1.Introduction,While classical laboratory and animal data have long established cannabinoid genotoxicity,it is only recently,with the application of modern analytical techniques,that the scale of epidemiological disea...1.Introduction,While classical laboratory and animal data have long established cannabinoid genotoxicity,it is only recently,with the application of modern analytical techniques,that the scale of epidemiological disease that may be attributable to cannabinoid exposure has been revealed.The importance and urgency of this work is heightened by the increased cannabis use that is accompanying the relaxation of legislation around cannabis use in many places,the widespread global movement toward cannabis legalization,and the general increase in the cannabinoid potency of available strains.Building on an original pathfinding epidemiological study of congenital anomalies in Hawaii,the United States[1]and confirmed by similar findings from Colorado in the United States,Canada,and Australia[2-4],contemporary studies in the United States and Europe have found that 46/62 and 90/95 congenital anomalies[5,6],respectively,are causally related to various metrics of cannabinoid exposure.Similar studies of cancer in the United States and Europe have found that 25/28 and 33/40 cancers,respectively,could be related to indices of cannabinoid exposure[7].Importantly,there was an almost complete overlap of findings wherever data allowed comparison.Recent investigations have utilized mixed effects,panel,robust,and spatiotemporal regression modeling;inverse probability weighting;and expected values(E-values)as primary tools of causal inference[5-7].The E-value measures the extent to which an association can be ascribed to confounding by other extraneous covariates[8].It has a 95%confidence interval(CI).Values greater than 9 are considered high[9].展开更多
Background: Whilst several studies have demonstrated poor cardiovascular health in opiate dependence, its role as a cardiovascular risk factor has not been considered. Methods: Pulse wave analysis was undertaken by ra...Background: Whilst several studies have demonstrated poor cardiovascular health in opiate dependence, its role as a cardiovascular risk factor has not been considered. Methods: Pulse wave analysis was undertaken by radial arterial tonometry (SphygmoCor) in female control and opiate-dependent patients and compared to lifetime opiate use. Results: 222 opiate dependent women were compared to 175 controls. Opiate dependent patients were receiving treatment with buprenorphine (83.3%), methadone (13.5%), or naltrexone (3.2%). Non log transformed chronologic age (CA) for the two groups was 33.58 ± 0.57 (opiate) vs. 32.62 ± 0.96 (controls) years (mean ± S.E.M.;P = 0.39). Vascular Reference Age (RA) 39.30 ± 1.28, vs. 35.03 ± 1.41 the RA-CA difference (5.73 ± 1.02 vs. 2.41 ± 0.91) and the RA/CA ratio (1.16 ± 0.03 vs. 1.07 ± 0.02;all P < 0.02), and all measurements of central arterial stiffness (P < 0.02) were significantly worse for opiates compared to controls. When adjusted for CA, RA and central augmentation pressure and index were all worse by themselves and in interaction with CA (all P < 0.005). At 60 years the modelled RA’s were 83.79 and 67.52 years respectively. The opiate dose-duration interaction showed a dose-response effect with RA (P = 0.0033). After full adjustment for established cardiovascular risk factors, the dose-duration interaction remained significant (P = 10-6), was included in 10 other terms, and dose or duration was included in 15 other interactions. Conclusion: These data show that lifetime opiate use is significantly associated with increased arterial stiffness and vascular age and suggest a dose-response relationship. This relationship is robust and persists after full multivariate adjustment. These findings carry far-reaching implications for opiate-induced generalized acceleration of organismal ageing.展开更多
文摘1.Introduction,While classical laboratory and animal data have long established cannabinoid genotoxicity,it is only recently,with the application of modern analytical techniques,that the scale of epidemiological disease that may be attributable to cannabinoid exposure has been revealed.The importance and urgency of this work is heightened by the increased cannabis use that is accompanying the relaxation of legislation around cannabis use in many places,the widespread global movement toward cannabis legalization,and the general increase in the cannabinoid potency of available strains.Building on an original pathfinding epidemiological study of congenital anomalies in Hawaii,the United States[1]and confirmed by similar findings from Colorado in the United States,Canada,and Australia[2-4],contemporary studies in the United States and Europe have found that 46/62 and 90/95 congenital anomalies[5,6],respectively,are causally related to various metrics of cannabinoid exposure.Similar studies of cancer in the United States and Europe have found that 25/28 and 33/40 cancers,respectively,could be related to indices of cannabinoid exposure[7].Importantly,there was an almost complete overlap of findings wherever data allowed comparison.Recent investigations have utilized mixed effects,panel,robust,and spatiotemporal regression modeling;inverse probability weighting;and expected values(E-values)as primary tools of causal inference[5-7].The E-value measures the extent to which an association can be ascribed to confounding by other extraneous covariates[8].It has a 95%confidence interval(CI).Values greater than 9 are considered high[9].
文摘Background: Whilst several studies have demonstrated poor cardiovascular health in opiate dependence, its role as a cardiovascular risk factor has not been considered. Methods: Pulse wave analysis was undertaken by radial arterial tonometry (SphygmoCor) in female control and opiate-dependent patients and compared to lifetime opiate use. Results: 222 opiate dependent women were compared to 175 controls. Opiate dependent patients were receiving treatment with buprenorphine (83.3%), methadone (13.5%), or naltrexone (3.2%). Non log transformed chronologic age (CA) for the two groups was 33.58 ± 0.57 (opiate) vs. 32.62 ± 0.96 (controls) years (mean ± S.E.M.;P = 0.39). Vascular Reference Age (RA) 39.30 ± 1.28, vs. 35.03 ± 1.41 the RA-CA difference (5.73 ± 1.02 vs. 2.41 ± 0.91) and the RA/CA ratio (1.16 ± 0.03 vs. 1.07 ± 0.02;all P < 0.02), and all measurements of central arterial stiffness (P < 0.02) were significantly worse for opiates compared to controls. When adjusted for CA, RA and central augmentation pressure and index were all worse by themselves and in interaction with CA (all P < 0.005). At 60 years the modelled RA’s were 83.79 and 67.52 years respectively. The opiate dose-duration interaction showed a dose-response effect with RA (P = 0.0033). After full adjustment for established cardiovascular risk factors, the dose-duration interaction remained significant (P = 10-6), was included in 10 other terms, and dose or duration was included in 15 other interactions. Conclusion: These data show that lifetime opiate use is significantly associated with increased arterial stiffness and vascular age and suggest a dose-response relationship. This relationship is robust and persists after full multivariate adjustment. These findings carry far-reaching implications for opiate-induced generalized acceleration of organismal ageing.
