Longitudinal Patterns of Drug Injection Behavior in the ALIVE Study Cohort,1988–2000: Description and Determinants

N. Galai1,2 , M. Safaeian1, D. Vlahov1,3, A. Bolotin2 and D. D. Celentano1

1 Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD.
2 Department of Epidemiology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
3 Center for Urban Epidemiologic Studies, New York Academy of Medicine, New York, NY.

Received for publication September 26, 2002; accepted for publication April 18, 2003.


    ABSTRACT
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
The objective of this study was to characterize longitudinal patterns of drug injection behavior for individuals and to identify their early determinants. Participants were 1,339 injection drug users recruited into the AIDS Link to Intravenous Experience (ALIVE) Study in Baltimore, Maryland, through community outreach efforts. The study was initiated in 1988, and follow-up continued through 2000, with semiannual visits. Patterns of self-reported drug injection (yes/no) were defined for each participant, based on the number of drug-use transitions. The effect of baseline factors was assessed using multinomial logistic regression models. Over the 12-year study period, four patterns were noted: 29% of participants remained persistent drug injectors, 20% ceased injection, 14% relapsed once, and 37% had multiple transitions. Persistent injectors had the shortest follow-up and the highest mortality. For persons who changed their behavior, 3.4 years elapsed before their first cessation attempt, on average. Factors differentiating the groups included history of incarceration, young age, participation in drug treatment programs, recent overdose, and commercial sex. The observed long-term injection patterns are consistent with the view of drug addiction as a chronic disease. This view emphasizes the need for prolonged efforts to sustain cessation and to prevent adverse health and social outcomes among injection drug users.

behavior; HIV; longitudinal studies; recurrence; substance abuse, intravenous

Abbreviations: Abbreviations: AIDS, acquired immunodeficiency syndrome; ALIVE, AIDS Link to Intravenous Experience; HIV, human immunodeficiency virus.


    INTRODUCTION
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
While drug addiction has long been recognized as having characteristics similar to those of chronic disease conditions, few studies have attempted to empirically substantiate the full natural history of drug abuse across the life course of drug users. With the spread of the human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) epidemic in many developed countries, injection drug users have become a focus of risk-reduction intervention efforts, because they account for a substantial proportion of HIV/AIDS cases (1). Most HIV-preventive interventions focus on changing drug injection habits, including promoting abstinence through drug treatment, reducing the sharing of injection equipment, increasing needle hygiene practices, and encouraging participation in needle-exchange programs. Many of the large epidemiologic studies launched since the late 1980s have focused on HIV transmission dynamics, HIV pathogenesis, and morbidity and mortality. Frequently, drug injection has been viewed in these epidemiologic studies as a risk factor for infection, primarily with HIV and hepatitis C virus as the outcomes. In the addiction studies literature, there has been a greater focus on the examination of social and psychological factors associated with substance abuse and the success of different treatment methods (2, 3).

Drug users are a difficult group to follow prospectively, and therefore many studies of these populations are restricted to short-term changes in behavior. In light of this, many investigators also recruit participants from drug treatment facilities, a practice that is certainly subject to selection bias. A recent US study evaluated over one million drug users who were discharged from drug treatment programs and found great reductions in drug and alcohol use during the 5 years following treatment (4). Similar findings of treatment-associated lower frequencies of drug use, drug injection, and needle-sharing were observed in studies conducted in the United States, Europe, and Hong Kong (59). In other populations of drug users, general trends of decreased drug injection over time have been noticed. A short-term study of drug users treated in a hospital reported a 40 percent rate of cessation of injection after approximately 2 years, but more than 50 percent of the participants remained injection drug users (10). In the United Kingdom, a 10-year study of a small group of injection drug users treated in general practice clinics showed a move from injection drug use to oral drug use, a change probably related to the HIV epidemic (11). However, it is not clear how these "average trends" translate into personal histories or trajectories of drug use. In particular, are there identifiable subgroups of users who cease drug use and users who persist in the habit over relatively long periods of time?

