Patterns of Cannabis- and Substance-Related Congenital General Anomalies in Europe: A Geospatiotemporal and Causal Inferential Study
Abstract
:1. Introduction
2. Methods
3. Results
3.1. Data Presentation
3.2. Bivariate Analysis
3.2.1. Continuous Data
3.2.2. Categorical Bivariate Analysis
3.3. Multivariate Analysis
3.3.1. Panel Regression
3.3.2. Geospatial Analysis
3.4. Causal Inference
E-Values
4. Discussion
4.1. Main Results
4.2. Choice of Anomalies
4.3. Qualitative Causal Inference
4.4. Quantitative Causal Inference
4.5. Mechanisms
4.6. Epigenomic Controls
4.7. Morphogen Gradients
4.8. Exponential Genotoxic Effects
4.9. Generalizability
4.10. Strengths and Limitations
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Anomaly | Mean ± S.E. Increasing | Mean ± S.E. Decreasing | Relative Rate Incr./Decr. | Student’s t | p-Value |
---|---|---|---|---|---|
VATER/VACTERL | 0.46 (0.42, 0.5) | 0.02 (0.03, 0.07) | 31.820 | 8.3870 | 7.49× 10−13 |
Teratogenic Synds | 1.07 (0.52, 1.62) | 0.28 (−0.09, 0.23) | 3.830 | 6.1691 | 1.81 × 10−8 |
Matern Infect Malform | 0.73 (0.44, 1.02) | 0.15 (−0.08, 0.2) | 4.748 | 5.7942 | 1.01 × 10−7 |
Situs inversus | 0.63 (−0.06, 1.32) | 0.35 (−0.05, 0.15) | 1.789 | 3.6097 | 5.18 × 10−4 |
Fetal Alcohol | 0.25 (0.01, 0.49) | 0.12 (−0.04, 0.12) | 2.161 | 2.3870 | 0.0186 |
Lateral anomalies | 1.52 (−0.48, 3.52) | 1.02 (−0.33, 0.45) | 1.497 | 1.5385 | 0.1374 |
Valproate syndrome | 0.05 (0.01, 0.09) | 0.02 (0, 0.04) | 2.104 | 1.2358 | 0.2190 |
Conjoined twins | 0.12 (−0.04, 0.28) | 0.08 (−0.02, 0.06) | 1.448 | 1.1442 | 0.2555 |
Skeletal dysplasias | 1.55 (−0.9, 4) | 1.25 (−0.21, 0.33) | 1.239 | 1.1265 | 0.2656 |
Amniotic band | 0.34 (−0.19, 0.87) | 0.27 (−0.14, 0.22) | 1.261 | 0.6950 | 0.4902 |
All Anomalies | 233.39 (−251.87, 718.65) | 247.58 (−0.14, 0.22) | 0.943 | 0.6372 | 0.5271 |
Anomaly | Substance | Mean Anomaly Rate | Estimate | Std. Error | Sigma | t_Statistic | p_Value | E-Value Estimate | E-Value Lower Bound |
---|---|---|---|---|---|---|---|---|---|
VATER/VACTERL | Daily.Interpol. | 0.4377 | 20.8858 | 4.6484 | 0.4252 | 4.4932 | 4.4932 | 1.81 × 10−5 | 5.19 × 1019 |
Teratogenic Synds | Daily.Interpol. | 1.0683 | 29.9733 | 6.8274 | 0.6408 | 4.3901 | 4.3901 | 2.56 × 10−5 | 6.10 × 1018 |
Lateral anomalies | Daily.Interpol. | 1.7332 | 26.6028 | 6.7914 | 0.6212 | 3.9172 | 3.9172 | 1.60 × 10−4 | 1.68 × 1017 |
Matern Infect Malform | Daily.Interpol. | 0.6880 | 22.6665 | 5.8194 | 0.5462 | 3.8950 | 3.8950 | 1.67 × 10−4 | 5.02 × 1016 |
Teratogenic Synds | LMCannabis_Herb | 1.0683 | 11.1368 | 2.1817 | 0.6263 | 5.1046 | 5.1046 | 1.26 × 10−6 | 2.13 × 107 |
Situs inversus | Daily.Interpol. | 0.5932 | 12.3967 | 4.2919 | 0.4029 | 2.8884 | 2.8884 | 0.0046 | 2.90 × 1012 |
Lateral anomalies | LMCannabis_Herb | 1.7332 | 10.0481 | 2.3741 | 0.6147 | 4.2324 | 4.2324 | 4.96 × 10−5 | 5.78 × 106 |
Matern Infect Malform | LMCannabis_Herb | 0.6880 | 8.2647 | 1.8585 | 0.5335 | 4.4469 | 4.4469 | 1.96 × 10−5 | 2.65 × 106 |
Skeletal dysplasias | Daily.Interpol. | 1.8050 | 19.3566 | 7.0728 | 0.6639 | 2.7368 | 2.7368 | 0.0072 | 6.67 × 1011 |
Lateral anomalies | Herb | 1.7332 | 8.3890 | 1.8336 | 0.6072 | 4.5752 | 4.5752 | 1.31 × 10−5 | 5.76 × 105 |
Teratogenic Synds | Herb | 1.0683 | 7.7193 | 1.6312 | 0.6343 | 4.7322 | 4.7322 | 6.13 × 10−6 | 1.29 × 105 |
Matern Infect Malform | Herb | 0.6880 | 6.2822 | 1.3652 | 0.5308 | 4.6016 | 4.6016 | 1.05 × 10−5 | 9.51 × 104 |
Situs inversus | LMCannabis_Herb | 0.5932 | 5.1389 | 1.3379 | 0.3840 | 3.8410 | 3.8410 | 1.97 × 10−4 | 3.88 × 105 |
Situs inversus | Herb | 0.5932 | 4.0862 | 0.9779 | 0.3802 | 4.1784 | 4.1784 | 5.60 × 10−5 | 3.53 × 104 |
Fetal Alcohol | LMCannabis_Herb | 0.2458 | 4.3930 | 1.2221 | 0.3508 | 3.5945 | 3.5945 | 4.73 × 10−4 | 1.78 × 105 |
VATER/VACTERL | LM_Cannabis | 0.4377 | 6.5421 | 2.0669 | 0.4436 | 3.1652 | 3.1652 | 0.0020 | 1.35 × 106 |
Teratogenic Synds | LM_Cannabis | 1.0683 | 8.8997 | 2.7367 | 0.6624 | 3.2519 | 3.2519 | 0.0015 | 4.09 × 105 |
Lateral anomalies | LM_Cannabis | 1.7332 | 8.9858 | 2.9721 | 0.6378 | 3.0234 | 3.0234 | 0.0031 | 7.39 × 105 |
VATER/VACTERL | LMCannabis_Herb | 0.4377 | 5.1942 | 1.7200 | 0.4453 | 3.0199 | 3.0199 | 0.0032 | 8.14 × 104 |
Matern Infect Malform | LM_Cannabis | 0.6880 | 6.4725 | 2.3045 | 0.5577 | 2.8087 | 2.8087 | 0.0058 | 7.72 × 104 |
Skeletal dysplasias | LMCannabis_Herb | 1.8050 | 6.5116 | 2.2481 | 0.6453 | 2.8965 | 2.8965 | 0.0045 | 1.94 × 104 |
Teratogenic Synds | LM.Cannabis × Herb.THC × Daily.Interpol. | 1.0683 | 3.1437 | 0.7564 | 0.6457 | 4.1562 | 4.1562 | 6.32 × 10−5 | 167.39 |
Lateral anomalies | Resin | 1.7332 | 3.0137 | 0.7391 | 0.6363 | 4.0773 | 4.0773 | 9.46 × 10−5 | 148.33 |
Fetal Alcohol | Herb | 0.2458 | 2.6533 | 0.9181 | 0.3570 | 2.8898 | 2.8898 | 0.0046 | 1.73 × 103 |
Matern Infect Malform | LM.Cannabis × Herb.THC × Daily.Interpol. | 0.6880 | 2.3897 | 0.6433 | 0.5492 | 3.7149 | 3.7149 | 3.18 × 10−4 | 104.39 |
Lateral anomalies | LM.Cannabis × Herb.THC × Daily.Interpol. | 1.7332 | 2.4982 | 0.7511 | 0.6325 | 3.3259 | 3.3259 | 0.0012 | 72.26 |
All Anomalies | Resin | 255.4744 | 1.2426 | 0.3661 | 0.3291 | 3.3942 | 3.3942 | 9.72 × 10−4 | 61.62 |
Fetal Alcohol | Daily.Interpol. | 0.2458 | 8.2930 | 3.9391 | 0.3697 | 2.1053 | 2.1053 | 0.0375 | 1.46 × 109 |
Lateral anomalies | LMCannabis_Resin | 1.7332 | 2.1164 | 0.5631 | 0.6436 | 3.7586 | 3.7586 | 2.95 × 10−4 | 39.37 |
Skeletal dysplasias | Herb | 1.8050 | 4.2006 | 1.6733 | 0.6506 | 2.5103 | 2.5103 | 0.0134 | 711.51 |
Amniotic band | LMCannabis_Resin | 0.3730 | 1.0556 | 0.3089 | 0.3699 | 3.4170 | 3.4170 | 9.02 × 10−4 | 26.33 |
Skeletal dysplasias | LM.Cannabis × Herb.THC × Daily.Interpol. | 1.8050 | 2.2295 | 0.7751 | 0.6617 | 2.8764 | 2.8764 | 0.0048 | 42.40 |
Situs inversus | LM.Cannabis × Herb.THC × Daily.Interpol. | 0.5932 | 1.3525 | 0.4721 | 0.4031 | 2.8647 | 2.8647 | 0.0050 | 41.87 |
