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Mortalities of methamphetamine, opioid, and ketamine abusers in Shanghai and Wuhan, China
Journal Pre-proof Mortalities of Methamphetamine, Opioid, and Ketamine Abusers in Shanghai and Wuhan, China Feng Li, Jinchen Liu, Paul S.F. Yip, Xuesong Lu, Sihai Liu
PII:
S0379-0738(19)30505-5
DOI:
https://doi.org/10.1016/j.forsciint.2019.110093
Reference:
FSI 110093
To appear in:
Forensic Science International
Received Date:
18 July 2019
Revised Date:
20 November 2019
Accepted Date:
25 November 2019
Please cite this article as: Li F, Liu J, Yip PSF, Lu X, Liu S, Mortalities of Methamphetamine, Opioid, and Ketamine Abusers in Shanghai and Wuhan, China, Forensic Science International (2019), doi: https://doi.org/10.1016/j.forsciint.2019.110093
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Mortalities of Drug Abusers in China 1
Mortalities of Methamphetamine, Opioid, and Ketamine Abusers in Shanghai and Wuhan, China
Running head: Mortalities of Drug Abusers in China
Feng Li 1, Jinchen Liu 2, Paul S.F. Yip 1, Xuesong Lu 3, Sihai Liu 4
HKJC Centre for Suicide Research and Prevention, The University of Hong Kong,
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1
Pokfulam, Hong Kong SAR, China.
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Hong Kong Jockey Club Building for Interdisciplinary Research, 5 Sassoon Road,
College of Life Science, Lanzhou University, China.
3
Criminal Science Institute, Pudong District of Shanghai Municipal Public Security
Bureau, Shanghai, China.
Jiang’an District of Wuhan Municipal Public Security Bureau, Wuhan, Hubei, China.
Feng Li, Centre for Suicide Research and Prevention, The
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Corresponding author:
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2
University of Hong Kong, Hong Kong
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Tel: (852) 6576 8434 Email: [email protected] Postal address: Hong Kong Jockey Club Centre for Suicide
Research and Prevention, The University of Hong Kong, Hong Kong Jockey Club Building for Interdisciplinary Research, 5 Sassoon Road, Pokfulam, Hong Kong SAR, China.
Highlights
Mortalities of Drug Abusers in China 2
Death of prescription opioid abusers was absent in Shanghai and Wuhan.
Heroin-related mortality rates have declined in Shanghai and Wuhan.
Methamphetamine-related mortality rates have increased in Wuhan.
Synthetic drug abuse by females in Shanghai and Wuhan should be underscored.
Abstract
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Studies on the mortalities of drug abusers in China are scarce. This study explores the deaths of methamphetamine, opioid, and ketamine abusers in Shanghai (2004-2017) and Wuhan
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(2005-2017). Chi-square/Fisher’s exact tests were used to compare the differences in terms of region, gender, age, cause of death, and the method used in the last drug abuse. Poisson
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regression models were used to estimate the rate ratios (“RRs”) and annual percentage changes
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(“APCs”). 314 heroin, 43 methamphetamine, and 4 ketamine abusers were included. Furthermore, simultaneously, 6 abusers used heroin and methamphetamine, and 7 abusers used
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methamphetamine and ketamine. Heroin-related deaths have declined in Shanghai (APC, -16.1; 95% CI, -18.4 to -11.3) and Wuhan (APC, -16.0; 95% CI, -18.9 to -10.6), whereas
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methamphetamine-related deaths have increased in Wuhan (APC, 12.8; 95% CI, 0.0 to 29.2). On the whole, in the two cities, males were more frequently observed than females in heroin-
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related deaths (4.4, 230/52). However, the gender ratios for methamphetamine- (1.8, 34/19) and ketamine-related deaths (1.2, 6/5) were close to one. In view of the mortality rates of the drug abusers in most Chinese cities were still unclear, it is thus important to improve mortality surveillance of the drug abusers at the national level.
Keywords: Methamphetamine; heroin; ketamine; mortality
Introduction
Mortalities of Drug Abusers in China 3
Drug abuse is a global health concern. The China Food and Drug Administration (“CFDA”) reported that 276,980 Chinese were drug abusers [1]. However, this number could be severely underestimated [2], since the China National Narcotic Control Committee (“CNNCC”) estimated that 2.5 million Chinese were drug abusers [3]. The CNNCC is managed by the police departments whereas the CFDA collects voluntary reports from various government agencies. It is thus possible that only a small portion of drug abusers had been reported to the CFDA. As to the drugs being abused, in 2000, heroin, a subcategory of opioids, was most
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common (96%) [4]. However, by 2016, methamphetamine (“MA”) was more frequently used
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than heroin [1], and ketamine had also emerged [1]. The MA subcategories include ice (“冰
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毒”, usually made into shapes of ice crystals) and maguo (“麻果/麻古丸”, usually made into shapes of tablets). As reported by the CFDA, in 2016, by percentage, the five most commonly
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abused drugs were ice (47.9%), heroin (45.0%), maguo (7.2%), ketamine (2.5%), and methadone (1.2%) [1]. However, the CNNCC reported slightly different percentages, that in
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2016, 60.5% of the abused drugs were synthetic drugs (e.g., MA and ketamine), 31.8% were opioids, and 1.4% were cannabis/cocaine [3].
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Drug abuse can cause many deaths. Acute deaths related to congestive cardiomyopathy, focal coagulation necrosis in the myocardium, ventricular rupture, and arrhythmia can result
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from MA abuse [5-7]. MA also causes cerebrovascular cerebral hemorrhage [8]. The abuse of opioids can result in respiratory depression, miosis, stupor, and decreased oxygen saturation [9]. If not treated with opioid receptor antagonists or rescue/resuscitative breathing, acute deaths could occur [10]. Ketamine causes respiratory depression, and might result in deaths similar to that of opioids [11, 12]. The combined use of these drugs could also be lethal: for example, ketamine along with opioids and MA could result in death by intracerebral hemorrhage [11]. Drug abuse not only increases the possibility of natural causes of death [1315] but also the likelihood of injury-related deaths [13, 16]. Therefore, the mortality risk of
Mortalities of Drug Abusers in China 4
drug abusers could be much higher than that of the general population [14, 16, 17]. In China, the total number of drug abusers is high [2, 3], but the accurate mortality rate was not available. As observed by the lack of death reports of MA, opioid, and ketamine abusers in the national data sets, deaths of drug abusers have not been well documented in China. The CFDA and CNNCC statistics did not include any mortality data [1, 3]. The Ministry of Health (“MOH”) classified all accidental poisoning deaths as one category [18]. Although the Disease
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Surveillance Points (“DSP”) reported mortality rates related to drug poisoning, the DSP merged the poisoning of opioid analgesics, antipyretics, and antirheumatics into one category; and the
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poisoning of narcotics and psychodysleptics into another category [19]. Therefore, none of the four national data sets was able to record the deaths of drug abusers.
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As an alternative, scholars used regional data to study the mortalities of drug abusers. At
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present, only four city-level studies are available (see Table 1). Two of the four studies were cohort studies, which included all causes of death of the MA or heroin abusers [20, 21].
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According to the two cohort studies, the crude mortality rates (per 1,000 person-years) were 1.9 among MA abusers and 77.3 among heroin abusers [20, 21]. International cohort studies
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suggest that the corresponding rates ranged from 0.0 to 29.5 among MA abusers [8] and 5.0 to 77.6 among opioid abusers [22]. Thus, the mortality rates for the Chinese MA abusers were
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close to the lower rates while the rates for the Chinese heroin abusers were close to the upper rates reported by the international studies. As to the other two Chinese studies, they only reported heroin poisoning deaths [23, 24]. INSERT TABLE 1 ABOUT HERE
The limitations of the existing four studies are notable. First, a change in abused drugs took place between the years 2000 and 2016, the proportion of heroin abuse dropped while that of MA increased [1-3]. Therefore, it is possible that the heroin-related mortality rates decreased
Mortalities of Drug Abusers in China 5
while the MA-related rates increased. However, the three studies on the deaths of heroin abusers were conducted during the 1990s and early 2000s [21, 23, 24], while the only study on the deaths of MA abusers was conducted during the 2010s [20]. In the absence of a study for a long period, it is therefore unknown whether the change in abused drugs would influence the mortality trends of specific drug abusers. Second, the three studies of heroin-related deaths were all carried out in western China [21, 23, 24]. The only study of MA-related deaths was
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conducted in southern China [20]. However, to the best of the authors’ knowledge, no study has revealed drug-related mortality rates in northern, central, or eastern China. Third, the
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mortality rates related to ketamine abuse in China are not known thus far. Fourth, as MA, opioids, and ketamine have different adverse effects [10, 12, 25], the causes of death among
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these three kinds of drug abusers could be quite different. However, no study has compared the
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causes of death among different drug abusers in China.
Due to the limitations and drawbacks accentuated above, it is of importance to study the
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deaths of the MA, opioid, and ketamine abusers in a specific region and then follow up for a long period to monitor any changes. The two large cities, Shanghai and Wuhan, were selected
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as pilot sites for the present study. Shanghai is in eastern China and is the most prosperous city in Mainland China. Wuhan is the capital of Hubei Province and the most prosperous metropolis
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in central China [26]. The CFDA suggested that the prevalence of drug abuse in Shanghai is more serious than in Wuhan (by about 3.6 times) [1]. Accordingly, the number of deaths of drug abusers in Shanghai was probably higher than in Wuhan. This study employed police data from the two cities, with the objectives to compare the
causes of death and evaluate the mortality rates and trends of MA, opioids, and ketamine abusers.
Methods
Mortalities of Drug Abusers in China 6
Data source The Chinese police are responsible for unnatural death investigations [27]. In addition, sudden natural deaths that occur outside hospitals are also within the police jurisdiction [28, 29]. This study uses the police data in Pudong, Shanghai (2004-2017) and Jiang’an, Wuhan (2005-2017). Pudong is the most populous district (population about 5.5 million) of Shanghai [28]; Jiang’an (population about 1 million) is an urban district of Wuhan [30].
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Under the national regulations, biological samples of the deceased should be routinely collected during the initial death investigation [31]. Blood and urine samples were collected by
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the field forensic examiner who arrived first at the scene. If autopsy examination was
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preformed, the blood and other biological samples (e.g., liver samples) were also collected during the autopsy. However, these samples were not collected from severely corrupted bodies.
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Furthermore, the primary goal of the death investigation was to identify homicides [28]. When the possibility of homicide was excluded (e.g., from the suicide notes and medical history
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supporting a suicide verdict), the relatives could reject the forensic examinations [32]. Therefore, blood and urine samples were not collected for few deaths.
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As MA, opioids, and ketamine were commonly abused drugs in China, laboratory tests on these drugs were performed. The initial screening of MA, opioids, and ketamine was performed
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by checking for MA, morphine, and ketamine in the human urine tests (Shanghai, Colloidal Gold Method, Beijing Biosino-Agiauuc Bio-technology Inc; Wuhan, Colloidal Gold Method, Hangzhou Abon Bio-technology Inc). For positive initial screening tests, confirmatory tests were then performed by Gas Chromatography and Mass Spectrometry (“GC-MS”) (in Shanghai, by Agilent Technologies, 7890A/5975C; in Wuhan, by Agilent Technologies, 7890B/5977A). The GC-MS tests were performed under the national standards “SF/Z JD0107014-2015” [33], “GB/T 29635-2013” [34], “GB/T 29636-2013” [35], and “GB/T
Mortalities of Drug Abusers in China 7
29637-2013” [36]. The old national standards were not available (e.g., the national standard “GB/T 29635-2013” was announced in 2013, and the previous standard was no longer available on the government websites). The GC-MS tests in the two regions were able to distinguish heroin from methadone and morphine [33, 34]. However, due to the main component of ice and maguo being the same, the tests did not distinguish MA into subcategories [35]. In Shanghai and Wuhan, 3,4-methylenedioxymethamphetamine (“MDMA”), cocaine, and
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cannabis had not been included in the initial screening tests, thus no death of these drug abusers was reported.