In a small study examining changes in drug use between two interviews carried out approximately 2 years apart, Morrison noted the "myriad of personal, social, and economic factors which combine to facilitate and maintain drug involvement" (12, p. 213). This is true not only at the population level but also at the individual level. At any given time point, an individual’s behavior may be influenced by factors that are varying over time, such as employment opportunities, family status, housing situation, incarceration, and the availability and cost of specific drugs. Several recent papers have presented findings from longitudinal studies of cohorts of injection drug users. These studies focused either on the population trends, shown as a series of cross-sectional snapshots of the cohort, or on transitions between cessation and reinitiation of drug injection (1318). Various factors were found to be associated with short-term changes, including age, gender, ethnicity, HIV serostatus, prostitution, frequency of injection, use of noninjection drugs, and methadone treatment.

It is of interest to explore the possibility that beyond transient (situational) factors, there are recognizable patterns of use that are typical of individuals. Characterizing the existence and frequency of such individual patterns was the focus of this study. In contrast to previous studies, we attempted to characterize the common patterns observed within individuals over a long portion of the drug-use career in a large cohort of well-characterized injection drug users. Our specific objectives were to characterize intraindividual longitudinal patterns of drug injection and to evaluate their association with baseline demographic and behavioral factors. Understanding what these patterns are and identifying early determinants may provide important insight, especially for the development of effective treatment programs.


    MATERIALS AND METHODS
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Design and study population
During the period February 1988 through March 1989, 2,946 active injection drug users were recruited into the AIDS Link to Intravenous Experience (ALIVE) Study in Baltimore, Maryland, through community outreach efforts. Participants underwent a screening interview in which data on sociodemographic factors, history of drug use and sexual practices over the previous 10 years, and the time of initiation of drug injection were obtained. Follow-up visits at the study clinic were scheduled at 6-month intervals and included a personal interview eliciting detailed information on behaviors in the previous 6 months, use of health care services, a physical examination, and various laboratory tests, including HIV testing. Diagnoses of AIDS were confirmed through abstraction of medical records, and death outcomes were matched with information in the National Death Index. Details on the study methods have been published elsewhere (19). The study was approved by the institutional review board of the Johns Hopkins Bloomberg School of Public Health.

Because the present analysis focused on long-term behavior patterns, the population was restricted to 1,413 injection drug users who had made at least four follow-up visits and who reported having injected drugs during the 6 months prior to their first regular study visit. Follow-up continued for 12 years, through December 2000. A total of 250 participants (17.7 percent) had a gap in follow-up that exceeded 2 years. For 176 (70.4 percent) of those participants, a trajectory was defined based on the longer sequence of visits either before or after the gap (see below). The other 74 participants, those without four consecutive visits or with more than one large gap in follow-up, were excluded. Thus, the analysis was finally based on 1,339 individuals corresponding to 20,072 visits. Follow-up time was calculated as the number of years between the last available visit and the first trajectory visit. This follow-up time was shorter than the total observation time in the study, that is, from baseline to death or censoring.

Definition of injection trajectories and statistical analysis
The main outcome of interest was the series of binary indicators of self-reported drug injection (yes/no), based on the repeated visits for each individual, over the entire follow-up period. The first goal of the analysis was to define classes of injection patterns based on this binary outcome. These patterns were then defined by the number of drug-use transitions made by an individual during the follow-up period. A transition could be a change from reported injection at one visit to a report of no injection at the next visit (yes -> no) or a change from no injection to injection (no -> yes). Four main groups were thus defined for the analysis, considering the different implications of these behavior patterns from the perspective of long-term drug addiction:

I. No transitions (persistent injectors): Persons who reported drug injection at every visit.

II. One transition (cessation): Persons reporting injecting drugs for some time who then stopped and reported no injection at all subsequent visits.

III. Two transitions (a single relapse): Persons reporting injecting drugs and then stopping who subsequently relapsed and continued to report injecting at all later visits.

IV. Three or more transitions (multiple relapses and cessations): Persons whose behavior fluctuated from injecting to not injecting over time.