Teratogenic Synds | LMCannabis_Resin | 1.0683 | 1.8066 | 0.5687 | 0.6810 | 3.1768 | 3.1768 | 0.0020 | 21.85 |
Fetal Alcohol | LM.Cannabis × Herb.THC × Daily.Interpol. | 0.2458 | 1.1590 | 0.4278 | 0.3653 | 2.7090 | 2.7090 | 0.0078 | 35.39 |
Teratogenic Synds | LM.Cannabis × Resin.THC × Daily.Interpol. | 1.0683 | 1.2927 | 0.3585 | 0.6708 | 3.6062 | 3.6062 | 4.91 × 10−4 | 11.03 |
Fetal Alcohol | LMCannabis_Resin | 0.2458 | 0.8989 | 0.3077 | 0.3684 | 2.9213 | 2.9213 | 0.0043 | 17.90 |
Matern Infect Malform | LMCannabis_Resin | 0.6880 | 1.3658 | 0.4763 | 0.5703 | 2.8674 | 2.8674 | 0.0050 | 17.16 |
All Anomalies | Herb | 255.4744 | 2.2466 | 1.0012 | 0.3893 | 2.2438 | 2.2438 | 0.0267 | 381.13 |
Matern Infect Malform | LM.Cannabis × Resin.THC × Daily.Interpol. | 0.6880 | 0.9847 | 0.3031 | 0.5672 | 3.2483 | 3.2483 | 0.0016 | 9.18 |
VATER/VACTERL | LM.Cannabis × Herb.THC × Daily.Interpol. | 0.4377 | 1.3541 | 0.5352 | 0.4507 | 2.5300 | 2.5300 | 0.0129 | 30.28 |
Lateral anomalies | LM.Cannabis × Resin.THC × Daily.Interpol. | 1.7332 | 1.1244 | 0.3521 | 0.6555 | 3.1934 | 3.1934 | 0.0019 | 9.00 |
Amniotic band | LMCannabis_Herb | 0.3730 | 3.2048 | 1.4989 | 0.4302 | 2.1381 | 2.1381 | 0.0345 | 1.76 × 103 |
VATER/VACTERL | Cocaine | 0.4377 | 0.3393 | 0.0527 | 0.3931 | 6.4369 | 6.4369 | 3.72 × 10−9 | 3.81 |
Skeletal dysplasias | LMCannabis_Resin | 1.8050 | 1.3870 | 0.5266 | 0.6306 | 2.6337 | 2.6337 | 0.0097 | 14.28 |
Skeletal dysplasias | LM.Cannabis × Resin.THC × Daily.Interpol. | 1.8050 | 1.0055 | 0.3440 | 0.6436 | 2.9233 | 2.9233 | 0.0043 | 7.75 |
All Anomalies | LMCannabis_Resin | 255.4744 | 0.7027 | 0.2813 | 0.3368 | 2.4982 | 2.4982 | 0.0140 | 12.83 |
All Anomalies | LM.Cannabis × Resin.THC × Daily.Interpol. | 255.4744 | 0.4992 | 0.1811 | 0.3388 | 2.7572 | 2.7572 | 0.0070 | 7.11 |
Matern Infect Malform | Cocaine | 0.6880 | 0.3460 | 0.0644 | 0.5169 | 5.3762 | 5.3762 | 3.80 × 10−7 | 3.08 |
Fetal Alcohol | LM.Cannabis × Resin.THC × Daily.Interpol. | 0.2458 | 0.5533 | 0.2024 | 0.3787 | 2.7344 | 2.7344 | 0.0074 | 7.02 |
Teratogenic Synds | Cocaine | 1.0683 | 0.3971 | 0.0780 | 0.6266 | 5.0903 | 5.0903 | 1.34 × 10−6 | 2.96 |
Amniotic band | LM.Cannabis × Resin.THC × Daily.Interpol. | 0.3730 | 0.5439 | 0.2053 | 0.3842 | 2.6491 | 2.6491 | 0.0094 | 6.71 |
VATER/VACTERL | LM.Cannabis × Herb.THC: LM.Cannabis × Resin.THC × Daily.Interpol. | 0.4377 | 0.9512 | 0.4034 | 0.4610 | 2.3582 | 2.3582 | 0.0204 | 12.55 |
Lateral anomalies | Cocaine | 1.7332 | 0.3713 | 0.0815 | 0.6077 | 4.5565 | 4.5565 | 1.41 × 10−5 | 2.88 |
VATER/VACTERL | LM.Cannabis × Resin.THC × Daily.Interpol. | 0.4377 | 0.6332 | 0.2464 | 0.4587 | 2.5702 | 2.5702 | 0.0117 | 6.48 |
Situs inversus | LM.Cannabis × Resin.THC × Daily.Interpol. | 0.5932 | 0.5669 | 0.2250 | 0.4211 | 2.5194 | 2.5194 | 0.0134 | 6.27 |
Situs inversus | Cocaine | 0.5932 | 0.2054 | 0.0471 | 0.3781 | 4.3619 | 4.3619 | 2.74 × 10−5 | 2.66 |
Situs inversus | LMCannabis_Resin | 0.5932 | 0.7543 | 0.3444 | 0.4123 | 2.1905 | 2.1905 | 0.0307 | 10.04 |
Skeletal dysplasias | Cocaine | 1.8050 | 0.2686 | 0.0794 | 0.6378 | 3.3820 | 3.3820 | 9.72 × 10−4 | 2.29 |
All Anomalies | Cocaine | 255.4744 | 0.1491 | 0.0476 | 0.3821 | 3.1349 | 3.1349 | 0.0022 | 2.21 |
Fetal Alcohol | Annual_Alcohol | 0.2458 | 0.0793 | 0.0169 | 0.3393 | 4.6992 | 4.6992 | 7.02 × 10−6 | 1.78 |
All Anomalies | Daily.Interpol. | 255.4744 | 0.1426 | 0.0481 | 0.3836 | 2.9645 | 2.9645 | 0.0037 | 2.15 |
VATER/VACTERL | Amphetamine | 0.4377 | 0.1506 | 0.0582 | 0.4501 | 2.5891 | 2.5891 | 0.0110 | 2.05 |
Amniotic band | Annual_Alcohol | 0.3730 | 0.0709 | 0.0208 | 0.4186 | 3.4067 | 3.4067 | 8.95 × 10−4 | 1.61 |
Teratogenic Synds | Annual_Alcohol | 1.0683 | 0.0942 | 0.0333 | 0.6690 | 2.8296 | 2.8296 | 0.0055 | 1.53 |
Valproate syndrome | Cocaine | 0.0434 | 0.0362 | 0.0169 | 0.1354 | 2.1472 | 2.1472 | 0.0338 | 1.87 |
Parameter Values | Model Parameters | ||||
---|---|---|---|---|---|
Parameter | Estimate (C.I.) | p-Value | Parameter | Value | Significance |
Additive | |||||
Rate ~ Tobacco + Alcohol + LM.Cannabis × Herb.THC × Daily.Interpol. + LM.Cannabis × Resin.THC × Daily.Interpol. + Daily.Interpol. + LM.Cannabis × Resin.THC + Amphetamines + Cocaine + Income) | |||||
LM.Cannabis × Resin.THC | 0.94 (0.53, 1.36) | 8.96 × 10−6 | psi | 0.9116 | <2.2 × 10−16 |
Cocaine | 0.09 (0.02, 0.17) | 0.0136 | rho | 0.6488 | 2.81 × 10−12 |
lambda | −0.4147 | 0.00167 | |||
Interactive | |||||
Rate ~ Tobacco + LM.Cannabis × Resin.THC * Herb + LM.Cannabis × Resin.THC × Daily.Interpol. + LM.Cannabis × Herb.THC × Daily.Interpol. + Alcohol + Amphetamines + Cocaine + Income | |||||
Herb | 2.02 (1.13, 2.9) | 8.09 × 10−6 | psi | 0.9073 | <2.2 × 10−16 |
LM.Cannabis × Herb.THC × Daily.Interpol. | 0.05 (0.01, 0.1) | 2.23 × 10−2 | rho | −0.5330 | 1.50 × 10−5 |
lambda | 0.5605 | 2.34 × 10−7 | |||
2 Lags | |||||
Rate ~ Tobacco + LM.Cannabis × Resin.THC * Herb + LM.Cannabis × Resin.THC × Daily.Interpol. + LM.Cannabis × Herb.THC × Daily.Interpol. + Alcohol + Amphetamines + Cocaine + Income | |||||
LM.Cannabis × Resin.THC | 0.74 (0.24, 1.23) | 0.0037 | psi | 0.9215 | <2.2 × 10−16 |
LM.Cannabis × Resin.THC × Daily.Interpol. | 0.06 (0.01, 0.1) | 0.0198 | rho | 0.6514 | 1.89 × 10−8 |
Cocaine | −0.09 (−0.17, −0.01) | 0.0304 | lambda | −0.406 | 0.013 |
Parameter Values | Model Parameters | ||||
---|---|---|---|---|---|
Parameter | Estimate (C.I.) | p-Value | Parameter | Value | Significance |
Additive | |||||
Rate ~ Tobacco + Alcohol + LM.Cannabis × Herb.THC × Daily.Interpol. + LM.Cannabis × Resin.THC × Daily.Interpol. + Daily.Interpol. + LM.Cannabis × Resin.THC + Amphetamines + Cocaine + Income) | |||||
Alcohol | 0.07 (0, 0.13) | 0.0472 | psi | 0.5261 | 5.52 × 10−12 |
Daily.Interpol. | 15.4 (2.37, 28.43) | 0.0205 | Log.Lik. | −26.1038 | |
Income | 0 (0, 0) | 0.0011 | |||