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Except one death with a positive heroin test resulted from a homicidal injection was excluded [37], all deaths with positive drug tests were included in this study. As all the deaths
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included in this study were not homicides, the drugs were thus presumed to have been
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voluntarily taken by the drug abusers. There were 333 drug-related deaths in total (Shanghai, 176; Wuhan, 157). In addition, although recording negative drug test results, deaths that
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occurred among the police registered drug abusers were also included (Shanghai, 23; Wuhan, 18). The police registered drug abusers referred to those people who had at least been caught
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once and found that they had used MA, heroin or ketamine at the time of their detainment, and those who had voluntarily reported to the police of their MA/heroin/ketamine abuse. Drug
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dealers who had not taken the drugs themselves were not regarded as police registered drug abusers. The combination of drug-related deaths and deaths of previous drug abusers formed the total deaths of the drug abusers in this study.
Data analyses Demographic variables were classified by region (Shanghai and Wuhan), gender, and age. Age was divided into four bands, 15-24, 25-34, 35-44, and 45 years and above. As to drug-
Mortalities of Drug Abusers in China 8
related deaths, the methods used in the last drug abuse were shown. According to the police body examination reports, some drug abusers had fresh injection traces. Therefore, the methods were divided into intravenous/subcutaneous injections, and others. Chi-square and Fisher’s exact tests were used to test the statistical differences of the drugrelated deaths in terms of the cause of death, region, gender, age, and the method used in the last drug abuse. To evaluate the trends in mortality rates, Poisson regression models were used to calculate the annual percentage changes (“APCs”). Poisson regression models were used to
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calculate the mortality rate ratios (“RRs”) of the region. The number of deaths was the
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dependent variable and the number of the general population was the offset. R package
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(Windows, 3.5.0) was used for statistical analyses.
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Results
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Demographics
Overall, 374 deaths were recorded, including 297 males (mean age 37.9; SD, 9.1) and 77
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females (mean age 34.7; SD, 9.0). It should be noted that in 13 deaths (Shanghai, 3; Wuhan, 10), more than one drug had been detected. In any multidrug poisoning death, the complex
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interactions could not be completely delineated [11], thus, in the police body examination reports, all the drugs were presumed to have been contributed to the deaths. All opioid-related deaths were among heroin abusers. There were 263 male heroin abusers (mean age 38.4; SD, 9.0) and 57 female heroin abusers (mean age 36.9; SD, 8.3); 34 male MA abusers (mean age 37.5; SD, 9.3) and 22 female MA abusers (mean age 30.6; SD, 9.1); 6 male ketamine abusers (mean age 32.5; SD, 8.5) and 5 female ketamine abusers (mean age 28.8; SD 9.6). Regarding combined drug abusers, 6 used MA and heroin, 7 used MA and ketamine. As these deaths had
Mortalities of Drug Abusers in China 9
been counted twice, the sum of independent MA, heroin, and ketamine abusers (n = 387) was greater than the total number of deaths (n = 374).
Causes of death of the drug abusers Table 2 shows the causes of death. Among the drug-related deaths, 6 were found to have used MA and heroin simultaneously, they died of drug poisoning with undetermined intent (n
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= 5) and fall with undetermined intent (n = 1). 7 deaths were found to have used MA and
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ketamine simultaneously, they died of drug poisoning with undetermined intent (n = 3) and fall with undetermined intent (n = 4). After excluding the combined drug abusers, heroin poisoning
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was the most significant cause of death for single heroin-related deaths (270/276). Among these heroin poisoning deaths, the only accidental death was caused by the packing of heroin inside
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the body and the only suicide was determined by the suicide note left by the deceased. As for
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the remainder, their intentions were ruled as undetermined (n = 268). Regarding the single MArelated deaths, MA poisoning with undetermined intent was the first cause of death (n = 24). Fall was the second cause of death for single MA-related deaths (n = 8): most falls had
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undetermined intents (n = 6), the remaining falls were suicides (n = 2). Regarding single ketamine-related deaths (n = 4), 3 died of falls, 2 with undetermined intent, the remaining 1
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was a suicide. Only 1 died of ketamine poisoning. As to the deaths of previous drug abusers, compared with the deaths of previous heroin
abusers (n = 38), deaths of previous MA abusers (n = 3) were much less frequently observed, and no death of previous ketamine users was recorded. Most previous heroin abusers died of natural causes (n = 22), followed by suicides by fall (n = 8), and hanging (n = 6). Due to the number of deaths of previous drug abusers being small, only drug-related deaths were included in the statistical analyses.
Mortalities of Drug Abusers in China 10
INSERT TABLE 2 ABOUT HERE
Statistical analyses of the drug-related deaths Table 3 provides the results of the statistical analyses. Two-step analyses were employed. In the beginning, combined drug-related deaths were assigned to different drug-related deaths (e.g., combined MA and heroin abusers were assigned to both MA-related deaths and heroin-
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related deaths). And then the combined drug-related deaths were removed so that only single
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drug-related deaths were included.
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INSERT TABLE 3 ABOUT HERE
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When combined drug abusers were included, regional differences were significant (p < 0.01). In both cities, heroin-related deaths were more frequently observed than MA-related
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deaths (Shanghai, 146/33; Wuhan, 136/20). However, ketamine-related deaths were only reported in Wuhan (n = 11). Gender (p < 0.001) and age (p < 0.05) differences were notable.
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The gender ratio was very close to one in MA- (1.8, 34/19) and ketamine-related (1.2, 6/5) deaths. However, males were much more frequently recorded in heroin-related deaths than
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females (4.4, 230/52). Heroin-related deaths tended to be older (mean age, 37.8; SD, 8.8) than MA-related deaths (mean age, 34.8; SD, 9.7) and ketamine-related deaths (mean age, 30.8; SD, 9.2). The causes of death were different among the three kinds of drug abusers (p < 0.001). Nearly all heroin-related deaths were caused by drug poisoning (97.5%, 275/282). However, falls (24.5%, 13/53) were commonly observed in MA-related deaths. Ketamine abusers were most likely to die of falls (63.6%, 7/11), death due to single ketamine poisoning was rare (9.0%, 1/11). Drug abusers used different methods on their last drug abuse (p < 0.001). Most heroin
Mortalities of Drug Abusers in China 11
abusers used intravenous/subcutaneous injections (89.4%, 236/264), while MA abusers (12.0%, 6/50) and ketamine abusers (20.0%, 2/10) used injections much less frequently. After excluding the combined drug-related deaths from the data set, differences remained on the region, cause of death, and method used in the last drug abuse. However, gender and age differences were no longer significant. Females were more frequently observed than males
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in combined drug-related deaths (7/6).
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The mortality trends and rate ratios
Figure 1 and Table 4 demonstrate the mortality rates among the general population. In the
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calculation, combined drug-related deaths were assigned to different drug-related deaths. In
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Shanghai, crude mortality rates of heroin abusers (APC, -13.9; 95% CI, -16.3 to -9.6) and heroin-related deaths (APC, -16.1; 95% CI, -18.4 to -11.3) declined. In Wuhan, crude mortality
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rates of heroin abusers (APC, -14.0; 95% CI, -16.9 to -9.0) and heroin-related deaths (APC, 16.0; 95% CI, -18.9 to -10.6) also declined. However, the MA-related mortality rates increased
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in Wuhan (APC, 12.8; 95% CI, 0.0 to 29.2). INSERT TABLE 4 ABOUT HERE
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INSERT FIGURE 1 ABOUT HERE
During the entire period of study, the crude mortality rates of drug abusers among the
general population in Wuhan were higher than in Shanghai, this was observed to be from heroin abusers (RR, 4.44; 95% CI, 3.57 to 5.53) and MA abusers (RR, 3.18; 95% CI, 1.83 to 5.40). Furthermore, deaths of ketamine abusers were only reported in Wuhan.
Discussion
Mortalities of Drug Abusers in China 12
This study for the first time compares the causes of death among Chinese MA, opioids, and ketamine abusers. In addition, the mortality trends among the three kinds of drug abusers are compared. The most notable findings were that all opioid-related deaths happened among heroin abusers, whereas death from prescription opioid abusers was not reported. Most heroin abusers died of drug overdoses while natural causes were ranked the second cause of death. Heroin-related mortality rates have decreased in both cities, whereas the MA-related mortality
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rates have increased in Wuhan. Deaths related to prescription opioids in China could be rare. In Shanghai and Wuhan, all
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opioid poisonings were caused by heroin, this result confirmed that heroin was the predominantly abused opioid in China [1]. As to other opioids, morphine was used in the
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treatment of terminal diseases, and methadone, in heroin addiction [4, 38]. However, deaths
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caused by morphine and methadone poisoning were not reported. By comparison, in some western nations (e.g., in New Zealand and the USA), more than one-third of opioid poisoning
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deaths were caused by prescription opioids [9, 38]. The absence of prescription opioid poisoning deaths in Shanghai and Wuhan could have two explanations. First, prescription
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opioids could have been well-managed by hospitals. In addition, Chinese patients tended to reject the use of opioids to relieve pain [39]. Second, prescription opioid poisoning deaths could
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have been treated as natural deaths by hospital physicians, and since natural deaths inside hospitals were not within the Chinese police jurisdiction [30], the police were not informed. Probably, both reasons explain the absence of prescription opioid poisoning deaths in the police files of the two cities.
In the world at large, natural causes were the primary cause of death for opioid abusers
(AIDS was the most prominent natural cause), followed by drug overdose. However, high heterogeneity was also observed among nations [15, 22]. This study found that drug overdose was the main cause of death for heroin abusers in Shanghai and Wuhan. In the present study,
Mortalities of Drug Abusers in China 13
275 out of 320 heroin abusers died of drug poisoning. By comparison, 22 heroin abusers died of natural causes, and only 1 of AIDS. Despite the police data failing to include natural deaths occurring inside hospitals, a cohort study in Sichuan Province where 376 voluntary heroin abusers participated, showed similar results. In the Sichuan study, drug overdose was the primary cause of death (64.3%, 18/28), only 4 deaths were due to natural causes with no AIDS death reported [21]. Although about 4.6% to 15.4% of the Chinese heroin abusers tested
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positive for HIV [4, 21, 40], the two studies showed that few heroin abusers died of AIDS. Under the national regulation in 1995 and 2011, all drug abusers caught by the police were
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required to take the compulsory detoxification. However, it is presumed that the reuse of heroin after compulsory detoxification or a large amount of heroin injection resulted in heroin
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overdose [21, 24]. Most of the heroin-related deaths were found to have used
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intravenous/subcutaneous injections (89.4%, 236/264). Moreover, the purity of heroin was not consistent, making it difficult for heroin abusers to calculate the amount of the substance to be
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injected [24]. The above reasons accounted for most of the Chinese heroin abusers dying of drug overdoses before they could die of other natural causes.
