Chronic Drug Users Research Articles

Bioinformatics-driven untargeted metabolomic profiling for clinical screening of methamphetamine abuse.

Amphetamine-type stimulants are very common, and their usage is becoming a very big social problem all over the world. Thousands of addicts encounter several health problems including mental, metabolic, behavioral and neurological disorders. In addition to these, there are several reports about the elevated risk of tendency on committing criminal cases by addicted persons. Hence, methamphetamine addiction is not only an individual health problem but also a social problem. In our study, we aimed to investigate the pathogenesis of chronic usage of methamphetamine via untargeted metabolomics approach. 38 plasma samples were carefully collected and extracted for untargeted metabolomics assay. A liquid-liquid extraction was performed to get as much metabolite as possible from the samples. After the extraction procedure, samples were transferred into vials and they were evaluated via time of flight mass spectrometry instrument. Significantly, altered metabolites were identified by the fold analysis and Welch's test between the groups. 42 different compounds were annotated regarding to data-dependent acquisition method. Pathway analysis were also performed to understand the hazardous effect of methamphetamine on human body. It has been reported that drug exposure may affect several metabolic pathways for amino acids, fats, energy metabolism and vitamins. An alternative bioinformatic model was also developed and validated in order to predict the chronic methamphetamine drug users in any criminal cases. This generated model passes the ROC curve analysis and permutation test and classify the controls and drug users correctly by evaluating the metabolic alterations between the groups.

Effectiveness of Orthopantomograms as a Screening Tool for Osteoporosis: A Case-Control Study.

Introduction Osteoporosis is a disease that is characterised by low bone mineral density (BMD), and loss of structural and biomechanical properties that are essential in maintaining bone homeostasis. Osteoporosis is diagnosed by clinical measurement of BMD and is the best predictor of osteoporosis. The study was conducted with the aim of assessing the effectiveness of orthopantomogram (OPG) as a screening tool for osteoporosis in postmenopausal women and chronic drug users. Objectives The primary objective of the current study was to assess the mandibular cortical width and antegonial index in postmenopausal women and chronic drug users, the secondary objective was to compare the mandibular cortical width and antegonial index of postmenopausal women and chronic drug users with that of the control group (healthy individual). Methods Three groups were taken in this study with a sample size of 300 with 100 OPG in each group. The groups categorised in the study were postmenopausal women, patients under drugs (glucocorticoids, proton pump inhibitor, anti-epileptic drugs, selective serotonin reuptake inhibitor) and the control group and the parameters assessed were antegonial index and mandibular cortical width. Results Results were tabulated and analysed using Statistical Package for the Social Sciences (IBM SPSS Statistics for Windows, IBM Corp., Version 26.0, Armonk, NY). The normality tests Kolmogorov-Smirnov and Shapiro-Wilks test results reveal that the variables (both indices) follow the normal distribution. The mandibular cortical width was 3.44, 2.66 and 2.96 in the normal, postmenopausal women and women on drugs respectively. The antegonial index was 163.5, 157.2 and 158.8 in the normal, postmenopausal women and women on drugs respectively. Conclusion From the above results, it is evident that there is a statistically significant reduction in antegonial index and mandibular cortical width in postmenopausal women compared to normal individuals.Alterations of this value are suggestive that early pre-clinical changes of osteoporosis can be detected in the high-risk group using OPG.

Increasing incidence of Xylazine as a toxic adulterating substance in postmortem forensic toxicology casework

