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Drug, Healthcare and Patient Safety 2019The U.S. Food and Drug Administration Adverse Event Reporting System (FAERS), contains information on adverse drug events and medication error reports submitted to the...
BACKGROUND
The U.S. Food and Drug Administration Adverse Event Reporting System (FAERS), contains information on adverse drug events and medication error reports submitted to the FDA through the MedWatch program. A significant number of adverse events reported in the FAERS database have been for opioid use. The objective of this study was to determine the frequency counts and associated deaths of opioid drug names in the FAERS database.
METHODS
Drug data were obtained from the DRUG and OUTCOME files in the database. Drugs identified included: morphine, fentanyl, oxycodone, hydrocodone, tramadol, hydromorphone, methadone, codeine, oxymorphone, meperidine, propoxyphene, diphenoxylate, and heroin. Frequency counts and concomitant deaths of opioid drug names were determined via the MySQL database management system.
RESULTS
Fifteen different opioid drugs identified in the FAERS database were associated with ADEs, including death, and 3 drugs (oxycodone, hydrocodone, fentanyl) accounted for more than half of the reports. The highest frequency count value was 158,181 for oxycodone, which represents approximately 20.2% of the frequency counts for the opioids. The lowest frequency count value was 2,161 for dextromethorphan, which represents approximately 0.3% of the total. The opioid with the highest proportion of deaths to drug count was heroin (71.8%), followed by dextromethorphan (55.6%), methadone (37.2%), morphine (26.8%), and propoxyphene (23.7%).
CONCLUSION
The FAERS database represents an important source for detection and reporting of adverse drug events (ADEs), in particular the opioids and related drugs. It remains a challenge to estimate the true incidence of ADEs for this class of drugs in the general population.
PubMed: 31695510
DOI: 10.2147/DHPS.S214771 -
Medical Care Jan 2020Experts cautioned that patients affected by the November 2010 withdrawal of the opioid analgesic propoxyphene might receive riskier prescriptions. To explore this, we...
OBJECTIVE
Experts cautioned that patients affected by the November 2010 withdrawal of the opioid analgesic propoxyphene might receive riskier prescriptions. To explore this, we compared drug receipts and outcomes among propoxyphene users before and aftermarket withdrawal.
STUDY DESIGN
Using OptumLabs data, we studied 3 populations: commercial, Medicare Advantage (MA) aged (age 65+ y) and MA disabled (age below 65 y) enrollees. The exposed enrollees received propoxyphene in the 3 months before market withdrawal (n=13,622); historical controls (unexposed) received propoxyphene 1 year earlier (n=9971). Regression models estimated daily milligrams morphine equivalent (MME), daily prescription acetaminophen dose, potentially toxic acetaminophen doses, nonopioid prescription analgesics receipt, emergency room visits, and diagnosed falls, motor vehicle accidents, and hip fractures.
PRINCIPAL FINDINGS
Aged MA enrollees illustrate the experience of all 3 populations examined. Following the market withdrawal, propoxyphene users in the exposed cohort experienced an abrupt decline of 69% in average daily MME, compared with a 14% decline in the unexposed. Opioids were discontinued by 34% of the exposed cohort and 18% of the unexposed. Tramadol and hydrocodone were the most common opioids substituted for propoxyphene. The proportion of each group receiving ≥4 g of prescription acetaminophen per day decreased from 12% to 2% in the exposed group but increased from 6% to 8% among the unexposed. Adverse events were rare and not significantly different in exposed versus unexposed groups.
CONCLUSIONS
After propoxyphene market withdrawal, many individuals experienced abrupt discontinuation of opioids. Policymakers might consider supporting appropriate treatment transitions and monitoring responses following drug withdrawals.
Topics: Aged; Analgesics, Opioid; Dextropropoxyphene; Drug Substitution; Female; Humans; Hydrocodone; Male; Medicare; Middle Aged; Morphine; Regression Analysis; Safety-Based Drug Withdrawals; Tramadol; United States; Withholding Treatment
PubMed: 31651743
DOI: 10.1097/MLR.0000000000001221 -
Plant Physiology and Biochemistry : PPB Nov 2019The growth promoting activities of the isolated endophyte Aspergillus terreus from Aloe barbendsis was studied in the salt stressed Pennisetum glaucum (pearl millet). A...
