James K. Cunningham

Increased risk of Parkinson's disease in individuals hospitalized with conditions related to the use of methamphetamine or other amphetamine-type drugs

BACKGROUND Since methamphetamine and other amphetamine-type stimulants (meth/amphetamine) can damage dopaminergic neurons, researchers have long speculated that these drugs may predispose users to develop Parkinsons disease (PD), a dopamine deficiency neurological disorder. METHODS We employed a retrospective population-based cohort study using all linked statewide California inpatient hospital episodes and death records from January 1, 1990 through December 31, 2005. Patients at least 30 years of age were followed for up to 16 years. Competing risks analysis was used to determine whether the meth/amphetamine cohort had elevated risk of developing PD (ICD-9 332.0; ICD-10 G20) in comparison to a matched population-proxy appendicitis group and a matched cocaine drug control group. Individuals admitted to hospital with meth/amphetamine-related conditions (n=40,472; ICD-9 codes 304.4, 305.7, 969.7, E854.2) were matched on age, race, sex, date of index admission, and patterns of hospital admission with patients with appendicitis conditions (n=207,831; ICD-9 codes 540-542) and also individuals with cocaine-use disorders (n=35,335; ICD-9 codes 304.2, 305.6, 968.5). RESULTS The meth/amphetamine cohort showed increased risk of PD compared to both that of the matched appendicitis group [hazard ratio (HR)=1.76, 95% CI: 1.12-2.75, p=0.017] and the matched cocaine group [HR=2.44, 95% CI: 1.32-4.41, p=0.004]. The cocaine group did not show elevated hazard of PD compared to the matched appendicitis group [HR=1.04, 95% CI: 0.56-1.93, p=0.80]. CONCLUSION These data provide evidence that meth/amphetamine users have above-normal risk for developing PD.

Methamphetamine Use and Schizophrenia: A Population-Based Cohort Study in California

OBJECTIVE Clinical investigators in Japan have long suggested that exposure to methamphetamine might cause a persistent schizophrenia-like psychosis. This possibility is discounted in the Western literature. To investigate the relationship between drug use and later schizophrenia, the authors conducted a large-scale cohort study of drug users initially free of persistent psychosis. METHOD A population-based cohort study was conducted using data from California inpatient hospital discharge records from 1990 through 2000. Patients with methamphetamine-related conditions (N=42,412) and those with other drug use disorders (cannabis, cocaine, alcohol, and opioids) were propensity score-matched to individuals with primary appendicitis who served as a population proxy comparison group; the methamphetamine cohort was also matched to the other drug cohorts. Cox modeling was used to estimate differences between matched groups in the rates of subsequent admission with schizophrenia diagnoses. RESULTS The methamphetamine cohort had a significantly higher risk of schizophrenia than the appendicitis group (hazard ratio=9.37) and the cocaine, opioid, and alcohol groups (hazard ratios ranging from 1.46 to 2.81), but not significantly different from that of the cannabis group. The risk of schizophrenia was higher in all drug cohorts than in the appendicitis group. CONCLUSIONS Study limitations include difficulty in confirming schizophrenia diagnoses independent of drug intoxication and the possibility of undetected schizophrenia predating drug exposure. The studys findings suggest that individuals with methamphetamine-related disorders have a higher risk of schizophrenia than those with other drug use disorders, with the exception of cannabis use disorders. The elevated risk in methamphetamine users may be explained by shared etiological mechanisms involved in the development of schizophrenia.

Incidence of Parkinson's disease among hospital patients with methamphetamine-use disorders.

Because methamphetamine exposure to experimental animals can damage brain dopamine neurones, we examined whether hospital patients diagnosed with methamphetamine‐related disorders might have greater risk of subsequent admission with a Parkinsons disease diagnosis. This was a population‐based cohort study using all statewide inpatient hospital discharge records from July 1, 1990, through June 30, 2000, in California, USA, in which subjects aged at least 50 years were followed for up to 10 years. Individuals with reported methamphetamine‐related conditions (n = 1,863; ICD‐9 codes 304.4, 305.7, 969.7, and E854.2) were matched on demographic variables and follow‐up time with those with primary appendicitis conditions (n = 9,315). The appendicitis group had a Parkinsons disease incidence rate no different than the rate found among members of a large health maintenance organization in California. Cox regression procedures were used to estimate group differences in the rates of receiving a subsequent inpatient diagnosis of Parkinsons disease (ICD‐9 332.0). The methamphetamine group showed increased risk of a subsequent admission with Parkinsons disease compared with that of the matched appendicitis group (adjusted hazard ratio = 2.65, 95% CI, 1.17–5.98, P= 0.019). Study limitations include a population limited to hospital admissions, an uncertainty regarding diagnostic validity of the ICD‐9 code 332.0 (Parkinsons disease), and a small number of incident cases with suspected Parkinsons disease. We strongly emphasize the preliminary nature of the findings. Nevertheless, these data, requiring replication, provide some evidence that methamphetamine users might be at greater than normal risk for developing Parkinsons disease.