Xylazine, an alpha-2 receptor agonist used in veterinary medicine for its sedative and muscle relaxant effects, has been reported periodically in forensic toxicology casework since the 1980s. Xylazine is not approved for human use but has seen more widespread positivity as a result of its use as an adulterant in illicit opioids, known as “Tranq Dope”, in the United States. Xylazine has been designated a toxic adulterating substance, due to its causation of hypotension and bradycardia, CNS and respiratory depression, and the development of skin lesions, slowed wound healing and frequent, persistent or worsening skin infections in chronic intravenous drug users. These effects have contributed to a marked increase poly drug deaths over the last three years involving xylazine. The aim of this study was to evaluate xylazine positivity in death investigation casework, document concentrations of the drug in fatalities and compare those to concentrations in living subjects in impaired driving cases, evaluate patterns of combined drug use, and to provide guidance on the incorporation of xylazine as a finding into cause of death determination in drug overdose fatalities. Xylazine is a basic drug with a molecular weight of 220.34 Daltons, and is easily recovered in basic blood extracts, and detected either in gas chromatography/mass spectrometry or liquid chromatography/tandem mass spectrometry (LCMSMS) workflows. In our laboratory, screening was performed by liquid chromatography time of flight mass spectrometry (LCTOF), with confirmation and quantitation by LCMSMS, with screening and confirmatory cut-offs of 5 ng/mL. he prevalence and concentrations of xylazine in 2.5-years of driving-under-the-influence-of-drugs (DUID) and medicolegal-death-investigation (MDI) cases (January 2019-June 2021) was investigated. Of over 170,000 cases screened for xylazine during this time frame, 97% were classified as MDI. During the study period, quantitative xylazine results were reported for 3,215 of the 3,691 cases which screened positive. The prevalence and geographical spread of xylazine increased and included 37 US States, three Canadian provinces and Puerto Rico. Overall, 2.8% of DUID, and 2.1% of MDI cases screened positive for xylazine with concentrations of 5.1–450 ng/mL (mea n = 36 ng/mL) and 5.0–11,000 ng/mL (mea n = 41 ng/mL), respectively. Two MDI cases which had xylazine concentrations of 9,100 and 11,000 ng/mL were drug overdose suicides that did not involve any opioids. Opioids, primarily fentanyl and/or a fentanyl byproduct/metabolite were detected in 100% of xylazine positive DUID cases, and all but two MDI cases. After opioids, stimulants, phyto-cannabinoids and benzodiazepines were the most common drug classes detected in conjunction with xylazine in both DUID and MDI casework. The primary difference in these cases was the type of stimulant detected with cocaine (including cocaine metabolites) being the most commonly detected stimulant in MDI cases, while methamphetamine was more commonly detected in DUID cases. In summary, xylazine exposure in opioid drug users continued to increase during the study period, with most exposure resulting from the adulteration of illicit opioids, although suicide cases involving ingestion of xylazine alone were reported. There is extensive overlap in the concentrations of xylazine between living and deceased individuals making it challenging to interpret the role of the drug in MDI or DUID cases without careful consideration of other case information. The interaction of effects of xylazine and opioids however make it advisable to include xylazine in the drugs contributing to death in cases where both are detected.

Rebamipide as a Potential Alternative Gastroprotective Agent to Proton Pump Inhibitor in Elderly Chronic Nonsteroidal Anti-Inflammatory Drug Users without Risk Factors.

PurposeThe use of proton pump inhibitors (PPI) is recommended to prevent nonsteroidal anti-inflammatory drug (NSAID)-induced gastrointestinal (GI) complications. The incidence of several adverse effects during the long-term use of PPI prompts the search for other alternatives. Limited studies have evaluated the efficacy of rebamipide, a widely used mucoprotective drug, as a gastroprotective agent (GPA) compared to PPI, focusing on the elderly chronic NSAID users, nor with GI risk stratification. We aimed to determine the population who would get benefit from the use of rebamipide as an alternative to PPI to prevent traditional nonsteroidal anti-inflammatory drug (tNSAID)-associated GI complications.Patients and MethodsWe identified 41,889 and 35,708 elderly chronic tNSAID users with PPI and rebamipide co-therapy, respectively, from the national claims database. Outcome was defined as hospitalization or emergency department visits due to serious GI complications. Propensity score-matched cohorts were constructed and compared within risk strata.ResultsIn high and moderate risk groups with two risk factors, rebamipide showed a higher risk of serious GI complication compared to PPI (aHR 2.63, 95% CI 1.24–5.59 and aHR 2.42, 95% CI 1.21–4.83, respectively). However, in elderly patients without risk factors, there was no significant difference in the risk of serious GI complications between PPI and rebamipide (aHR 0.69, 95% CI 0.27–1.76).ConclusionThis study suggested that rebamipide can be considered as an alternative to PPI in elderly chronic tNSAID users without risk factors. However, elderly patients with other risk factors should use PPI rather than rebamipide. Therefore, the presence of GI risk factors needs to be evaluated in elderly chronic tNSAID users to prescribe the most suitable GPA in clinical practice.