Interactive | |||||
Rate ~ Tobacco * Daily.Interpol. + LM.Cannabis × Herb.THC + LM.Cannabis × Resin.THC × Daily.Interpol. + LM.Cannabis × Herb.THC × Daily.Interpol. + Alcohol + Amphetamines + Cocaine + Income | |||||
Tobacco | 0.04 (0, 0.07) | 0.0383 | psi | 0.2864 | 0.00512 |
Daily.Interpol. | 118 (50.77, 185.23) | 0.0006 | |||
Alcohol | 0.1 (0.05, 0.16) | 0.0002 | |||
Cocaine | 0.29 (0.06, 0.51) | 0.0121 | |||
Income | 0 (0, 0) | 0.0097 | |||
Tobacco: Daily.Interpol. | −4.97 (−7.56, −2.38) | 0.0002 | |||
2 Lags | |||||
Rate ~ Tobacco * Daily.Interpol. + LM.Cannabis × Herb.THC + LM.Cannabis × Resin.THC × Daily.Interpol. + LM.Cannabis × Herb.THC × Daily.Interpol. + Alcohol + Amphetamines + Cocaine + Income | |||||
Tobacco | 0.04 (0, 0.07) | 0.029285 | Least Squares | ||
Daily.Interpol. | 184 (103.84, 264.16) | 6.56 × 10−6 | S.D. | 0.3114 | |
Alcohol | 0.11 (0.06, 0.16) | 1.90 × 10−5 | Log.Lik. | −22.2103 | |
Cocaine | 0.33 (0.09, 0.57) | 0.0072 | |||
Income | 0 (0, 0) | 0.0291 | |||
Tobacco: Daily.Interpol. | −7.43 (−10.33, −4.53) | 4.97 × 10−7 | |||
4 Lags | |||||
Rate ~ Tobacco * Daily.Interpol. + LM.Cannabis × Herb.THC + LM.Cannabis × Resin.THC × Daily.Interpol. + LM.Cannabis × Herb.THC × Daily.Interpol. + Alcohol + Amphetamines + Cocaine + Income | |||||
Tobacco | 0.06 (0.03, 0.09) | 0.0002 | Least Squares | ||
Daily.Interpol. | 277 (197.82, 356.18) | 6.81 × 10−12 | S.D. | 0.2859 | |
LM.Cannabis × Herb.THC | 7.9 (2.84, 12.96) | 0.0022 | |||
Alcohol | 0.09 (0.04, 0.13) | 0.0001 | |||
Income | 0 (0, 0) | 3.26 × 10−5 | |||
Tobacco: Daily.Interpol. | −10.6 (−13.68, −7.52) | 1.29 × 10−11 | |||
6 Lags | |||||
Rate ~ Tobacco * Daily.Interpol. + LM.Cannabis × Herb.THC + LM.Cannabis × Resin.THC × Daily.Interpol. + LM.Cannabis × Herb.THC × Daily.Interpol. + Alcohol + Amphetamines + Cocaine + Income | |||||
Tobacco | 0.12 (0.07, 0.16) | 9.80 × 10−7 | Least Squares | ||
Daily.Interpol. | 375 (255.44, 494.56) | 8.10 × 10−10 | S.D. | 0.2953 | |
LM.Cannabis × Herb.THC: LM.Cannabis × Resin.THC × Daily.Interpol. | −0.31 (−0.46, −0.17) | 3.13 × 10−5 | |||
Income | 0 (0, 0) | 4.57 × 10−6 | |||
Tobacco: Daily.Interpol. | −13.8 (−18.43, −9.17) | 4.95 × 10−9 |
Parameter Values | Model Parameters | ||||
---|---|---|---|---|---|
Parameter | Estimate (C.I.) | p-Value | Parameter | Value | Significance |
Additve Model without Cannabis Terms | |||||
Rate ~ Alcohol + Cocaine + Income | |||||
Alcohol | 0.09 (0.04, 0.15) | 0.0010 | psi | 3.73 × 10−7 | |
Resin | 0.24 (0.1, 0.38) | 0.0007 | S.D. | 0.3495 | |
Income | 0 (0, 0) | 0.0059 | Log.Lik. | −28.449 | |
Spatial Hausman Test | |||||
Chi.Squared | 8.12 | ||||
Deg.Freedom | 3 | ||||
p-Value | 0.0436 | ||||
Models at 2 Lags without Cannabis Terms | |||||
Alcohol | 0.07 (0.02, 0.11) | 0.0029 | Least Squares | ||
Cocaine | 0.4 (0.28, 0.52) | 2.90 × 10−11 | S.D. | 0.3796 | |
Log.Lik. | −39.6349 | ||||
Spatial Hausman Test | |||||
Chi.Squared | 82.41 | ||||
Deg.Freedom | 3 | ||||
p-Value | <2.2 × 10−16 |
Parameter Values | Model Parameters | ||||
---|---|---|---|---|---|
Parameter | Estimate (C.I.) | p-Value | Parameter | Value | Significance |
Additive | |||||
Rate ~ Tobacco + Alcohol + LM.Cannabis × Herb.THC × Daily.Interpol. + LM.Cannabis × Resin.THC × Daily.Interpol. + Daily.Interpol. + LM.Cannabis × Resin.THC + Amphetamines + Cocaine + Income) | |||||
Tobacco | 0.05 (0.03, 0.06) | 3.96 × 10−9 | rho | −0.4998 | 7.08 × 10−5 |
Alcohol | 0.06 (0.03, 0.08) | 1.32 × 10−5 | lambda | 0.4343 | 9.82 × 10−5 |
Herb | 2.46 (1.1, 3.82) | 0.0004 | |||
Amphetamines | −0.11 (−0.17, −0.05) | 0.0004 | |||
Income | 0 (0, 0) | 5.36 × 10−8 | |||
Interactive | |||||
Rate ~ Tobacco + LM.Cannabis × Resin.THC * Herb + LM.Cannabis × Herb.THC × Daily.Interpol. + LM.Cannabis × Resin.THC × Daily.Interpol. + Alcohol + Amphetamines + Cocaine + Income | |||||
Tobacco | 0.05 (0.03, 0.06) | 3.96 × 10−9 | rho | −0.4998 | 7.10 × 10−5 |
Herb | 2.46 (1.1, 3.82) | 0.0004 | lambda | 0.4343 | 9.79 × 10−5 |
Alcohol | 0.06 (0.03, 0.08) | 1.32 × 10−5 | |||
Amphetamines | −0.11 (−0.17, −0.05) | 0.0004 | |||
Income | 0 (0, 0) | 5.36 × 10−8 | |||
2 Lags | |||||
Rate ~ Tobacco + LM.Cannabis × Resin.THC * Herb + LM.Cannabis × Resin.THC × Daily.Interpol. + LM.Cannabis × Herb.THC × Daily.Interpol. + Alcohol + Amphetamines + Cocaine + Income | |||||
Tobacco | 0.05 (0.04, 0.07) | 1.36 × 10−10 | rho | −0.6212 | 3.41 × 10−9 |
LM.Cannabis × Resin.THC × Daily.Interpol. | 1.41 (0.47, 2.35) | 0.0034 | lambda | 0.4866 | 1.44 × 10−7 |
LM.Cannabis × Herb.THC × Daily.Interpol. | −2.92 (−5.06, −0.78) | 0.0076 | |||
Alcohol | 0.07 (0.04, 0.1) | 9.45 × 10−6 | |||
Amphetamines | −0.18 (−0.26, −0.1) | 1.09 × 10−5 | |||
Income | 0 (0, 0) | 6.49 × 10−12 |
Parameter Values | Model Parameters | ||||
---|---|---|---|---|---|
Parameter | Estimate (C.I.) | p-Value | Parameter | Value | Significance |
Additive | |||||
Rate ~ Tobacco + Alcohol + LM.Cannabis × Herb.THC × Daily.Interpol. + LM.Cannabis × Resin.THC × Daily.Interpol. + Daily.Interpol. + LM.Cannabis × Resin.THC + Amphetamines + Cocaine + Income) | |||||
Alcohol | 0.04 (0.01, 0.07) | 0.0169 | Least Squares | ||
Herb | 2.99 (1.11, 4.87) | 0.0019 | S.D. | 0.2519 | |
Amphetamines | −0.2 (−0.27, −0.12) | 1.74 × 10−7 | |||
Cocaine | 0.2 (0.11, 0.28) | 9.22 × 10−6 | |||
Income | 0 (0, 0) | 4.11 × 10−6 | |||
Interactive | |||||
Rate ~ Tobacco + LM.Cannabis × Resin.THC * Herb + LM.Cannabis × Resin.THC × Daily.Interpol. + LM.Cannabis × Herb.THC × Daily.Interpol. + Alcohol + Amphetamines + Cocaine + Income | |||||
Herb | 2.99 (1.11, 4.87) | 0.0019 | Least Squares | ||
Alcohol | 0.04 (0.01, 0.07) | 0.0169 | S.D. | 0.2519 | |
Amphetamines | −0.2 (−0.27, −0.12) | 1.74 × 10−7 | |||
Cocaine | 0.2 (0.11, 0.28) | 9.22 × 10−6 | |||
Income | 0 (0, 0) | 4.11 × 10−6 | |||
1 Lags | |||||
