2·63 [1·10-6·28]) were associated with significantly higher odds of inducing remission compared to certolizumab pegol (all moderate confidence); infliximab and azathioprine combination therapy was also associated with significantly higher odds of inducing remission than vedolizumab (3·76 [1·01-14·03]; low confidence). On the basis of ten randomised controlled trials including 2479 patients with previous biologic exposure, adalimumab after loss of response to infliximab (OR 2·82 [95% CI 1·20-6·62]; low confidence), and risankizumab (2·10 [1·12-3·92]; moderate confidence), were associated with higher odds of inducing remission than vedolizumab. No differences between active interventions were observed in maintenance trials. Most trials were at low or uncertain risk of bias.
INTERPRETATION
Although biologic treatment choices in patients with moderate-to-severe Crohn's disease must be individualised for each patient, this analysis suggests that either infliximab with azathioprine or adalimumab might be preferred as a first-line therapy, and adalimumab (after infliximab loss of response) or risankizumab might be preferred as a second-line therapy, for induction of clinical remission.
FUNDING
None.
Topics: Adalimumab; Adult; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Azathioprine; Benzene Derivatives; Biological Therapy; Carboxylic Acids; Case-Control Studies; Crohn Disease; Drug Therapy, Combination; Female; Humans; Immunosuppressive Agents; Infliximab; Interleukin-12 Subunit p40; Interleukin-23 Subunit p19; Male; Network Meta-Analysis; Placebos; Randomized Controlled Trials as Topic; Remission Induction; Safety; Severity of Illness Index; Treatment Outcome; Tumor Necrosis Factor Inhibitors; Ustekinumab
PubMed: 34688373
DOI: 10.1016/S2468-1253(21)00312-5 -
International Journal of Environmental... Dec 2020(1) Background: There is increasing awareness that the quality of the indoor environment affects our health and well-being. Indoor air quality (IAQ) in particular has an...
(1) Background: There is increasing awareness that the quality of the indoor environment affects our health and well-being. Indoor air quality (IAQ) in particular has an impact on multiple health outcomes, including respiratory and cardiovascular illness, allergic symptoms, cancers, and premature mortality. (2) Methods: We carried out a global systematic literature review on indoor exposure to selected air pollutants associated with adverse health effects, and related household characteristics, seasonal influences and occupancy patterns. We screened records from six bibliographic databases: ABI/INFORM, Environment Abstracts, Pollution Abstracts, PubMed, ProQuest Biological and Health Professional, and Scopus. (3) Results: Information on indoor exposure levels and determinants, emission sources, and associated health effects was extracted from 141 studies from 29 countries. The most-studied pollutants were particulate matter (PM and PM); nitrogen dioxide (NO); volatile organic compounds (VOCs) including benzene, toluene, xylenes and formaldehyde; and polycyclic aromatic hydrocarbons (PAHs) including naphthalene. Identified indoor PM sources include smoking, cooking, heating, use of incense, candles, and insecticides, while cleaning, housework, presence of pets and movement of people were the main sources of coarse particles. Outdoor air is a major PM source in rooms with natural ventilation in roadside households. Major sources of NO indoors are unvented gas heaters and cookers. Predictors of indoor NO are ventilation, season, and outdoor NO levels. VOCs are emitted from a wide range of indoor and outdoor sources, including smoking, solvent use, renovations, and household products. Formaldehyde levels are higher in newer houses and in the presence of new furniture, while PAH levels are higher in smoking households. High indoor particulate matter, NO and VOC levels were typically associated with respiratory symptoms, particularly asthma symptoms in children. (4) Conclusions: Household characteristics and occupant activities play a large role in indoor exposure, particularly cigarette smoking for PM, gas appliances for NO, and household products for VOCs and PAHs. Home location near high-traffic-density roads, redecoration, and small house size contribute to high indoor air pollution. In most studies, air exchange rates are negatively associated with indoor air pollution. These findings can inform interventions aiming to improve IAQ in residential properties in a variety of settings.