Spontaneous pneumomediastinum associated with COVID-19: Rare complication of 2020 pandemic

Spontaneous pneumomediastinum (SPM) is a rare condition, more commonly seen in patients with history of asthma, chronic obstructive pulmonary disease, infections, or drug users. Today, we face one novel virus that has cause an outbreak of acute respiratory illness, affecting over a million individuals worldwide. New knowledge is been gained of the virus and possible complications are been seen. Following, we present the case of a 71-year-old man with diagnosis of COVID-19 pneumonia complicated with spontaneous pneumomediastinum.

Underutilization of gastrointestinal prophylaxis in high-risk chronic nonsteroidal anti-inflammatory drug users in Korea.

Background The increasing use of antithrombotic therapies in older patients has led to an increased risk of gastrointestinal (GI) bleeding in chronic nonsteroidal anti-inflammatory drug (NSAID) users. Therefore, there is a pressing need for GI prophylaxis in these high-risk patients. Objective To analyze prescribing patterns and factors associated with the use of gastroprotective agents (GPAs) among high-risk, chronic NSAID users. Setting National claims database including 20% of the total Korean population aged ≥ 65years. Method In this cross-sectional study, we identified older adults prescribed traditional NSAIDs for > 90days and classified them into high- and ultra-high-risk groups if they had one or two or more GI risk factors, respectively. Proton pump inhibitors or misoprostol prescribed for more than 80% of traditional NSAID treatment days was regarded as appropriate GI prophylaxis. Main outcome measure Prevalence and associated factors with appropriate GI prophylaxis. Results Among 69,992 chronic traditional NSAID users, 38.8% and 9.4% belonged to the high and ultra-high-risk groups; 13.2% and 19.9% received appropriate GI prophylaxis, respectively. The most frequently used GPA was histamine H2 antagonists. Multiple NSAID use, concomitant antiplatelets and anticoagulants, and prior GI ulcer history increased the likelihood of receiving appropriate GI prophylaxis. Advanced age (≥ 85years), indications other than arthritis, and neurology specialists negatively affected appropriate GI prophylaxis use. Conclusion Approximately one in five chronic NSAID users, considered ultra-high risk, are prescribed appropriate GI prophylaxis in Korea. Advanced age, indications, and specialties of the prescriber all need to be considered when selecting target populations for interventions.

Underutilization of Peptic Ulcer Disease Prophylaxis Among Elderly Users of Antiplatelets and Anticoagulants.

Peptic ulcer disease (PUD) develops in approximately 25% of chronic users of non-steroidal anti-inflammatory drugs (NSAIDs). The incidence of uncomplicated PUD has been declining over the past 3 decades unlike that of complicated PUD in the elderly. An expert consensus document published jointly in 2008 by the American College of Gastroenterology (ACG), the American College of Cardiology Foundation (ACCF), and the American Heart Association (AHA) provided recommendations on prevention of PUD among users of antiplatelets and anticoagulants. This work aimed to evaluate physicians' compliance with these guidelines in a tertiary academic setting. We examined our medical record database for the 9month period extending from April 2018 until December 2018. Using this database, we identified elderly patients (> 64years old) who were chronic (> 3months) users of low dose aspirin (81mg once daily) and had an indication for PUD prophylaxis as per the ACG-ACCF-AHA guideline document. We performed a retrospective chart review of patients included in this study. Descriptive statistics were compared using χ2 and independent sample t tests. A total of 852 patients were included in this study. The mean age was 75years old, and 43% of patients were females. In addition to aspirin, patients were prescribed P2Y12 inhibitors (45.5%), direct oral anticoagulants (DOACs) (23%), warfarin (12%), steroids (9%) or enoxaparin (1%). Users of DOACs were most commonly prescribed apixaban (16%), followed by rivaroxaban (6%) and dabigatran (1%). Overall, only 40% of patients with an indication for PUD prophylaxis received a proton pump inhibitor. PUD prophylaxis may be underutilized in elderly patients. This finding, along with increasing rates of NSAID use and an aging population, may help explain the increased incidence of complicated PUD in the elderly. Efforts are needed to raise physician awareness of PUD prophylaxis guidelines.