Impact of methamphetamine precursor chemical legislation, a suppression policy, on the demand for drug treatment

Research is needed to help treatment programs plan for the impacts of drug suppression efforts. Studies to date indicate that heroin suppression may increase treatment demand. This study examines whether treatment demand was impacted by a major US methamphetamine suppression policy -- legislation regulating precursor chemicals. The precursors ephedrine and pseudoephedrine, in forms used by large-scale methamphetamine producers, were regulated in August 1995 and October 1997, respectively. ARIMA-intervention time-series analysis was used to examine the impact of each precursors regulation on monthly voluntary methamphetamine treatment admissions (a measure of treatment demand), including first-time admissions and re-admissions, in California (1992-2004). Cocaine, heroin, and alcohol treatment admissions were used as quasi-control series. The 1995 regulation of ephedrine was found to be associated with a significant reduction in methamphetamine treatment admissions that lasted approximately 2 years. The 1997 regulation of pseudoephedrine was associated with a significant reduction that lasted approximately 4 years. First-time admissions declined more than re-admissions. Cocaine, heroin, and alcohol admissions were generally unaffected. While heroin suppression may be associated with increased treatment demand as suggested by research to date, this study indicates that methamphetamine precursor regulation was associated with decreases in treatment demand. A possible explanation is that, during times of suppression, heroin users may seek treatment to obtain substitute drugs (e.g., methadone), while methamphetamine users have no comparable incentive. Methamphetamine suppression may particularly impact treatment demand among newer users, as indicated by larger declines in first-time admissions.

Methamphetamine suppression and route of administration: precursor regulation impacts on snorting, smoking, swallowing and injecting

AIMS The route of drug administration affects risk for dependence and medical harm. This study examines whether routes used by methamphetamine treatment participants were impacted by a major drug suppression policy-federal regulation of the methamphetamine precursor chemicals ephedrine and pseudoephedrine. DESIGN Autoregressive-integrated moving average (ARIMA) intervention time-series analysis. SETTING California (1992-2004). INTERVENTIONS Ephedrine single-ingredient products regulation, implemented August 1995; ephedrine with other active medicinal ingredients regulation, implemented October 1996; pseudoephedrine products regulation, implemented October 1997. MEASUREMENTS Monthly counts of non-coerced methamphetamine treatment admissions reporting snorting, smoking, swallowing or injecting. Findings After rising sharply, snorting, smoking, swallowing and injecting admissions dropped 50%, 43%, 26% and 26%, respectively, when the 1995 regulation was implemented. Snorting also dropped 38% at the time of the 1997 regulation. Snorting, swallowing and injecting remained at lower levels to the end of the study period. Smoking resurged (40%) at the time of the 1996 regulation and continued rising. CONCLUSIONS Precursor regulation was associated with changes in the administration of methamphetamine. Injecting, the route with the greatest health risk, entered a long-term reduction. So, too, did snorting and swallowing, two routes with lower risk for dependence. In contrast, smoking, which has a relatively high risk for dependence, dropped, then rebounded and entered a long-term rise. A possible explanation is that injecting, snorting and swallowing were largely linked with US domestic methamphetamine production, which has yet to recover from the regulations. While Mexican production, which was impacted only temporarily by the regulations and has supplanted domestic production, may have helped to diffuse smoking, a route with which it is historically correlated.