Topics: Air Pollutants; Air Pollution, Indoor; Child; Humans; Particulate Matter; Polycyclic Aromatic Hydrocarbons; Volatile Organic Compounds
PubMed: 33276576
DOI: 10.3390/ijerph17238972 -
Occupational and Environmental Medicine Sep 2020Recent evidence has accumulated that the immune system is intimately intertwined with cancer development. Two key characteristics of carcinogens in which the immune... (Review)
Review
OBJECTIVE
Recent evidence has accumulated that the immune system is intimately intertwined with cancer development. Two key characteristics of carcinogens in which the immune system plays a central role are chronic inflammation and immunosuppression. In this systematic review, we investigated the association of chronic inflammatory and immunosuppressive outcomes with benzene, a widely used industrial chemical. Benzene has been confirmed to cause acute myeloid leukaemia and suspected to cause non-Hodgkin lymphoma, two cancers of the blood-forming system that affect immune cells.
METHODS
We systematically searched PubMed and Embase for all relevant studies using a combination of Medical Subject Headings (MeSH) and selected key words. The detailed review protocol, including search strategy, was registered with PROSPERO, the international prospective register of systematic reviews (#CRD42019138611).
RESULTS
Based on all human studies selected in the final review, we report new evidence of a benzene-induced immunosuppressive effect on the immune system and activation of the immune system to cause inflammation. In particular, benzene significantly lowers the number of white blood cells, particularly lymphocytes such as CD4 T-cells, B-cells and natural killer cells, and increases proinflammatory biomarkers at low levels of exposure.
CONCLUSION
To the best of our knowledge, this is the first comprehensive review of benzene's immunotoxicity in humans. Based on results obtained from this review, we propose two potential immunotoxic mechanisms of how benzene induces leukaemia/lymphoma: (1) cancer invasion caused by proinflammatory cytokine production, and (2) cancer promotion via impaired immunosurveillance. Further studies will be required to confirm the connection between benzene exposure and its effects on the immune system.
PubMed: 32938756
DOI: 10.1136/oemed-2020-106517 -
The Lancet. Planetary Health Sep 2021Non-Hodgkin lymphoma comprises a heterogeneous group of cancers with unresolved aetiology, although risk factors include environmental exposures to toxic chemicals.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Non-Hodgkin lymphoma comprises a heterogeneous group of cancers with unresolved aetiology, although risk factors include environmental exposures to toxic chemicals. Although the ubiquitous pollutant benzene is an established leukemogen, its potential to cause non-Hodgkin lymphoma has been widely debated. We aimed to examine the potential link between benzene exposure and risk of non-Hodgkin lymphoma in humans by evaluating a wide array of cohort and case-control studies using electronic systematic review.
METHODS
We did a comprehensive systematic review and meta-analysis of all qualified human epidemiological studies that assessed the relationship between benzene exposure and non-Hodgkin lymphoma. We queried the PubMed and Embase databases for relevant articles published before June 5, 2019, and applied the SysRev platform for study selection. All peer-reviewed human cohort and case-control studies that reported non-Hodgkin lymphoma risk estimates specifically for benzene exposure were eligible for inclusion. Studies that calculated relative risks (RRs) for industries or job types without identifying those specifically exposed to benzene, that combined non-Hodgkin lymphoma with other cancer types, or that reported many different solvent exposures together were excluded. From each study, two investigators independently extracted information on the study design, location, years, sample size, participation rates, age, sex, sources of cases and controls, diagnosis, histological verification, exposure assessment, results, adjustment, and statistical analysis, and subsequently assessed study quality. We calculated the meta-analysis relative risk (meta-RR) and CIs using the fixed effect and random effect models, as well as assessing publication bias.
FINDINGS
Our search yielded 2481 articles. After screening and removal of duplicates, 20 case-control studies and eight cohort studies were included in our meta-analysis, which included a total of 9587 patients with non-Hodgkin lymphoma. We reported an increased meta-relative risk (meta-RR) of 33% in highly exposed groups, when data were available (meta-RR 1·33 [95% CI 1·13-1·57], n=28). The meta-RR rose to 1·51 (1·22-1·87, n=18) in the studies that provided results specifically for highly exposed individuals. In particular, we reported a doubling of this risk for diffuse large B-cell lymphoma, a major non-Hodgkin lymphoma subtype (1·67 [1·01-2·77]). We also detected increased risks for follicular lymphoma (1·47 [0·95-2·27]) and hairy cell leukaemia (1·77 [0·99-3·16]), though they were not statistically significant. Funnel plot, Egger's test (p=0·77) and Begg's test (p=0·98) did not show evidence of publication bias. We evaluated the major aspects of causal inference and found evidence to support all the Hill considerations for assigning causation.