PDB75 EFFECT OF CHRONIC EXPOSURE TO PSYCHOTROPIC MEDICATION ON THE INCIDENCE OF NEW-ONSET TYPE 2 DIABETES MELLITUS IN ADULTS, A RETROSPECTIVE COHORT STUDY USING PRESCRIPTION CLAIMS FROM COLOMBIA

Drug-induced diabetes is an increasingly important cause of diabetes mellitus worldwide. Certain psychotropic drugs may cause weight gain, but the long-term effect of this on the incidence of type 2 diabetes (T2DM) is not clear. This study compared the 5-year incidence of diabetes in a cohort of chronic user of psychotropic drugs and a cohort of patients unexposed. A retrospective cohort study was made using an outpatient prescription database for approximately 6.5 million people insured by the NHSC. Two cohorts were selected from non-diabetic patients aged 18 to 64 years old; new chronic users (≥6 months) of psychotropic drugs (N=2,118) and a cohort of patients unexposed (N=1,877). Patients were followed between 2012 and 2016. The outcome of the study was the occurrence of a diabetic event (first prescription of drugs for the treatment of diabetes). Incidence rates were compared by cohorts. Data was processed and analyzed using R studio. During 14,754 years of follow-up, the cumulative incidence of diabetic events was 5.1% (n=204); 3.6% (n=67) in unexposed and 6.5% (n=137) in exposed. The mean time until NOD was 28.7±17.3 months in unexposed and 31.7±16.0 months in exposed (p=0.238). The number needed to harm was 34. The incidence rate ratio (IRR) significantly higher for exposed in the first (IRR = 2.378, 95%CI 1.291 – 4.379) and second (IRR = 2.009, 95%CI 1.084 – 3.725) years of follow-up and for the entire follow up period (IRR = 1.661, 95%CI 1.240 – 2.225), but not in the third to fifth year of follow up. Chronic users of psychiatric drugs had a higher incidence of diabetes than not exposed patients during the first and second year of treatment.

Association between chronic ACE inhibitor exposure and decreased odds of severe disease in patients with COVID-19.

Objective:Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Renin-angiotensin-aldosterone-system (RAAS) inhibitors may increase the expression of angiotensin-converting enzyme 2, which is the receptor for SARS-CoV-2 Spike protein. The consequences of using angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) during the COVID-19 pandemic are unknown.Methods:A retrospective cohort study aiming to identify the odds of severe disease (defined as either hospitalization of ≥14 days, admission to the intensive care unit, or death) associated with exposure to ACEi or ARB was conducted. Adult patients (age ≥18 years) with COVID-19 admitted to the İstanbul Faculty of Medicine Corona Center between March 9 and May 11, 2020, were included. Chronic users of ACEi, ARB, or other antihypertensive drugs were matched according to age, sex, sick days before hospitalization, comorbidities, smoking, number of antihypertensive regimens, doxazosin use, furosemide use, and serum creatinine level. Odds ratios (OR) of having severe disease were calculated.Results:In total, 611 patients were admitted with COVID-19, confirmed by either reverse-transcriptase polymerase chain reaction or computed tomography (CT). There were 363 males, and the age ranged from 18 to 98 years, with an average age of 57±15 years. Of these, 165 participants had severe disease (53 deaths, case fatality rate: 8.7%). Among those with hypertension (n=249), ARB exposure was compatible with decreased odds (OR=0.60, 95% CI: 0.27–1.36, p=0.31) of severe disease though not statistically significant, while ACEi exposure significantly reduced the risk of severe disease (OR=0.37, 95% CI: 0.15–0.87, p=0.03). ACEi exposure was associated with milder infiltrations seen on baseline CT, lower C-reactive protein and ferritin, higher monocytes, shorter hospitalization, and less requirement for specific empirical treatments (favipiravir and meropenem).Conclusion:Our data suggest that exposure to ACEi drugs may have favorable effects in the context of COVID-19 pneumonia.

