Shedding Light on Hidden Methamphetamine Abuse: A Nation-wide 7-year Post-mortem Study in Taiwan.

BACKGROUND: The number of methamphetamine-related deaths has been increasing in recent decades. However, current data primarily rely on a few large-scale national surveys, highlighting the need for diverse data sources. Post-mortem studies offer advantages that compensate for the limitations of cohort studies. In this study, we aimed to (1) examine mortality rates and years of potential life lost, (2) compare proportionate mortality with previous cohort studies, and (3) quantitatively investigate causes of death as potential risk factors associated with each manner of death. METHODS: We analyzed 740 cases from 2013 to 2019 in Taiwan. RESULTS: The mean age of cases was 38.4 years, with a notable loss of 30 or more years of potential life, and 79.6% were male. The crude mortality rate was 0.45 per 100,000 person-years. The proportionate mortality indicated that autopsy dataset, compared to cohort studies, provided more accurate estimations for accidental deaths, equivalent suicides, underestimated natural deaths, and overestimated homicides. Accidental deaths were evident in 67% of cases with 80% attributed to drug intoxication. Multiple substances were detected in 61% of cases, with psychiatric medications detected in 43% of cases. Higher methamphetamine concentrations and a greater proportion of multiple substances and benzodiazepines were detected in suicidal deaths. Among accidental deaths, traffic accidents (7.9%) were the second most common cause, particularly motorcycle riders. CONCLUSION: Using autopsy dataset as a secondary source, we identified that over half of the cases involved drug intoxication-related accidental deaths. The significant proportion of cases involving multiple substances, psychiatric medications, and drug-impaired driving raises concerns.

Stimulant safe supply: a potential opportunity to respond to the overdose epidemic.

BACKGROUND: Occurring against the backdrop of an overdose crisis, stimulant use and stimulant-involved deaths in North America are increasing at an alarming rate. Many of these deaths are being attributed to fentanyl and related analogs, which have been increasingly found within street-level stimulant supplies. Within this, people experiencing socio-economic marginalization are at the greatest risk of overdose and other harms from adulterated stimulants. Current treatments for stimulant use disorder have limited effectiveness, and even less applicability to the lived realities of marginalized stimulant users. Emerging technologies, such as drug checking, are being implemented to support safer stimulant use, but the accessibility and utility of these technologies to stimulant users are framed by experiences of vulnerability that render them largely ineffective. STIMULANT SAFE SUPPLY: Solutions that provide a legal and safe supply of non-adulterated stimulants of known quality, and within a health care framework, are needed to directly address the risk of an increasingly adulterated stimulant supply. Similar innovative opioid-focused interventions are being piloted with medications that have a similar pharmacological effect as their illicit counterparts. While there are currently no approved pharmacotherapies for stimulant use, research has demonstrated a number of stimulant medications that are promising substitutes for cocaine and methamphetamine use. Much like with opioid-focused pharmacotherapies, having a consistent and safe supply of stimulants can lead to improved health outcomes and will drastically reduce overdose risk. However, for a stimulant safe supply intervention to be a success, it must provide the high and performance-enhancing effects that people seek from the illicit market, which requires doses and user agency that trials to date have not provided. CONCLUSION: Efforts are needed to investigate the feasibility of pharmacological stimulant-based interventions that address safe supply needs. The promise of similar opioid-focused approaches in addressing both overdose-related risks and experiences related to vulnerability underscores the need to advance safe supply approaches targeted towards people who use stimulants. Given the current overdose crisis and rising stimulant use across North America, the implementation and evaluation of such novel stimulant-focused interventions should be a public health priority.

Nod-like receptor protein 3 and nod-like receptor protein 1 inflammasome activation in the hippocampal region of postmortem methamphetamine chronic user.