INTERPRETATION
Our findings suggest a causal link between benzene exposure and non-Hodgkin lymphoma, especially for diffuse large B-cell lymphoma.
FUNDING
National Institute of Environmental Health Sciences.
Topics: Benzene; Case-Control Studies; Cohort Studies; Humans; Lymphoma, Non-Hodgkin; Risk Factors
PubMed: 34450064
DOI: 10.1016/S2542-5196(21)00149-2 -
Occupational benzene exposure and the risk of genetic damage: a systematic review and meta-analysis.BMC Public Health Jul 2020Benzene, an important component of organic solvents, is commonly used in industry. Meanwhile, benzene is a human carcinogen leading to leukemia. Although the links... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Benzene, an important component of organic solvents, is commonly used in industry. Meanwhile, benzene is a human carcinogen leading to leukemia. Although the links between benzene and various types of genetic damage indicators have been evaluated in several studies, but their results remain inconsistent. So we conducted a meta-analysis, and to explore the influence of low concentration benzene exposure on workers' genetic damage indicators using 3.25 mg/m as the boundary value, in order to provide a basis for improved prevention and control of the harm from benzene exposure to the occupational population.
METHODS
We conducted a search of five databases, including Pub Med, Web of Science, China National Knowledge Infrastructure (CNKI), Wan Fang Data and Chongqing VIP, to identify relevant articles up to December 25, 2018. Two researchers independently extracted and evaluated the data according to the inclusion and exclusion criteria of the literature. The imported articles were managed by Endnote X7, and the data were extracted and sorted by Excel 2013. We utilized Stata 12.0 software to perform the meta-analysis in the present study.
RESULTS
A total of 68 eligible articles were finally included for the synthetic analyses. The meta-analysis results showed that occupational benzene exposure led to significantly increased Micronucleus (MN) frequency, Sister chromatid exchange (SCE) frequency, Chromosome aberration (CA) frequency, Olive Tail moment (OTM), Tail moment (TM), Tail length (TL), and Tail DNA% (T DNA%) compared to the control group (P < 0.05), and the pooled effect value estimates were 1.36, 0.98, 0.76, 1.06, 0.96, 1.78, and 1.42, respectively. Subsequent analysis of the effect of low concentration benzene exposure on genetic damage found significantly increased MN frequency increased compared with the control group (P < 0.05).
CONCLUSIONS
Occupational benzene exposure can affect multiple genetic damage indicators. Even at an exposure concentration lower than 3.25 mg/m, benzene exposure has genotoxicity. These data provide an important scientific basis for the further revision of occupational disease prevention strategies. At the same time, increased attention should be focused on the health monitoring of the occupational population exposed to benzene, and health management should be strengthened to improve the health of the occupational population.
Topics: Adult; Benzene; Carcinogens; Case-Control Studies; Chromosome Aberrations; DNA Damage; Female; Humans; Industry; Male; Occupational Diseases; Occupational Exposure; Recombination, Genetic; Risk Factors
PubMed: 32669091
DOI: 10.1186/s12889-020-09215-1 -
International Journal of Environmental... Feb 2024Lung cancer is a leading cause of death with nearly 1.8 million deaths estimated worldwide in 2020. Although benzene is classified as a human carcinogen (Group 1) on the... (Meta-Analysis)
Meta-Analysis Review
Lung cancer is a leading cause of death with nearly 1.8 million deaths estimated worldwide in 2020. Although benzene is classified as a human carcinogen (Group 1) on the basis of its association with acute myeloid/non-lymphocytic leukaemia, there is still limited evidence that it may influence lung cancer risk. This study examined the potential link between benzene exposure and risk of lung cancer using a systematic review of epidemiological studies and meta-analysis. We searched through PubMed, Web of Science and Scopus databases up to 10 February 2023 to identify all articles on the association between benzene exposure and lung cancer (incidence or prevalence) and/or mortality. We extracted the risk estimates of the highest and the lowest reported categories of benzene exposure and conducted a meta-analysis using a random-effects model. Heterogeneity and publication bias were analysed using an I test and funnel plots asymmetry, respectively. Twenty-one studies were included in the final analysis, with a total of 10,750 lung cancer cases and 2899 lung cancer deaths. Overall, risk estimates of lung cancer prevalence and mortality in association with benzene exposure were 1.20 ( = 14; 95% CI 1.05-1.37) and 1.15 ( = 13; 95% CI 1.02-1.30), respectively. In all cases, heterogeneity was quite large, while no significant publication bias was observed. When only studies that adjusted for smoking habit were selected, the risk for lung cancer increased by up to 34% ( = 9; 95% CI 1.10-1.64). Our data, which show a strong association between benzene exposure and lung cancer risk, may have important public health implications. However, further studies are needed to identify the lung cancer risk associated with benzene exposure considering different smoking conditions.
