Outcome of A Large Cohort of Patients with Methamphetamine Dependence: A Multifacet Approach
Date Issued
2011
Date
2011
Author(s)
Kuo, Chian-Jue
Abstract
Background:
Since the 1990s, the abuse of methamphetamine has become one of the fastest growing illicit drug problems worldwide, particular in South-east Asia, Australia, and North America. Methamphetamine (MAMP) was reported to induce the physical and mental harms; the earlier ones include cardiovascular disorders and the later include depression, psychosis, and suicide. Methamphetamine use leads to increased likelihood of premature death. However, the empirical information regarding the mortality outcome and causes of death is limited in the literature. Besides, methamphetamine has a well-known cardiotoxicity in the humankind. Given the non-invasiveness, low cost, and wide availability, the electrocardiogram (ECG) may be a useful tool for assisting in the clinical assessment of various harms and prediction of future outcome in patients with methamphetamine dependence. A recent systematic review highlighted only eight cohort studies that investigated the mortality of amphetamine users in the literature, and three of these studies had a sample size of 500 or larger. The project was proposed to follow up a large cohort of inpatients (N=1254) with methamphetamine dependence who had ever been hospitalized due to methamphetamine-related problems by means of a record-linkage study for obtaining their mortality information. Based on the nested case-control study design and standardized chart reviewing process, the risk factors for suicide mortality and natural death separately are explored. Additionally, a healthy study group will be enrolled as the control group for the comparison of electrocardiographic abnormalities with the methamphetamine-dependent group.
Design and Methods:
Part I. In a consecutive series of 1,254 inpatients with methamphetamine dependence (diagnosed according to DSM-III-R and DSM-IV criteria) admitted to a psychiatric center in northern Taiwan from January 1, 1990, through December 31, 2007, was defined as the cohort and retrospectively studied. Diagnostic and sociodemographic data for each subject were extracted from the medical records based on a brief chart review process. Mortality data were obtained by linking to the National Death Certification System (1990-2007) and standardised mortality ratios (SMRs) were estimated. Totally, around 150 deceased subjects are estimated to be found.
Part II. Based on the link process in part I, 38 deaths due to suicide were identified as cases, and 76 controls were randomly selected using risk-set density sampling in a 2:1 ratio, matched for age, sex, and the year of index admission. A standardized comprehensive chart review process was adopted to collate sociodemographic, psychopathological and clinical information for each study subject. Multivariate conditional logistic regression analysis was used to identify correlates of suicide among these patients.
Part III. Based on the link process in part I, forty-five cases died of natural causes, each of which was then matched with four living controls on age, sex and the year of index admission using risk-set sampling. Clinical data and laboratory results during hospitalization were obtained through a standardized review of medical records.
Part IV. This study enrolled two groups, a large-size roster of subjects (N=387) derived from a cohort of inpatients with methamphetamine dependence and a healthy control group (n=300), for the comparison of comprehensive ECG indices based on the Minnesota code classification. A standardized chart review process was adopted to collate sociodemographic and clinical information for each study subject. The laboratory (Epicare) for standardized ECG readings was blinded to all of clinical data and grouping information. ECG readings were classified into normal and abnormal (minor, major) by 5 categorical indices: myocardial infarction or ischemia, conduction defect, arrhythmias, atrial enlargement or ventricular hypertrophy, and prolonged ventricular repolarization. Differences of indices of electrocardiograms between the two groups were standardized against those of a healthy control group, with adjustment for covariates derived from the differences between methamphetamine and control groups. Based on the nested case-control study, this study also explored the ECG abnormality in association with all-cause, natural, unnatural and cardiovascular deaths separately.
Results:
Part I. During the study period, 130 patients died. Of them, 63.1% died from unnatural deaths, while the remaining 36.9% died from natural deaths. Relative to the general population, the cohort had excessive mortality (SMR of 6.02) and women had a higher SMR for unnatural deaths than men (p = 0.001).
Part II. For the sociodemographic and symptom profiles at the latest admission, financial independence lowered the risk (adjusted risk ratio aRR = 0.33, p < .05) whereas visual hallucinations elevated the risk (aRR = 2.57, p < .05) for suicide. For the profiles during the post-discharge period, financial independence (aRR = 0.11, p < .05) remained associated with reduced risk to suicide, whereas suicide attempt (aRR = 8.78, p < .05) and depressive syndrome (aRR = 3.28, p = .059) were associated with increased risk of suicide.