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The decision on the manner of death was also quite unique in China. The primary goal of death investigations in China was to identify homicides [28]. As shown in the present study,
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except for 1 suicide and 1 accidental death, the other heroin poisonings were ruled to have undetermined intents (n = 268). Although these deaths were very likely due to accidents occurred during heroin abuse, the possibility of them being suicides was not ruled out. However, as the police have ruled out the possibility of homicides, the investigations were thus closed, and the relatives were also unlikely to support further investigations. Hence, the intents of most heroin poisoning deaths were ruled to be undetermined. In China, heroin poisoning was rarely reported as a method of suicide [41, 42]. By comparison, in the USA, suicides by opioids were much more popular, where 2.2% to 4.4% of
Mortalities of Drug Abusers in China 14
all the suicides were caused by opioid poisoning [43]. In Pudong, Shanghai, for example, during the period of 2004-2017, the ratio of suicide verdicts to undetermined heroin poisoning deaths was 18.8 (2656/141) [28]. As some suicides by heroin poisoning could be misclassified as undetermined heroin poisonings, the proportion of suicides by heroin could thus be underestimated in Shanghai. Likewise, the proportion of suicides by heroin could also be underestimated in China as well.
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Nonetheless, declining trends of heroin-related deaths were observed in Shanghai and Wuhan, suggesting that the reduced heroin abuse among the Chinese people [1, 3] could have
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lowered the risk of opioid-related deaths, or, better social and medical support reduce the
in northern and southern China were still not known.
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mortality risk of heroin abusers. However, it should be noted that opioid-related mortality rates
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MA-related mortality risk, on the other hand, might increase in the future. Around the world, MA abusers have lower mortality risk than opioid abusers [15, 44, 45]. Especially in
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China, the mortality risk of MA abusers could be much lower than heroin abusers (refer to Table 1). Although the trend in MA abuse has increased rapidly [1, 3], due to the relatively
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lower mortality risk related to MA abuse, MA-related mortalities might not increase simultaneously. Despite it still being uncertain whether age is an important factor in influencing
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the mortality risk of MA abusers [8], MA abuse increases the possibility of sexually transmitted diseases (e.g., hepatitis B) [46, 47]. In addition, several studies suggested that mortality risk increased with age among the other drug abusers (e.g., opioid abusers) [48, 49]. The increase in MA abuse in China has only lasted for less than two decades [2, 3], but given the accumulated effect of MA abuse, there is a concern that natural and injury-related mortality rates could increase in the long run. Worldwide, compared with opioid-related mortalities, MA related-mortalities receive less attention. Also, reports of MA-related mortality rates among the general population could be
Mortalities of Drug Abusers in China 15
scarce [45]. In the southern half of Osaka, Japan, the mortality rate of MA abusers (per 100,000 general population) was 0.19 during the period of 1994-1998 [13]. This rate is similar to Wuhan (0.18) but higher than in Shanghai (0.06). However, a much higher rate was reported in Yunfu city in the Guangdong Province (0.91) [20]. The results might imply that MA abuse in Guangdong could be more serious than in Shanghai, Wuhan, and Osaka. Although screening tests for ketamine were performed in both cities, deaths of ketamine
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abusers were only reported in Wuhan. It could be inferred that ketamine abuse in Wuhan could be more prevalent than in Shanghai. In addition, most of the ketamine abusers (63.6%, 7/11)
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used MA at the same time, thus the characteristics of ketamine abusers could greatly resemble those of the MA abusers. However, death due to single ketamine poisoning was rare (9.1%,
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1/11). Likewise, the findings in New York also suggest that deaths caused by single ketamine
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poisoning could be rare [11].
Female deaths caused by MA and ketamine abuse should be emphasized. Previous studies
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suggested that Chinese drug abusers were characterized as male predominant [4, 40]. However, in the present study, the gender ratios of MA- (1.8, 34/19) and ketamine-related deaths (1.2,
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6/5) were close to one. The results implied that either the number of female MA and ketamine abusers had been underreported, or female MA and ketamine abusers were more vulnerable to
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death than their male counterparts. Therefore, the surveillance of MA and ketamine abuse in Chinese females should be improved. In particular, a study in Shandong revealed that about 30% of the 1,211 female sex workers had used MA [47], thus the surveillance on drug abuse by female sex workers should be particularly emphasized. The number of Chinese drug abusers is probably much higher than the number reported
by the CFDA (276,980) [1]. As reported by the CFDA, drug abuse in Shanghai was more severe than in Wuhan. However, in Wuhan, the mortality rates of heroin and MA abusers among the general population were much higher than in Shanghai. The inconsistencies imply that drug
Mortalities of Drug Abusers in China 16
abuse in Wuhan could be more likely to be underreported. Although the CNNCC reported a much higher number of drug abusers (about 2.5 million) [3], the CNNCC report had not specified regional variations, making it hard to make comparisons with the police recorded mortality rates.
Limitations and suggestions
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First, many demographic variables were not completely recorded in the police files (e.g.,
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marital status, education attainment, and job description). Thus, these variables were not included in the present study. Second, except for carbon monoxide, MA, heroin, and ketamine,
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other substances were also found in the postmortem laboratory tests. To be specific, alcohol
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was found in 18 drug abusers, diazepam in 2 drug abusers, while estazolam, triazolam, and dextromethorphan were found in 1 drug abuser. Nonetheless, the mixed drug effects were not
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taken into consideration. Third, in China, autopsies were not compulsory for natural deaths [28, 30]. Due to the low autopsy rate, the causes of death could hardly be determined [30]. As
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manifested in the present study, the causes of death were determined in only 30.4% (7/23) of the natural deaths. Fourth, as the exact number of drug abusers living in Shanghai and Wuhan
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could not be retrieved, this study was unable to calculate the standard mortality ratio of drug abusers.
Fifth and most importantly, so far, among all the Chinese official mortality data sources,
the mortality rates of drug abusers can only be ascertained through regional police files [23, 24]. However, police data could underestimate the mortality rates. The police have no jurisdiction over natural deaths occurring inside hospitals. Also, the relatives of the deceased have the right to reject the drug tests when the possibility of homicide has been ruled out. The tests of MDMA, cocaine, and cannabis are not routinely performed by the police. Furthermore,
Mortalities of Drug Abusers in China 17
urine and blood tests are not applicable to severely decomposed bodies. The screening tests for MA, opioids, and ketamine could have false-negative results, confirmatory tests were not performed to certify the false-negative results. Inevitably, all the above factors could lead to the underreporting of deaths of drug abusers. To improve on the mortality surveillance on drug abusers in the short-term, it is thus suggested that regardless of the causes of death, data on the deaths with positive drug tests as
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well as deaths of registered drug abusers should be collected by the drug administration authorities. In the long run, to minimize the underreporting of deaths of drug abusers, GC-MS
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tests for all the commonly abused drugs (including MDMA, cannabis, and cocaine) were recommended. The corresponding drug control and rehabilitation plans should be benefited
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from the more detailed mortality data of drug abusers.
Conclusion
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Studies on the mortalities of Chinese drug abusers are scarce. This study investigates the characteristics of deaths of MA, opioid, and ketamine abusers in Shanghai (2004-2017) and
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Wuhan (2005-2017). Most heroin abusers died of heroin poisoning while natural causes were ranked as the second cause of death. Death caused by prescription opioid poisoning was not
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reported. Heroin-related mortality rates have decreased in both cities, whereas the MA-related mortality rates have increased in Wuhan. It is anticipated that the mortality risk of MA abusers could further increase in the future. The gender ratios in MA- and ketamine-related deaths were close to one, thus the surveillance on MA and ketamine abuse by the females should be improved.
Declaration This manuscript or any other substantially similar paper has not been published.
Mortalities of Drug Abusers in China 18
Conflict of interest All authors declare that they have no conflict of interest.
Funding This research has not received any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Jinchen Liu: Data curation and Writing
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Paul S.F. Yip: Supervision, Reviewing, and Editing
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Xuesong Lu: Resources and Writing
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Sihai Liu: Resources and Writing
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Feng Li: Conceptualization, Methodology and Writing
Mortalities of Drug Abusers in China 19
References
Jo ur
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[1] China Food and Drug Administration, National Drug Abuse Surveillance Report., 2016 (accessed 10/10.2019). [2] C. Zhao, Z. Liu, D. Zhao, Y. Liu, J. Liang, Y. Tang, J. Zheng, Drug abuse in China, Annals of the New York Academy of Sciences 1025 (2004) 439-445. [3] China National Narcotic Control Committee, China illicit drug report. , 2016 (accessed 12/12.2018). [4] W.-J. Du, Y.-T. Xiang, Z.-M. Wang, Y. Chi, Y. Zheng, X.-N. Luo, Z.-J. Cai, G.S. Ungvari, J. Gerevich, Socio-demographic and clinical characteristics of 3129 heroin users in the first methadone maintenance treatment clinic in China, Drug and alcohol dependence 94(1-3) (2008) 158-164. [5] W. Jacobs, Fatal amphetamine-associated cardiotoxicity and its medicolegal implications, The American journal of forensic medicine and pathology 27(2) (2006) 156-160. [6] R. Kuroda, M. Nakajima, H. Nagai, H. Maeda, J. Kashima, K. Saka, K. Shintani-Ishida, A. Igarashi, K.i. Yoshida, Small focal coagulation necrosis in the myocardium of a young methamphetamine user, International journal of cardiology 164(1) (2013) e5-e6. [7] S.B. Karch, The unique histology of methamphetamine cardiomyopathy: a case report, Forensic science international 212(1-3) (2011) e1-e4. [8] J. Singleton, L. Degenhardt, W. Hall, T. Zabransky, Mortality among amphetamine users: a systematic review of cohort studies, Drug and Alcohol Dependence 105(1-2) (2009) 1-8. [9] T.J. Inocencio, N.V. Carroll, E.J. Read, D.A. Holdford, The economic burden of opioid-related poisoning in the United States, Pain medicine 14(10) (2013) 1534-1547. [10] N. Dasgupta, M.J. Funk, J.S. Brownstein, Comparing unintentional opioid poisoning mortality in metropolitan and non-metropolitan counties, United States, 1999–2003, Geography and drug addiction, Springer2008, pp. 175-192. [11] J. Gill, M. Stajic, Ketamine in non-hospital and hospital deaths in New York City, Journal of Forensic Science 45(3) (2000) 655-658. [12] S. Sassano‐Higgins, D. Baron, G. Juarez, N. Esmaili, M. Gold, A review of ketamine abuse and diversion, Depression and anxiety 33(8) (2016) 718-727. [13] B.-L. Zhu, S. Oritani, K. Shimotouge, K. Ishida, L. Quan, M.Q. Fujita, M. Ogawa, H. Maeda, Methamphetamine-related fatalities in forensic autopsy during 5 years in the southern half of Osaka city and surrounding areas, Forensic science international 113(1-3) (2000) 443-447. [14] C.T. Lee, V.C. Chen, H.K. Tan, S.-Y. Chou, K.-H. Wu, C.-H. Chan, M. Gossop, Suicide and other-cause mortality among heroin users in Taiwan: a prospective study, Addictive behaviors 38(10) (2013) 26192623. [15] R.M. Pavarin, A. Fioritti, S. Sanchini, Mortality trends among heroin users treated between 1975 and 2013 in Northern Italy: Results of a longitudinal study, Journal of substance abuse treatment 77 (2017) 166-173. [16] D.M. Herbeck, M.-L. Brecht, K. Lovinger, Mortality, causes of death, and health status among methamphetamine users, Journal of addictive diseases 34(1) (2015) 88-100. [17] M. Stenbacka, A. Leifman, A. RomelsjÖ, Mortality and cause of death among 1705 illicit drug users: a 37 year follow up, Drug and alcohol review 29(1) (2010) 21-27. [18] Ministry of Health, Annual statistics. , 2017 (accessed 10/10.2018). [19] L. Wang, Y. Wu, P. Yin, P. Cheng, Y. Liu, D.C. Schwebel, J. Qi, P. Ning, J. Liu, X. Cheng, Poisoning deaths in China, 2006–2016, Bulletin of the World Health Organization 96(5) (2018) 314. [20] N. Ou, Forensic Analysis of 16 deaths related to Methamphetamine, Heilongjiang Science Information 32 (2016) 83.