All-cause mortality among individuals with disorders related to the use of methamphetamine: A comparative cohort study

BACKGROUND Understanding the mortality rate of methamphetamine users, especially in relation to other drug users, is a core component of any evaluation of methamphetamine-related harms. Although methamphetamine abuse has had a major impact on United States (U.S.) drug policy and substance-abuse treatment utilization, large-scale cohort studies assessing methamphetamine-related mortality are lacking. METHODS The current study identified cohorts of individuals hospitalized in California from 1990 to 2005 with ICD-9 diagnoses of methamphetamine- (n=74,139), alcohol- (n=582,771), opioid- (n=67,104), cannabis- (n=46,548), or cocaine-related disorders (n=48,927), and these groups were followed for up to 16 years. Age-, sex-, and race-adjusted standardized mortality rates (SMRs) were generated. RESULTS The methamphetamine cohort had a higher SMR (4.67, 95% CI 4.53, 4.82) than did users of cocaine (2.96, 95% CI 2.87, 3.05), alcohol (3.83, 95% CI 3.81, 3.85), and cannabis (3.85, 95% CI 3.67, 4.03), but lower than opioid users (5.71, 95% CI 5.60, 5.81). CONCLUSIONS Our study demonstrates that individuals with methamphetamine-use disorders have a higher mortality risk than those with diagnoses related to cannabis, cocaine, or alcohol, but lower mortality risk than persons with opioid-related disorders. Given the lack of long-term cohort studies of mortality risk among individuals with methamphetamine-related disorders, as well as among those with cocaine- or cannabis-related conditions, the current study provides important information for the assessment of the comparative drug-related burden associated with methamphetamine use.

Effects of the minimum legal drinking age on alcohol-related health service use in hospital settings in Ontario: A regression-discontinuity approach

OBJECTIVES We assessed the impact of the minimum legal drinking age (MLDA) on hospital-based treatment for alcohol-related conditions or events in Ontario, Canada. METHODS We conducted regression-discontinuity analyses to examine MLDA effects with respect to diagnosed alcohol-related conditions. Data were derived from administrative records detailing inpatient and emergency department events in Ontario from April 2002 to March 2007. RESULTS Relative to youths slightly younger than the MLDA, youths just older than the MLDA exhibited increases in inpatient and emergency department events associated with alcohol-use disorders (10.8%; P = .048), assaults (7.9%; P < .001), and suicides related to alcohol (51.8%; P = .01). Among young men who had recently crossed the MLDA threshold, there was a 2.0% increase (P = .01) in hospitalizations for injuries. CONCLUSIONS Young adults gaining legal access to alcohol incur increases in hospital-based care for a range of serious alcohol-related conditions. Our regression-discontinuity approach can be used in future studies to assess the effects of the MLDA across different settings, and our estimates can be used to inform cost-benefit analyses across MLDA scenarios.

Non-injection drug use and hepatitis C among drug treatment clients in west central Mexico

BACKGROUND Research on hepatitis C virus (HCV) prevalence among non-injecting drug treatment clients in the United States, Europe and Asia indicate substantial differences by place. To date, little or no research on HCV and non-injection drug use (NIDU) has been conducted in Mexico. METHODS We examined the prevalence of HCV, hepatitis B virus (HBV), and HIV among non-injecting drug users (NIDUs) in community-based drug treatment (N=122) and NIDUs in a prison-based drug treatment program (N=30), both located in west central Mexico. RESULTS Among the community clients, prevalence was 4.1% (95% confidence interval [CI]: 1.8-9.2) for HCV, 5.7% for HBV (95% CI: 2.8-11.4), and 1.6% for HIV (95% CI: 0.4-5.8). Among the in-prison clients, prevalence was 40.0% (95% CI: 24.6-57.7) for HCV, 20.0% for HBV (95% CI: 9.5-37.3), and 6.7% for HIV (95% CI: 1.9-21.3). None of the clients were aware of being infected. CONCLUSION The HCV prevalence found for the NIDU community treatment clients ranks among the lower HCV estimates published for NIDUs in treatment to date. The prevalence found for the in-prison clients ranks among the higher, raising a concern of possible elevated HCV infection among NIDUs in the west central Mexico prison--one compounded by the finding that none of this studys clients knew they were HCV positive.