Rate ~ Tobacco + LM.Cannabis × Resin.THC * Herb + LM.Cannabis × Resin.THC × Daily.Interpol. + LM.Cannabis × Herb.THC × Daily.Interpol. + Alcohol + Amphetamines + Cocaine + Income | |||||
Herb | 2.37 (0.23, 4.51) | 0.0299 | Least Squares | ||
Amphetamines | −0.19 (−0.27, −0.1) | 1.64 × 10−5 | S.D. | 0.3024 | |
Cocaine | 0.18 (0.08, 0.28) | 0.0003 | |||
Income | 0 (0, 0) | 5.31 × 10−5 |
Parameter Values | Model Parameters | ||||
---|---|---|---|---|---|
Parameter | Estimate (C.I.) | p-Value | Parameter | Value | Significance |
Additive | |||||
Rate ~ Tobacco + Alcohol + LM.Cannabis × Herb.THC × Daily.Interpol. + LM.Cannabis × Resin.THC × Daily.Interpol. + Daily.Interpol. + LM.Cannabis × Resin.THC + Amphetamines + Cocaine + Income) | |||||
Alcohol | 0.12 (0.06, 0.18) | 2.50 × 10−5 | rho | 0.4947 | 4.86 × 10−5 |
LM.Cannabis × Resin.THC | 3.31 (1.42, 5.2) | 0.0006 | lambda | −0.5897 | 1.68 × 10−8 |
LM.Cannabis × Resin.THC × Daily.Interpol. | −1.83 (−3.58, −0.08) | 0.0412 | |||
LM.Cannabis × Herb.THC × Daily.Interpol. | 2.09 (0.01, 4.17) | 0.0476 | |||
Amphetamines | −0.15 (−0.28, −0.03) | 0.0182 | |||
Cocaine | 0.29 (0.14, 0.44) | 0.0001 | |||
Income | 0 (0, 0) | 3.88 × 10−7 | |||
Interactive | |||||
Rate ~ Tobacco + LM.Cannabis × Resin.THC * Herb + LM.Cannabis × Resin.THC × Daily.Interpol. + LM.Cannabis × Herb.THC × Daily.Interpol. + Alcohol + Amphetamines + Cocaine + Income | |||||
LM.Cannabis × Resin.THC | 3.31 (1.42, 5.2) | 0.0006 | rho | 0.4947 | 4.89 × 10−5 |
LM.Cannabis × Resin.THC × Daily.Interpol. | −1.83 (−3.58, −0.08) | 0.0412 | lambda | −0.5897 | 1.69 × 10−8 |
LM.Cannabis × Herb.THC × Daily.Interpol. | 2.09 (0.01, 4.17) | 0.0476 | |||
Alcohol | 0.12 (0.06, 0.18) | 2.50 × 10−5 | |||
Amphetamines | −0.15 (−0.28, −0.03) | 0.0182 | |||
Cocaine | 0.29 (0.14, 0.44) | 0.0001 | |||
Income | 0 (0, 0) | 3.88 × 10−7 | |||
2 Lags | |||||
Rate ~ Tobacco + LM.Cannabis × Resin.THC * Herb + LM.Cannabis × Resin.THC × Daily.Interpol. + LM.Cannabis × Herb.THC × Daily.Interpol. + Alcohol + Amphetamines + Cocaine + Income | |||||
LM.Cannabis × Resin.THC | 1.65 (0.34, 2.96) | 0.0134 | rho | 0.4855 | 0.00038 |
LM.Cannabis × Resin.THC × Daily.Interpol. | −0.05 (−0.09, −0.01) | 0.0083 | lambda | −0.6324 | 1.91 × 10−8 |
Alcohol | 0.14 (0.08, 0.21) | 1.01 × 10−5 | |||
Amphetamines | −0.18 (−0.33, −0.04) | 0.014951 | |||
Cocaine | 0.32 (0.16, 0.49) | 0.0002 | |||
Income | 0 (0, 0) | 1.66 × 10−5 |
Parameter Values | Model Parameters | ||||
---|---|---|---|---|---|
Parameter | Estimate (C.I.) | p-Value | Parameter | Value | Significance |
Additive | |||||
Rate ~ Tobacco + Alcohol + LM.Cannabis × Herb.THC × Daily.Interpol. + LM.Cannabis × Resin.THC × Daily.Interpol. + Daily.Interpol. + LM.Cannabis × Resin.THC + Amphetamines + Cocaine + Income) | |||||
Tobacco | 0.06 (0.03, 0.09) | 7.85 × 10−6 | rho | −0.2466 | 0.1750 |
Alcohol | 0.16 (0.1, 0.21) | 7.80 × 10−9 | lambda | 0.2035 | 0.2040 |
LM.Cannabis × Resin.THC | −2.08 (−3.75, −0.41) | 0.0146 | S.D. | 0.4193 | |
Herb | 4.39 (1.45, 7.33) | 0.0035 | Log.Lik | −63.7327 | |
LM.Cannabis × Resin.THC × Daily.Interpol. | 3.86 (1.74, 5.98) | 0.0003 | |||
LM.Cannabis × Herb.THC × Daily.Interpol. | −7.12 (−11.06, −3.18) | 0.0004 | |||
Amphetamines | −0.31 (−0.44, −0.18) | 1.55 × 10−6 | |||
Cocaine | 0.41 (0.21, 0.61) | 7.76 × 10−5 | |||
Income | 0 (0, 0) | 7.22 × 10−8 | |||
Interactive | |||||
Rate ~ Tobacco * Herb + LM.Cannabis × Resin.THC × Daily.Interpol. + LM.Cannabis × Resin.THC + LM.Cannabis × Herb.THC × Daily.Interpol. + Alcohol + Amphetamines + Cocaine + Income | |||||
Tobacco | 0.14 (0.08, 0.19) | 1.90 × 10−7 | rho | −0.2964 | 0.0830 |
Herb | 25.8 (12.3, 39.3) | 0.0002 | lambda | 0.2477 | 0.0959 |
LM.Cannabis × Resin.THC × Daily.Interpol. | 4.13 (2.11, 6.15) | 5.65 × 10−5 | |||
LM.Cannabis × Resin.THC | −1.58 (−3.19, 0.03) | 0.053753 | |||
LM.Cannabis × Herb.THC × Daily.Interpol. | −8.65 (−12.49, −4.81) | 9.86 × 10−6 | |||
Alcohol | 0.2 (0.14, 0.26) | 1.60 × 10−11 | |||
Amphetamines | −0.36 (−0.49, −0.24) | 1.32 × 10−8 | |||
Cocaine | 0.54 (0.33, 0.74) | 4.82 × 10−7 | |||
Income | 0 (0, 0) | 4.93 × 10−5 | |||
Tobacco: Herb | −0.88 (−1.42, −0.34) | 0.0014 | |||
2 Lags | |||||
Rate ~ Tobacco * LM.Cannabis × Resin.THC × Daily.Interpol. + Herb + LM.Cannabis × Resin.THC + LM.Cannabis × Herb.THC × Daily.Interpol. + Alcohol + Amphetamines + Cocaine + Income | |||||
Tobacco | 0.04 (0.01, 0.07) | 9.22 × 10−3 | rho | −0.4671 | 0.0021 |
LM.Cannabis × Resin.THC × Daily.Interpol. | 5 (1.71, 8.29) | 0.0029 | lambda | 0.3779 | 0.0091 |
Herb | 4.95 (1.01, 8.89) | 0.0137 | |||
LM.Cannabis × Resin.THC | −4.14 (−7.28, −1) | 0.0098 | |||
LM.Cannabis × Herb.THC × Daily.Interpol. | −5.9 (−9.8, −2) | 0.0030 | |||
Alcohol | 0.14 (0.09, 0.19) | 2.04 × 10−8 | |||
Amphetamines | −0.25 (−0.36, −0.13) | 3.03 × 10−5 | |||
Cocaine | 0.33 (0.13, 0.54) | 0.0014 | |||
Income | 0 (0, 0) | 3.79 × 10−3 |
Parameter Values | Model Parameters | ||||
---|---|---|---|---|---|
Parameter | Estimate (C.I.) | p-Value | Parameter | Value | Significance |
Additive Model without Cannabis Terms | |||||
Rate ~ Tobacco + Alcohol + Amphetamines + Cocaine + Income | |||||
Income | 0 (0, 0) | 2.57 × 10−12 | Least Squares | ||
S.D. | 0.6399 | ||||
Log.Lik. | −106.99 | ||||
Spatial Hausman Test | |||||
Chi.Squared | 184.20 | ||||
Deg.Freedom | 2 | ||||
p-Value | <2.2 × 10−16 |
Anomaly | Term | p-Value | E-Value Estimate | Lower Bound E-Value |
---|---|---|---|---|
All Anomalies | ||||
Additive | ||||
LM.Cannabis × Resin.THC × Daily.Interpol. | 0.0001 | 1.75 | 1.45 | |
Interactive | ||||
LM.Cannabis × Herb.THC × Daily.Interpol. | <2.2 × 10−16 | 212.22 | 106.93 | |
LM.Cannabis × Resin.THC × Daily.Interpol.: LM.Cannabis × Herb.THC × Daily.Interpol. | 7.81 × 10−15 | 5.67 | 4.29 | |
1 Lag | ||||
Tobacco: LM.Cannabis × Resin.THC × Daily.Interpol. | <2.2 × 10−16 | 1.42 | 1.38 | |