Formal assessment of factors associated with each pattern was performed using multinomial regression in univariate and multivariate models. In this formulation, the dependent variable has four possible outcomes corresponding to the patterns described above, with group I, the persistent injectors, chosen as the reference category. In effect, three logistic-type regression models are constructed, for each of groups II–IV relative to the reference group. The same variables appear in each equation, but the coefficient, ß, may differ. Interpretation of the results is based on the eß terms expressing the odds ratio for being in, for example, group II rather than group I for a specific predictor (risk factor). Analysis was performed using SAS (SAS Institute, Inc., Cary, North Carolina) and Stata (Stata Corporation, College Station, Texas) software.

All candidate variables, measured at the screening interview or the first study visit, were examined for their univariate associations with the four behavior patterns. Only factors with a potentially significant association at the p <= 0.10 level are shown, and these were all introduced into the initial multivariate models. The final model used a threshold of 0.05 for statistical significance. Variables screened but not shown included African-American race, family status, having children at home, educational level, employment, HIV, clinical status and use of health services, use of noninjection drugs (marijuana, heroin, cocaine), and duration of drug use.

Rates of mortality are given as simple percentages, and rates of loss to follow-up were calculated as the percentage of those participants known to be alive who had not been seen in the last 3 years, that is, since January 1998. AIDS rates were calculated on the basis of any clinical AIDS diagnosis recorded during the entire follow-up period.


    RESULTS
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Of the 1,339 injection drug users included in the analysis, 391 (29.2 percent) remained persistent injectors (no transitions) over the entire 12-year follow-up period, 263 (19.6 percent) ceased injection without relapse (one transition), 191 (14.3 percent) relapsed once (two transitions) and then steadily continued to use drugs, and 494 (36.9 percent) had multiple cessations and relapses. A summary of follow-up length and intensity is shown in table 1. The overall mean follow-up time was 7.8 years (standard deviation, 3.5), and the average number of visits was 15.0 (standard deviation, 6.7). Recall that follow-up time here is the length of the trajectory and is somewhat shorter than the total amount of follow-up time. The persistent injectors (group I) had the shortest follow-up, with a mean of 6.1 years (standard deviation, 3.5), which was largely due to the high rates of mortality (42.5 percent) and loss to follow-up (32.0 percent) in this group. The AIDS rate in this group was similar to the rates in the other groups and thus does not explain the shorter follow-up among persistent injectors. The multiple-transitions group (group IV) had the longest follow-up (mean = 9.1 years; standard deviation, 2.9) and corresponding low rates of mortality (18.0 percent) and loss to follow-up (15.3 percent) in comparison with the other groups. However, the intensity of follow-up was similar across groups (an average of 2.0 visits per year).


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TABLE 1. Distribution of participants according to pattern of intravenous drug injection over a 12-year follow-up period, ALIVE* Study, Baltimore, Maryland, 1988–2000
 
The participants who met the inclusion criteria but were excluded because of long gaps in follow-up (74/1,413 (5.2 percent)) differed from the analysis group in that they tended to include fewer females (8.1 percent vs. 22.8 percent, p = 0.003) and fewer persons with children at home (32.9 percent vs. 45.1 percent, p = 0.06), had a higher percentage of persons with a history of incarceration in the 10 years prior to study entry (78.6 percent vs. 66.7 percent, p = 0.04), and had a lower prevalence of HIV infection at baseline (17.8 percent vs. 34.5 percent, p = 0.003). The groups did not differ significantly with respect to other characteristics at baseline.

The common topologies of individual injection behavior over time and the average amount of time between transitions are shown in figure 1. In this figure, the multiple-transition group (group IV) is partitioned into three subgroups with three, four, or more than four transitions for illustration. The average time interval between the first study visit and the first cessation transition (yes -> no) for the 948 participants who reported not injecting at least once during follow-up was 3.4 years (standard deviation, 2.8) (table 1). Group IV had the shortest time to first cessation (mean = 2.7 years; 95 percent confidence interval: 2.5, 2.9) in comparison with groups II and III (means of 4.0 years (95 percent confidence interval: 3.6, 4.4) and 4.3 years (95 percent confidence interval: 3.8, 4.7), respectively). Note that group IVa, representing a single relapse with subsequent cessation, had a somewhat longer time to first relapse (mean = 1.5 years) than group III, for which relapse was not reversed (mean = 1.1 years).



