Appendix: Supplementary tables [posted as supplied by author]

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Appendix: Supplementary tables [posted as supplied by author] Table A. Hazard ratios and 95% confidence intervals for the associations between subtypes of opium use in relation to overall mortality Opium types none Number of participants (person years) 41,558 (196,825) 8,487 (38,103) 7,308 (33,249) Number of deaths (Crude rate 1 ) 1,440 (731) 705 (1,850) 605 (1,819) Cox HR Unadjusted Adjusted 2 2.26 (2.06 1.86 (1.68 Any Type to 2.47) to 2.06) 2.21 (2.01 1.83 (1.65 Teriak only to 2.43) to 2.03) Sukhteh only 6 (27) 0 (0) - - Shireh only 721 (3,174) 66 (2,079) 2.65 (2.07 2.19 (1.70 to 3.39) to 2.82) Heroin only 4 (13) 3 (22,149) 34.0 (10.9 25.4 (8.11 to 105) to 79.4) Combinations 3 359 (1,639) 31 (1,891) 2.28 (1.60 1.78 (1.24 to 3.26) to 2.56) ref 1 Crude death rate in 10 5 person years 2 Adjusted for gender, ethnicity, education level, marital status, residential place, and cigarette smoking 3 All two-way and three-way, and four-way combinations of opium use; the large majority (75%) were a combination of teriak and shireh use ref

Table B. Hazard ratios and 95% confidence intervals for opium cumulative use in relation to overall and cause-specific mortality in the Golestan Cohort Study Never users Ex-users Current users 1 st quintile ( 1200) Opium cumulative use in current opium users 2 nd quintile 3 rd quintile 4 th quintile 5 th quintile (1201-4696) (4697-12418) (12419-30681) ( 30682) All causes N. of deaths 1,440 63 642 121 123 111 130 157 - Cox HR, all ref 1.29 (1.00 to 1.67) 1.94 (1.75 to 2.16) 1.94 (1.61 to 2.35) 2.00 (1.65 to 2.41) 1.75 (1.43 to 2.13) 1.98 (1.64 to 2.39) 2.03 (1.70 to 2.43) 0.115 Cox HR, bef. dis. ref 1.27 (0.98 to 1.65) 1.70 (1.52 to 1.90) 1.43 (1.14 to 1.79) 1.71 (1.39 to 2.10) 1.69 (1.36 to 2.08) 1.93 (1.60 to 2.33) 1.98 (1.65 to 2.39) <0.001 Circulatory causes N. of deaths 738 38 297 58 63 50 68 58 - Cox HR, all ref 1.57 (1.12 to 2.20) 1.84 (1.58 to 2.14) 1.88 (1.43 to 2.46) 2.08 (1.60 to 2.71) 1.60 (1.19 to 2.15) 2.11 (1.63 to 2.74) 1.55 (1.17 to 2.06) 0.898 Cox HR, bef. dis. ref 1.40 (0.98 to 1.99) 1.53 (1.30 to 1.80) 1.11 (0.78 to 1.59) 1.49 (1.09 to 2.03) 1.62 (1.19 to 2.20) 2.04 (1.57 to 2.64) 1.41 (1.04 to 1.91) 0.015 Cancer causes N. of deaths 312 8 129 17 21 19 28 44 - Cox HR, all ref 0.77 (0.38 to 1.57) 1.73 (1.37 to 2.18) 1.26 (0.77 to 2.07) 1.55 (0.99 to 2.44) 1.34 (0.83 to 2.15) 1.95 (1.30 to 2.92) 2.50 (1.77 to 3.54) 0.006 Cox HR, bef. dis. ref 0.81 (0.39 to 1.64) 1.79 (1.41 to 2.26) 1.40 (0.85 to 2.30) 1.46 (0.91 to 2.35) 1.44 (0.88 to 2.34) 1.96 (1.31 to 2.94) 2.60 (1.82 to 3.72) 0.006 Respiratory causes N. of deaths 43 4 48 8 10 7 11 12 - Cox HR, all ref 2.02 (0.70 to 5.84) 4.05 (2.52 to 6.52) 3.74 (1.72 to 8.14) 4.61 (2.24 to 9.47) 3.10 (1.34 to 7.13) 4.63 (2.28 to 9.40) 4.19 (2.06 to 8.52) 0.541 Cox HR, bef. dis. ref 2.01 (0.69 to 5.82) 3.85 (2.36 to 6.29) 2.54 (0.98 to 6.58) 5.65 (2.86 to 11.1) 2.38 (0.91 to 6.22) 4.05 (1.94 to 8.46) 4.51 (2.20 to 9.23) 0.365 Digestive causes N. of deaths 37 4 28 5 7 7 3 6 - Cox HR, all ref 3.01 (1.02 to 8.85) 3.14 (1.80 to 5.47) 2.79 (1.07 to 7.24) 4.25 (1.83 to 9.89) 4.09 (1.75 to 9.56) 1.67 (0.50 to 5.62) 2.96 (1.17 to 7.49) 0.489 Cox HR, bef. dis. ref 3.06 (1.04 to 9.02) 3.16 (1.78 to 5.60) 3.05 (1.17 to 7.98) 3.88 (1.58 to 9.53) 5.26 (2.33 to 11.9) 0.56 (0.07 to 4.17) 3.37 (1.32 to 8.57) 0.369 Infectious causes N. of deaths 21 1 29 9 6 3 2 9 - Cox HR, all ref 1.37 (0.18 to 10.5) 6.05 (3.17 to 11.6) 9.94 (4.37 to 22.6) 6.56 (2.53 to 17.0) 3.17 (0.91 to 11.1) 2.09 (0.47 to 9.30) 8.12 (3.31 to 19.9) 0.650 Cox HR, bef. dis. ref 1.25 (0.16 to 9.70) 5.23 (2.66 to 10.3) 8.21 (3.32 to 20.3) 5.47 (1.97 to 15.2) 2.21 (0.50 to 9.85) 3.87 (1.25 to 12.0) 6.37 (2.41 to 16.8) 0.834 All Cox HRs are adjusted for gender, ethnicity, education level, marital status, residential place, and cigarette smoking Excluding subjects who started opium use after being diagnosed with a serious disease (ischemic heart disease, cerebrovascular accidents, hypertension, or diabetes mellitus) Quantities in parentheses are the cumulative opium use amounts in nokhod-days unit P for trend is calculated by assigning consecutive integers to quintiles of cumulative opium use in current opium users P for trend