LM.Cannabis × Resin.THC × Daily.Interpol.: LM.Cannabis × Herb.THC × Daily.Interpol. | <2.2 × 10−16 | 1.69 | 1.62 | |
2 Lags | ||||
LM.Cannabis × Herb.THC × Daily.Interpol. | 0.0176 | 4.47 × 1015 | 1.76 × 103 | |
Tobacco: LM.Cannabis × Resin.THC × Daily.Interpol. | 2.66 × 10−8 | 1.77 | 1.57 | |
LM.Cannabis × Resin.THC × Daily.Interpol.: LM.Cannabis × Herb.THC × Daily.Interpol. | 0.0303 | 73.47 | 2.36 | |
VACTERL | ||||
Additive | ||||
LM.Cannabis × Resin.THC × Daily.Interpol. | 1.52 × 10−12 | 230.82 | 72.72 | |
Herb | 0.0042 | 1.42 × 104 | 37.93 | |
Interactive | ||||
Tobacco: LM.Cannabis × Resin.THC × Daily.Interpol. | 4.72 × 10−5 | 1.26 | 1.18 | |
1 Lag | ||||
Daily.Interpol. | 0.0185 | 3.32 × 1059 | 1.67 × 1011 | |
4 Lags | ||||
LM.Cannabis × Herb.THC × Daily.Interpol. | 0.0009 | 5.93 × 1038 | 1.56 × 1017 | |
FAS | ||||
Additive | ||||
LM.Cannabis × Resin.THC × Daily.Interpol. | 1.44 × 10−13 | 17.04 | 10.05 | |
Interactive | ||||
LM.Cannabis × Resin.THC × Daily.Interpol. | 0.0020 | 1.57 × 104 | 61.02 | |
LM.Cannabis × Resin.THC × Daily.Interpol.: LM.Cannabis × Herb.THC × Daily.Interpol. | 0.0016 | 4.78 | 2.31 | |
2 Lags | ||||
LM.Cannabis × Resin.THC × Daily.Interpol. | 6.97 × 10−7 | 1.00 × 1018 | 3.56 × 1011 | |
Herb | 0.0070 | 4.29 × 104 | 36.32 | |
Tobacco: LM.Cannabis × Herb.THC × Daily.Interpol. | 1.31 × 10−5 | 6.65 | 3.61 | |
Situs Inversus | ||||
Additive | ||||
LM.Cannabis × Herb.THC × Daily.Interpol. | 0.0034 | 8.35 | 2.86 | |
LM.Cannabis × Herb.THC | 5.44 × 10−6 | 7.97 × 1010 | 6.73 × 105 | |
Interactive | ||||
LM.Cannabis × Herb.THC × Daily.Interpol. | 0.0061 | 50.05 | 4.74 | |
Tobacco: Resin | 1.26 × 10−5 | 3.01 | 2.15 | |
2 Lags | ||||
LM.Cannabis × Herb.THC × Daily.Interpol. | 1.88 × 10−7 | 1.38 × 1016 | 4.79 × 1010 | |
LM.Cannabis × Herb.THC | 0.0030 | 2.55 × 1013 | 1.07 × 104 | |
Daily.Interpol. | 0.0056 | 9.76 × 1021 | 1.20 × 107 | |
Tobacco: LM.Cannabis × Resin.THC × Daily.Interpol. | 1.36 × 10−5 | 7.48 | 3.88 | |
Lateralization | ||||
Additive | ||||
Resin | 0.0003 | 186.86 | 16.72 | |
LM.Cannabis × Herb.THC × Daily.Interpol. | 0.0039 | 892.53 | 15.10 | |
Interactive | ||||
LM.Cannabis × Herb.THC × Daily.Interpol. | 0.0061 | 263.18 | 9.83 | |
Tobacco: Resin | 1.26 × 10−5 | 75.09 | 10.63 | |
2 Lags | ||||
Resin | 7.39 × 10−6 | 50.49 | 13.06 | |
Teratogenic Syndromes | ||||
Additive | ||||
LM.Cannabis × Resin.THC × Daily.Interpol. | <2.2 × 10−16 | 356.29 | 145.49 | |
Interactive | ||||
LM.Cannabis × Herb.THC × Daily.Interpol. | 6.64 × 10−8 | 1.86 × 104 | 850.04 | |
Tobacco: LM.Cannabis × Resin.THC × Daily.Interpol. | <2.2 × 10−16 | 2.10 | 1.95 | |
2 Lags | ||||
lag(LpmResinDailyInt, 2) | 5.52 × 10−9 | 39.30 | 15.60 |
Anomaly | Term | p-Value | E-Value Estimate | Lower Bound E-Value |
---|---|---|---|---|
All Anomalies | ||||
Additive | ||||
LM.Cannabis × Resin.THC | 8.96 × 10−6 | 8.49 × 103 | 213.85 | |
Interactive | ||||
Herb | 8.09 × 10−6 | 2.87 × 104 | 1.08 × 103 | |
LM.Cannabis × Herb.THC × Daily.Interpol. | 2.23 × 10−2 | 1.92 | 1.34 | |
2 Lags | ||||
LM.Cannabis × Resin.THC | 0.0037 | 18.72 | 3.60 | |
LM.Cannabis × Resin.THC × Daily.Interpol. | 0.0198 | 1.65 | 1.20 | |
VACTERL | ||||
Additive | ||||
Daily.Interpol. | 0.0205 | 2.61 × 1016 | 647.17 | |
Interactive | ||||
Daily.Interpol. | 0.0006 | Infinity | 2.53 × 1067 | |
2 Lags | ||||
Daily.Interpol. | 6.56 × 10−6 | Infinity | 6.52 × 10138 | |
4 Lags | ||||
Daily.Interpol. | 6.81 × 10−12 | Infinity | Infinity | |
LM.Cannabis × Herb.THC | 0.0022 | 1.65 × 1011 | 1.76 × 104 | |
6 Lags | ||||
Daily.Interpol. | 8.10 × 10−10 | Infinity | Infinity | |
FAS | ||||
Additive | ||||
Herb | 0.0004 | 1.41 × 104 | 104.35 | |
Interactive | ||||
Herb | 0.0004 | 1.41 × 104 | 104.35 | |
2 Lags | ||||
LM.Cannabis × Resin.THC × Daily.Interpol. | 0.0034 | 23.51 | 1.53 | |
Situs Inversus | ||||
Additive | ||||
Herb | 0.0019 | 9.61 × 104 | 107.71 | |
Interactive | ||||
Herb | 0.0019 | 9.61 × 104 | 107.71 | |
1 Lags | ||||
Herb | 0.0299 | 1.05 × 104 | 4.10 | |
Lateralization | ||||
Additive | ||||
LM.Cannabis × Resin.THC | 0.0006 | 1.83 × 103 | 36.69 | |
LM.Cannabis × Herb.THC × Daily.Interpol. | 0.0476 | 149.75 | 1.29 | |
Interactive | ||||
LM.Cannabis × Resin.THC | 0.0006 | 1.83 × 103 | 36.69 | |
LM.Cannabis × Herb.THC × Daily.Interpol. | 0.0476 | 149.75 | 1.29 | |
2 Lags | ||||
LM.Cannabis × Resin.THC | 0.0134 | 54.61 | 3.41 | |
Teratogenic Syndromes | ||||
Additive | ||||
Herb | 0.0035 | 1.77 × 105 | 155.66 | |
LM.Cannabis × Resin.THC × Daily.Interpol. | 0.0003 | 2.91 × 103 | 33.76 | |
Interactive | ||||
Herb | 0.0002 | 7.54 × 1017 | 2.85 × 105 | |
LM.Cannabis × Resin.THC × Daily.Interpol. | 5.65 × 10−5 | 2.63 × 103 | 29.12 | |
2 Lags | ||||
LM.Cannabis × Resin.THC × Daily.Interpol. | 0.0029 | 2.02 × 105 | 21.03 | |
Herb | 0.0137 | 2.28 × 105 | 107.43 |
No. | E-Value Estimate | Lower Bound E-Value |
---|---|---|
1 | Infinity | Infinity |
2 | Infinity | Infinity |
3 | Infinity | 6.52 × 10138 |
4 | Infinity | 2.53 × 1067 |
5 | 3.32 × 1059 | 1.56 × 1017 |
6 | 5.93 × 1038 | 3.56 × 1011 |
7 | 9.76 × 1021 | 1.67 × 1011 |
8 | 1.00 × 1018 | 4.79 × 1010 |
9 | 7.54 × 1017 | 1.20 × 107 |
10 | 2.61 × 1016 | 6.73 × 105 |
11 | 1.38 × 1016 | 2.85 × 105 |
12 | 4.47 × 1015 | 1.76 × 104 |
13 | 2.55 × 1013 | 1.07 × 104 |
14 | 1.65 × 1011 | 1.76 × 103 |
15 | 7.97 × 1010 | 1.08 × 103 |
16 | 2.28 × 105 | 850.04 |
17 | 2.02 × 105 | 647.17 |
18 | 1.77 × 105 | 213.85 |
19 | 9.61 × 104 | 155.66 |
20 | 9.61 × 104 | 145.49 |
21 | 4.29 × 104 | 107.71 |
22 | 2.87 × 104 | 107.71 |
23 | 1.86 × 104 | 107.43 |
24 | 1.57 × 104 | 106.93 |
25 | 1.42 × 104 | 104.35 |
26 | 1.41 × 104 | 104.35 |
27 | 1.41 × 104 | 72.72 |
28 | 1.05 × 104 | 61.02 |
29 | 8.49 × 103 | 37.93 |
30 | 2.91 × 103 | 36.69 |
31 | 2.63 × 103 | 36.69 |
32 | 1.83 × 103 | 36.32 |
33 | 1.83 × 103 | 33.76 |
34 | 892.53 | 29.12 |