OBJECTIVE AND BACKGROUND: Methamphetamine (Meth) is one of the most important central nervous system (CNS) stimulant abuse drugs that cause long-term or permanent damage to different regions of the brain, particularly hippocampus, by neuronal apoptosis and inflammation. In this study, we evaluated Nod-like Receptor Protein 3(NLRP3) and Nod-like Receptor Protein1 (NLRP1) Inflammasome Activation in the Hippocampal Region of postmortem Meth Chronic User. METHODS: Molecular and histological analyses were conducted on the brain of 14 non-addicted and 11 Meth users separately. The expression level of NLRP1, NLRP3 was measured using western blotting and immunohistochemistry (IHC) techniques. Histopathological assessment was performed with stereological Cell Counting of hippocampal cells stained with hematoxylin and eosin (H et E). Moreover, Tunel staining was carried out in order to detect any kind of DNA damage. RESULTS: Based on our findings using western blotting and immunohistochemistry assay, overexpression of NLRP1 and NLRP3 proteins in the hippocampal region of Meth addicts was observed. The stereological analysis in the hippocampus of the human brain revealed increased neurodegeneration. Furthermore, the increased rate of apoptosis and cell death were significant and confirmed by Tunel assay in the hippocampus of Meth groups. CONCLUSION: Chronic Meth abuse could result in increases of NLRP1 and NLRP3 and induction of inflammation and apoptosis in the hippocampus in Meth groups (Tab. 1, Fig. 9, Ref. 40).

Clinical Characteristics and Outcomes of Patients with Amphetamine-Associated Cardiomyopathy in South Auckland, New Zealand.

BACKGROUND: Amphetamine-associated cardiomyopathy (AAC) is becoming an increasingly recognised entity. The characteristics and outcomes of these patients are poorly understood. METHODS: Thirty patients admitted with heart failure and echocardiographic evidence of cardiomyopathy between 2005 and 2014 and who had a documented history of amphetamine abuse that was considered an important factor in the causation of their cardiomyopathy were retrospectively identified. RESULTS: Mean age at presentation was 40±10 years with a male predominance (n=25, 83%). The majority were of indigenous Maori ethnicity. At presentation, four patients were in cardiogenic shock. Five patients required intensive care unit (ICU) admission for inotropic support and mechanical ventilation. Fifteen had severe left ventricular (LV) dilation (mean LV end-diastolic dimension 6.8±1.0cm) and all patients had severe LV dysfunction (mean LV ejection fraction 22±8%). Despite optimal heart failure therapy, LV size remained significantly dilated with minimal improvement in LV function. During median follow-up of 18 months, five patients died from end-stage heart failure and 17 had at least one readmission with decompensated heart failure. CONCLUSION: Amphetamine-associated cardiomyopathy was seen predominantly in young indigenous Maori men. They presented with severe cardiomyopathy, often requiring ICU admission. Severe LV dilation and significant LV dysfunction persisted despite treatment and mortality was high.

Mortality, causes of death and risk factors for death among primary amphetamine users in the Swedish criminal justice system.

This study examined mortality and predictors of death in 1,396 primary amphetamine users (85% males) who were interviewed with the Addiction Severity Index in the Swedish criminal justice system during 2000-2006 and followed through 2008. Forty-nine clients deceased (standardized mortality ratio 4.1 [3.0-5.4]), at least 84% of deaths were violent or drug-related (12% suicides), and Cox regression analysis indicated that death was associated with frequent use of sedatives and less frequent use of amphetamine. No female deaths were observed; death and male gender were associated in binary analysis. Implications for diagnostics and treatment are discussed.

MDMA and the "ecstasy paradigm".

For nearly 30 years, there has been a steady flow of research papers highlighting the dangers of MDMA and the implications for ecstasy users. After such a long time, it would be reasonable to expect that these dangers would be obvious due to the large number of ecstasy users. The available evidence does not indicate that there are millions of ecstasy users experiencing any problems linked to their ecstasy use. The "precautionary principle" suggests that, in the absence of knowing for certain, "experts" should argue that MDMA be avoided. However, this may have been taken too far, as the dire warnings do not seem to be reducing with the lack of epidemiological evidence of clinically relevant problems. The "ecstasy paradigm" is one way of articulating this situation, in that the needs of research funders and publication bias lead to a specific set of subcultural norms around what information is acceptable in the public domain. By digging a little deeper, it is easy to find problems with the evidence base that informs the public debate around MDMA. The key question is whether it is acceptable to maintain this status quo given the therapeutic potential of MDMA.