1226 Under-Utilization of Proton Pump Inhibitors in the Prevention of NSAID-Related Peptic Ulcer Disease in the Elderly

INTRODUCTION: Peptic ulcer disease (PUD) develops in approximately 25% of chronic users of non-steroidal anti-inflammatory drugs (NSAIDs). The incidence of uncomplicated PUD has been declining over the past 3 decades unlike that of complicated PUD especially in the elderly. We aimed to evaluate physician compliance with the American College of Gastroenterology (ACG) guidelines on the prevention of NSAID-related PUD complications in a tertiary academic setting. METHODS: We examined the Saint Louis University Hospital medical record database for a 9-month period extending from April 2018 until December 2018. Using this database, we identified 2,064 adult elderly patients (>64 years old) who were chronic (>3 months) users of low dose aspirin (81 mg once daily). We performed a retrospective analysis of patients who were at least on aspirin and had an indication for PUD prophylaxis as per ACG guidelines. Data collected from patient charts included age, gender, relevant medications (including proton pump inhibitors (PPI), aspirin, P2Y12 inhibitors, direct oral anticoagulants (DOACs), warfarin, or oral steroids), and whether prophylaxis was provided as per the ACG guidelines. RESULTS: A total of 301 adult elderly patients who were at least on aspirin and had an indication for PUD prophylaxis were identified in this study. The mean age was 75 years old. Six percent of included patients had a history of peptic ulcer disease. In addition to aspirin, patients were using P2Y12 inhibitors (clopidogrel or ticagrelor, 50%), DOACs (24%), warfarin (11%), or steroids (9%). DOAC users were prescribed apixaban (16%), rivaroxaban (7%), or dabigatran (1%) (Table 1). All antiplatelets, anticoagulants, and steroids were prescribed by non-gastroenterologists. Only 35% of patients with an indication for PUD prophylaxis received a PPI. The prophylaxis rates were highest for patients with a history of peptic ulcer disease (62%) and were lowest for users of P2Y12 inhibitors (29%). There were no statistically significant age or gender related differences in the rates of compliance when independent sample t and chi square tests were performed (Table 1). CONCLUSION: Peptic ulcer disease prophylaxis with proton pump inhibitors may be underutilized in elderly patients. This finding, along with increasing rates of NSAID use and aging population, may help explain the increased incidence of complicated PUD in the elderly. Efforts are needed to raise physician awareness of PUD prophylaxis guidelines.

Neuroimaging reward, craving, learning, and cognitive control in substance use disorders: review and implications for treatment.

Substance use disorder is a leading causes of preventable disease and mortality. Drugs of abuse cause molecular and cellular changes in specific brain regions and these neuroplastic changes are thought to play a role in the transition to uncontrolled drug use. Neuroimaging has identified neural substrates associated with problematic substance use and may offer clues to reduce its burden on the patient and society. Here, we provide a narrative review of neuroimaging studies that have examined the structures and circuits associated with reward, cues and craving, learning, and cognitive control in substance use disorders. Most studies use advanced MRI or positron emission tomography (PET). Many studies have focused on the dopamine neurons of the ventral tegmental area, and the regions where these neurons terminate, such as the striatum and prefrontal cortex. Decreases in dopamine receptors and transmission have been found in chronic users of drugs, alcohol, and nicotine. Recent studies also show evidence of differences in structure and function in substance users relative to controls in brain regions involved in salience evaluation, such as the insula and anterior cingulate cortex. Balancing between reward-related bottom-up and cognitive-control-related top-down processes is discussed in the context of neuromodulation as a potential treatment. Finally, some of the challenges for understanding substance use disorder using neuroimaging methods are discussed.