Table C. Estimated hazard ratios for all cause and cause-specific mortality in ever opium user groups in total and also after excluding events that happened in first 6, 12, 18, and 24 months of follow up. Adjusted Cox HRs in opium users Adjusted Cox HRs in opium users after excluding deaths happened in first 6 months 12 months 18 months 24 months No.* Cox HR (95%CI) No.* Cox HR (95%CI) No.* Cox HR (95%CI) No.* Cox HR (95%CI) All causes 1.86 (1.68 to 2.06) 1977 1.84 (1.65 to 2.05) 1772 1.81 (1.62 to 2.03) 1552 1.81 (1.60 to 2.05) 1319 1.85 (1.62 to 2.11) Circulatory causes 1.81 (1.56 to 2.09) 980 1.86 (1.59 to 2.16) 867 1.83 (1.55 to 2.15) 769 1.88 (1.58 to 2.23) 654 1.99 (1.65 to 2.40) Cancer causes 1.61 (1.28 to 2.03) 416 1.51 (1.19 to 1.92) 373 1.43 (1.11 to 1.84) 321 1.39 (1.05 to 1.82) 271 1.43 (1.06 to 1.94) Respiratory causes 3.78 (2.36 to 6.04) 86 3.59 (2.19 to 5.88) 79 3.54 (2.11 to 5.93) 70 3.86 (2.22 to 6.70) 62 3.15 (1.76 to 5.66) Digestive causes 3.12 (1.82 to 5.37) 67 3.07 (1.77 to 5.31) 60 2.96 (1.66 to 5.29) 52 3.08 (1.65 to 5.75) 44 2.99 (1.51 to 5.90) Infectious causes 5.47 (2.87 to 10.4) 47 5.45 (2.81 to 10.6) 45 5.20 (2.65 to 10.2) 37 4.56 (2.17 to 9.59) 34 5.02 (2.31 to 10.9) * The number of outcomes

