Epidemiology of Δ8THC-Related Carcinogenesis in USA: A Panel Regression and Causal Inferential Study.
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ABSTRACT:
SUBMITTER: Reece AS
PROVIDER: S-EPMC9265369 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Δ8-Tetrahydrocannabinol (Δ8THC) is marketed in many US states as 'legal weed'. Concerns exist relating to class-wide genotoxic cannabinoid effects. We conducted an epidemiological investigation of Δ8THC-related genotoxicity expressed as 57 congenital anomaly (CA) rates (CARs) in the USA. CARs were taken from the Centers for Disease Control, Atlanta, Georgia. Drug exposure data were taken from the National Survey of Drug Use and Health, with a response rate of 74.1%. Ethnicity and income data were taken from the US Census Bureau. National cannabinoid exposure was taken from Drug Enforcement Agency publications and multiplied by state cannabis use data to derive state-based estimates of Δ8THC exposure. At bivariate continuous analysis, Δ8THC was associated with 23 CAs on raw CA rates, 33 CARs after correction for early termination for anomaly estimates and 41 on a categorical analysis comparing the highest and lowest exposure quintiles. At inverse probability weighted multivariable additive and interactive models lagged to 0, 2 and 4 years, Δ8THC was linked with 39, 8, 4 and 9 CAs. Chromosomal, cardiovascular, gastrointestinal, genitourinary, limb, central nervous system (CNS) and face systems were particularly affected. The minimum E-values ranged to infinity. Both the number of anomalies implicated and the effect sizes demonstrated were much greater for Δ8THC than for tobacco and alcohol combined. Δ8THC appears epidemiologically to be more strongly associated with many CAs than for tobacco and alcohol and is consistent with a cannabinoid class genotoxic/epigenotoxic effect. Quantitative causality criteria were fulfilled, and causal relationships either for Δ8THC or for cannabinoid/s, for which it is a surrogate marker, may be in operation.
| S-EPMC9245652 | biostudies-literature
Project description:With reports from Australia, Canada, USA, Hawaii and Colorado documenting a link between cannabis and congenital anomalies (CAs), this relationship was investigated in Europe. Data on 90 CAs were accessed from Eurocat. Tobacco and alcohol consumption and median household income data were from the World Bank. Amphetamine, cocaine and last month and daily use of cannabis from the European Monitoring Centre for Drugs and Drug Addiction. Cannabis herb and resin Δ9-tetrahydrocannabinol concentrations were from published reports. Data were processed in R. Twelve thousand three hundred sixty CA rates were sourced across 16 nations of Europe. Nations with a higher or increasing rate of daily cannabis use had a 71.77% higher median CA rates than others [median ± interquartile range 2.13 (0.59, 6.30) v. 1.24 (0.15, 5.14)/10 000 live births (P = 4.74 × 10-17; minimum E-value (mEV) = 1.52]. Eighty-nine out of 90 CAs in bivariate association and 74/90 CAs in additive panel inverse probability weighted space-time regression were cannabis related. In inverse probability weighted interactive panel models lagged to zero, two, four and six years, 76, 31, 50 and 29 CAs had elevated mEVs (< 2.46 × 1039) for cannabis metrics. Cardiovascular, central nervous, gastrointestinal, genital, uronephrology, limb, face and chromosomalgenetic systems along with the multisystem VACTERL syndrome were particularly vulnerable targets. Data reveal that cannabis is related to many CAs and fulfil epidemiological criteria of causality. The triple convergence of rising cannabis use prevalence, intensity of daily use and Δ9-tetrahydrocannabinol concentration in herb and resin is powerfully implicated as a primary driver of European teratogenicity, confirming results from elsewhere.