Topics: Humans; Benzene; Lung Neoplasms; Occupational Exposure; Risk; Leukemia, Myeloid, Acute
PubMed: 38397694
DOI: 10.3390/ijerph21020205 -
Health Science Reports Sep 2021Benzene is a group I carcinogen, which has been associated with leukemia and myelodysplastic syndrome. Moreover, it has been proposed that polymorphisms in benzene... (Review)
Review
BACKGROUND AND AIMS
Benzene is a group I carcinogen, which has been associated with leukemia and myelodysplastic syndrome. Moreover, it has been proposed that polymorphisms in benzene metabolizing genes influence the outcomes of benzene exposure in the human body. This systematic review aims to elucidate the existent relationship between genetic polymorphisms and the risk of developing adverse health effects in benzene-exposed workers.
METHODS
Three databases were systematically searched until April 2020. The preferred reporting items for systematic reviews and meta-analyses method was used to select articles published between 2005 and 2020. Quality assessment and risk of bias were evaluated by the Newcastle-Ottawa scale.
RESULTS
After full-text evaluation, 36 articles remained out of 645 initially screened. The most studied health effects within the reviewed papers were chronic benzene poisoning, hematotoxicity, altered urinary biomarkers of exposure, micronucleus/chromosomal aberrations, and gene methylation. Furthermore, some polymorphisms on , , , , and , among other genes, showed a statistically significant relationship with an increased risk of developing at least one of these effects on benzene-exposed workers. However, there was no consensus among the reviewed papers on which specific polymorphisms were the ones associated with the adverse health-related outcomes, except for the rs1800566 and the null genotypes. Additionally, the smoking habit was identified as a confounder, demonstrating worse health outcomes in exposed workers that smoked.
CONCLUSION
Though there is a positive relationship between genetic polymorphisms and detrimental health outcomes for benzene-exposed workers, broader benzene-exposed cohorts that take into account the genetic diversity of the population are needed in order to determine which specific polymorphisms incur in health risks.
PubMed: 34295994
DOI: 10.1002/hsr2.327 -
European Respiratory Review : An... Mar 2015Volatile organic compounds (VOCs) are ubiquitous domestic pollutants. Their role in asthma/allergy development and exacerbations is uncertain. This systematic review... (Review)
Review
Volatile organic compounds (VOCs) are ubiquitous domestic pollutants. Their role in asthma/allergy development and exacerbations is uncertain. This systematic review investigated whether domestic VOC exposure increases the risk of developing and/or exacerbating asthma and allergic disorders. We systematically searched 11 databases and three trial repositories, and contacted an international panel of experts to identify published and unpublished experimental and epidemiological studies. 8455 potentially relevant studies were identified; 852 papers were removed after de-duplication, leaving 7603 unique papers that were screened. Of these, 278 were reviewed in detail and 53 satisfied the inclusion criteria. Critical appraisal of the included studies indicated an overall lack of high-quality evidence and substantial risk of bias in this body of knowledge. Aromatics (i.e. benzenes, toluenes and xylenes) and formaldehyde were the main VOC classes studied, both in relation to the development and exacerbations of asthma and allergy. Approximately equal numbers of studies reported that exposure increased risks and that exposure was not associated with any detrimental effects. The available evidence implicating domestic VOC exposure in the risk of developing and/or exacerbating asthma and allergy is of poor quality and inconsistent. Prospective, preferably experimental studies, investigating the impact of reducing/eliminating exposure to VOC, are now needed in order to generate a more definitive evidence base to inform policy and clinical deliberations in relation to the management of the now substantial sections of the population who are either at risk of developing asthma/allergy or living with established disease.