Interpreting oral fluid drug results in prisoners: monitoring current drug intake and detection times for drugs self-administered prior to detention

Although urine is the most common matrix for prisoner drug testing, oral fluid offers a possible alternative. Identifying new drug intake by a prisoner results in negative sanctions. Detection times in oral fluid after chronic drug intake may be extended. Within the prison, admission population is chronic drug users. Our aim was to investigate detection windows for drugs of abuse in oral fluid from prisoners. Nineteen frequent drug-abusing prisoners provided oral fluid and urine at admission and each morning thereafter for 9 consecutive days. The most positive findings were for amphetamine/methamphetamine, cannabis and benzodiazepines. Maximum detection times in oral fluid were ≥ 9 days for diazepam, methadone and methamphetamine, with corresponding urinary detection times of ≥ 9, 7 and 6 days, respectively. Maximum oral fluid detection times were 9 days for clonazepam, 8 for oxazepam, 3 for amphetamine and nitrazepam, and 2 for tetrahydrocannabinol, with positive urinary detection times of 8, ≥ 9, 5, 7 and ≥ 9 days, respectively. Cocaine, morphine and 6-acetylmorphine were all positive only 1 day in oral fluid; cocaine and morphine were positive 1 and 2 days, respectively, in urine, while 6-acetylmorphine was not detected in urine. We confirmed oral fluid as a viable matrix for monitoring drugs of abuse in prisoners. Windows of detection for benzodiazepines and amphetamines were up to 1 week, which is an important consideration for evaluating oral fluid drug testing results. Some likely new drug exposures were observed based on urine and oral fluid drug results, but there were few data to guide these interpretations.

Substance Abuse Policy in Thailand: Current Challenges and Future Strategies

Substance abuse has been an important social and public health problem in Thailand for decades. The National Household Survey on Substance and Alcohol Use in Thailand, which has been conducted six times, shows that substance abuse has steadily increased. Extrapolated country-wide in recent data, the estimated number of people who have used at least one addictive substance at some time in their lives was 2,964,444 or 5.8% of the total population aged 12 - 65 years. Kratom, Methamphetamine, methamphetamine hydrochloride crystal (ice), and cannabis were the most prevalent substances of abuse. Historical documentation and policy reports were used in this study. The objectives of this study were to complete a document review, determine the effectiveness of previous measures to control illegal substance abuse in Thailand, and consider options for the future. Controlling illegal substance abuse in the future and minimizing total harm requires a delicate balance of efforts to reduce the prevalence, quantity, and harmful effects of substances. Drug policy interventions should be continually evaluated for their effectiveness. The strategies relevant to drug policy, apart from primary prevention, are health services for chronic drug users, reform of criminal sanctions against drug addicts, and legalization of kratom.

Substance Abuse Policy in Thailand: Current Challenges and Future Strategies

Substance abuse has been an important social and public health problem in Thailand for decades. The National Household Survey on Substance and Alcohol Use in Thailand, which has been conducted six times, shows that substance abuse has steadily increased. Extrapolated country-wide from recent data, the estimated number of people who have used at least one addictive substance at some time in their lives was 2,964,444 or 5.8% of the total population aged 12–65 years old. Kratom, methamphetamine, methamphetamine hydrochloride crystal (ice), and cannabis were the most prevalent substances of abuse. Historical documentation and policy reports were used in this study. The objectives of this study were to complete a document review, determine the effectiveness of previous measures to control illegal substance abuse in Thailand, and consider options for the future. Controlling illegal substance abuse in the future and minimizing total harm requires a delicate balance of efforts to reduce the prevalence, quantity, and harmful effects of substances. Drug policy interventions should be continually evaluated for their effectiveness. The strategies relevant to drug policy, apart from primary prevention, are provision of health services for chronic drug users, reform of criminal sanctions against drug addicts, and legalization of kratom.