35 | 356.29 | 21.03 |
36 | 263.18 | 16.72 |
37 | 230.82 | 15.60 |
38 | 212.22 | 15.10 |
39 | 186.86 | 13.06 |
40 | 149.75 | 10.63 |
41 | 149.75 | 10.05 |
42 | 75.09 | 9.83 |
43 | 73.47 | 4.74 |
44 | 54.61 | 4.29 |
45 | 50.49 | 4.10 |
46 | 50.05 | 3.88 |
47 | 39.30 | 3.61 |
48 | 23.51 | 3.60 |
49 | 18.72 | 3.41 |
50 | 17.04 | 2.86 |
51 | 8.35 | 2.36 |
52 | 7.48 | 2.31 |
53 | 6.65 | 2.15 |
54 | 5.67 | 1.95 |
55 | 4.78 | 1.62 |
56 | 3.01 | 1.57 |
57 | 2.10 | 1.53 |
58 | 1.92 | 1.45 |
59 | 1.77 | 1.38 |
60 | 1.75 | 1.34 |
61 | 1.69 | 1.29 |
62 | 1.65 | 1.29 |
63 | 1.42 | 1.20 |
64 | 1.26 | 1.18 |
No. | Anomaly | Regression | Model Type | Term | p-Value | E-Value Estimate | Lower Bound E-Value |
---|---|---|---|---|---|---|---|
1 | All Anomalies | Panel | 2 Lags | LM.Cannabis × Herb.THC × Daily.Interpol. | 0.0176 | 4.47 × 1015 | 1.76 × 103 |
2 | All Anomalies | Spatial | Interactive | Herb | 8.09 × 10−6 | 2.87 × 104 | 1.08 × 103 |
3 | All Anomalies | Spatial | Additive | LM.Cannabis × Resin.THC | 8.96 × 10−6 | 8.49 × 103 | 213.85 |
4 | All Anomalies | Panel | Interactive | LM.Cannabis × Herb.THC × Daily.Interpol. | <2.2 × 10−16 | 212.22 | 106.93 |
5 | All Anomalies | Panel | Interactive | LM.Cannabis × Resin.THC × Daily.Interpol.: LM.Cannabis × Herb.THC × Daily.Interpol. | 7.81 × 10−15 | 5.67 | 4.29 |
6 | All Anomalies | Spatial | 2 Lags | LM.Cannabis × Resin.THC | 0.0037 | 18.72 | 3.60 |
7 | All Anomalies | Panel | 2 Lags | LM.Cannabis × Resin.THC × Daily.Interpol.: LM.Cannabis × Herb.THC × Daily.Interpol. | 0.0303 | 73.47 | 2.36 |
8 | All Anomalies | Panel | 1 Lag | LM.Cannabis × Resin.THC × Daily.Interpol.: LM.Cannabis × Herb.THC × Daily.Interpol. | <2.2 × 10−16 | 1.69 | 1.62 |
9 | All Anomalies | Panel | 2 Lags | Tobacco: LM.Cannabis × Resin.THC × Daily.Interpol. | 2.66 × 10−8 | 1.77 | 1.57 |
10 | All Anomalies | Panel | Additive | LM.Cannabis × Resin.THC × Daily.Interpol. | 0.0001 | 1.75 | 1.45 |
11 | All Anomalies | Panel | 1 Lag | Tobacco: LM.Cannabis × Resin.THC × Daily.Interpol. | <2.2 × 10−16 | 1.42 | 1.38 |
12 | All Anomalies | Spatial | Interactive | LM.Cannabis × Herb.THC × Daily.Interpol. | 2.23 × 10−2 | 1.92 | 1.34 |
13 | All Anomalies | Spatial | 2 Lags | LM.Cannabis × Resin.THC × Daily.Interpol. | 0.0198 | 1.65 | 1.20 |
14 | FAS | Panel | 2 Lags | LM.Cannabis × Resin.THC × Daily.Interpol. | 6.97 × 10−7 | 1.00 × 1018 | 3.56 × 1011 |
15 | FAS | Spatial | Additive | Herb | 0.0004 | 1.41 × 104 | 104.35 |
16 | FAS | Spatial | Interactive | Herb | 0.0004 | 1.41 × 104 | 104.35 |
17 | FAS | Panel | Interactive | LM.Cannabis × Resin.THC × Daily.Interpol. | 0.0020 | 1.57 × 104 | 61.02 |
18 | FAS | Panel | 2 Lags | Herb | 0.0070 | 4.29 × 104 | 36.32 |
19 | FAS | Panel | Additive | LM.Cannabis × Resin.THC × Daily.Interpol. | 1.44 × 10−13 | 17.04 | 10.05 |
20 | FAS | Panel | 2 Lags | Tobacco: LM.Cannabis × Herb.THC × Daily.Interpol. | 1.31 × 10−5 | 6.65 | 3.61 |
21 | FAS | Panel | Interactive | LM.Cannabis × Resin.THC × Daily.Interpol.: LM.Cannabis × Herb.THC × Daily.Interpol. | 0.0016 | 4.78 | 2.31 |
22 | FAS | Spatial | 2 Lags | LM.Cannabis × Resin.THC × Daily.Interpol. | 0.0034 | 23.51 | 1.53 |
23 | Lateralization | Panel | Additive | Resin | 0.0003 | 186.86 | 16.72 |
24 | Lateralization | Panel | Additive | LM.Cannabis × Herb.THC × Daily.Interpol. | 0.0039 | 892.53 | 15.10 |
25 | Lateralization | Panel | 2 Lags | Resin | 7.39 × 10−6 | 50.49 | 13.06 |
26 | Lateralization | Panel | Interactive | Tobacco: Resin | 1.26 × 10−5 | 75.09 | 10.63 |
27 | Lateralization | Panel | Interactive | LM.Cannabis × Herb.THC × Daily.Interpol. | 0.0061 | 263.18 | 9.83 |
28 | Lateralization | Spatial | Additive | LM.Cannabis × Resin.THC | 0.0006 | 1.83 × 103 | 36.69 |
29 | Lateralization | Spatial | Interactive | LM.Cannabis × Resin.THC | 0.0006 | 1.83 × 103 | 36.69 |
30 | Lateralization | Spatial | 2 Lags | LM.Cannabis × Resin.THC | 0.0134 | 54.61 | 3.41 |
31 | Lateralization | Spatial | Additive | LM.Cannabis × Herb.THC × Daily.Interpol. | 0.0476 | 149.75 | 1.29 |
32 | Lateralization | Spatial | Interactive | LM.Cannabis × Herb.THC × Daily.Interpol. | 0.0476 | 149.75 | 1.29 |
33 | Situs Inversus | Panel | 2 Lags | LM.Cannabis × Herb.THC × Daily.Interpol. | 1.88 × 10−7 | 1.38 × 1016 | 4.79 × 1010 |
34 | Situs Inversus | Panel | 2 Lags | Daily.Interpol. | 0.0056 | 9.76 × 1021 | 1.20 × 107 |
35 | Situs Inversus | Panel | Additive | LM.Cannabis × Herb.THC | 5.44 × 10−6 | 7.97 × 1010 | 6.73 × 105 |
36 | Situs Inversus | Panel | 2 Lags | LM.Cannabis × Herb.THC | 0.0030 | 2.55 × 1013 | 1.07 × 104 |
37 | Situs Inversus | Spatial | Additive | Herb | 0.0019 | 9.61 × 104 | 107.71 |
38 | Situs Inversus | Spatial | Interactive | Herb | 0.0019 | 9.61 × 104 | 107.71 |
39 | Situs Inversus | Panel | Interactive | LM.Cannabis × Herb.THC × Daily.Interpol. | 0.0061 | 50.05 | 4.74 |
40 | Situs Inversus | Spatial | 1 Lags | Herb | 0.0299 | 1.05 × 104 | 4.10 |
41 | Situs Inversus | Panel | 2 Lags | Tobacco: LM.Cannabis × Resin.THC × Daily.Interpol. | 1.36 × 10−5 | 7.48 | 3.88 |
42 | Situs Inversus | Panel | Additive | LM.Cannabis × Herb.THC × Daily.Interpol. | 0.0034 | 8.35 | 2.86 |
43 | Situs Inversus | Panel | Interactive | Tobacco: Resin | 1.26 × 10−5 | 3.01 | 2.15 |
44 | Teratogenic Syndromes | Spatial | Interactive | Herb | 0.0002 | 7.54 × 1017 | 2.85 × 105 |
45 | Teratogenic Syndromes | Panel | Interactive | LM.Cannabis × Herb.THC × Daily.Interpol. | 6.64 × 10−8 | 1.86 × 104 | 850.04 |
46 | Teratogenic Syndromes | Spatial | Additive | Herb | 0.0035 | 1.77 × 105 | 155.66 |
47 | Teratogenic Syndromes | Panel | Additive | LM.Cannabis × Resin.THC × Daily.Interpol. | <2.2 × 10−16 | 356.29 | 145.49 |
48 | Teratogenic Syndromes | Spatial | 2 Lags | Herb | 0.0137 | 2.28 × 105 | 107.43 |