Mortalities of Drug Abusers in China 20
Jo ur
na
lP
re
-p
ro
of
[21] L. Zhang, Y. Ruan, Z. Jiang, Z. Yang, S. Liu, F. Zhou, Y. He, L. Yin, G. QIn, Y. Shao, An 1-year Prospective Cohort Study on Mortality of Injecting Drug Users, Chinese Journal of Epidemiology 26(3) (2005) 190-193. [22] L. Degenhardt, C. Bucello, B. Mathers, C. Briegleb, H. Ali, M. Hickman, J. McLaren, Mortality among regular or dependent users of heroin and other opioids: a systematic review and meta‐analysis of cohort studies, Addiction 106(1) (2011) 32-51. [23] H. Hu, Y. Chen, X. Wang, D. Sun, Z. Liao, Y. Ding, Investigation and Analysis of Death from Heroin Poisoning in Chengdu District, Acta Academiae of Medicinae Wannan 23(4) (2004) 303-304. [24] W. Li, L. Wan, J. Yin, B. Sun, Analysis of 500 Deaths Related to Heroin Injection, Chinese Journal of Forensic Medicine 11(4) (1996) 242-243. [25] M. Akhgari, H. Mobaraki, A. Etemadi-Aleagha, Histopathological study of cardiac lesions in methamphetamine poisoning-related deaths, DARU Journal of Pharmaceutical Sciences 25(1) (2017) 5. [26] F. Li, J. Zeng, J. Huang, J. Zhang, Y. Chen, H. Yan, W. Huang, X. Lu, P.S. Yip, Work-related and nonwork-related accident fatal falls in Shanghai and Wuhan, China, Safety Science 117 (2019) 43-48. [27] F. Li, S. Liu, X. Lu, Y. Ou, P.S.F. Yip, Application of the Injury Scales in Homicides, Forensic Science International 292 (2018) 83-89. [28] F. Li, X. Lu, Y. Ou, P.S. Yip, The influence of undetermined deaths on suicides in Shanghai, China, Social psychiatry and psychiatric epidemiology 54(1) (2019) 111-119. [29] F. Li, X. Lu, Infant deaths in Pudong, Shanghai, China: A Retrospective Study of the Police Data and Comparison with the Centre for Disease Control Data, Journal of Forensic and Legal Medicine 62 (2019) 7-13. [30] F. Li, H.C. Chan, S. Liu, H. Jia, H. Li, Y. Hu, Z. Wang, W. Huang, Carbon monoxide poisoning as a cause of death in Wuhan, China: A retrospective six-year epidemiological study (2009–2014), Forensic Science International 253 (2015) 112-118. [31] The Chinese Ministry of Justice, The Regulations of Forensic Autopsy Examination (SF/Z JD0101002-2015)., 2015 (accessed 10/10.2019). [32] F. Li, X. Lu, P.S. Yip, A Study of the Characteristics of Suicide Notes in China, Crisis (2019). [33] The Chinese Ministry of Justice, The Regulation of GC-MS Examination on 108 Drugs (SF/Z JD0107014-2015). , 2015 (accessed 10/10.2019). [34] The Chinese Public Security Bureau, GC and GC-MS examination methods for heroin in suspected drug (GB/T 29635-2013). , 2013 (accessed 10/10.2019). [35] The Chinese Public Security Bureau, GC ,HPLC and GC-MS examination methods for methylamphetamine in suspected drug (GB/T 29636-2013). , 2013 (accessed 10/10.2019). [36] The Chinese Public Security Bureau, GC and GC-MS examination methods for ketamine in suspected drug (GB/T 29637-2013). , 2013 (accessed 10/10.2019). [37] F. Li, J. Tang, One homcide case by using heroin injection, Journal of Forensic Medicine 26(1) (2010) 14. [38] D. Reith, J. Fountain, M. Tilyard, Opioid poisoning deaths in New Zealand (2001–2002), NZMed J 118(1209) (2005) 1-8.
Mortalities of Drug Abusers in China 21
Jo ur
na
lP
re
-p
ro
of
[39] Y. Huang, Current status of pain management in China: an overview, European Journal of Pain 5(SA) (2001) 67-71. [40] S. Lai, W. Liu, J. Chen, J. Yang, Z.-J. Li, R.-J. Li, F.-X. Liang, S.-L. Liang, Q.-Y. Zhu, X.-F. Yu, Changes in HIV-1 incidence in heroin users in Guangxi Province, China, Journal of acquired immune deficiency syndromes (1999) 26(4) (2001) 365-370. [41] J. Sun, X. Guo, J. Ma, J. Zhang, C. Jia, A. Xu, Seasonality of suicide in Shandong China, 1991–2009: Associations with gender, age, area and methods of suicide, Journal of Affective Disorders 135(1-3) (2011) 258-266. [42] A. Page, S. Liu, D. Gunnell, T. Astell-Burt, X. Feng, L. Wang, M. Zhou, Suicide by pesticide poisoning remains a priority for suicide prevention in China: Analysis of national mortality trends 2006–2013, Journal of Affective Disorders 208 (2017) 418-423. [43] J.B. Braden, M.J. Edlund, M.D. Sullivan, Suicide deaths with opioid poisoning in the United States: 1999–2014, American journal of public health 107(3) (2017) 421-426. [44] L.-J. Liang, D. Huang, M.-L. Brecht, Y.-I. Hser, Differences in mortality among heroin, cocaine, and methamphetamine users: a hierarchical bayesian approach, Journal of drug issues 40(1) (2010) 121140. [45] R.C. Callaghan, J.K. Cunningham, M. Verdichevski, J. Sykes, S.R. Jaffer, S.J. Kish, All-cause mortality among individuals with disorders related to the use of methamphetamine: a comparative cohort study, Drug and alcohol dependence 125(3) (2012) 290-294. [46] Y. Huang, S. Wu, Y. Tian, Analysis on Data fo Methamphetamine Abuse from 2013 to 2015 in Shandong Province, Chinese Journal of Pharmacoepidemiology 3 (2017) 199-203. [47] M. Liao, Z. Jiang, X. Zhang, D. Kang, Z. Bi, X. Liu, J. Fu, N. Zhang, W. Mao, B. Jiang, Syphilis and methamphetamine use among female sex workers in Shandong Province, China, Sexually transmitted diseases 38(1) (2011) 57-62. [48] E.L. Merrall, S.M. Bird, S.J. Hutchinson, Mortality of those who attended drug services in Scotland 1996–2006: record-linkage study, International Journal of Drug Policy 23(1) (2012) 24-32. [49] M. Pierce, S.M. Bird, M. Hickman, T. Millar, National record linkage study of mortality for a large cohort of opioid users ascertained by drug treatment or criminal justice sources in England, 2005– 2009, Drug and alcohol dependence 146 (2015) 17-23.
Mortalities of Drug Abusers in China 22
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Figure 1. Crude mortality rates among the general population
Authors
Data source and study design
Regions study
Ou [20]
Police, cohort study
Li et al. [24]
Hu et al. [23]
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Table 1. Studies of MA- and heroin-related deaths in Mainland China
oo
f
Mortalities of Drug Abusers in China 23
Deaths of MA abusers
Mortality rates of MA abusers in the general population (per 100,000)
Mortality rates for 1,000 MA abuseryears (for cohort studies)
Heroin abuse population (for cohort studies)
About 1,646
16
0.91a
1.9a
MA abuse population (for cohort studies)
Deaths of heroin abusers
Mortality rates of heroin abusers in the general population (per 100,000)
Mortality rates of 1,000 heroin abuser-years (for cohort studies)
NA
NA
NA
NA
General Population (100,000)
Yunfu City, Guangdong Province, China
20102014
3.5
Police, case series
Kunming City, Yunnan Province, China
19901995
About 50
NA
NA
NA
NA
NA
500
1.67a
NA
Police, case series
Chengdu City, Sichuan Province, China
19962002
110.3
NA
NA
NA
NA
NA
396
0.51a
NA
Jo ur na l
Pr
e-
Periods of study
of
Crude mortality rate.
b
Standardized mortality rate.
NA
NA
NA
pr
NA
Jo ur na l
a
20022003
e-
Liangshan Autonomous Prefecture, Sichuan Province, China
Pr
Zhang et al. [21]
Recruit volunteers, cohort study
oo
f
Mortalities of Drug Abusers in China 24
NA
376
28
NA
77.3a/47.6b
f
Mortalities of Drug Abusers in China 25
0/7 0/15 2/6 0/0 1/8 0/1 1/0
0/0 0/1 0/1 1/0 2/1 2/0 0/0
Single ketaminerelated deaths/previous ketamine abusers 0/0 0/0 0/0 0/0 1/0 0/0 0/0
2
0/0
2/0
1
1/0
Drug poisoning
301
Falls Drowning Thermal injuries Hemorrhagic shock
14 2 3 1
Single heroinNumber of related drug abusers deaths/previous heroin abusers
Accidents
Undetermined intent
a
e-
27
7 16 9 1 13 3 1
Pr
Suicides
Determined causes a Undetermind causes Hanging Drowning Falls Hemorrhagic shock Drug poisoning Carbon monoxide poisoning Drug poisoning
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23
pr
Number Manners of death of drug Causes of death abusers
Natural causes
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Table 2. Causes of death among all the drug users
3
321
Single MArelated deaths/previous MA abusers
MA- and MAand heroinketaminerelated related deaths deaths 0 0 0 0 0 0 0
0 0 0 0 0 0 0
0/0
0
0
0/0
0/0
0
0
268/0
24/0
1/0
5
3
0/1 0/0 2/0 1/0
6/0 2/0 1/0 0/0
2/0 0/0 0/0 0/0
1 0 0 0
4 0 0 0
Determined causes include heart failure, pulmonary tuberculosis, diabetes mellitus, hepatitis, AIDS, and intracranial hemorrhage.
f
Mortalities of Drug Abusers in China 26
MArelated deaths
Ketaminerelated 2/Fisher's exact tests for the differences deaths
33 (30)
0 (0)
20 (10)
11 (4)
Shanghai Wuhan
146 (143) a 136 (133)
Male
17 (17) 84 (83) 98 (95) 64 (62)
Drug poisoning
275 (270) 2 (1) 0 (0) 1 (1) 2 (2) 0 (0) 2 (2)
Falls Drowning Hemorrhagic shock Hanging Carbon monoxide poisoning Thermal injuries Method used in the last drug abuse Intravenous/subcutaneous 236 injections (233)
11.55** (3.73 b)
34 (28)
6 (3)
19 (12)
5 (1)
8 (5) 18 (16) 16 (12) 11 (7)
4 (1) 4 (3) 1 (0) 2 (0)
13.64* a (8.79 b)
32 (24)
4 (1)
98.65*** b (85.58*** b)
13 (8) 3 (3) 2 (2) 0 (0) 2 (2) 1 (1)
7 (3) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0)
6 (2)
2 (1)
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Female Age c 15-24 25-34 35-44 45 and above Causes of death
230 (227) 52 (49)
Pr
Gender
14.14** (12.17** b)
e-
Regions
pr
Heroinrelated deaths
oo
Table 3. Statistical comparison of the drug-related deaths
152.39*** e (125.14*** be)
28 (25) 18 (18)
44 (36) 3 (2)
8 (3) 1 (0)
oo
Others Unknown d
f
Mortalities of Drug Abusers in China 27
Number in the parentheses excluded the combined drug-related deaths.
b
Due to the small numbers, Fisher's exact tests were used.
c
Information on age of some decedents was not recorded.
d
Due to decomposition, thermal injuries, human activities, or other factors, the existence of fresh injection trace was not determined.
pr
a
Due to the unknown method of drug abuse not included, the result was generated by 3 by 2 2/Fisher’s exact test. *p < 0.5, **p < 0.05, ***p < 0.001.