MDPV in forensic routine cases: Psychotic and aggressive behavior in relation to plasma concentrations

The new psychoactive substance 3,4-methylenedioxypyrovalerone (MDPV) belongs to the group of synthetic cathinones and is purchased mainly as “research chemical” or “bath salt” on the illegal drug market, also in South Bavaria. MDPV was detected in blood and urine samples from 2010 on in 50 authentic routine cases in a forensic setting. Plasma concentrations in 46 cases with available blood specimens ranged from approximately 1.0 to 301μg/L (median 23.7; mean 47.9μg/L), detected by a fully validated LC–MS/MS method. Subjects aged between 16 and 54 years (median 36; mean 35 years) and reflected experienced chronic drug users. Accused offences were mainly violent crimes such as bodily harm, robberies, homicides and acts of resistance. A lot of subjects showed highly aggressive and violent behavior with endangerment of self and others and/or psychotic symptoms as confusion, hallucinations or paranoia. The risk for such behavior rises with MDPV plasma concentrations above as low as 30μg/L, whereby a time interval of 1.5h on average between incident and/or observation of impairment and blood sampling has to be taken into account. Comprehensive toxicological analysis proved poly-drug use in almost all cases including opiates/opioids, benzodiazepines and other sedatives, antidepressants and other stimulants, also other new psychoactive substances. Alcohol was detected only in three cases. Co-consumed benzodiazepines seem not be able to completely prevent psychotic effects despite their use as first-line treatment for patients with synthetic cathinone poisonings. The study demonstrates that relatively low plasma concentrations of MDPV could be associated with mental impairment which is relevant in the assessment of forensic cases.

Differences in combinations and concentrations of drugs of abuse in fatal intoxication and driving under the influence cases

BackgroundIn toxicology, international classification systems focus on single intoxicants as the cause of death. It is, however, well known that very few drug related deaths are caused by a single substance and that information concerning the drug concentrations as well as the combinations of drugs are essential in order to ascertain the cause of death. The aim of the study was to assess whether those prone to fatal intoxications differ significantly from chronic drug users – in terms of demographics and drug exposure patterns. Material and methodsFatal psychoactive drug intoxications in Norway during 2012, where a forensic autopsy including toxicological analysis were performed, were included. Analytical findings in blood were compared with concentrations in blood from apprehended drivers under the influence of drugs and ethanol (DUID) during the same time period. The opioid and benzodiazepine concentrations were assessed as morphine and diazepam equivalents, respectively, in order to compare concentrations across the different groups. ResultsA total of 194 autopsy cases and 4811 DUID cases were included. Opioids were detected in around 90% of the drug intoxication cases, but in only 16% of the DUID cases. The number of substances detected in fatal intoxications was 4.9 compared to 2.6 in the DUID cases. The total opioid concentrations were significantly higher in the fatal intoxication cases compared to DUID cases (229ng/mL versus 56.9ng/mL morphine equivalents, respectively). Benzodiazepines were detected in 90% of the fatal cases. Only one fatal opioid mono-intoxication was found; a case with a very high methadone concentration (1238ng/mL). DiscussionMono-intoxication with heroin was not seen in any of the fatal intoxications in Norway, and single drug intoxications were rare (1.5%). Fatal intoxications were caused by a combination of drugs with significantly more substances as well as higher total drug concentrations among the fatal cases compared to the DUID cases. The combination of opioids and benzodiazepines seemed to represent an increased risk of death. ConclusionThe total load of drugs influence the degree of intoxication and the total concentration level must be considered, including the total number of substances. Our findings imply that international statistics regarding an opioid being the main intoxicant should have a shift in focus towards combinations of drugs (especially opioids and benzodiazepines) as a major risk factor for fatal drug overdoses.

New Guidelines Support Deprescribing of Proton Pump Inhibitors

New Guidelines Support Deprescribing of Proton Pump Inhibitors

Addictive behaviors and healthcare renunciation for economic reasons in a French population-based sample