The growth promoting activities of the isolated endophyte Aspergillus terreus from Aloe barbendsis was studied in the salt stressed Pennisetum glaucum (pearl millet). A significant (P = 0.05) increase in the root-shoot lengths, fresh and dry weights and chlorophyll content of pearl millet seedlings was noticed after colonization by A. terreus under normal conditions. At 100 mM NaCl stress and A. terreus inoculation, the growth rate of pearl millet seedlings were significantly (P = 0.05) inhibited. Furthermore, the IAA production, relative water content (RWC), chlorophyll, soluble sugar, phenol and flavonoid contents were significantly decreased, whereas proline content and lipid peroxidation were increased. On the contrary, pearl millet seedlings inoculated with A. terreus retained significantly (P = 0.05) higher amounts of RWC, chlorophyll, soluble sugar, phenol and flavonoid contents under 100 mM salt stress. The higher IAA production in A. terreus associated seedlings rescued the plant growth and development under salt stress. Moreover, the LC MS/MS analysis of A. terreus cultural filtrate revealed the presence of quinic acid, ellagic acid, calycosin, wogonin, feruloylquinic acid, caffeic acid phenylethyl ester, D-glucoside, myricetin, propoxyphene and aminoflunitrazepam. The results of the study conclude that innoculation of A. terreus improves the NaCl tolerance in pearl millet by ameliorating the physicochemical attributes of the host plants.
Topics: Aspergillus; Caffeic Acids; Chromatography, Liquid; Flavanones; Flavonoids; Indoleacetic Acids; Isoflavones; Pennisetum; Salinity; Seedlings; Sodium Chloride; Tandem Mass Spectrometry
PubMed: 31563093
DOI: 10.1016/j.plaphy.2019.09.038 -
Asian Journal of Psychiatry Aug 2019Prescription drug suicide merits study to guide the development of strategies to reduce suicide risk. We examined prescription drug suicide specifically in non-abusers...
BACKGROUND
Prescription drug suicide merits study to guide the development of strategies to reduce suicide risk. We examined prescription drug suicide specifically in non-abusers of prescription drugs; this is a relatively unexplored subject.
METHODS
Six-year data on prescription drug suicide in non-abusers were extracted from the records of the Department of Forensic Medicine at the All India Institute of Medical Sciences, New Delhi. These records contained information obtained from the scene of the suicide, from interviews with relatives of the deceased, and from forensic toxicological analyses at two laboratories.
RESULTS
There were 27 (8%) cases of prescription drug suicide in non-abusers out of 338 cases of suicidal poisoning. The mean age of this sample was 26 years. The sample was 74% male. Nearly half of the cases (44%) were students. A combination of dextropropoxyphene with dicyclomine, with or without paracetamol, was used by 41% of cases. Overdose was achieved through the ingestion of 10-40 (median, 30) tablets or by the injection of 2-3 (median, 2) vials of medication. In 52% of cases, it appeared that the drugs had been procured over the counter.
CONCLUSIONS
It is reassuring that the absolute number of prescription drug suicides in non-abusers was small; the findings, however, are important because they could serve as a baseline for assessing time trends in future studies. For the present, we suggest that prescription drugs of potential abuse, especially those containing opioids and antispasmodics, should be prescribed and dispensed judiciously, especially to youth.
Topics: Adult; Analgesics, Opioid; Drug Overdose; Female; Forensic Medicine; Humans; India; Male; Parasympatholytics; Physicians; Prescription Drugs; Retrospective Studies; Students; Suicide; Universities; Young Adult
PubMed: 31374376
DOI: 10.1016/j.ajp.2019.07.039 -
Archives of Pathology & Laboratory... Feb 2020Urine drug testing is frequently ordered by health care providers. Immunoassays are widely used for drug testing, yet have potential limitations, including variable...
CONTEXT.—
Urine drug testing is frequently ordered by health care providers. Immunoassays are widely used for drug testing, yet have potential limitations, including variable cross-reactivity. The last decade has seen worsening of a prescription drug abuse epidemic.
OBJECTIVE.—
To use data from a College of American Pathologists proficiency testing survey, Urine Drug Testing, Screening, to determine and summarize the characteristics, performance, and limitations of immunoassays.
DESIGN.—
Seven years of proficiency surveys were reviewed (2011-2017).
RESULTS.—
Rapid growth was seen in participant volumes for specific immunoassays for synthetic opioids (eg, buprenorphine, fentanyl, oxycodone) and 3,4-methylenedioxymethamphetamine ("ecstasy"). Participant volumes remained high for immunoassays targeting less commonly abused drugs such as barbiturates and phencyclidine. For opiate immunoassays, the number of laboratories using a 2000 ng/mL positive cutoff remained stable, and an increasing number adopted a 100 ng/mL cutoff. Opiate and amphetamine immunoassays showed high variability in cross-reactivity for drugs other than the assay calibrator. Assays targeting a single drug or metabolite generally performed well on drug challenges.