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Pr
e-
e
f
Mortalities of Drug Abusers in China 28
Wuhan
Annual percentage changes (95% CI) -13.9 (-16.3 to -9.6)*** -16.1 (-18.4 to -11.3)*** 4.4 (-4.6 to 14.3) 4.4 (-4.7 to 14.5) -14.0 (-16.9 to -9.0)*** -16.0 (-18.9 to -10.6)*** 11.0 (-1.0 to 25.8) 12.8 (0.0 to 29.2)* 8.8 (-7.5 to 28.8)
pr
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*p < 0.5, **p < 0.05, ***p < 0.001.
Pr
e-
Shanghai
Rates (95% CI) Heroin abusers 0.3 (0.2 to 0.3) Heroin-related deaths 0.2 (0.2 to 0.3) MA abusers 0.1 (0.0 to 0.1) MA-related deaths 0.1 (0.0 to 0.1) Heroin abusers 1.3 (1.1 to 1.5) Heroin-related deaths 1.1 (1.0 to 1.3) MA abusers 0.2 (0.1 to 0.3) MA-related deaths 0.2 (0.1 to 0.2) Ketamine-related deaths 0.1 (0.0 to 0.1)
oo
Table 4. Crude mortality rates (per 100,000 general population) and trends among the three kinds of drug abusers
PII:
S0379-0738(19)30505-5
DOI:
https://doi.org/10.1016/j.forsciint.2019.110093
Reference:
FSI 110093
To appear in:
Forensic Science International
Received Date:
18 July 2019
Revised Date:
20 November 2019
Accepted Date:
25 November 2019
Please cite this article as: Li F, Liu J, Yip PSF, Lu X, Liu S, Mortalities of Methamphetamine, Opioid, and Ketamine Abusers in Shanghai and Wuhan, China, Forensic Science International (2019), doi: https://doi.org/10.1016/j.forsciint.2019.110093
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Mortalities of Drug Abusers in China 1
Mortalities of Methamphetamine, Opioid, and Ketamine Abusers in Shanghai and Wuhan, China
Running head: Mortalities of Drug Abusers in China
Feng Li 1, Jinchen Liu 2, Paul S.F. Yip 1, Xuesong Lu 3, Sihai Liu 4
HKJC Centre for Suicide Research and Prevention, The University of Hong Kong,
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1
Pokfulam, Hong Kong SAR, China.
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Hong Kong Jockey Club Building for Interdisciplinary Research, 5 Sassoon Road,
College of Life Science, Lanzhou University, China.
3
Criminal Science Institute, Pudong District of Shanghai Municipal Public Security
Bureau, Shanghai, China.
Jiang’an District of Wuhan Municipal Public Security Bureau, Wuhan, Hubei, China.
Feng Li, Centre for Suicide Research and Prevention, The
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Corresponding author:
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2
University of Hong Kong, Hong Kong
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Tel: (852) 6576 8434 Email: [email protected] Postal address: Hong Kong Jockey Club Centre for Suicide
Research and Prevention, The University of Hong Kong, Hong Kong Jockey Club Building for Interdisciplinary Research, 5 Sassoon Road, Pokfulam, Hong Kong SAR, China.
Highlights
Mortalities of Drug Abusers in China 2
Death of prescription opioid abusers was absent in Shanghai and Wuhan.
Heroin-related mortality rates have declined in Shanghai and Wuhan.
Methamphetamine-related mortality rates have increased in Wuhan.
Synthetic drug abuse by females in Shanghai and Wuhan should be underscored.
Abstract
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Studies on the mortalities of drug abusers in China are scarce. This study explores the deaths of methamphetamine, opioid, and ketamine abusers in Shanghai (2004-2017) and Wuhan
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(2005-2017). Chi-square/Fisher’s exact tests were used to compare the differences in terms of region, gender, age, cause of death, and the method used in the last drug abuse. Poisson
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regression models were used to estimate the rate ratios (“RRs”) and annual percentage changes
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(“APCs”). 314 heroin, 43 methamphetamine, and 4 ketamine abusers were included. Furthermore, simultaneously, 6 abusers used heroin and methamphetamine, and 7 abusers used
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methamphetamine and ketamine. Heroin-related deaths have declined in Shanghai (APC, -16.1; 95% CI, -18.4 to -11.3) and Wuhan (APC, -16.0; 95% CI, -18.9 to -10.6), whereas
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methamphetamine-related deaths have increased in Wuhan (APC, 12.8; 95% CI, 0.0 to 29.2). On the whole, in the two cities, males were more frequently observed than females in heroin-
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related deaths (4.4, 230/52). However, the gender ratios for methamphetamine- (1.8, 34/19) and ketamine-related deaths (1.2, 6/5) were close to one. In view of the mortality rates of the drug abusers in most Chinese cities were still unclear, it is thus important to improve mortality surveillance of the drug abusers at the national level.
Keywords: Methamphetamine; heroin; ketamine; mortality
Introduction
Mortalities of Drug Abusers in China 3
Drug abuse is a global health concern. The China Food and Drug Administration (“CFDA”) reported that 276,980 Chinese were drug abusers [1]. However, this number could be severely underestimated [2], since the China National Narcotic Control Committee (“CNNCC”) estimated that 2.5 million Chinese were drug abusers [3]. The CNNCC is managed by the police departments whereas the CFDA collects voluntary reports from various government agencies. It is thus possible that only a small portion of drug abusers had been reported to the CFDA. As to the drugs being abused, in 2000, heroin, a subcategory of opioids, was most
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common (96%) [4]. However, by 2016, methamphetamine (“MA”) was more frequently used
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than heroin [1], and ketamine had also emerged [1]. The MA subcategories include ice (“冰
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毒”, usually made into shapes of ice crystals) and maguo (“麻果/麻古丸”, usually made into shapes of tablets). As reported by the CFDA, in 2016, by percentage, the five most commonly
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abused drugs were ice (47.9%), heroin (45.0%), maguo (7.2%), ketamine (2.5%), and methadone (1.2%) [1]. However, the CNNCC reported slightly different percentages, that in
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2016, 60.5% of the abused drugs were synthetic drugs (e.g., MA and ketamine), 31.8% were opioids, and 1.4% were cannabis/cocaine [3].
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Drug abuse can cause many deaths. Acute deaths related to congestive cardiomyopathy, focal coagulation necrosis in the myocardium, ventricular rupture, and arrhythmia can result
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from MA abuse [5-7]. MA also causes cerebrovascular cerebral hemorrhage [8]. The abuse of opioids can result in respiratory depression, miosis, stupor, and decreased oxygen saturation [9]. If not treated with opioid receptor antagonists or rescue/resuscitative breathing, acute deaths could occur [10]. Ketamine causes respiratory depression, and might result in deaths similar to that of opioids [11, 12]. The combined use of these drugs could also be lethal: for example, ketamine along with opioids and MA could result in death by intracerebral hemorrhage [11]. Drug abuse not only increases the possibility of natural causes of death [1315] but also the likelihood of injury-related deaths [13, 16]. Therefore, the mortality risk of
Mortalities of Drug Abusers in China 4
drug abusers could be much higher than that of the general population [14, 16, 17]. In China, the total number of drug abusers is high [2, 3], but the accurate mortality rate was not available. As observed by the lack of death reports of MA, opioid, and ketamine abusers in the national data sets, deaths of drug abusers have not been well documented in China. The CFDA and CNNCC statistics did not include any mortality data [1, 3]. The Ministry of Health (“MOH”) classified all accidental poisoning deaths as one category [18]. Although the Disease
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Surveillance Points (“DSP”) reported mortality rates related to drug poisoning, the DSP merged the poisoning of opioid analgesics, antipyretics, and antirheumatics into one category; and the
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poisoning of narcotics and psychodysleptics into another category [19]. Therefore, none of the four national data sets was able to record the deaths of drug abusers.
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As an alternative, scholars used regional data to study the mortalities of drug abusers. At
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present, only four city-level studies are available (see Table 1). Two of the four studies were cohort studies, which included all causes of death of the MA or heroin abusers [20, 21].
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According to the two cohort studies, the crude mortality rates (per 1,000 person-years) were 1.9 among MA abusers and 77.3 among heroin abusers [20, 21]. International cohort studies
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suggest that the corresponding rates ranged from 0.0 to 29.5 among MA abusers [8] and 5.0 to 77.6 among opioid abusers [22]. Thus, the mortality rates for the Chinese MA abusers were
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close to the lower rates while the rates for the Chinese heroin abusers were close to the upper rates reported by the international studies. As to the other two Chinese studies, they only reported heroin poisoning deaths [23, 24]. INSERT TABLE 1 ABOUT HERE
The limitations of the existing four studies are notable. First, a change in abused drugs took place between the years 2000 and 2016, the proportion of heroin abuse dropped while that of MA increased [1-3]. Therefore, it is possible that the heroin-related mortality rates decreased
Mortalities of Drug Abusers in China 5
while the MA-related rates increased. However, the three studies on the deaths of heroin abusers were conducted during the 1990s and early 2000s [21, 23, 24], while the only study on the deaths of MA abusers was conducted during the 2010s [20]. In the absence of a study for a long period, it is therefore unknown whether the change in abused drugs would influence the mortality trends of specific drug abusers. Second, the three studies of heroin-related deaths were all carried out in western China [21, 23, 24]. The only study of MA-related deaths was
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conducted in southern China [20]. However, to the best of the authors’ knowledge, no study has revealed drug-related mortality rates in northern, central, or eastern China. Third, the
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mortality rates related to ketamine abuse in China are not known thus far. Fourth, as MA, opioids, and ketamine have different adverse effects [10, 12, 25], the causes of death among
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these three kinds of drug abusers could be quite different. However, no study has compared the
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causes of death among different drug abusers in China.