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FIGURE 1. Common longitudinal patterns of drug injection among injection drug users (IDUs) over a 12-year follow-up period, AIDS Link to Intravenous Experience (ALIVE) Study, Baltimore, Maryland, 1988–2000. Each panel shows a group of participants defined by their number of drug-use transitions during follow-up. The steps correspond to transitions between yes/no injection states, and the length of each step shows the average amount of time spent in each state. The numbers on the figure show the mean number of years of follow-up in each injection state and (in parentheses) 95% confidence intervals. In the last panel, sample sizes decreased for each step beyond the fifth transition and were 131, 94, 52, 36, and 22, respectively.

 
Univariate associations of various factors, measured at study entry, with the four future patterns of injection behavior are given in table 2. Associations were estimated with a multinomial logistic regression model, and the results are expressed as odds ratios, with the persistent injectors (group I) used as the reference group. Each factor has three odds ratios: the odds for the cessation group (group II) versus the persistent group (group I), the odds for the single-relapse group (group III) versus the persistent group, and the odds for the multiple-relapse group (group IV) versus the persistent group.


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TABLE 2. Patterns of intravenous drug injection over a 12-year period according to factors measured at the baseline visit, ALIVE{dagger} Study, Baltimore, Maryland, 1988–2000{ddagger}
 
Of the sociodemographic factors (table 2), younger age at enrollment, especially age less than 30 years, was significantly associated with cessation of injection or with cessation followed by relapses, and lower legal income was associated positively with cessation and negatively with a single relapse. Females were more likely to be in the cessation group. Of the behavioral variables, referring to the 6-month prior to the first study visit (table 2), both drug and sex-related behaviors showed significant univariate associations with specific injection trajectories. Injection of only one drug and participation in a methadone maintenance program at baseline were associated with multiple transitions. Conversely, frequent injection (at least daily), visiting "shooting galleries," and having reported a recent episode of overdose at baseline were associated with being in the persistent-injector group. Daily use of alcohol was strongly associated with being a persistent injector, and cigarette smoking was negatively associated with cessation. Regarding sexual behaviors, participants who reported trading sex for drugs or money and having an injection drug user as a sexual partner were less likely to make transitions out of injection status. Homosexual men represented a small subset in our cohort and tended to make transitions but were significantly associated only with the single-relapse group.

Table 3 shows the relations of history of drug use and lifetime experiences with future long-term individual patterns of injection. Having been incarcerated in the past 10 years had a strong negative association with cessation but not with other patterns. Ever being in drug treatment of any form had a weak negative association with single relapse. There was a special interest in the association between behaviors immediately following initiation of drug injection and the development of the drug injection career. Young age at initiation (age <17 years) was marginally associated with not having multiple transitions. Participants who started with a "moderate" frequency of 1–6 injections per week were significantly less likely to have two or more transitions. Injection drug users who shared syringes with more than two persons during that initiation period were also more likely to become persistent injectors. Those who peaked quickly to their maximal injection frequency, within 1 year of initiation, were significantly more likely to have multiple relapses than those who took longer to reach their peak frequency.


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TABLE 3. Patterns of intravenous drug injection over a 12-year period according to lifetime experiences (history of specific behaviors prior to study entry), ALIVE{dagger} Study, Baltimore, Maryland, 1988–2000{ddagger}
 