Part III. For clinical characteristics at the index admission, multivariate conditional logistic regression revealed that the adjusted risk ratio for natural death was 10.69 (p < .001) in the group with markedly elevated aspartate aminotransferase (> 80 U/L) and 4.71 (p < .01) in the mildly elevated group (40–80 U/L), with reference to the normal group (< 40 U/L). As for alanine aminotransferase, the adjusted risk ratios were 5.22 (p < .01) and 5.13 (p < .01). For the profiles at the latest admission during the study period, the use of antipsychotic drugs was identified to be associated with lowered risk.
Part IV. After adjusting the covariates regarding the differences between two groups, only three indices of continuous indices had the adjusted z score greater than 0.5 (medium effect size), including PR duration (-0.9422), QTc duration (0.9062) and QTI (0.9021). The differences for these indices were around 1.0 standard deviation.
Methamphetamine-dependent group had a higher proportion of arrhythmia than the healthy control group (17.6% vs. 8.7%, p=0.001), whereas other 4 indices were not significant different between two groups. Methamphetamine-dependent group were likely to have major abnormality of electrocardiogram compared with control group (4.4% vs. 1.3%, p=0.015), along with minor abnormality (47.8% vs. 39.7%, p=0.003).
Additionally, stratified by the status of methamphetamine use, current users were not significantly different from recent users except higher heart beat rates. The electrocardiographic abnormalities were not associated with duration of methamphetamine use in methamphetamine group.
Conclusions.
Part I. A substantial proportion of the deceased died of natural deaths, but most of them died of unnatural deaths. The findings show significant evidence to provide a valuable insight for the premature deaths in the specific population. Part II. Both protective and risk factors for suicide mortality were found among inpatients with methamphetamine dependence, and the findings have implications for clinical intervention and prevention. Part III. This study highlights the damage of methamphetamine use to multiple organ systems, which is associated with natural death, along with the necessity of intensive follow-up among individuals with elevated aspartate or alanine aminotransferases.
Part IV. This study confirmed the electrocardiographic abnormality in methamphetamine-dependent groups, predominantly shortened PR and prolonged QT intervals. Furthermore, it is highly suggestive for screening methamphetamine users with electrocardiographic abnormality, as a potentially treatable or manageable form of cardiotoxicity.
Since the 1990s, the abuse of methamphetamine has become one of the fastest growing illicit drug problems worldwide, particular in South-east Asia, Australia, and North America. Methamphetamine (MAMP) was reported to induce the physical and mental harms; the earlier ones include cardiovascular disorders and the later include depression, psychosis, and suicide. Methamphetamine use leads to increased likelihood of premature death. However, the empirical information regarding the mortality outcome and causes of death is limited in the literature. Besides, methamphetamine has a well-known cardiotoxicity in the humankind. Given the non-invasiveness, low cost, and wide availability, the electrocardiogram (ECG) may be a useful tool for assisting in the clinical assessment of various harms and prediction of future outcome in patients with methamphetamine dependence. A recent systematic review highlighted only eight cohort studies that investigated the mortality of amphetamine users in the literature, and three of these studies had a sample size of 500 or larger. The project was proposed to follow up a large cohort of inpatients (N=1254) with methamphetamine dependence who had ever been hospitalized due to methamphetamine-related problems by means of a record-linkage study for obtaining their mortality information. Based on the nested case-control study design and standardized chart reviewing process, the risk factors for suicide mortality and natural death separately are explored. Additionally, a healthy study group will be enrolled as the control group for the comparison of electrocardiographic abnormalities with the methamphetamine-dependent group.
Design and Methods:
Part I. In a consecutive series of 1,254 inpatients with methamphetamine dependence (diagnosed according to DSM-III-R and DSM-IV criteria) admitted to a psychiatric center in northern Taiwan from January 1, 1990, through December 31, 2007, was defined as the cohort and retrospectively studied. Diagnostic and sociodemographic data for each subject were extracted from the medical records based on a brief chart review process. Mortality data were obtained by linking to the National Death Certification System (1990-2007) and standardised mortality ratios (SMRs) were estimated. Totally, around 150 deceased subjects are estimated to be found.
Part II. Based on the link process in part I, 38 deaths due to suicide were identified as cases, and 76 controls were randomly selected using risk-set density sampling in a 2:1 ratio, matched for age, sex, and the year of index admission. A standardized comprehensive chart review process was adopted to collate sociodemographic, psychopathological and clinical information for each study subject. Multivariate conditional logistic regression analysis was used to identify correlates of suicide among these patients.