CONCLUSIONS.—
Survey results indicate strong clinical interest in urine drug testing and some adoption of new assays. However, urine drug testing availability does not parallel prevailing patterns of drug prescribing and abuse patterns. In particular, specific immunoassays for synthetic opioids and a lower positive cutoff for opiate immunoassays may be underused, whereas immunoassays for barbiturates, methadone, propoxyphene, and phencyclidine may be overused. Laboratories are encouraged to review their test menu, cutoffs, and assay performance and adjust their test offerings based on clinical needs and technical capabilities.
Topics: Analgesics, Opioid; Humans; Immunoassay; Laboratory Proficiency Testing; Retrospective Studies; Substance Abuse Detection
PubMed: 31313960
DOI: 10.5858/arpa.2018-0562-CP -
Open Journal of Psychiatry & Allied... 2019People with opioid use disorder have significant anxiety and depression which can be because of neuroplastic changes due to use of opioid or because of use as a...
BACKGROUND
People with opioid use disorder have significant anxiety and depression which can be because of neuroplastic changes due to use of opioid or because of use as a self-medication to relieve depression and anxiety. During the last one decade, opioid use has reached an alarming proportion in Sikkim, India; but, any research related to anxiety and depression among opioid users has not been done.
AIMS
To assess for depression and anxiety disorders among the opioid dependence syndrome (ODS) participants and its severity, and to find the association with the sociodemographic characteristics.
METHOD
One hundred participants from three different drug detoxification and rehabilitation centres who were diagnosed with ODS as per the ICD-10, Diagnostic Criteria for Research were assessed cross-sectionally with the Addiction Severity Index to find out the substances abused and psychiatric morbidity. Anxiety, depression, and mania were graded with the Hamilton rating scales for anxiety and depression, and the Young Mania Rating Scale.
RESULTS
Mean age of participants was 29.6 (±6.24) years. Ninety six per cent were males. Most of the participants were using multiple opioid preparations. Thirty four per cent were using dextropropoxyphene containing pain killer followed by six per cent using codeine containing cough syrup. Eighty two per cent had depression; however, only 13% were found to have severe depression. Fifty six per cent had anxiety and six per cent were found to have mania. Most of the participants with ODS were single, attended at least secondary education, from urban locality, and were from high socioeconomic status.
CONCLUSION
anxiety and depression are highly prevalent among ODS people. Treatment should not be limited to management of ODS but also the comorbid psychiatric illness.
PubMed: 31263773
DOI: 10.5958/2394-2061.2019.00030.2 -
PloS One 2019Opioids constitute a cornerstone of pain relief treatment. However, opioid safety during pregnancy has not been well established. Recent studies reported an association...
INTRODUCTION
Opioids constitute a cornerstone of pain relief treatment. However, opioid safety during pregnancy has not been well established. Recent studies reported an association between in utero opioid exposure and spina bifida.
METHODS
In order to further evaluate the association of opioids exposure during pregnancy with adverse pregnancy outcomes, we conducted a large historical cohort by linking four databases: medications dispensations, births, pregnancy terminations for medical reasons and infant hospitalizations during the years of 1999-2009. Confounders that were controlled for included maternal age, ethnicity, maternal diabetes, smoking status, parity, obesity, year and folic acid intake. A secondary analysis for total major malformations and for spina bifida was performed using propensity score matching for first trimester exposure.
RESULTS
Of the 101,586 women included in the study, 3003 were dispensed opioids during the first trimester. Intrauterine exposure to opioids was not associated with overall major malformations (adjusted odds ratio (aOR) 0.97, 95% CI 0.83-1.13), cardiovascular malformations (aOR = 0.89, 95% CI 0.70-1.13) other malformations by systems or spina bifida in particular. However, the risk for spina bifida among newborns and abortuses who were exposed to codeine was four times higher than that of the unexposed (aOR = 4.42, 95% CI 1.60-12.23). This association remained significant in a secondary analysis using propensity score matching. Third trimester exposure to opioids was not associated with low birth weight (aOR = 1.08, 95% CI 0.77-1.52), perinatal death (aOR = 1.38, 95% CI 0.64-2.99) and other adverse pregnancy outcomes.
CONCLUSIONS
These findings suggest that opioids exposure (as a homogenous group) is not a significant risk factor for overall major malformations. Exposure to codeine during the first trimester was found to be associated with increased risk of spina bifida. However, this finding was based on a small number of cases and need to be verified in future work.
Topics: Abnormalities, Drug-Induced; Adolescent; Adult; Analgesics, Opioid; Cardiovascular Abnormalities; Codeine; Cohort Studies; Dextropropoxyphene; Female; Humans; Infant, Newborn; Israel; Male; Middle Aged; Pregnancy; Pregnancy Outcome; Pregnancy Trimester, First; Pregnancy Trimester, Third; Risk Factors; Spinal Dysraphism; Young Adult
PubMed: 31260464
DOI: 10.1371/journal.pone.0219061 -
The Science of the Total Environment May 2019Opioids, both as prescription drugs and abuse substances, have been a hot topic and a focus of discussion in the media for the last few years. Although the literature...