20-year trends in Australian methamphetamine-related deaths, 2001-2020.

BACKGROUND: Over the past two decades methamphetamine-related harms have increased in Australia. Previous analysis of methamphetamine-related deaths has covered limited timeframes, and largely focused on drug-toxicity deaths. This paper examines long-term trends in methamphetamine-related deaths over 20 years, including deaths due to a range of specific causes. METHODS: Descriptive analyses were conducted on Australian methamphetamine-related deaths (2001-2023) by cause, extracted from the National Coronial Information System, an online database containing deaths reported to coroners in Australia and New Zealand. Joinpoint trend analyses were used to assess changes over time between 2001 and 2020 (with data from 2021 to 2023 likely incomplete and thus excluded). RESULTS: Unintentional drug toxicity was the cause of 49.8 % of methamphetamine-related deaths, intentional self-harm (including toxicity) 23.3 %, unintentional injury 15.1 %, natural causes 9.6 %, and assaults 2.3 %. Between 2001 and 2020, joinpoint analysis showed three trend change points among all-cause methamphetamine-related mortality rates, resulting in four distinct periods: two periods where they increased (2001-2006 - annual percentage change (APC) = 15.4 %; 2009-2016 - APC 25.5 %), and two where they decreased (2006-2009 - APC = -11.8 %; 2017-2020 - APC = -2.9 %). Similar patterns were evident among rates of intentional self-harm and unintentional injury. Deaths caused by unintentional drug toxicity saw two trend change points (2011, 2016), and rates increased across all three periods. Natural cause deaths had three trend change points (2007, 2010, 2015), and rates continued to rise after 2015, largely driven by increases in circulatory diseases. CONCLUSION: Cause-specific models highlighted diverse trends. Recent trends show unintentional drug toxicity deaths have slightly increased, intentional self-harm stabilised, and unintentional injury and assault deaths have declined. Deaths from natural causes involving methamphetamine continued to increase, highlighting a public health concern and a potential need for early circulatory disease screening among people who use methamphetamine.

Trajectories of drug use and mortality outcomes among adults followed over 18 years.

BACKGROUND: For adults in general population community settings, data regarding long-term course and outcomes of illicit drug use are sparse, limiting the formulation of evidence-based recommendations for drug use screening of adults in primary care. OBJECTIVE: To describe trajectories of three illicit drugs (cocaine, opioids, amphetamines) among adults in community settings, and to assess their relation to all-cause mortality. DESIGN: Longitudinal cohort, 1987/88-2005/06. SETTING: Community-based recruitment from four cities (Birmingham, Chicago, Oakland, Minneapolis). PARTICIPANTS: Healthy adults, balanced for race (black and white) and gender were assessed for drug use from 1987/88-2005/06, and for mortality through 12/31/2008 (n = 4301) MEASUREMENTS: Use of cocaine, amphetamines, and opioids (last 30 days) was queried in the following years: 1987/88, 1990/91, 1992/93, 1995/96, 2000/01, 2005/06. Survey-based assessment of demographics and psychosocial characteristics. Mortality over 18 years. RESULTS: Trajectory analysis identified four groups: Nonusers (n = 3691, 85.8%), Early Occasional Users (n = 340, 7.9%), Persistent Occasional Users (n = 160, 3.7%), and Early Frequent/Later Occasional Users (n = 110, 2.6%). Trajectories conformed to expected patterns regarding demographics, other substance use, family background and education. Adjusting for demographics, baseline health status, health behaviors (alcohol, tobacco), and psychosocial characteristics, Early Frequent/Later Occasional Users had greater all-cause mortality (Hazard Ratio, HR = 4.94, 95% CI = 1.58-15.51, p = 0.006). LIMITATIONS: Study is restricted to three common drugs, and trajectory analyses represent statistical approximations rather than identifiable "types". Causal inferences are tentative. CONCLUSIONS: Four trajectories describe illicit drug use from young adulthood to middle age. Two trajectories, representing over one third of adult users, continued use into middle age. These persons were more likely to continue harmful risk behaviors such as smoking, and more likely to die.