Results from the multivariate multinomial regression model are shown in table 4. The multivariate results demonstrate that different factors identify classification in the four specific patterns of drug injection careers. Other than younger age, which differentiated groups III and IV from the persistent injectors (group I), only one other variable (of 13 included in the final model) was common in the examination of group differences from the persistent injectors: Both relapse groups were less likely to trade sex for drugs or money than group I (and the direction was similar with marginal significance for group II). Otherwise, specific individual factors differentiated each group from persistent users. The comparison of persistent injectors with those who stopped using injection drugs and never relapsed showed that those who quit were significantly less likely to have a history of incarceration at any time in the 10 years prior to study enrollment. The only other factors marginally associated with the cessation group were low income, detoxification, and male homosexual sex. In comparison with persistent injectors, those who stopped using drugs but then relapsed and continued injecting (group III) were similar with respect to drug-use history but differed with respect to age (younger), were less likely to engage in sex for money or drugs, and were significantly more likely to give a history of male homosexual sex. Finally, comparison of the persistent injectors with the multiple-relapse group (group IV) showed that the latter were younger, more likely to use cocaine alone at their first visit (as compared with any other drug or drugs in combination), were more likely to have participated in methadone treatment immediately prior to study entry, were less likely to give a history of recent drug overdose in the 6 months before enrollment, were less likely to trade sex for money or drugs, were less likely to share drug injection equipment with multiple persons within the first 3 months of drug use, and were more likely at initiation to be young and to peak quickly to maximal injection frequency. Thus, the four groups are quite differentiated with respect to demographic factors, drug involvement, and factors associated with introduction to injection drug use.


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TABLE 4. Adjusted associations of factors measured at the baseline visit with specific patterns of drug injection over the following 12-year period, ALIVE{dagger} Study, Baltimore, Maryland, 1988–2000{ddagger}
 

    DISCUSSION
 TOP
 ABSTRACT
 INTRODUCTION
 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
This study of drug users prospectively followed for more than a decade offers a descriptive tool with which to characterize the typology of individual injection careers. Rather than focus on visit-to-visit changes, the individual trajectories reflect the dynamics of personal behavior over time. Perhaps the most important finding from this study is that so few opiate injectors were able to resolve their drug addiction. While the majority (71 percent) did experience some period of abstinence over the decade of observation, most subsequently relapsed to injection. Only a minority of our cohort members (19.6 percent) succeeded in ceasing injection drug use completely during the study period. The insidious nature of drug addiction is very clearly demonstrated by these observational data. At every semiannual clinic visit, participants underwent pretest HIV counseling and individually tailored risk reduction counseling, and they received both their HIV test results and posttest counseling at a subsequent visit. In addition, active referrals were made to drug treatment programs (methadone maintenance, detoxification, extended residential treatment, Narcotics Anonymous), where the waiting list was waived. However, only a minority of our participants availed themselves of drug treatment, despite our staff’s best effort to promote abstinence. This resistance and delayed entry to treatment has been observed by others (20). These difficulties also emphasize the need to increase the availability of treatment slots and overcome barriers to access (21).

Many sociodemographic factors and drug-use practices failed to discriminate between the four trajectory groups in our multivariate analysis. Among the sociodemographic variables that failed to differentiate drug-use patterns were education, marital status, and having dependent children. These factors generally represent greater stability and a decreased likelihood of becoming severely involved in drug use. Possibly, these factors were confounded with behavioral factors that were included in the analysis.

Among the drug-use practices, we could find no discrimination between groups for frequency of drug use both at the time of drug-use onset or in the 6 months before the baseline visit. In addition, behaviors commonly associated with drug involvement, including visiting shooting galleries and recent needle-sharing, were not associated with any specific pattern after adjustment for all other factors. Alcohol abuse is commonly implicated in opiate addiction. However, reports of heavy alcohol use at baseline lost the significant association with persistent injection after adjustment. Notably, being HIV-seropositive at baseline did not predict any particular injection pattern, in contrast with another study that found associations between HIV serostatus and change in injection behavior (22).

Of great interest is that only a history of incarceration differentiated persons who successfully stopped using drugs from those who continued to use injection drugs over a 12-year period. Sociodemographic factors, drug-use patterns, drug treatment, and sexual behaviors did not have independent discriminatory power to distinguish between persistent injectors and those who ceased drug use. Thus, drug involvement and severity factors do not appear to provide any useful information for predicting who will be successful in overcoming drug use. It is possible that additional psychological factors, such as depression, could provide a partial explanation, but this information was not obtained at study entry.