| S-EPMC8824558 | biostudies-literature
Project description:BACKGROUND:Cardiovascular anomalies are the largest group of congenital anomalies and the major cause of death in young children, with various data linking rising atrial septal defect incidence (ASDI) with prenatal cannabis exposure. Objectives / Hypotheses. Is cannabis associated with ASDI in USA? Is this relationship causal? METHODS:Geospatiotemporal cohort study, 1991-2016. Census populations of adults, babies, congenital anomalies, income and ethnicity. Drug exposure data on cigarettes, alcohol abuse, past month cannabis use, analgesia abuse and cocaine taken from National Survey of Drug Use and Health (78.9% response rate). Cannabinoid concentrations from Drug Enforcement Agency. Inverse probability weighted (ipw) regressions. Analysis conducted in R. RESULTS:ASDI rose nationally three-fold from 27.4 to 82.8 / 10,000 births 1991-2014 during a period when tobacco and alcohol abuse were falling but cannabis was rising. States including Nevada, Kentucky, Mississippi and Tennessee had steeply rising epidemics (Time: Status ?-estimate?=?10.72 (95%C.I. 8.39-13.05), P?<?2.0?×?10 -?16). ASDI was positively related to exposure to cannabis and most cannabinoids. Drug exposure data was near-complete from 2006 thus restricting spatial modelling from 2006 to 2014, N?=?282. In geospatial regression models cannabis: alcohol abuse term was significant (?-estimate?=?19.44 (9.11, 29.77), P?=?2.2?×?10 -?4); no ethnic or income factors survived model reduction. Cannabis legalization was associated with a higher ASDI (Time: Status ?-estimate?=?0.03 (0.01, 0.05), P?=?1.1?×?10 -3). Weighted panel regression interactive terms including cannabis significant (from ?-estimate?=?1418, (1080.6, 1755.4), P?=?7.3?×?10 -15). Robust generalized linear models utilizing inverse probability weighting interactive terms including cannabis appear (from ?-estimate?=?78.88, (64.38, 93.38), P?=?1.1?×?10 -8). Marginal structural models with machine-aided SuperLearning association of ASDI with high v. low cannabis exposure R.R.?=?1.32 (1.28, 1.36). Model e-values mostly >?1.5. CONCLUSIONS:ASDI is associated with cannabis use, frequency, intensity and legalization in a spatiotemporally significant manner, robust to socioeconomicodemographic adjustment and fulfilled causal criteria, consistent with multiple biological mechanisms and similar reports from Hawaii, Colorado, Canada and Australia. Not only are these results of concern in themselves, but they further imply that our list of the congenital teratology of cannabis is as yet incomplete, and highlight in particular cardiovascular toxicology of prenatal cannabinoid and drug exposure.
| S-EPMC7702707 | biostudies-literature
Project description:As prenatal and community cannabis exposures have recently been linked with congenital heart disease (CHD), it was of interest to explore these associations in Europe in a causal framework and space-time context. Congenital anomaly data from Eurocat, drug-use data from the European Monitoring Centre for Drugs and Drug Addiction, and income from the World Bank. Countries with rising daily cannabis use had in general higher congenital anomaly rates over time than those without (time: status interaction: β-Est. = 0.0267, P = 0.0059). At inverse probability-weighted panel regression, cannabis terms were positive and significant for CHD, severe CHD, atrial septal defect, ventricular septal defect, atrioventricular septal defect, patent ductus arteriosus, tetralogy of Fallot, vascular disruptions, double outlet right ventricle, transposition of the great vessels, hypoplastic right heart, and mitral valve anomalies from 1.75 × 10-19, 4.20 × 10-11, <2.2 × 10-16, <2.2 × 10-16, 1.58 × 10-12, 4.30 × 10-9, 4.36 × 10-16, 3.50 × 10-8, 5.35 × 10-12, <2.2 × 10-16, 5.65 × 10-5 and 6.06 × 10-10. At spatial regression, terms including cannabis were positive and significant for this same list of anomalies from 0.0038, 1.05 × 10-10, 0.0215, 8.94 × 10-6, 1.23 × 10-5, 2.05 × 10-5, 1.07 × 10-6, 8.77 × 10-5, 9.11 × 10-6, 0.0001, 3.10 × 10-7 and 2.17 × 10-7. 92.6% and 75.2% of 149 E-value estimates and minimum E-values were in high zone >9; 100.0% and 98.7% >1.25. Data show many congenital cardiac anomalies exhibit strong bivariate relationships with metrics of cannabis exposure. Causal inferential modelling for the twelve anomalies selected demonstrated convincing evidence of robust relationships to cannabis which survived adjustment and fulfilled epidemiological criteria for causal relationships. Space-time regression was similarly confirmatory. Epigenomic pathways constitute viable potential mechanisms. Given exponential genotoxic dose-response effects, careful and astute control of cannabinoid penetration is indicated.