The antemortem neurobehavior in fatal paramethoxymethamphetamine usage.

Paramethoxymethamphetamine (PMMA) is an emerging and prevalent psychoactive drug with a structure analogous to amphetamine and related psychostimulants. However, the neurobehavioral effect is only studied in experimental animals and is barely mentioned in human. The authors report the antemortem neurobehavioral manifestations in 8 patients with PMMA use. There were 2 different antemortem presentations. The first group of patients showed delirium, hypertalkativity, and incoherence speech and then turned into convulsion and death. They did not exhibit the typical hyperdopaminergic movement disorder. The second group of patients gradually fell asleep and then suffered respiratory or cardiovascular collapse. The heart blood PMMA level was higher in the second group than in the first group of patients. Forensic autopsy showed variable findings, ranging from no remarkable change to significant pathological damage similar to serotonin syndrome in both groups of patients. PMMA seems to enhance serotoninergism than dopaminergism, and exerts a concentration-related dual effect on human.

Mortality among amphetamine users with hepatitis C virus infection: A nationwide study.

AIMS: To investigate liver-related and all-cause mortality among amphetamine users with hepatitis C virus (HCV) infection and compare this with opioid users with HCV infection and the uninfected general population. METHODS: In this national register study of mortality in persons notified with HCV infection 1990-2015 and a substance-related diagnosis in Sweden, amphetamine users (n = 6,509) were compared with opioid users (n = 5,739) and a matched comparison group without HCV infection/substance use (n = 152,086). RESULTS: Amphetamine users were observed for 91,000 years and 30.1% deceased. Crude liver-related mortality was 1.8 times higher in amphetamine users than opioid users (crude mortality rate ratio 1.78, 95% CI 1.45-2.19), but there was no significant difference when adjusting for age and other defined risk factors. An alcohol-related diagnosis was associated with liver-related death and was more common among amphetamine users. Crude and adjusted liver-related mortality was 39.4 and 5.8 times higher, respectively, compared with the uninfected group. All-cause mortality was lower than in opioid users (adjusted mortality rate ratio 0.78, 95% CI 0.73-0.84), but high compared with the uninfected group. External causes of death dominated in younger ages whereas liver-related death was more common among older individuals. CONCLUSIONS: This national register study presents a higher crude risk of liver-related death among HCV-infected amphetamine users compared with opioid users or the uninfected general population. The higher risk of liver-related death compared with opioid users may be explained by lower competing death risk and higher alcohol consumption. Treatment of HCV infection and alcohol use disorders are needed to reduce the high liver-related mortality.

Methamphetamine deaths: Changing trends and diagnostic issues.

The term 'amphetamine' refers to a class of synthetic drugs which includes methamphetamine. The latter is a globally popular drug of abuse which induces euphoria, affecting cognitive/psychomotor performance and sleep. It also provokes risk taking and violent behaviour. The central effects of methamphetamine are due to the overproduction of neurotransmitters, resulting in high levels of dopamine. In recent years, there have been significant increases in cases of methamphetamine abuse in North and South America, Australia and Asia due to its ready availability and low cost. The following review examines changing trends in methamphetamine use and problems that arise diagnostically in medico-legal cases in determining the significance of post-mortem blood levels, the relationship of these to ante-mortem levels, the possible effects on physical and psychological behaviours and the possible contribution of the drug to a lethal episode.

Methamphetamine Use, Methamphetamine Use Disorder, and Associated Overdose Deaths Among US Adults.