49 | Teratogenic Syndromes | Spatial | Additive | LM.Cannabis × Resin.THC × Daily.Interpol. | 0.0003 | 2.91 × 103 | 33.76 |
50 | Teratogenic Syndromes | Spatial | Interactive | LM.Cannabis × Resin.THC × Daily.Interpol. | 5.65 × 10−5 | 2.63 × 103 | 29.12 |
51 | Teratogenic Syndromes | Spatial | 2 Lags | LM.Cannabis × Resin.THC × Daily.Interpol. | 0.0029 | 2.02 × 105 | 21.03 |
52 | Teratogenic Syndromes | Panel | 2 Lags | lag(LpmResinDailyInt, 2) | 5.52 × 10−9 | 39.30 | 15.60 |
53 | Teratogenic Syndromes | Panel | Interactive | Tobacco: LM.Cannabis × Resin.THC × Daily.Interpol. | <2.2 × 10−16 | 2.10 | 1.95 |
54 | VACTERL | Spatial | 4 Lags | Daily.Interpol. | 6.81 × 10−12 | Infinity | Infinity |
55 | VACTERL | Spatial | 6 Lags | Daily.Interpol. | 8.10 × 10−10 | Infinity | Infinity |
56 | VACTERL | Spatial | 2 Lags | Daily.Interpol. | 6.56 × 10−6 | Infinity | 6.52 × 10138 |
57 | VACTERL | Spatial | Interactive | Daily.Interpol. | 0.0006 | Infinity | 2.53 × 1067 |
58 | VACTERL | Panel | 4 Lags | LM.Cannabis × Herb.THC × Daily.Interpol. | 0.0009 | 5.93 × 1038 | 1.56 × 1017 |
59 | VACTERL | Panel | 1 Lag | Daily.Interpol. | 0.0185 | 3.32 × 1059 | 1.67 × 1011 |
60 | VACTERL | Spatial | 4 Lags | LM.Cannabis × Herb.THC | 0.0022 | 1.65 × 1011 | 1.76 × 104 |
61 | VACTERL | Spatial | Additive | Daily.Interpol. | 0.0205 | 2.61 × 1016 | 647.17 |
62 | VACTERL | Panel | Additive | LM.Cannabis × Resin.THC × Daily.Interpol. | 1.52 × 10−12 | 230.82 | 72.72 |
63 | VACTERL | Panel | Additive | Herb | 0.0042 | 1.42 × 104 | 37.93 |
64 | VACTERL | Panel | Interactive | Tobacco: LM.Cannabis × Resin.THC × Daily.Interpol. | 4.72 × 10−5 | 1.26 | 1.18 |
Anomaly | Number | Mean Minimum E-Value | Median Minimum E-Value | Minimum Minimum E-Value | Maximum Minimum E-Value | Mean E-Value Estimate | Median E-Value Estimate | Minimum E-Value Estimate | Maximum E-Value Estimate |
---|---|---|---|---|---|---|---|---|---|
VACTERL | 11 | 2.73 × 10306 | 1.67 × 1011 | 1.18 | 1.50 × 10307 | 5.45 × 10306 | 5.93 × 1038 | 1.26 | 1.50 × 10307 |
Situs Inversus | 11 | 4.36 × 109 | 107.71 | 2.15 | 4.79 × 1010 | 8.87 × 1020 | 9.61 × 104 | 3.01 | 9.76 × 1021 |
Teratogenic Syndromes | 10 | 2.86 × 104 | 70.595 | 1.95 | 285,000 | 7.54 × 1016 | 10,755.00 | 2.10 | 7.54 × 1017 |
FAS | 9 | 3.96 × 1010 | 36.32 | 1.53 | 3.56 × 1011 | 1.11 × 1017 | 14,100.00 | 4.78 | 1.00 × 1018 |
Lateralization | 10 | 14.471 | 11.845 | 1.29 | 36.69 | 548.226 | 168.31 | 50.49 | 1830 |
All Anomalies | 13 | 244.58 | 2.36 | 1.2 | 1760 | 3.44 × 1014 | 5.67 | 1.42 | 4.47 × 1015 |
No. | Anomaly | Regression | Model Type | Term | Group | p-Value | E-Value Estimate | Lower Bound E-Value |
---|---|---|---|---|---|---|---|---|
1 | VACTERL | Spatial | 4 Lags | Daily.Interpol. | Daily | 6.81 × 10−12 | Infinity | Infinity |
2 | VACTERL | Spatial | 6 Lags | Daily.Interpol. | Daily | 8.10 × 10−10 | Infinity | Infinity |
3 | VACTERL | Spatial | 2 Lags | Daily.Interpol. | Daily | 6.56 × 10−6 | Infinity | 6.52 × 10138 |
4 | VACTERL | Spatial | Interactive | Daily.Interpol. | Daily | 0.0006 | Infinity | 2.53 × 1067 |
5 | VACTERL | Panel | 1 Lag | Daily.Interpol. | Daily | 0.0185 | 3.32 × 1059 | 1.67 × 1011 |
6 | Situs Inversus | Panel | 2 Lags | Daily.Interpol. | Daily | 0.0056 | 9.76 × 1021 | 1.20 × 107 |
7 | VACTERL | Spatial | Additive | Daily.Interpol. | Daily | 0.0205 | 2.61 × 1016 | 647.17 |
8 | Teratogenic Syndromes | Spatial | Interactive | Herb | Herb | 0.0002 | 7.54 × 1017 | 2.85 × 105 |
9 | All Anomalies | Spatial | Interactive | Herb | Herb | 8.09 × 10−6 | 2.87 × 104 | 1.08 × 103 |
10 | Teratogenic Syndromes | Spatial | Additive | Herb | Herb | 0.0035 | 1.77 × 105 | 155.66 |
11 | Situs Inversus | Spatial | Additive | Herb | Herb | 0.0019 | 9.61 × 104 | 107.71 |
12 | Situs Inversus | Spatial | Interactive | Herb | Herb | 0.0019 | 9.61 × 104 | 107.71 |
13 | Teratogenic Syndromes | Spatial | 2 Lags | Herb | Herb | 0.0137 | 2.28 × 105 | 107.43 |
14 | FAS | Spatial | Additive | Herb | Herb | 0.0004 | 1.41 × 104 | 104.35 |
15 | FAS | Spatial | Interactive | Herb | Herb | 0.0004 | 1.41 × 104 | 104.35 |
16 | VACTERL | Panel | Additive | Herb | Herb | 0.0042 | 1.42 × 104 | 37.93 |
17 | FAS | Panel | 2 Lags | Herb | Herb | 0.0070 | 4.29 × 104 | 36.32 |
18 | Situs Inversus | Spatial | 1 Lags | Herb | Herb | 0.0299 | 1.05 × 104 | 4.10 |
19 | Teratogenic Syndromes | Panel | 2 Lags | lag (LpmResinDailyInt, 2) | Herb | 5.52 × 10−9 | 39.30 | 15.60 |
20 | Situs Inversus | Panel | Additive | LM.Cannabis × Herb.THC | Herb | 5.44 × 10−6 | 7.97 × 1010 | 6.73 × 105 |
21 | VACTERL | Spatial | 4 Lags | LM.Cannabis × Herb.THC | Herb | 0.0022 | 1.65 × 1011 | 1.76 × 104 |
22 | Situs Inversus | Panel | 2 Lags | LM.Cannabis × Herb.THC | Herb | 0.0030 | 2.55 × 1013 | 1.07 × 104 |
23 | VACTERL | Panel | 4 Lags | LM.Cannabis × Herb.THC × Daily.Interpol. | Herb | 0.0009 | 5.93 × 1038 | 1.56 × 1017 |
24 | Situs Inversus | Panel | 2 Lags | LM.Cannabis × Herb.THC × Daily.Interpol. | Herb | 1.88 × 10−7 | 1.38 × 1016 | 4.79 × 1010 |
25 | All Anomalies | Panel | 2 Lags | LM.Cannabis × Herb.THC × Daily.Interpol. | Herb | 0.0176 | 4.47 × 1015 | 1.76 × 103 |
26 | Teratogenic Syndromes | Panel | Interactive | LM.Cannabis × Herb.THC × Daily.Interpol. | Herb | 6.64 × 10−8 | 1.86 × 104 | 850.04 |
27 | All Anomalies | Panel | Interactive | LM.Cannabis × Herb.THC × Daily.Interpol. | Herb | <2.2 × 10−16 | 212.22 | 106.93 |
28 | Lateralization | Panel | Additive | LM.Cannabis × Herb.THC × Daily.Interpol. | Herb | 0.0039 | 892.53 | 15.10 |
29 | Lateralization | Panel | Interactive | LM.Cannabis × Herb.THC × Daily.Interpol. | Herb | 0.0061 | 263.18 | 9.83 |
30 | Situs Inversus | Panel | Interactive | LM.Cannabis × Herb.THC × Daily.Interpol. | Herb | 0.0061 | 50.05 | 4.74 |
31 | Situs Inversus | Panel | Additive | LM.Cannabis × Herb.THC × Daily.Interpol. | Herb | 0.0034 | 8.35 | 2.86 |