BackgroundHealthcare renunciation for economic reasons is a major health concern, but it has been scarcely investigated among drug users, even if drug users constitute a vulnerable population in need of medical care. This study investigated associations of healthcare renunciation for economic reasons and addictive behaviors (alcohol, tobacco, cannabis, illicit drug use, and gambling) in a population-based sample of adults living in France, a country with universal health coverage. MethodsData were collected using the 2014 Health Barometer, a French cross-sectional survey conducted among a random representative sample of the general population aged 18–64 (n=12,852). Measures included healthcare renunciation, substance use (alcohol, tobacco, cannabis, and other illicit drugs) and gambling. Experimental/recreational and heavy/chronic use were assessed. Logistic regressions were used to test the relationship between healthcare renunciation and addictive behaviors, controlling for relevant covariates. ResultsA total of 25% of the participants had renounced care at least once in the previous twelve months. Most variables of drug use were significantly associated with increased healthcare renunciation. This was the case for heavy/hazardous use and experimental/recreational use. Regular gambling was not associated with healthcare renunciation, but disordered gambling was. ConclusionThis study showed that addictive behaviors, including substance use and gambling, were part of the burden of vulnerability of people who forgo care. Therefore, drug use and gambling patterns should be a focus in the development of policies to reduce health inequalities, not only for heavy and chronic drug users.

Dopamine homeostasis: brain functional connectivity in reward deficiency syndrome.

Reward deficiency syndrome (RDS) was first proposed by Kenneth Blum in 1995 to provide a clinically relevant and predictive term for conditions involving deficits in mesocorticolimbic dopamine function. Genetic, molecular, and neuronal alterations in key components of this circuitry contribute to a reward deficit state that can drive drug-seeking, consumption, and relapse. Among the dysfunctions observed in RDS are dysregulated resting state networks, which recently have been assessed in detail in chronic drug users by, positron emission tomography, functional magnetic resonance imaging, and functional connectivity analysis. A growing number of studies are helping to determine the putative roles of dopamine and glutamatergic neurotransmission in the regulation of activity in resting state networks, particularly in brain reward circuitry affected in drug use disorders. Indeed, we hypothesize in the present review that loss of homeostasis of these systems may lead to 'unbalanced' functional networks that might be both cause and outcome of disrupted synaptic communication between cortical and subcortical systems essential for controlling reward, emotional control, sensation seeking, and chronic drug use.

Sleep Regulates Incubation of Cocaine Craving.

After withdrawal from cocaine, chronic cocaine users often experience persistent reduction in total sleep time, which is accompanied by increased sleep fragmentation resembling chronic insomnia. This and other sleep abnormalities have long been speculated to foster relapse and further drug addiction, but direct evidence is lacking. Here, we report that after prolonged withdrawal from cocaine self-administration, rats exhibited persistent reduction in nonrapid-eye-movement (NREM) and rapid-eye-movement (REM) sleep, as well as increased sleep fragmentation. In an attempt to improve sleep after cocaine withdrawal, we applied chronic sleep restriction to the rats during their active (dark) phase of the day, which selectively decreased the fragmentation of REM sleep during their inactive (light) phase without changing NREM or the total amount of daily sleep. Animals with improved REM sleep exhibited decreased incubation of cocaine craving, a phenomenon depicting the progressive intensification of cocaine seeking after withdrawal. In contrast, experimentally increasing sleep fragmentation after cocaine self-administration expedited the development of incubation of cocaine craving. Incubation of cocaine craving is partially mediated by progressive accumulation of calcium-permeable AMPA receptors (CP-AMPARs) in the nucleus accumbens (NAc). After withdrawal from cocaine, animals with improved REM sleep exhibited reduced accumulation of CP-AMPARs in the NAc, whereas increasing sleep fragmentation accelerated NAc CP-AMPAR accumulation. These results reveal a potential molecular substrate that can be engaged by sleep to regulate cocaine craving and relapse, and demonstrate sleep-based therapeutic opportunities for cocaine addiction. Significance statement: Sleep abnormalities are common symptoms in chronic drug users long after drug withdrawal. These withdrawal-associated sleep symptoms, particularly reduction in total sleep time and deteriorating sleep quality, have been speculated to foster relapse and further drug addiction, but direct evidence is lacking. Here we show in rats that the sleep pattern was persistently changed long after withdrawal from cocaine self-administration, and demonstrate that sleep interventions can bidirectionally regulate cocaine craving and seeking after withdrawal. We further demonstrate that glutamatergic synapses in the nucleus accumbens are potential neuronal targets for sleep intervention to influence cocaine craving after withdrawal. These results provide a strong rationale supporting sleep-based therapies for cocaine addiction.