Importance: Mortality associated with methamphetamine use has increased markedly in the US. Understanding patterns of methamphetamine use may help inform related prevention and treatment. Objective: To assess the national trends in and correlates of past-year methamphetamine use, methamphetamine use disorder (MUD), injection, frequent use, and associated overdose mortality from 2015 to 2019. Design, Setting, and Participants: This cross-sectional study analyzed methamphetamine use, MUD, injection, and frequent use data from participants in the 2015 to 2019 National Surveys on Drug Use and Health (NSDUH). Mortality data were obtained from the 2015 to 2019 National Vital Statistics System Multiple Cause of Death files. Exposures: Methamphetamine use. Main Outcomes and Measures: Methamphetamine use, MUD, injection, frequent use, and overdose deaths. Results: Of 195 711 NSDUH respondents aged 18 to 64 years, 104 408 were women (weighted percentage, 50.9%), 35 686 were Hispanic individuals (weighted percentage, 18.0%), 25 389 were non-Hispanic Black (hereafter, Black) individuals (weighted percentage, 12.6%), and 114 248 were non-Hispanic White (hereafter, White) individuals (weighted percentage, 60.6%). From 2015 to 2019, overdose deaths involving psychostimulants other than cocaine (largely methamphetamine) increased 180% (from 5526 to 15 489; P for trend <.001); methamphetamine use increased 43% (from 1.4 million [95% CI, 1.2-1.6 million] to 2.0 million [95% CI, 1.7-2.3 million]; P for trend = .002); frequent methamphetamine use increased 66% (from 615 000 [95% CI, 512 000-717 000] to 1 021 000 [95% CI, 860 000-1 183 000]; P for trend = .002); methamphetamine and cocaine use increased 60% (from 402 000 [95% CI, 306 000-499 000] to 645 000 [95% CI, 477 000-813 000]; P for trend = .001); and MUD without injection increased 105% (from 397 000 [95% CI, 299 000-496 000] to 815 000 [95% CI, 598 000-1 033 000]; P for trend = .006). The prevalence of MUD or injection surpassed the prevalence of methamphetamine use without MUD or injection in each year from 2017 to 2019 (60% to 67% vs 37% to 40%; P for trend ≤.001). Adults with MUD or using injection were more likely to use methamphetamine frequently (52.68%-53.84% vs 32.59%; adjusted risk ratio, 1.62-1.65; 95% CI, 1.35-1.94). From 2015 to 2019, the adjusted prevalence of MUD without injection more than tripled among heterosexual women (from 0.24% to 0.74%; P < .001) and lesbian or bisexual women (from 0.21% to 0.71%; P < .001) and more than doubled among heterosexual men (from 0.29% to 0.79%; P < .001) and homosexual or bisexual men (from 0.29% to 0.80%; P = .007). It increased over 10-fold among Black individuals (from 0.06% to 0.64%; P < .001), nearly tripled among White individuals (from 0.28% to 0.78%; P < .001), and more than doubled among Hispanic individuals (from 0.39% to 0.82%; P < .001). Risk factors for methamphetamine use, MUD, injection, and frequent use included lower educational attainment, lower annual household income, lack of insurance, housing instability, criminal justice involvement, comorbidities (eg, HIV/AIDS, hepatitis B or C virus, depression), suicidal ideation, and polysubstance use. Conclusions and Relevance: This cross-sectional study found consistent upward trends in overdose mortality, greater risk patterns of methamphetamine use, and populations at higher risk for MUD diversifying rapidly, particularly those with socioeconomic risk factors and comorbidities. Evidence-based prevention and treatment interventions are needed to address surges in methamphetamine use and MUD.

Methamphetamine-related postmortem cases in Jeddah, Saudi Arabia.