Due to the limitations and drawbacks accentuated above, it is of importance to study the
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deaths of the MA, opioid, and ketamine abusers in a specific region and then follow up for a long period to monitor any changes. The two large cities, Shanghai and Wuhan, were selected
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as pilot sites for the present study. Shanghai is in eastern China and is the most prosperous city in Mainland China. Wuhan is the capital of Hubei Province and the most prosperous metropolis
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in central China [26]. The CFDA suggested that the prevalence of drug abuse in Shanghai is more serious than in Wuhan (by about 3.6 times) [1]. Accordingly, the number of deaths of drug abusers in Shanghai was probably higher than in Wuhan. This study employed police data from the two cities, with the objectives to compare the
causes of death and evaluate the mortality rates and trends of MA, opioids, and ketamine abusers.
Methods
Mortalities of Drug Abusers in China 6
Data source The Chinese police are responsible for unnatural death investigations [27]. In addition, sudden natural deaths that occur outside hospitals are also within the police jurisdiction [28, 29]. This study uses the police data in Pudong, Shanghai (2004-2017) and Jiang’an, Wuhan (2005-2017). Pudong is the most populous district (population about 5.5 million) of Shanghai [28]; Jiang’an (population about 1 million) is an urban district of Wuhan [30].
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Under the national regulations, biological samples of the deceased should be routinely collected during the initial death investigation [31]. Blood and urine samples were collected by
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the field forensic examiner who arrived first at the scene. If autopsy examination was
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preformed, the blood and other biological samples (e.g., liver samples) were also collected during the autopsy. However, these samples were not collected from severely corrupted bodies.
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Furthermore, the primary goal of the death investigation was to identify homicides [28]. When the possibility of homicide was excluded (e.g., from the suicide notes and medical history
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supporting a suicide verdict), the relatives could reject the forensic examinations [32]. Therefore, blood and urine samples were not collected for few deaths.
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As MA, opioids, and ketamine were commonly abused drugs in China, laboratory tests on these drugs were performed. The initial screening of MA, opioids, and ketamine was performed
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by checking for MA, morphine, and ketamine in the human urine tests (Shanghai, Colloidal Gold Method, Beijing Biosino-Agiauuc Bio-technology Inc; Wuhan, Colloidal Gold Method, Hangzhou Abon Bio-technology Inc). For positive initial screening tests, confirmatory tests were then performed by Gas Chromatography and Mass Spectrometry (“GC-MS”) (in Shanghai, by Agilent Technologies, 7890A/5975C; in Wuhan, by Agilent Technologies, 7890B/5977A). The GC-MS tests were performed under the national standards “SF/Z JD0107014-2015” [33], “GB/T 29635-2013” [34], “GB/T 29636-2013” [35], and “GB/T
Mortalities of Drug Abusers in China 7
29637-2013” [36]. The old national standards were not available (e.g., the national standard “GB/T 29635-2013” was announced in 2013, and the previous standard was no longer available on the government websites). The GC-MS tests in the two regions were able to distinguish heroin from methadone and morphine [33, 34]. However, due to the main component of ice and maguo being the same, the tests did not distinguish MA into subcategories [35]. In Shanghai and Wuhan, 3,4-methylenedioxymethamphetamine (“MDMA”), cocaine, and
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cannabis had not been included in the initial screening tests, thus no death of these drug abusers was reported.
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Except one death with a positive heroin test resulted from a homicidal injection was excluded [37], all deaths with positive drug tests were included in this study. As all the deaths
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included in this study were not homicides, the drugs were thus presumed to have been
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voluntarily taken by the drug abusers. There were 333 drug-related deaths in total (Shanghai, 176; Wuhan, 157). In addition, although recording negative drug test results, deaths that
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occurred among the police registered drug abusers were also included (Shanghai, 23; Wuhan, 18). The police registered drug abusers referred to those people who had at least been caught
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once and found that they had used MA, heroin or ketamine at the time of their detainment, and those who had voluntarily reported to the police of their MA/heroin/ketamine abuse. Drug
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dealers who had not taken the drugs themselves were not regarded as police registered drug abusers. The combination of drug-related deaths and deaths of previous drug abusers formed the total deaths of the drug abusers in this study.
Data analyses Demographic variables were classified by region (Shanghai and Wuhan), gender, and age. Age was divided into four bands, 15-24, 25-34, 35-44, and 45 years and above. As to drug-
Mortalities of Drug Abusers in China 8
related deaths, the methods used in the last drug abuse were shown. According to the police body examination reports, some drug abusers had fresh injection traces. Therefore, the methods were divided into intravenous/subcutaneous injections, and others. Chi-square and Fisher’s exact tests were used to test the statistical differences of the drugrelated deaths in terms of the cause of death, region, gender, age, and the method used in the last drug abuse. To evaluate the trends in mortality rates, Poisson regression models were used to calculate the annual percentage changes (“APCs”). Poisson regression models were used to
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calculate the mortality rate ratios (“RRs”) of the region. The number of deaths was the
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dependent variable and the number of the general population was the offset. R package
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(Windows, 3.5.0) was used for statistical analyses.
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Results
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Demographics
Overall, 374 deaths were recorded, including 297 males (mean age 37.9; SD, 9.1) and 77
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females (mean age 34.7; SD, 9.0). It should be noted that in 13 deaths (Shanghai, 3; Wuhan, 10), more than one drug had been detected. In any multidrug poisoning death, the complex
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interactions could not be completely delineated [11], thus, in the police body examination reports, all the drugs were presumed to have been contributed to the deaths. All opioid-related deaths were among heroin abusers. There were 263 male heroin abusers (mean age 38.4; SD, 9.0) and 57 female heroin abusers (mean age 36.9; SD, 8.3); 34 male MA abusers (mean age 37.5; SD, 9.3) and 22 female MA abusers (mean age 30.6; SD, 9.1); 6 male ketamine abusers (mean age 32.5; SD, 8.5) and 5 female ketamine abusers (mean age 28.8; SD 9.6). Regarding combined drug abusers, 6 used MA and heroin, 7 used MA and ketamine. As these deaths had
Mortalities of Drug Abusers in China 9
been counted twice, the sum of independent MA, heroin, and ketamine abusers (n = 387) was greater than the total number of deaths (n = 374).
Causes of death of the drug abusers Table 2 shows the causes of death. Among the drug-related deaths, 6 were found to have used MA and heroin simultaneously, they died of drug poisoning with undetermined intent (n
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= 5) and fall with undetermined intent (n = 1). 7 deaths were found to have used MA and
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ketamine simultaneously, they died of drug poisoning with undetermined intent (n = 3) and fall with undetermined intent (n = 4). After excluding the combined drug abusers, heroin poisoning
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was the most significant cause of death for single heroin-related deaths (270/276). Among these heroin poisoning deaths, the only accidental death was caused by the packing of heroin inside
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the body and the only suicide was determined by the suicide note left by the deceased. As for
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the remainder, their intentions were ruled as undetermined (n = 268). Regarding the single MArelated deaths, MA poisoning with undetermined intent was the first cause of death (n = 24). Fall was the second cause of death for single MA-related deaths (n = 8): most falls had
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undetermined intents (n = 6), the remaining falls were suicides (n = 2). Regarding single ketamine-related deaths (n = 4), 3 died of falls, 2 with undetermined intent, the remaining 1
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was a suicide. Only 1 died of ketamine poisoning. As to the deaths of previous drug abusers, compared with the deaths of previous heroin
abusers (n = 38), deaths of previous MA abusers (n = 3) were much less frequently observed, and no death of previous ketamine users was recorded. Most previous heroin abusers died of natural causes (n = 22), followed by suicides by fall (n = 8), and hanging (n = 6). Due to the number of deaths of previous drug abusers being small, only drug-related deaths were included in the statistical analyses.
Mortalities of Drug Abusers in China 10
INSERT TABLE 2 ABOUT HERE
Statistical analyses of the drug-related deaths Table 3 provides the results of the statistical analyses. Two-step analyses were employed. In the beginning, combined drug-related deaths were assigned to different drug-related deaths (e.g., combined MA and heroin abusers were assigned to both MA-related deaths and heroin-
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related deaths). And then the combined drug-related deaths were removed so that only single
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drug-related deaths were included.
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INSERT TABLE 3 ABOUT HERE
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When combined drug abusers were included, regional differences were significant (p < 0.01). In both cities, heroin-related deaths were more frequently observed than MA-related
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deaths (Shanghai, 146/33; Wuhan, 136/20). However, ketamine-related deaths were only reported in Wuhan (n = 11). Gender (p < 0.001) and age (p < 0.05) differences were notable.
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The gender ratio was very close to one in MA- (1.8, 34/19) and ketamine-related (1.2, 6/5) deaths. However, males were much more frequently recorded in heroin-related deaths than
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females (4.4, 230/52). Heroin-related deaths tended to be older (mean age, 37.8; SD, 8.8) than MA-related deaths (mean age, 34.8; SD, 9.7) and ketamine-related deaths (mean age, 30.8; SD, 9.2). The causes of death were different among the three kinds of drug abusers (p < 0.001). Nearly all heroin-related deaths were caused by drug poisoning (97.5%, 275/282). However, falls (24.5%, 13/53) were commonly observed in MA-related deaths. Ketamine abusers were most likely to die of falls (63.6%, 7/11), death due to single ketamine poisoning was rare (9.0%, 1/11). Drug abusers used different methods on their last drug abuse (p < 0.001). Most heroin
Mortalities of Drug Abusers in China 11
abusers used intravenous/subcutaneous injections (89.4%, 236/264), while MA abusers (12.0%, 6/50) and ketamine abusers (20.0%, 2/10) used injections much less frequently. After excluding the combined drug-related deaths from the data set, differences remained on the region, cause of death, and method used in the last drug abuse. However, gender and age differences were no longer significant. Females were more frequently observed than males
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in combined drug-related deaths (7/6).
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The mortality trends and rate ratios
Figure 1 and Table 4 demonstrate the mortality rates among the general population. In the
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calculation, combined drug-related deaths were assigned to different drug-related deaths. In
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Shanghai, crude mortality rates of heroin abusers (APC, -13.9; 95% CI, -16.3 to -9.6) and heroin-related deaths (APC, -16.1; 95% CI, -18.4 to -11.3) declined. In Wuhan, crude mortality
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rates of heroin abusers (APC, -14.0; 95% CI, -16.9 to -9.0) and heroin-related deaths (APC, 16.0; 95% CI, -18.9 to -10.6) also declined. However, the MA-related mortality rates increased
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in Wuhan (APC, 12.8; 95% CI, 0.0 to 29.2). INSERT TABLE 4 ABOUT HERE
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INSERT FIGURE 1 ABOUT HERE
During the entire period of study, the crude mortality rates of drug abusers among the
general population in Wuhan were higher than in Shanghai, this was observed to be from heroin abusers (RR, 4.44; 95% CI, 3.57 to 5.53) and MA abusers (RR, 3.18; 95% CI, 1.83 to 5.40). Furthermore, deaths of ketamine abusers were only reported in Wuhan.