Topics: Asthma; Humans; Hypersensitivity; Volatile Organic Compounds
PubMed: 25726560
DOI: 10.1183/09059180.00000714 -
Environmental Health : a Global Access... Jun 2010A substantial number of epidemiologic studies have provided estimates of the relation between exposure to benzene at work and the risk of leukemia, but the results have... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
A substantial number of epidemiologic studies have provided estimates of the relation between exposure to benzene at work and the risk of leukemia, but the results have been heterogeneous. To bridge this gap in knowledge, we synthesized the existing epidemiologic evidence on the relation between occupational exposure to benzene and the risk of leukemia, including all types combined and the four main subgroups acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), and chronic myeloid leukemia (CML).
METHODS
A systematic literature review was carried out using two databases 'Medline' and 'Embase' from 1950 through to July 2009. We selected articles which provided information that can be used to estimate the relation between benzene exposure and cancer risk (effect size).
RESULTS
In total 15 studies were identified in the search, providing 16 effect estimates for the main analysis. The summary effect size for any leukemia from the fixed-effects model was 1.40 (95% CI, 1.23-1.57), but the study-specific estimates were strongly heterogeneous (I2 = 56.5%, Q stat = 34.47, p = 0.003). The random-effects model yielded a summary- effect size estimate of 1.72 (95% CI, 1.37-2.17). Effect estimates from 9 studies were based on cumulative exposures. In these studies the risk of leukemia increased with a dose-response pattern with a summary-effect estimate of 1.64 (95% CI, 1.13-2.39) for low (< 40 ppm-years), 1.90 (95% CI, 1.26-2.89) for medium (40-99.9 ppm-years), and 2.62 (95% CI, 1.57-4.39) for high exposure category (> 100 ppm-years). In a meta-regression, the trend was statistically significant (P = 0.015). Use of cumulative exposure eliminated heterogeneity. The risk of AML also increased from low (1.94, 95% CI, 0.95-3.95), medium (2.32, 95% CI, 0.91-5.94) to high exposure category (3.20, 95% CI, 1.09-9.45), but the trend was not statistically significant.
CONCLUSIONS
Our study provides consistent evidence that exposure to benzene at work increases the risk of leukemia with a dose-response pattern. There was some evidence of an increased risk of AML and CLL. The meta-analysis indicated a lack of association between benzene exposure and the risk of CML.
Topics: Benzene; Humans; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Acute; Occupational Exposure; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Risk Factors
PubMed: 20584305
DOI: 10.1186/1476-069X-9-31 -
RSC Advances Sep 20212,3-Dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) is the most widely used quinone with a high reduction potential, and it commonly mediates hydride transfer reactions and... (Review)
Review
2,3-Dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) is the most widely used quinone with a high reduction potential, and it commonly mediates hydride transfer reactions and shows three accessible oxidation states: quinone (oxidized), semiquinone (one-electron-reduced), and hydroquinone (two-electron-reduced). DDQ has found broad utility as a stoichiometric oxidant in the functionalization of activated C-H bonds and the dehydrogenation of saturated C-C, C-O, and C-N bonds. The cost and toxicity of DDQ triggered recent efforts to develop methods that employ catalytic quantities of DDQ in combination with alternative stoichiometric oxidants. The aerobic catalytic approach was established for the selective oxidation of non-sterically hindered electron-rich benzyl methyl ethers and benzylic alcohols, and effectively extended to the oxidative deprotection of -methoxybenzyl ethers to generate the alcohols in high selectivity. A combination of DDQ and protic acid is known to oxidize several aromatic donors to the corresponding cation radicals. The excited-state DDQ converts benzyls, heteroarenes, fluoroarenes, benzene, and olefins into their radical cation forms as well as chloride and other anions into their respective radicals. These reactive intermediates have been employed for the generation of C-C and C-X (N, O, or Cl) bonds in the synthesis of valuable natural products and organic compounds. To the best of our knowledge, however, there is still no review article exclusively describing the applications of DDQ in organic synthesis. Therefore, in the present review, we provide an overview of DDQ-induced organic transformations with their scope, limitations and the proposed reaction mechanisms.
PubMed: 35479576
DOI: 10.1039/d1ra04575j