A more than 500% increase in the number of deaths involving methamphetamine occurred between 2016 and 2018 in Jeddah, Saudi Arabia. As such, this report employed a validated liquid chromatography tandem mass spectrometry method to quantify methamphetamine and its metabolites in bodily fluids from 47 postmortem cases in which methamphetamine was involved. The mean age of the deceased was 33 years old (median: 30, range: 16-63), and 94% were male. Methamphetamine was co-ingested with another drug in 32 of the cases (68%); however, the deaths were only due to the combined toxicity of methamphetamine and another drug in 15 of the cases (32%). Of note, 13 of these deaths (28% of all deaths) involved heroin. When methamphetamine was the sole cause of death (32% of the studied cases), the median concentrations of methamphetamine and amphetamine were 527 and 128 ng/mL. When methamphetamine was combined toxicity with another drug, the median concentrations of methamphetamine and amphetamine decreased to 161 and 53 ng/mL. When deaths were unrelated to methamphetamine, the median concentrations of methamphetamine and amphetamine were 130 and 44 ng/mL, respectively. The highest median methamphetamine concentration was found in urine (5281 ng/mL), followed by stomach contents (878 ng/mL), bile (762 ng/mL), vitreous humor (3 ng/mL), and blood (208 ng/mL). Almost 40% of the studied cases involved violence, 61% were accidental, 21% were suicides, 17% were homicides, and 2% were natural deaths. Methamphetamine is highly addictive. Increases in deaths have been seen in various countries. More awareness, education and treatment programs are required to reduce the likelihood of addiction, crimes, suicide, and other fatalities resulting from methamphetamine abuse.

Overview of amphetamine-type stimulant mortality data--UK, 1997-2007.

BACKGROUND/AIMS: Despite being amphetamine derivatives, MDMA and its analogues show a number of clinical pharmacological differences with respect to both amphetamine (AMP) and methylamphetamine (METH). We aimed here at reporting and analysing information relating to the socio-demographics and clinical circumstances of the AMP-type stimulant-related deaths for the whole of the UK. METHODS: Data (1997-2007) were taken from the National Programme on Substance Abuse Deaths (np-SAD) database, collecting information from UK coroners/procurators fiscal. To calculate rates of fatalities per 100,000 users, appropriate AMP/METH and ecstasy users' numbers were taken from the 2001-2007 British Crime Survey. RESULTS: Overall, 832 AMP/METH- and 605 ecstasy (mostly MDMA and methylenedioxyamphetamine/MDA)-related deaths were respectively identified. In comparison with AMP/METH victims, the ecstasy ones were more likely to be younger (28.3 vs. 32.7 years; p < 0.0001) and less likely to be known as drug users (PR = 1.9; CI 1.5-2.6). Ecstasy was more likely to be identified on its own than AMP/METH (p = 0.0192). Contributory factors were more frequently mentioned by coroners in the 'AMP/METH-only' (106 cases) group than in the 'ecstasy-only' (104 cases) one (p = 0.0043). Both poly- and monodrug AMP/METH fatalities per 100,000 16- to 59-year-old users were significantly more represented than ecstasy fatalities (respectively 17.87 +/- 4.77 deaths vs. 10.89 +/- 1.27; p = 0.000; 2.09 +/- 0.88 vs. 1.75 +/- 0.56; p = 0.0096). However, mono-intoxication ecstasy fatalities per 100,000 16- to 24-year-old users were significantly more represented than AMP/METH fatalities (1.67 +/- 0.52 vs. 0.8 +/- 0.65; p = 0.0007). CONCLUSION: With respect to AMP/METH, ecstasy was here more typically identified in victims who were young, healthy, and less likely to be known as drug users. AMP/METH high mortality rates may be explained by users' high levels of physical co-morbidity; excess ecstasy-related fatality rates in young users may be a reason for concern. Although the coroners' response rate was of 90-95%, study limitations include both reporting inconsistency over time and lack of routine information on drug intake levels prior to death.

Clinical characteristics and outcomes of methamphetamine-associated versus non-methamphetamine intracerebral hemorrhage.