See Me Smoke-Free: Protocol for a Research Study to Develop and Test the Feasibility of an mHealth App for Women to Address Smoking, Diet, and Physical Activity

Background This paper presents the protocol for an ongoing research study to develop and test the feasibility of a multi-behavioral mHealth app. Approximately 27 million women smoke in the US, and more than 180,000 women die of illnesses linked to smoking annually. Women report greater difficulties quitting smoking. Concerns about weight gain, negative body image, and low self-efficacy may be key factors affecting smoking cessation among women. Recent studies suggest that a multi-behavioral approach, including diet and physical activity, may be more effective at helping women quit. Guided imagery has been successfully used to address body image concerns and self-efficacy in our 3 target behaviors—exercise, diet and smoking cessation. However, it has not been used simultaneously for smoking, diet, and exercise behavior in a single intervention. While imagery is an effective therapeutic tool for behavior change, the mode of delivery has generally been in person, which limits reach. mHealth apps delivered via smart phones offer a unique channel through which to distribute imagery-based interventions. Objective The objective of our study is to evaluate the feasibility of an mHealth app for women designed to simultaneously address smoking, diet, and physical activity behaviors. The objectives are supported by three specific aims: (1) develop guided imagery content, user interface, and resources to reduce weight concern, and increase body image and self-efficacy for behavior change among women smokers, (2) program a prototype of the app that contains all the necessary elements of text, graphics, multimedia and interactive features, and (3) evaluate the feasibility, acceptability, and preliminary efficacy of the app with women smokers. Methods We created the program content and designed the prototype application for use on the Android platform in collaboration with 9 participants in multiple focus groups and in-depth interviews. We programmed and tested the application’s usability with 6 participants in preparation for an open, pre- and posttest trial. Currently, we are testing the feasibility and acceptability of the application, evaluating the relationship of program use to tobacco cessation, dietary behaviors, and physical activity, and assessing consumer satisfaction with approximately 70 women smokers with Android-based smart phones. Results The study was started January 1, 2014. The app was launched and feasibility testing began in April 1, 2015. Participants were enrolled from April 1-June 30, 2015. During that time, the app was downloaded over 350 times using no paid advertising. Participants were required to use the app “most days” for 30 days or they would be dropped from the study. We enrolled 151 participants. Of those, 78 were dropped or withdrew from the study, leaving 73 participants. We have completed the 30-day assessment, with a 92% response rate. The 90-day assessment is ongoing. During the final phase of the study, we will be conducting data analyses and disseminating study findings via presentations and publications. Feasibility will be demonstrated by successful participant retention and a high level of app use. We will examine individual metrics (eg, duration of use, number of screens viewed, change in usage patterns over time) and engagement with interactive activities (eg, activity tracking). Conclusions We will aggregate these data into composite exposure scores that combine number of visits and overall duration to calculate correlations between outcome and measures of program exposure and engagement. Finally, we will compare app use between participants and non-participants using Google Analytics.

Mexico's precursor chemical controls: Emergence of less potent types of methamphetamine in the United States

BACKGROUND This study examines whether Mexicos controls on ephedrine and pseudoephedrine, the two precursor chemicals that yield the most potent form of methamphetamine, d-methamphetamine, impacted the prevalence/availability of less potent types of methamphetamine in the United States-types associated with the alternative precursor chemical P2P. METHOD Using ARIMA-intervention time series analysis of monthly drug exhibits (a prevalence/availability indicator) from the System to Retrieve Information from Drug Evidence (STRIDE), we tested whether Mexicos controls, which began in 2005, were associated with growth/decline in d-methamphetamine and growth/decline in P2P-associated, less potent l-methamphetamine, racemic methamphetamine (a 50:50 ratio of d- and l-isomers), and mixed isomer methamphetamine (an unequal ratio of d- and l-isomers). Heroin, cocaine and marijuana exhibits were used for quasi-control (01/2000-04/2011). RESULTS Mixed-isomer exhibits constituted about 4% of the methamphetamine exhibits before Mexicos controls, then rose sharply in association with them and remained elevated, constituting about 37% of methamphetamine exhibits in 2010. d-Methamphetamine exhibits dropped sharply; l-methamphetamine and racemic methamphetamine exhibits had small rises. d-Methamphetamine exhibits partially recovered in the US West, but little recovery occurred in the US Central/South. Quasi-control series were generally unaffected. CONCLUSION The US methamphetamine market changed. Widespread emergence of less potent methamphetamine occurred in conjunction with Mexicos controls. And prevalence/availability of the most potent type of the drug, d-methamphetamine, declined, a partial recovery in the West notwithstanding. Granting that lower potency drugs typically engender less dependence and attendant problems, these findings suggest that, following Mexicos controls, the potential harm of a sizeable amount of the US methamphetamine supply decreased.