| S-EPMC9364688 | biostudies-literature
Project description:Introduction. Of the many congenital anomalies (CAs) recently linked with community cannabis exposure, arguably the most concerning are neurological CAs (NCAs). We therefore conducted a detailed study of this in fourteen European nations. Methods. Congenital anomaly data were from Eurocat. Drug exposure data were from European Monitoring Centre for Drugs and Drug Addiction. Income from World bank. Results. The Netherlands, Spain, France and Bulgaria reported increasing rates of many NCAs. The NCA rate (NCAR) was higher in nations with increasing daily cannabis use when compared to those without (p = 0.0204, minimum E-value (mEV) = 1.35). At bivariate analysis, the mEVs of the following NCAs were significantly cannabis related: severe microcephaly 2.14 × 1013, craniosynostosis 5.27 × 1011, nervous system 4.87 × 1011, eye 2.73 × 107, microphthalmos 4.07 × 106, anencephalus 710.37, hydrocephalus 245.64, spina bifida 14.86 and neural tube defects 13.15. At inverse probability, weighted panel regression terms including cannabis were significantly related to the following series of anomalies: nervous system, anencephalus, severe microcephalus, microphthalmos, neural tube defect and spina bifida from p = 5.09 × 10−8, <2.2 × 10−16, <2.2 × 10−16, 4.84 × 10−11, <2.2 × 10−16 and 9.69 × 10−7. At geospatial regression, this same series of anomalies had terms including cannabis significant from p = 0.0027, 1.53 × 10−7, 3.65 × 10−6, 2.13 × 10−8, 0.0002 and 9.76 × 10−12. 88.0% of 50 E-value estimates and 72.0% of mEVs > 9. This analysis therefore demonstrates both close association of cannabis exposure with multiple NCAs across space-time and also fulfills the quantitative criteria of causal inferential analysis. Conclusions. Nine NCARs on bivariate and six NCARs on multivariable regression were cannabis related and fulfilled quantitative epidemiological criteria for causality and are consistent with other series. Particular concerns relate to exponential dose−response effects demonstrated in the laboratory and epidemiological studies. Great caution with community cannabinoid penetration is warranted. Data indicate that cannabis is a significant environmental teratogen and thus imply that cannabinoids should be regulated similarly to the manner in which all other important genotoxins are carefully controlled by communities for their self-sustaining longevity and the protection of generations yet to come.
| S-EPMC9819725 | biostudies-literature
Project description:As body wall congenital anomalies (BWCAs) have a long history of being associated with prenatal or community cannabis exposure (CCE), it was of interest to investigate these epidemiological relationships in Europe given the recent increases in cannabis use prevalence, daily intensity, and Δ9-tetrahydrocannabinol (THC) potency. Methods: This study makes use of BWCA data from Eurocat, drug exposure data from the European Monitoring Centre for Drugs and Drug Addiction, and income from the World Bank. Results: The mapping analysis showed that BWCARs increased in France, Spain, and the Netherlands. The bivariate mapping analysis showed that the BWCA rates (BWCAR) and the cannabis resin THC concentration rose simultaneously in France, the Netherlands, Bulgaria, Sweden, and Norway. The bivariate ranking of the BWCARs by median minimum E-value (mEV) was omphalocele > diaphragmatic hernia > abdominal wall defects > gastroschisis. With inverse probability weighted multivariable panel regression, the series of BWCAs, including gastroschisis, omphalocele, and diaphragmatic hernia, was positively related to various metrics of cannabis use from p = 2.45 × 10−14, 4.77 × 10−7 and <2.2 × 10−16. With geospatial regression, the same series of BWCAs was related to cannabis metrics from p = 0.0016, 5.28 × 10−6 and 4.88 × 10−9. Seventeen out of twenty-eight (60.7%) of the E-value estimates were >9 (high range), as were 14/28 (50.0%) of the mEVs. Conclusion: The data confirm the close relationship of the BWCARs with the metrics of CCE, fulfill the quantitative criteria of causal inference, and underscore the salience of the public health impacts of cannabinoid teratogenicity. Of major concern is the rising CCE impacting exponential cannabinoid genotoxic dose-response relationships. CCE should be carefully restricted to protect the food chain, the genome, and the epigenome of coming generations.
| S-EPMC9330494 | biostudies-literature
Project description:In observational studies, potential confounders may distort the causal relationship between an exposure and an outcome. However, under some conditions, a causal dose-response curve can be recovered using the G-computation formula. Most classical methods for estimating such curves when the exposure is continuous rely on restrictive parametric assumptions, which carry significant risk of model misspecification. Nonparametric estimation in this context is challenging because in a nonparametric model these curves cannot be estimated at regular rates. Many available nonparametric estimators are sensitive to the selection of certain tuning parameters, and performing valid inference with such estimators can be difficult. In this work, we propose a nonparametric estimator of a causal dose-response curve known to be monotone. We show that our proposed estimation procedure generalizes the classical least-squares isotonic regression estimator of a monotone regression function. Specifically, it does not involve tuning parameters, and is invariant to strictly monotone transformations of the exposure variable. We describe theoretical properties of our proposed estimator, including its irregular limit distribution and the potential for doubly-robust inference. Furthermore, we illustrate its performance via numerical studies, and use it to assess the relationship between BMI and immune response in HIV vaccine trials.