Methamphetamine use has emerged as a risk factor for intracerebral hemorrhage (ICH). We aim to investigate the clinical characteristics and outcomes of methamphetamine-associated ICH (Meth-ICH) versus Non-Meth-ICH. Patients with ICH between January 2011 and December 2017 were studied. Meth-ICH and Non-Meth-ICH were defined by history of abuse and urine drug screen (UDS). The clinical features of the 2 groups were explored. Among the 677 consecutive patients, 61 (9.0%) were identified as Meth-ICH and 350 as Non-Meth ICH. Meth-ICH was more common in Hispanics (14.6%) and Whites (10.1%) as compared to Asians (1.2%). Patients with Meth-ICH were more often younger (51.2 vs. 62.2 years, p < 0.001), male (77.0% vs. 61.4.0%, p < 0.05), and smokers (44.3% vs. 13.4%, p < 0.001). Non-Meth-ICH was more likely to have history of hypertension (72.61% v. 59%, p < 0.05) or antithrombotic use (10.9% vs. 1.6%, p < 0.05). There was no significant difference in clinical severity, hospital length of stay (LOS), rate of functional independence (29.5% vs. 25.7%, p = 0.534), or mortality (18.0% vs. 24.6%, p = 0.267) between the 2 groups. Methamphetamine use was not an independent predictor of poor outcome. Despite difference in demographics, Meth-ICH is similar to Non-Meth ICH in hospital course and outcome.

Comparison of Clinical Characteristics and Outcomes of Patients With Reversible Versus Persistent Methamphetamine-Associated Cardiomyopathy.

Anecdotal cases of reversible methamphetamine-associated cardiomyopathy (rMAC) have been reported, but not well understood. This study sought to determine the clinical characteristics, outcomes and predictors of reversibility among patients with rMAC as compared with patients with persistent MAC (pMAC). We retrospectively studied adult MAC patients with left ventricular ejection fraction (LVEF) ≤40% at a single center between 2004 and 2018. rMAC was defined as increase in LVEF by ≥20 points or to ≥50%. Those with persistent LVEF ≤40% constituted the pMAC group. 357 MAC cases were identified: 250 patients had pMAC and 107 had rMAC. After a median follow-up of 45 months (interquartile range 27 to 70), LVEF increased by 28.3 ± 6.9% in rMAC (p <0.001), whereas it was unchanged in pMAC (Δ: -0.5 ± 8.7%, p = 0.350). Heart failure hospitalizations and New York Heart Association Class III/IV heart failure were both significantly reduced for rMAC than the pMAC group. All-cause mortality was 21.6% overall, 28% in pMAC and 6.5% in the rMAC group (p <0.001). Kaplan-Meier survival curves demonstrated significantly higher cumulative survival for rMAC (Log Rank p <0.001). Multivariable logistic regression identified MA cessation (odds ratio/OR: 4.23, 95% confidence interval/CI: 2.47 to 7.38, p <0.001) and baseline right ventricular end systolic area (OR: 0.92, 95% CI: 0.87 to 0.97, p = 0.001) as strongly predictive of MAC reversal. In conclusion, MAC reversal is not uncommon and is associated with significant clinical improvement including reduced mortality. It can be facilitated by MA cessation when the cardiac chambers, especially the right ventricle, are not severely dilated.

Methamphetamines in trauma: effect on injury patterns and outcome.

BACKGROUND: The association of methamphetamine exposure and outcomes after trauma is not known. METHODS: This study included trauma patients who underwent alcohol and illicit drug screening. Patients who had a screen positive for Methamphetamine only [METH (+)] were compared with patients with a completely negative screen for illicit drugs or alcohol [TOX (-)]. Patients with polysubstance or alcohol abuse were excluded. Logistic regression was used to determine whether METH (+) status was independently associated with injury patterns or outcomes. Associations were further evaluated by patient matching with respect to age, gender, mechanism, injured body area abbreviated injury scores, and injury severity. RESULTS: There were 5,372 patients eligible where 526 (9.8%) were METH (+). On multivariate analysis, the METH (+) group had a significantly higher adjusted rate of intensive care unit (ICU) admission but there was no difference in mortality or complications or ICU stay. On matching, there was no difference in mortality (11.1% vs. 10.9%, p = 0.87), complication rate (5.6% vs. 4.2%, p = 0.40), and lengths of ICU and hospital stay but the METH (+) group had a higher rate of laparotomy. CONCLUSION: Patients exposed to Methamphetamines do not have increased mortality or complications or lengths of ICU and hospital stay. However, they are more likely to require admission to the ICU.