Part III. Based on the link process in part I, forty-five cases died of natural causes, each of which was then matched with four living controls on age, sex and the year of index admission using risk-set sampling. Clinical data and laboratory results during hospitalization were obtained through a standardized review of medical records.
Part IV. This study enrolled two groups, a large-size roster of subjects (N=387) derived from a cohort of inpatients with methamphetamine dependence and a healthy control group (n=300), for the comparison of comprehensive ECG indices based on the Minnesota code classification. A standardized chart review process was adopted to collate sociodemographic and clinical information for each study subject. The laboratory (Epicare) for standardized ECG readings was blinded to all of clinical data and grouping information. ECG readings were classified into normal and abnormal (minor, major) by 5 categorical indices: myocardial infarction or ischemia, conduction defect, arrhythmias, atrial enlargement or ventricular hypertrophy, and prolonged ventricular repolarization. Differences of indices of electrocardiograms between the two groups were standardized against those of a healthy control group, with adjustment for covariates derived from the differences between methamphetamine and control groups. Based on the nested case-control study, this study also explored the ECG abnormality in association with all-cause, natural, unnatural and cardiovascular deaths separately.
Results:
Part I. During the study period, 130 patients died. Of them, 63.1% died from unnatural deaths, while the remaining 36.9% died from natural deaths. Relative to the general population, the cohort had excessive mortality (SMR of 6.02) and women had a higher SMR for unnatural deaths than men (p = 0.001).
Part II. For the sociodemographic and symptom profiles at the latest admission, financial independence lowered the risk (adjusted risk ratio aRR = 0.33, p < .05) whereas visual hallucinations elevated the risk (aRR = 2.57, p < .05) for suicide. For the profiles during the post-discharge period, financial independence (aRR = 0.11, p < .05) remained associated with reduced risk to suicide, whereas suicide attempt (aRR = 8.78, p < .05) and depressive syndrome (aRR = 3.28, p = .059) were associated with increased risk of suicide.
Part III. For clinical characteristics at the index admission, multivariate conditional logistic regression revealed that the adjusted risk ratio for natural death was 10.69 (p < .001) in the group with markedly elevated aspartate aminotransferase (> 80 U/L) and 4.71 (p < .01) in the mildly elevated group (40–80 U/L), with reference to the normal group (< 40 U/L). As for alanine aminotransferase, the adjusted risk ratios were 5.22 (p < .01) and 5.13 (p < .01). For the profiles at the latest admission during the study period, the use of antipsychotic drugs was identified to be associated with lowered risk.
Part IV. After adjusting the covariates regarding the differences between two groups, only three indices of continuous indices had the adjusted z score greater than 0.5 (medium effect size), including PR duration (-0.9422), QTc duration (0.9062) and QTI (0.9021). The differences for these indices were around 1.0 standard deviation.
Methamphetamine-dependent group had a higher proportion of arrhythmia than the healthy control group (17.6% vs. 8.7%, p=0.001), whereas other 4 indices were not significant different between two groups. Methamphetamine-dependent group were likely to have major abnormality of electrocardiogram compared with control group (4.4% vs. 1.3%, p=0.015), along with minor abnormality (47.8% vs. 39.7%, p=0.003).
Additionally, stratified by the status of methamphetamine use, current users were not significantly different from recent users except higher heart beat rates. The electrocardiographic abnormalities were not associated with duration of methamphetamine use in methamphetamine group.
Conclusions.
Part I. A substantial proportion of the deceased died of natural deaths, but most of them died of unnatural deaths. The findings show significant evidence to provide a valuable insight for the premature deaths in the specific population. Part II. Both protective and risk factors for suicide mortality were found among inpatients with methamphetamine dependence, and the findings have implications for clinical intervention and prevention. Part III. This study highlights the damage of methamphetamine use to multiple organ systems, which is associated with natural death, along with the necessity of intensive follow-up among individuals with elevated aspartate or alanine aminotransferases.
Part IV. This study confirmed the electrocardiographic abnormality in methamphetamine-dependent groups, predominantly shortened PR and prolonged QT intervals. Furthermore, it is highly suggestive for screening methamphetamine users with electrocardiographic abnormality, as a potentially treatable or manageable form of cardiotoxicity.
Subjects
Methamphetamine
outcome
mortality
risk factor
suicide
natural death
electrocardiogram
abnormality
SDGs
Type
thesis
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