Table D Hazard ratios (95% confidence interval) for the association between opium use and overall mortality, after adjusting for several alternative covariates. Cox Regression Model Cox HRs in opium users (95% CI) Unadjusted model 2.26 (2.06 to 2.47) Adjusted Model 1: Adjusted for sex, residential place, ethnicity, marital status, education level, cigarette smoking 1.86 (1.68 to 2.06) Adjusted Model 2: model 1 plus adjustment for body mass index (kg/(cm) 2 ) as categorical variable (WHO classification) 1.82 (1.64 to 2.02) Adjusted Model 3: model 1 plus adjustment for body mass index (kg/(cm) 2 ) as continuous variable 1.84 (1.65 to 2.04) Adjusted Model 4: model 1 plus adjustment for height (cm) as a continuous variable 1.86 (1.68 to 2.06) Adjusted Model 5: model 1 plus adjustment for alcohol consumption 1.87 (1.68 to 2.07) Adjusted Model 6: model 1 plus adjustment for composite wealth score 1.81 (1.64 to 2.01) Adjusted Model 7: model 1 plus adjustment for intake of fruits and vegetables 1.88 (1.69 to 2.08) Adjusted Model 8: model 2 plus adjustment for alcohol consumption 1.82 (1.64 to 2.02) Adjusted Model 9: model 8 plus adjustment for composite wealth score 1.79 (1.61 to 1.98) Adjusted Model 10: model 9 plus adjustment for intake of fruits and vegetables 1.81 (1.63 to 2.01)

Table E. Hazard ratios and 95% confidence intervals for the association between methods of opium use (smoking, ingestion, or both) and overall and cause-specific mortality in Golestan Cohort Study Routes of opium administration Unadjusted Overall Cox HR Adjusted Overall Males Females All deaths Smoking 2.01 (1.80 to 2.26) 1.68 (1.48 to 1.90) 1.50 (1.29 to 1.73) 2.02 (1.61 to 2.54) Ingestion 2.55 (2.24 to 2.91) 2.08 (1.81 to 2.40) 1.76 (1.48 to 2.09) 2.92 (2.31 to 3.69) Both ways 2.85 (2.20 to 3.70) 2.34 (1.80 to 3.06) 2.06 (1.52 to 2.80) 3.47 (2.03 to 5.93) Circulatory deaths Smoking 2.02 (1.72 to 2.37) 1.75 (1.48 to 2.08) 1.47 (1.20 to 1.80) 2.45 (1.81 to 3.31) Ingestion 2.11 (1.73 to 2.57) 1.83 (1.48 to 2.26) 1.54 (1.19 to 1.99) 2.56 (1.80 to 3.65) Both ways 2.21 (1.47 to 3.31) 1.93 (1.27 to 2.92) 1.64 (1.02 to 2.66) 2.99 (1.32 to 6.76) Cancer deaths Smoking 1.82 (1.41 to 2.34) 1.48 (1.13 to 1.95) 1.56 (1.13 to 2.15) 1.35 (0.77 to 2.37) Ingestion 2.14 (1.58 to 2.90) 1.67 (1.21 to 2.31) 1.76 (1.21 to 2.58) 1.45 (0.75 to 2.79) Both ways 3.24 (1.93 to 5.45) 2.55 (1.49 to 4.35) 2.66 (1.48 to 4.77) 2.14 (0.52 to 8.81) Respiratory deaths Smoking 3.44 (2.00 to 5.90) 2.42 (1.34 to 4.36) 1.76 (0.85 to 3.63) 3.87 (1.50 to 10.0) Ingestion 7.89 (4.70 to 13.0) 5.35 (3.05 to 9.36) 3.38 (1.67 to 6.86) 10.4 (4.49 to 23.9) Both ways 12.6 (5.88 to 26.9) 8.44 (3.77 to 18.9) 6.36 (2.48 to 16.3) 15.4 (3.43 to 69.1) Digestive deaths Smoking 2.91 (1.57 to 5.39) 2.26 (1.16 to 4.40) 2.19 (1.01 to 4.75) 2.48 (0.68 to 9.02) Ingestion 5.81 (3.15 to 10.7) 4.64 (2.37 to 9.10) 4.40 (1.96 to 9.87) 5.13 (1.56 to 16.9) Both ways 5.84 (1.79 to 19.0) 4.59 (1.36 to 15.5) 5.82 (1.66 to 20.4) - Infectious deaths Smoking 5.53 (2.85 to 10.7) 4.66 (2.24 to 9.71) 3.06 (1.26 to 7.46) 6.37 (1.92 to 21.2) Ingestion 8.83 (4.38 to 17.8) 7.02 (3.21 to 15.3) 4.52 (1.66 to 12.3) 11.2 (3.68 to 34.1) Both ways 6.74 (1.57 to 28.9) 5.53 (1.23 to 24.8) 2.68 (0.33 to 21.5) 17.6 (2.17 to 142) Adjusted for gender, ethnicity, education level, marital status, residential place, and cigarette smoking

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