Mortality among people with regular or problematic use of amphetamines: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Amphetamines are the second most commonly used class of illicit drugs. We aimed to produce pooled estimates of mortality risks among people with regular or dependent use of amphetamines, with a focus upon all-cause mortality as well as specific causes of death. DESIGN: Systematic review and meta-analysis of cohorts of people with problematic use or dependence on amphetamines with data on all-cause or cause-specific mortality. SETTING AND PARTICIPANTS: Of 4240 papers, 30 were eligible, reporting on 25 cohorts that measured all-cause mortality, drug poisoning, suicide, accidental injuries, homicide and cardiovascular mortality. Cohorts (n = 35-74 139) were in North America, several Nordic countries and Asia Pacific. MEASUREMENT: Titles/abstracts were independently screened by one reviewer and excluded those reviewed by a second reviewer. Full-text screening was by two reviewers with discrepancies resolved via a third reviewer. We extracted data on crude mortality rates (CMR) per 100 person-years (py), standardized mortality ratios (SMRs). We imputed SMRs where possible if not reported by study authors. We also calculated mortality relative risks. Data were pooled using random-effects models; potential reasons for heterogeneity were explored using subgroup analyses and meta-regressions. FINDINGS: Twenty-three cohorts contributed data for the pooled all-cause CMR: 1.14 per 100 py [95% confidence interval (CI) = 0.92-1.42]. Pooled cause-specific mortality rates were: drug poisoning, 0.14 per 100 py (95% CI = 0.06-0.34); cardiovascular disease, 0.13 per 100 py (95% CI = 0.06-0.29); suicide, 0.20 per 100 py (95% CI = 0.07-0.55); accidental injury, 0.20 per 100 py (95% CI = 0.08-0.47) and homicide, 0.03 per 100 py (95% CI = 0.02-0.06). There was substantial heterogeneity for all pooled CMR estimates except homicide. The pooled all-cause SMR was 6.83 (95% CI = 5.27-8.84). Pooled cause-specific SMRS were: poisoning, 24.70 (95% CI = 16.67, 36.58); homicide, 11.90 (95% CI = 7.82-18.12); suicide, 12.20 (95% CI = 4.89-30.47); cardiovascular disease, 5.12 (95% CI = 3.74-7.00) and accidental injury, 5.12 (95% CI = 2.88-9.08). CONCLUSIONS: People with regular or dependent amphetamine use are at elevated risk of a range of causes of mortality compared with people without regular or dependent amphetamine use.

MDMA Induced Cardio-toxicity and Pathological Myocardial Effects: A Systematic Review of Experimental Data and Autopsy Findings.

3,4-Methylenedioxymethamphetamine (MDMA), more commonly known as "ecstasy," is a semi-synthetic entactogenic phenylethylamine. In recent years it has gained popularity as a recreational drug whose use has registered an upward trend especially among adolescents and young adults. Despite its unwarranted reputation of being a "safe" drug, the actual scientific data denote that it actually leaves a trail of cardio-toxicity, above and beyond its neurotoxicity and other somatic effects. Both experimental and clinical data, in fact, indicate that ecstasy can alter cardiac function leading to rhythm disturbances, myocardial infarction, and even sudden cardiac death. We reviewed and summarized the bio-medical literature on the cardiovascular response to MDMA both in humans and laboratory animals. The aim was to elucidate the various pathophysiological mechanisms involved, as well as the clinical, autoptic, and experimental findings underlying MDMA-induced cardio-toxicity. Finally, an illustrative case report of ecstasy-induced adolescent death due to acute cardio-toxicity was described so as to highlight some key features.