Discussion
Mortalities of Drug Abusers in China 12
This study for the first time compares the causes of death among Chinese MA, opioids, and ketamine abusers. In addition, the mortality trends among the three kinds of drug abusers are compared. The most notable findings were that all opioid-related deaths happened among heroin abusers, whereas death from prescription opioid abusers was not reported. Most heroin abusers died of drug overdoses while natural causes were ranked the second cause of death. Heroin-related mortality rates have decreased in both cities, whereas the MA-related mortality
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rates have increased in Wuhan. Deaths related to prescription opioids in China could be rare. In Shanghai and Wuhan, all
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opioid poisonings were caused by heroin, this result confirmed that heroin was the predominantly abused opioid in China [1]. As to other opioids, morphine was used in the
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treatment of terminal diseases, and methadone, in heroin addiction [4, 38]. However, deaths
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caused by morphine and methadone poisoning were not reported. By comparison, in some western nations (e.g., in New Zealand and the USA), more than one-third of opioid poisoning
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deaths were caused by prescription opioids [9, 38]. The absence of prescription opioid poisoning deaths in Shanghai and Wuhan could have two explanations. First, prescription
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opioids could have been well-managed by hospitals. In addition, Chinese patients tended to reject the use of opioids to relieve pain [39]. Second, prescription opioid poisoning deaths could
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have been treated as natural deaths by hospital physicians, and since natural deaths inside hospitals were not within the Chinese police jurisdiction [30], the police were not informed. Probably, both reasons explain the absence of prescription opioid poisoning deaths in the police files of the two cities.
In the world at large, natural causes were the primary cause of death for opioid abusers
(AIDS was the most prominent natural cause), followed by drug overdose. However, high heterogeneity was also observed among nations [15, 22]. This study found that drug overdose was the main cause of death for heroin abusers in Shanghai and Wuhan. In the present study,
Mortalities of Drug Abusers in China 13
275 out of 320 heroin abusers died of drug poisoning. By comparison, 22 heroin abusers died of natural causes, and only 1 of AIDS. Despite the police data failing to include natural deaths occurring inside hospitals, a cohort study in Sichuan Province where 376 voluntary heroin abusers participated, showed similar results. In the Sichuan study, drug overdose was the primary cause of death (64.3%, 18/28), only 4 deaths were due to natural causes with no AIDS death reported [21]. Although about 4.6% to 15.4% of the Chinese heroin abusers tested
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positive for HIV [4, 21, 40], the two studies showed that few heroin abusers died of AIDS. Under the national regulation in 1995 and 2011, all drug abusers caught by the police were
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required to take the compulsory detoxification. However, it is presumed that the reuse of heroin after compulsory detoxification or a large amount of heroin injection resulted in heroin
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overdose [21, 24]. Most of the heroin-related deaths were found to have used
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intravenous/subcutaneous injections (89.4%, 236/264). Moreover, the purity of heroin was not consistent, making it difficult for heroin abusers to calculate the amount of the substance to be
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injected [24]. The above reasons accounted for most of the Chinese heroin abusers dying of drug overdoses before they could die of other natural causes.
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The decision on the manner of death was also quite unique in China. The primary goal of death investigations in China was to identify homicides [28]. As shown in the present study,
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except for 1 suicide and 1 accidental death, the other heroin poisonings were ruled to have undetermined intents (n = 268). Although these deaths were very likely due to accidents occurred during heroin abuse, the possibility of them being suicides was not ruled out. However, as the police have ruled out the possibility of homicides, the investigations were thus closed, and the relatives were also unlikely to support further investigations. Hence, the intents of most heroin poisoning deaths were ruled to be undetermined. In China, heroin poisoning was rarely reported as a method of suicide [41, 42]. By comparison, in the USA, suicides by opioids were much more popular, where 2.2% to 4.4% of
Mortalities of Drug Abusers in China 14
all the suicides were caused by opioid poisoning [43]. In Pudong, Shanghai, for example, during the period of 2004-2017, the ratio of suicide verdicts to undetermined heroin poisoning deaths was 18.8 (2656/141) [28]. As some suicides by heroin poisoning could be misclassified as undetermined heroin poisonings, the proportion of suicides by heroin could thus be underestimated in Shanghai. Likewise, the proportion of suicides by heroin could also be underestimated in China as well.
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Nonetheless, declining trends of heroin-related deaths were observed in Shanghai and Wuhan, suggesting that the reduced heroin abuse among the Chinese people [1, 3] could have
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lowered the risk of opioid-related deaths, or, better social and medical support reduce the
in northern and southern China were still not known.
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mortality risk of heroin abusers. However, it should be noted that opioid-related mortality rates
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MA-related mortality risk, on the other hand, might increase in the future. Around the world, MA abusers have lower mortality risk than opioid abusers [15, 44, 45]. Especially in
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China, the mortality risk of MA abusers could be much lower than heroin abusers (refer to Table 1). Although the trend in MA abuse has increased rapidly [1, 3], due to the relatively
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lower mortality risk related to MA abuse, MA-related mortalities might not increase simultaneously. Despite it still being uncertain whether age is an important factor in influencing
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the mortality risk of MA abusers [8], MA abuse increases the possibility of sexually transmitted diseases (e.g., hepatitis B) [46, 47]. In addition, several studies suggested that mortality risk increased with age among the other drug abusers (e.g., opioid abusers) [48, 49]. The increase in MA abuse in China has only lasted for less than two decades [2, 3], but given the accumulated effect of MA abuse, there is a concern that natural and injury-related mortality rates could increase in the long run. Worldwide, compared with opioid-related mortalities, MA related-mortalities receive less attention. Also, reports of MA-related mortality rates among the general population could be
Mortalities of Drug Abusers in China 15
scarce [45]. In the southern half of Osaka, Japan, the mortality rate of MA abusers (per 100,000 general population) was 0.19 during the period of 1994-1998 [13]. This rate is similar to Wuhan (0.18) but higher than in Shanghai (0.06). However, a much higher rate was reported in Yunfu city in the Guangdong Province (0.91) [20]. The results might imply that MA abuse in Guangdong could be more serious than in Shanghai, Wuhan, and Osaka. Although screening tests for ketamine were performed in both cities, deaths of ketamine
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abusers were only reported in Wuhan. It could be inferred that ketamine abuse in Wuhan could be more prevalent than in Shanghai. In addition, most of the ketamine abusers (63.6%, 7/11)
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used MA at the same time, thus the characteristics of ketamine abusers could greatly resemble those of the MA abusers. However, death due to single ketamine poisoning was rare (9.1%,
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1/11). Likewise, the findings in New York also suggest that deaths caused by single ketamine
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poisoning could be rare [11].
Female deaths caused by MA and ketamine abuse should be emphasized. Previous studies
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suggested that Chinese drug abusers were characterized as male predominant [4, 40]. However, in the present study, the gender ratios of MA- (1.8, 34/19) and ketamine-related deaths (1.2,
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6/5) were close to one. The results implied that either the number of female MA and ketamine abusers had been underreported, or female MA and ketamine abusers were more vulnerable to
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death than their male counterparts. Therefore, the surveillance of MA and ketamine abuse in Chinese females should be improved. In particular, a study in Shandong revealed that about 30% of the 1,211 female sex workers had used MA [47], thus the surveillance on drug abuse by female sex workers should be particularly emphasized. The number of Chinese drug abusers is probably much higher than the number reported
by the CFDA (276,980) [1]. As reported by the CFDA, drug abuse in Shanghai was more severe than in Wuhan. However, in Wuhan, the mortality rates of heroin and MA abusers among the general population were much higher than in Shanghai. The inconsistencies imply that drug
Mortalities of Drug Abusers in China 16
abuse in Wuhan could be more likely to be underreported. Although the CNNCC reported a much higher number of drug abusers (about 2.5 million) [3], the CNNCC report had not specified regional variations, making it hard to make comparisons with the police recorded mortality rates.
Limitations and suggestions
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First, many demographic variables were not completely recorded in the police files (e.g.,
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marital status, education attainment, and job description). Thus, these variables were not included in the present study. Second, except for carbon monoxide, MA, heroin, and ketamine,
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other substances were also found in the postmortem laboratory tests. To be specific, alcohol
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was found in 18 drug abusers, diazepam in 2 drug abusers, while estazolam, triazolam, and dextromethorphan were found in 1 drug abuser. Nonetheless, the mixed drug effects were not
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taken into consideration. Third, in China, autopsies were not compulsory for natural deaths [28, 30]. Due to the low autopsy rate, the causes of death could hardly be determined [30]. As
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manifested in the present study, the causes of death were determined in only 30.4% (7/23) of the natural deaths. Fourth, as the exact number of drug abusers living in Shanghai and Wuhan
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could not be retrieved, this study was unable to calculate the standard mortality ratio of drug abusers.
Fifth and most importantly, so far, among all the Chinese official mortality data sources,
the mortality rates of drug abusers can only be ascertained through regional police files [23, 24]. However, police data could underestimate the mortality rates. The police have no jurisdiction over natural deaths occurring inside hospitals. Also, the relatives of the deceased have the right to reject the drug tests when the possibility of homicide has been ruled out. The tests of MDMA, cocaine, and cannabis are not routinely performed by the police. Furthermore,
Mortalities of Drug Abusers in China 17
urine and blood tests are not applicable to severely decomposed bodies. The screening tests for MA, opioids, and ketamine could have false-negative results, confirmatory tests were not performed to certify the false-negative results. Inevitably, all the above factors could lead to the underreporting of deaths of drug abusers. To improve on the mortality surveillance on drug abusers in the short-term, it is thus suggested that regardless of the causes of death, data on the deaths with positive drug tests as
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well as deaths of registered drug abusers should be collected by the drug administration authorities. In the long run, to minimize the underreporting of deaths of drug abusers, GC-MS
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tests for all the commonly abused drugs (including MDMA, cannabis, and cocaine) were recommended. The corresponding drug control and rehabilitation plans should be benefited
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from the more detailed mortality data of drug abusers.
Conclusion
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Studies on the mortalities of Chinese drug abusers are scarce. This study investigates the characteristics of deaths of MA, opioid, and ketamine abusers in Shanghai (2004-2017) and
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Wuhan (2005-2017). Most heroin abusers died of heroin poisoning while natural causes were ranked as the second cause of death. Death caused by prescription opioid poisoning was not
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reported. Heroin-related mortality rates have decreased in both cities, whereas the MA-related mortality rates have increased in Wuhan. It is anticipated that the mortality risk of MA abusers could further increase in the future. The gender ratios in MA- and ketamine-related deaths were close to one, thus the surveillance on MA and ketamine abuse by the females should be improved.
Declaration This manuscript or any other substantially similar paper has not been published.
Mortalities of Drug Abusers in China 18
Conflict of interest All authors declare that they have no conflict of interest.
Funding This research has not received any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Jinchen Liu: Data curation and Writing
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Paul S.F. Yip: Supervision, Reviewing, and Editing
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Xuesong Lu: Resources and Writing
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Sihai Liu: Resources and Writing
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Feng Li: Conceptualization, Methodology and Writing
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References
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of
[1] China Food and Drug Administration, National Drug Abuse Surveillance Report.