32 | All Anomalies | Spatial | Interactive | LM.Cannabis × Herb.THC × Daily.Interpol. | Herb | 2.23 × 10−2 | 1.92 | 1.34 |
33 | Lateralization | Spatial | Additive | LM.Cannabis × Herb.THC × Daily.Interpol. | Herb | 0.0476 | 149.75 | 1.29 |
34 | Lateralization | Spatial | Interactive | LM.Cannabis × Herb.THC × Daily.Interpol. | Herb | 0.0476 | 149.75 | 1.29 |
35 | All Anomalies | Spatial | Additive | LM.Cannabis × Resin.THC | Resin | 8.96 × 10−6 | 8.49 × 103 | 213.85 |
36 | Lateralization | Spatial | Additive | LM.Cannabis × Resin.THC | Resin | 0.0006 | 1.83 × 103 | 36.69 |
37 | Lateralization | Spatial | Interactive | LM.Cannabis × Resin.THC | Resin | 0.0006 | 1.83 × 103 | 36.69 |
38 | All Anomalies | Spatial | 2 Lags | LM.Cannabis × Resin.THC | Resin | 0.0037 | 18.72 | 3.60 |
39 | Lateralization | Spatial | 2 Lags | LM.Cannabis × Resin.THC | Resin | 0.0134 | 54.61 | 3.41 |
40 | FAS | Panel | 2 Lags | LM.Cannabis × Resin.THC × Daily.Interpol. | Resin | 6.97 × 10−7 | 1.00 × 1018 | 3.56 × 1011 |
41 | Teratogenic Syndromes | Panel | Additive | LM.Cannabis × Resin.THC × Daily.Interpol. | Resin | <2.2 × 10−16 | 356.29 | 145.49 |
42 | VACTERL | Panel | Additive | LM.Cannabis × Resin.THC × Daily.Interpol. | Resin | 1.52 × 10−12 | 230.82 | 72.72 |
43 | FAS | Panel | Interactive | LM.Cannabis × Resin.THC × Daily.Interpol. | Resin | 0.0020 | 1.57 × 104 | 61.02 |
44 | Teratogenic Syndromes | Spatial | Additive | LM.Cannabis × Resin.THC × Daily.Interpol. | Resin | 0.0003 | 2.91 × 103 | 33.76 |
45 | Teratogenic Syndromes | Spatial | Interactive | LM.Cannabis × Resin.THC × Daily.Interpol. | Resin | 5.65 × 10−5 | 2.63 × 103 | 29.12 |
46 | Teratogenic Syndromes | Spatial | 2 Lags | LM.Cannabis × Resin.THC × Daily.Interpol. | Resin | 0.0029 | 2.02 × 105 | 21.03 |
47 | FAS | Panel | Additive | LM.Cannabis × Resin.THC × Daily.Interpol. | Resin | 1.44 × 10−13 | 17.04 | 10.05 |
48 | FAS | Spatial | 2 Lags | LM.Cannabis × Resin.THC × Daily.Interpol. | Resin | 0.0034 | 23.51 | 1.53 |
49 | All Anomalies | Panel | Additive | LM.Cannabis × Resin.THC × Daily.Interpol. | Resin | 0.0001 | 1.75 | 1.45 |
50 | All Anomalies | Spatial | 2 Lags | LM.Cannabis × Resin.THC × Daily.Interpol. | Resin | 0.0198 | 1.65 | 1.20 |
51 | All Anomalies | Panel | Interactive | LM.Cannabis × Resin.THC × Daily.Interpol.: LM.Cannabis × Herb.THC × Daily.Interpol. | Resin | 7.81 × 10−15 | 5.67 | 4.29 |
52 | All Anomalies | Panel | 2 Lags | LM.Cannabis × Resin.THC × Daily.Interpol.: LM.Cannabis × Herb.THC × Daily.Interpol. | Resin | 0.0303 | 73.47 | 2.36 |
53 | FAS | Panel | Interactive | LM.Cannabis × Resin.THC × Daily.Interpol.: LM.Cannabis × Herb.THC × Daily.Interpol. | Resin | 0.0016 | 4.78 | 2.31 |
54 | All Anomalies | Panel | 1 Lag | LM.Cannabis × Resin.THC × Daily.Interpol.: LM.Cannabis × Herb.THC × Daily.Interpol. | Resin | <2.2 × 10−16 | 1.69 | 1.62 |
55 | Lateralization | Panel | Additive | Resin | Resin | 0.0003 | 186.86 | 16.72 |
56 | Lateralization | Panel | 2 Lags | Resin | Resin | 7.39 × 10−6 | 50.49 | 13.06 |
57 | FAS | Panel | 2 Lags | Tobacco: LM.Cannabis × Herb.THC × Daily.Interpol. | Herb | 1.31 × 10−5 | 6.65 | 3.61 |
58 | Situs Inversus | Panel | 2 Lags | Tobacco: LM.Cannabis × Resin.THC × Daily.Interpol. | Resin | 1.36 × 10−5 | 7.48 | 3.88 |
59 | Teratogenic Syndromes | Panel | Interactive | Tobacco: LM.Cannabis × Resin.THC × Daily.Interpol. | Resin | <2.2 × 10−16 | 2.10 | 1.95 |
60 | All Anomalies | Panel | 2 Lags | Tobacco: LM.Cannabis × Resin.THC × Daily.Interpol. | Resin | 2.66 × 10−8 | 1.77 | 1.57 |
61 | All Anomalies | Panel | 1 Lag | Tobacco: LM.Cannabis × Resin.THC × Daily.Interpol. | Resin | <2.2 × 10−16 | 1.42 | 1.38 |
62 | VACTERL | Panel | Interactive | Tobacco: LM.Cannabis × Resin.THC × Daily.Interpol. | Resin | 4.72 × 10−5 | 1.26 | 1.18 |
63 | Lateralization | Panel | Interactive | Tobacco: Resin | Resin | 1.26 × 10−5 | 75.09 | 10.63 |
64 | Situs Inversus | Panel | Interactive | Tobacco: Resin | Resin | 1.26 × 10−5 | 3.01 | 2.15 |
Group | Number | Mean Minimum E-Value | Median Minimum E-Value | Minimum Minimum E-Value | Maximum Minimum E-Value | Mean E-Value Estimate | Median E-Value Estimate | Minimum E-Value Estimate | Maximum E-Value Estimate |
---|---|---|---|---|---|---|---|---|---|
Daily | 7 | 4.29 × 10306 | 2.53 × 1067 | 647.17 | 1.50 × 10307 | 8.57 × 10306 | 1.50 × 10307 | 2.61 × 1016 | 1.50 × 10307 |
Herb | 28 | 5.57 × 1015 | 105.64 | 1.29 | 1.56 × 1017 | 2.12 × 1037 | 16,400 | 1.92 | 5.93 × 1038 |
Resin | 29 | 1.23 × 1010 | 4.29 | 1.18 | 3.56 × 1011 | 3.45 × 1016 | 50.49 | 1.26 | 1.00 × 1018 |
Comparison | W-Statistic | Alternative | p-Value |
---|---|---|---|
Lower E-Value, Daily_v_Herb | 184 | two.sided | 4.20 × 10−4 |
Lower E-Value, Daily_v_Resin | 200 | two.sided | 8.94 × 10−5 |
Lower E-Value, Herb_v_Resin | 592 | two.sided | 3.06 × 10−3 |
E-Value Estimate, Daily_v_Herb | 193 | two.sided | 9.59 × 10−5 |
E-Value Estimate, Daily_v_Resin | 202 | two.sided | 6.34 × 10−5 |
E-Value Estimate, Herb_v_Resin | 642 | two.sided | 1.70 × 10−4 |
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Reece, A.S.; Hulse, G.K. Patterns of Cannabis- and Substance-Related Congenital General Anomalies in Europe: A Geospatiotemporal and Causal Inferential Study. Pediatr. Rep. 2023, 15, 69-118. https://doi.org/10.3390/pediatric15010009
Reece AS, Hulse GK. Patterns of Cannabis- and Substance-Related Congenital General Anomalies in Europe: A Geospatiotemporal and Causal Inferential Study. Pediatric Reports. 2023; 15(1):69-118. https://doi.org/10.3390/pediatric15010009
Chicago/Turabian StyleReece, Albert Stuart, and Gary Kenneth Hulse. 2023. "Patterns of Cannabis- and Substance-Related Congenital General Anomalies in Europe: A Geospatiotemporal and Causal Inferential Study" Pediatric Reports 15, no. 1: 69-118. https://doi.org/10.3390/pediatric15010009