| S-EPMC8112616 | biostudies-literature
Project description:ObjectiveTo describe the epidemiology of paediatric pain-related visits to emergency departments (EDs) across the USA.DesignCross-sectional study.SettingA representative sample of US ED visits using data from the National Hospital Ambulatory Medical Care Survey (NHAMCS).ParticipantsPaediatric (age ≤18 years) ED visits in the 2017 NHAMCS data set.Data analysisEach visit was coded as pain-related or non-pain-related using the 'reason for visit' variable. Weighted proportions were calculated with 95% CIs. Logistic regression was used to compare odds of pain-related visits.Outcome measuresPrevalence of pain-related visits among paediatric ED visits.ResultsThere were an estimated 35 million paediatric ED visits in the USA in 2017, 55.6% (CI 53.3% to 57.8%) were pain related, which equates to 19.7 million annual visits. The prevalence of pain-related visits reached more than 50% of visits at age 6-7 and plateaued at relatively high proportions. Children of races other than white or black had lower odds of having a pain-related visit (OR 0.48, CI 0.29 to 0.81) than white children, as did children who were black, though the difference was not statistically significant (OR 0.88, CI 0.73 to 1.06). Relative to children covered by private insurance, children with Medicaid or CHIP (Children's Health Insurance Program) coverage had lower odds of a pain-related visit (OR 0.75, CI 0.60 to 0.93). Injuries represented 46.5% (CI 42.0% to 51.0%) of pain-related visits. Pain scores were reported in less than 50% of pain-related visits.ConclusionPain is the reason for visit in 55.6% of paediatric ED visits across the USA. The prevalence of pain-related visits peak before adolescence and it continues relatively high until the age 18. Injury, racial disparities in pain and poor pain score reporting should remain major topics of study in the paediatric population.
| S-EPMC8370556 | biostudies-literature
Project description:Background: Human papillomavirus (HPV) infection is considered as the most common viral sexually transmitted infection worldwide. This poses an increasingly interdisciplinary medical challenge. Since there is vast scattered information in databases about HPV and the correlated diseases, we decided to collect useful data so that the experts can get a more comprehensive view of HPV. Methods: In this article, HPV-associated diseases, prevalence, prevention, and new treatments are discussed. The retrieved articles reporting the latest data about the required information for our review were selected through searching in Web of Science, Scopus, Medline (PubMed), EMBASE, Cochrane Library, Ovid, and CINHAL with language limitations of English and German. Results: There are 2 groups of HPVs: (1) low-risk HPV types that can lead to genital warts, and (2) high-risk HPV types that are involved in HPV-associated oncogenesis. About 70% of all sexually active women are infected and most of these infections heal within many weeks or months. In the case of HPV-persistence, a risk of preneoplasia or carcinoma exists. These types of viruses are responsible for the existence of genitoanal, gastrointestinal, urinary tract, and head and neck tumors. There is still no definite successful treatment. The detection of HPV-related condylomata occurs macroscopically in women and men, and the diagnosis of the precursors of cervical carcinoma in women is possible by Pap smear. Conclusion: For extragenital manifestations, there is no structured early detection program. Meanwhile, studies on HPV vaccines confirm that they should be used for the primary prevention of HPV-dependent diseases. However, we need more research to find out the real advantages and disadvantages of vaccines.
| S-EPMC8278030 | biostudies-literature
Project description:Sutherland et al. (2011) suggested that, instead of risk factors for single neurodegenerative disorders (NDDs), there was a need to identify specific "drivers", i.e., risk factors with impact on specific deposits, such as amyloid-β, tau, or α-synuclein, acting across entities.Redefining drivers as "neither protein/gene- nor entity-specific features identifiable in the clinical and general epidemiology of conformational NDDs (CNDDs) as potential footprints of templating/spread/transfer mechanisms", we conducted an analysis of the epidemiology of ten CNDDs, searching for patterns.We identified seven potential drivers, each of which was shared by at least two CNDDs: 1) an age-at-exposure-related susceptibility to Creutzfeldt-Jakob disease (CJD) and several late-life CNDDs; 2) a relationship between age at onset, survival, and incidence; 3) shared genetic risk factors for CJD and late-life CNNDs; 4) partly shared personal (diagnostic, educational, behavioral, and social risk factors) predating clinical onset of late-life CNDDs; 5) two environmental risk factors, namely, surgery for sporadic CJD and amyotrophic lateral sclerosis, and Bordetella pertussis infection for Parkinson's disease; 6) reticulo-endothelial system stressors or general drivers (andropause or premenopausal estrogen deficiency, APOEɛ4, and vascular risk factors) for late-life CNDDs such as dementia/Alzheimer's disease, type-2 diabetes mellitus, and some sporadic cardiac and vascular degenerative diseases; and 7) a high, invariant incidence ratio of sporadic to genetic forms of mid- and late-life CNDDs, and type-2 diabetes mellitus.There might be a systematic epidemiologic pattern induced by specific proteins (PrP, TDP-43, SOD1, α-synuclein, amyloid-β, tau, Langerhans islet peptide, and transthyretin) or established combinations of these.
| S-EPMC4927850 | biostudies-other