Participants who stopped using drugs and then relapsed for the duration of the study period were younger than the persistent injectors but had a similar drug-use profile. Importantly, while these participants were less likely to give a history of sexual exchange, they were four times more likely to give a history of male homosexual sex. HIV rates among persons who report both same-gender sex and injection drug use have been rising in the United States, especially among ethnic minorities (of whom more than 90 percent were African-American in this study). Compared with the multiple-relapse group, this group had a significantly longer time to first cessation, which may suggest different behavioral dynamics.

The greatest differences seen in our analysis of drug-use trajectories were found in the comparison of the persistent injectors and the multiple-relapse group. The latter participants were younger, did not use "speedball" at baseline, and attempted to cope with their perceived drug use by seeking multiple treatment options (both methadone maintenance and detoxification programs). They also tended to have a pattern of drug-use onset that might be characterized as "less risky"—they were significantly less likely to give a recent history of overdose, to exchange sex, and to share syringes with multiple partners. Finally, they were more likely to be young initiators who peaked quickly to their maximal injection frequency. This multiple-relapse group, the largest in our cohort, can best be characterized as persons who are truly trying, albeit unsuccessfully, to stop their drug use. Innovative integrative programs for prevention of relapse have been recently described (23).

The high mortality rate among the persistent injectors clearly demonstrates the health risks of persistent drug injection. The principal causes of death were overdose, violence, infections, and AIDS. The shorter follow-up of this group is largely a function of elevated mortality. The selective higher mortality was also offered as a partial explanation for observed population trends of decline in injection rates (13), and it emphasizes the importance of evaluating personal trajectories. Further exploration of the association between longitudinal injection patterns and survival would be interesting.

The approach presented in this study offers a descriptive tool with which to characterize common patterns of individual behavior over time, when the outcome is measured as a dichotomous variable. Regression methods that are routinely used to describe such longitudinal trends assume a quantitative outcome and hence are not applicable for binary data. An attempt to study intraindividual changes in drug injection habits used drug frequency as the outcome and was based on fitting of individual slopes (24). However, this smoothing of the trend masks distinct periods of cessation and relapse. Our data show that the average time to first relapse is 10–18 months and therefore suggest that intervention efforts should continue throughout this critical period to support injection drug users who try to overcome their addiction.

The generalizability of our findings is limited in several respects. First, while our cohort was recruited predominantly (85 percent) through street referrals and hence was not a clinic- or treatment-based sample, study volunteers may differ from community-based residents who use drugs but do not volunteer for or remain in a long-term study. Almost all of our participants were inner-city African Americans from one East Coast city with a long history of heroin use. The high prevalence of HIV in our cohort suggests that drug-use practices in this community may differ from practices in locales (e.g., Los Angeles and San Diego, California) that have not experienced a significant HIV epidemic among drug injectors. Selective loss to follow-up could also have affected the comparison among groups. Furthermore, our data may have been subject to a degree of socially desirable responding by participants, who may know the interviewers and clinic staff quite well after spending a decade in the ALIVE Study. However, the relatively low rates of abstinence given in our interviews suggest that this may not have been a significant problem.

The long-term injection patterns described in this study are consistent with the view of drug addiction as a chronic disease (25). The importance of investigating the long-term course of addiction, with emphasis on the accumulated experience of the dependency over a lifetime rather than a focus on short-term prognoses and treatment success, has been noted in the context of alcohol addiction (26). This view emphasizes the need for prolonged ongoing programs to sustain cessation efforts by injection drug users, and at the same time provide harm-reduction counseling and medical care to those who continue injecting either intermittently or continuously, to prevent adverse health and social outcomes.


    ACKNOWLEDGMENTS
 
This research was supported by grants DA04334 and DA08009 from the National Institute on Drug Abuse.


    NOTES
 
Correspondence to Dr. Noya Galai, Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe Street, Baltimore, MD 21205 (e-mail: ngalai{at}jhsph.edu). Back


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 MATERIALS AND METHODS
 RESULTS
 DISCUSSION
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