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Jo ur
na
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re
-p
ro
of
[21] L. Zhang, Y. Ruan, Z. Jiang, Z. Yang, S. Liu, F. Zhou, Y. He, L. Yin, G. QIn, Y. Shao, An 1-year Prospective Cohort Study on Mortality of Injecting Drug Users, Chinese Journal of Epidemiology 26(3) (2005) 190-193. [22] L. Degenhardt, C. Bucello, B. Mathers, C. Briegleb, H. Ali, M. Hickman, J. McLaren, Mortality among regular or dependent users of heroin and other opioids: a systematic review and meta‐analysis of cohort studies, Addiction 106(1) (2011) 32-51. [23] H. Hu, Y. Chen, X. Wang, D. Sun, Z. Liao, Y. Ding, Investigation and Analysis of Death from Heroin Poisoning in Chengdu District, Acta Academiae of Medicinae Wannan 23(4) (2004) 303-304. [24] W. Li, L. Wan, J. Yin, B. Sun, Analysis of 500 Deaths Related to Heroin Injection, Chinese Journal of Forensic Medicine 11(4) (1996) 242-243. [25] M. Akhgari, H. Mobaraki, A. Etemadi-Aleagha, Histopathological study of cardiac lesions in methamphetamine poisoning-related deaths, DARU Journal of Pharmaceutical Sciences 25(1) (2017) 5. [26] F. Li, J. Zeng, J. Huang, J. Zhang, Y. Chen, H. Yan, W. Huang, X. Lu, P.S. Yip, Work-related and nonwork-related accident fatal falls in Shanghai and Wuhan, China, Safety Science 117 (2019) 43-48. [27] F. Li, S. Liu, X. Lu, Y. Ou, P.S.F. Yip, Application of the Injury Scales in Homicides, Forensic Science International 292 (2018) 83-89. [28] F. Li, X. Lu, Y. Ou, P.S. Yip, The influence of undetermined deaths on suicides in Shanghai, China, Social psychiatry and psychiatric epidemiology 54(1) (2019) 111-119. [29] F. Li, X. Lu, Infant deaths in Pudong, Shanghai, China: A Retrospective Study of the Police Data and Comparison with the Centre for Disease Control Data, Journal of Forensic and Legal Medicine 62 (2019) 7-13. [30] F. Li, H.C. Chan, S. Liu, H. Jia, H. Li, Y. Hu, Z. Wang, W. Huang, Carbon monoxide poisoning as a cause of death in Wuhan, China: A retrospective six-year epidemiological study (2009–2014), Forensic Science International 253 (2015) 112-118. [31] The Chinese Ministry of Justice, The Regulations of Forensic Autopsy Examination (SF/Z JD0101002-2015).
Mortalities of Drug Abusers in China 21
Jo ur
na
lP
re
-p
ro
of
[39] Y. Huang, Current status of pain management in China: an overview, European Journal of Pain 5(SA) (2001) 67-71. [40] S. Lai, W. Liu, J. Chen, J. Yang, Z.-J. Li, R.-J. Li, F.-X. Liang, S.-L. Liang, Q.-Y. Zhu, X.-F. Yu, Changes in HIV-1 incidence in heroin users in Guangxi Province, China, Journal of acquired immune deficiency syndromes (1999) 26(4) (2001) 365-370. [41] J. Sun, X. Guo, J. Ma, J. Zhang, C. Jia, A. Xu, Seasonality of suicide in Shandong China, 1991–2009: Associations with gender, age, area and methods of suicide, Journal of Affective Disorders 135(1-3) (2011) 258-266. [42] A. Page, S. Liu, D. Gunnell, T. Astell-Burt, X. Feng, L. Wang, M. Zhou, Suicide by pesticide poisoning remains a priority for suicide prevention in China: Analysis of national mortality trends 2006–2013, Journal of Affective Disorders 208 (2017) 418-423. [43] J.B. Braden, M.J. Edlund, M.D. Sullivan, Suicide deaths with opioid poisoning in the United States: 1999–2014, American journal of public health 107(3) (2017) 421-426. [44] L.-J. Liang, D. Huang, M.-L. Brecht, Y.-I. Hser, Differences in mortality among heroin, cocaine, and methamphetamine users: a hierarchical bayesian approach, Journal of drug issues 40(1) (2010) 121140. [45] R.C. Callaghan, J.K. Cunningham, M. Verdichevski, J. Sykes, S.R. Jaffer, S.J. Kish, All-cause mortality among individuals with disorders related to the use of methamphetamine: a comparative cohort study, Drug and alcohol dependence 125(3) (2012) 290-294. [46] Y. Huang, S. Wu, Y. Tian, Analysis on Data fo Methamphetamine Abuse from 2013 to 2015 in Shandong Province, Chinese Journal of Pharmacoepidemiology 3 (2017) 199-203. [47] M. Liao, Z. Jiang, X. Zhang, D. Kang, Z. Bi, X. Liu, J. Fu, N. Zhang, W. Mao, B. Jiang, Syphilis and methamphetamine use among female sex workers in Shandong Province, China, Sexually transmitted diseases 38(1) (2011) 57-62. [48] E.L. Merrall, S.M. Bird, S.J. Hutchinson, Mortality of those who attended drug services in Scotland 1996–2006: record-linkage study, International Journal of Drug Policy 23(1) (2012) 24-32. [49] M. Pierce, S.M. Bird, M. Hickman, T. Millar, National record linkage study of mortality for a large cohort of opioid users ascertained by drug treatment or criminal justice sources in England, 2005– 2009, Drug and alcohol dependence 146 (2015) 17-23.
Mortalities of Drug Abusers in China 22
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Figure 1. Crude mortality rates among the general population
Authors
Data source and study design
Regions study
Ou [20]
Police, cohort study
Li et al. [24]
Hu et al. [23]
pr
Table 1. Studies of MA- and heroin-related deaths in Mainland China
oo
f
Mortalities of Drug Abusers in China 23
Deaths of MA abusers
Mortality rates of MA abusers in the general population (per 100,000)
Mortality rates for 1,000 MA abuseryears (for cohort studies)
Heroin abuse population (for cohort studies)
About 1,646
16
0.91a
1.9a
MA abuse population (for cohort studies)
Deaths of heroin abusers
Mortality rates of heroin abusers in the general population (per 100,000)
Mortality rates of 1,000 heroin abuser-years (for cohort studies)
NA
NA
NA
NA
General Population (100,000)
Yunfu City, Guangdong Province, China
20102014
3.5
Police, case series
Kunming City, Yunnan Province, China
19901995
About 50
NA
NA
NA
NA
NA
500
1.67a
NA
Police, case series
Chengdu City, Sichuan Province, China
19962002
110.3
NA
NA
NA
NA
NA
396
0.51a
NA
Jo ur na l
Pr
e-
Periods of study
of
Crude mortality rate.
b
Standardized mortality rate.
NA
NA
NA
pr
NA
Jo ur na l
a
20022003
e-
Liangshan Autonomous Prefecture, Sichuan Province, China
Pr
Zhang et al. [21]
Recruit volunteers, cohort study
oo
f
Mortalities of Drug Abusers in China 24
NA
376
28
NA
77.3a/47.6b
f
Mortalities of Drug Abusers in China 25
0/7 0/15 2/6 0/0 1/8 0/1 1/0
0/0 0/1 0/1 1/0 2/1 2/0 0/0
Single ketaminerelated deaths/previous ketamine abusers 0/0 0/0 0/0 0/0 1/0 0/0 0/0
2
0/0
2/0
1
1/0
Drug poisoning
301
Falls Drowning Thermal injuries Hemorrhagic shock
14 2 3 1
Single heroinNumber of related drug abusers deaths/previous heroin abusers
Accidents
Undetermined intent
a
e-
27
7 16 9 1 13 3 1
Pr
Suicides
Determined causes a Undetermind causes Hanging Drowning Falls Hemorrhagic shock Drug poisoning Carbon monoxide poisoning Drug poisoning
Jo ur na l
23
pr
Number Manners of death of drug Causes of death abusers
Natural causes
oo
Table 2. Causes of death among all the drug users
3
321
Single MArelated deaths/previous MA abusers
MA- and MAand heroinketaminerelated related deaths deaths 0 0 0 0 0 0 0
0 0 0 0 0 0 0
0/0
0
0
0/0
0/0
0
0
268/0
24/0
1/0
5
3
0/1 0/0 2/0 1/0
6/0 2/0 1/0 0/0
2/0 0/0 0/0 0/0
1 0 0 0
4 0 0 0
Determined causes include heart failure, pulmonary tuberculosis, diabetes mellitus, hepatitis, AIDS, and intracranial hemorrhage.
f
Mortalities of Drug Abusers in China 26
MArelated deaths
Ketaminerelated 2/Fisher's exact tests for the differences deaths
33 (30)
0 (0)
20 (10)
11 (4)
Shanghai Wuhan
146 (143) a 136 (133)
Male
17 (17) 84 (83) 98 (95) 64 (62)
Drug poisoning
275 (270) 2 (1) 0 (0) 1 (1) 2 (2) 0 (0) 2 (2)
Falls Drowning Hemorrhagic shock Hanging Carbon monoxide poisoning Thermal injuries Method used in the last drug abuse Intravenous/subcutaneous 236 injections (233)
11.55** (3.73 b)
34 (28)
6 (3)
19 (12)
5 (1)
8 (5) 18 (16) 16 (12) 11 (7)
4 (1) 4 (3) 1 (0) 2 (0)
13.64* a (8.79 b)
32 (24)
4 (1)
98.65*** b (85.58*** b)
13 (8) 3 (3) 2 (2) 0 (0) 2 (2) 1 (1)
7 (3) 0 (0) 0 (0) 0 (0) 0 (0) 0 (0)
6 (2)
2 (1)
Jo ur na l
Female Age c 15-24 25-34 35-44 45 and above Causes of death
230 (227) 52 (49)
Pr
Gender
14.14** (12.17** b)
e-
Regions
pr
Heroinrelated deaths
oo
Table 3. Statistical comparison of the drug-related deaths
152.39*** e (125.14*** be)
28 (25) 18 (18)
44 (36) 3 (2)
8 (3) 1 (0)
oo
Others Unknown d
f
Mortalities of Drug Abusers in China 27
Number in the parentheses excluded the combined drug-related deaths.
b
Due to the small numbers, Fisher's exact tests were used.
c
Information on age of some decedents was not recorded.
d
Due to decomposition, thermal injuries, human activities, or other factors, the existence of fresh injection trace was not determined.
pr
a
Due to the unknown method of drug abuse not included, the result was generated by 3 by 2 2/Fisher’s exact test. *p < 0.5, **p < 0.05, ***p < 0.001.
Jo ur na l
Pr
e-
e
f
Mortalities of Drug Abusers in China 28
Wuhan
Annual percentage changes (95% CI) -13.9 (-16.3 to -9.6)*** -16.1 (-18.4 to -11.3)*** 4.4 (-4.6 to 14.3) 4.4 (-4.7 to 14.5) -14.0 (-16.9 to -9.0)*** -16.0 (-18.9 to -10.6)*** 11.0 (-1.0 to 25.8) 12.8 (0.0 to 29.2)* 8.8 (-7.5 to 28.8)
pr
Jo ur na l
*p < 0.5, **p < 0.05, ***p < 0.001.
Pr
e-
Shanghai
Rates (95% CI) Heroin abusers 0.3 (0.2 to 0.3) Heroin-related deaths 0.2 (0.2 to 0.3) MA abusers 0.1 (0.0 to 0.1) MA-related deaths 0.1 (0.0 to 0.1) Heroin abusers 1.3 (1.1 to 1.5) Heroin-related deaths 1.1 (1.0 to 1.3) MA abusers 0.2 (0.1 to 0.3) MA-related deaths 0.2 (0.1 to 0.2) Ketamine-related deaths 0.1 (0.0 to 0.1)
oo
Table 4. Crude mortality rates (per 100,000 general population) and trends among the three kinds of drug abusers