Opioids, both as prescription drugs and abuse substances, have been a hot topic and a focus of discussion in the media for the last few years. Although the literature published shows the occurrence of opioids and some of their metabolites in the aquatic environment, there are scarce data in the application of high resolution mass spectrometry (HRMS) for the analysis of these compounds in the environment. The use of HRMS allows increasing the number of opioids that can be studied as well as the detection of unknown opioids, their metabolites and potential transformation products. In this work, a retrospective analysis for the identification of opioids and their metabolites using a curated database was applied to surface water and wastewater samples taken in the state of Minnesota (U.S.) in 2009, which were previously analyzed by liquid chromatography/time-of-flight mass spectrometry (LC/TOF-MS) for antidepressants. The database comprised >200 opioids including natural opiates (e.g. morphine and codeine), their semi-synthetic derivatives (e.g. heroin, hydromorphone, hydrocodone, oxycodone, oxymorphone, meperidine and buprenorphine), fully synthetic opioids (e.g. fentanyl, methadone, tramadol, dextromethorphan and propoxyphene), as well as some of their metabolites (e.g. 6-monoacetylcodeine, dextrorphan, EDDP, normorphine and O-desmethyltramadol). Moreover, additional MS-MS experiments were performed to confirm their identification, as well as to recognize fragmentation patterns and diagnostic ions for several opioids. These data provide a better understanding of the historical occurrence of opioids and their metabolites in surface waters impacted by wastewater sources. The concentrations of individual opioids in surface water and wastewater effluent varied from 8.8 (EDDP) to 1640 (tramadol) ngL and from 12 (dihydrocodeine) to 1288 (tramadol) ngL, respectively. The opioids with higher overall frequency detections were tramadol, dextromethorphan and its metabolite, dextrorphan.
Topics: Analgesics, Opioid; Chromatography, Liquid; Codeine; Data Analysis; Environmental Monitoring; Fentanyl; Heroin; Hydrocodone; Hydromorphone; Minnesota; Morphine; Morphine Derivatives; Oxycodone; Retrospective Studies; Substance Abuse Detection; Tandem Mass Spectrometry; Tramadol; Wastewater; Water Pollutants, Chemical
PubMed: 30769311
DOI: 10.1016/j.scitotenv.2019.01.389 -
Journal of Affective Disorders Mar 2019Analgesics are used most frequently in fatal and non-fatal medicinal self-poisonings. Knowledge about their relative toxicity in overdose is important for clinicians and...
BACKGROUND
Analgesics are used most frequently in fatal and non-fatal medicinal self-poisonings. Knowledge about their relative toxicity in overdose is important for clinicians and regulatory agencies.
METHODS
Using data for 2005-2012 we investigated case fatality (number of suicides relative to number of non-fatal self-poisonings) of paracetamol, aspirin, codeine, dihydrocodeine, tramadol, paracetamol with codeine (co-codamol), paracetamol with dihydrocodeine (co-dydramol), ibuprofen and co-proxamol (paracetamol plus dextropropoxyphene; withdrawn in the UK in 2008 due to high toxicity). Data on suicides obtained from the Office for National Statistics and on non-fatal self-poisonings from the Multicentre Study of Self-harm in England. Case fatality was estimated for each drug, using paracetamol as the reference category.
RESULTS
Compared to paracetamol and based on single drug deaths the case fatality index of dihydrocodeine was considerably elevated (odds ratio (OR) 12.81, 95% Confidence Interval (CI) 10.19-16.12). Case fatality indices for tramadol (OR 4.05, 95% CI 3.38-4.85) and codeine (OR 2.21, 95% CI 1.81-2.70) were also significantly higher than for paracetamol. The results when multiple drug deaths were included produced similar results. The relative toxicity of co-proxamol far exceeded that of the other analgesics.
LIMITATIONS
Data on fatal self-poisonings were based on national data, whereas those for non-fatal poisonings were based on local data.
CONCLUSIONS
Dihydrocodeine and tramadol are particularly toxic in overdose and codeine is also relatively toxic. They should be prescribed with caution, particularly to individuals at risk of self-harm.
Topics: Acetaminophen; Adult; Analgesics; Codeine; Dextropropoxyphene; Drug Combinations; Drug Overdose; England; Female; Humans; Male; Middle Aged; Suicide
PubMed: 30634113
DOI: 10.1016/j.jad.2019.01.002 -
Forensic Science International Jan 2019This paper describes the performance of four Randox drug arrays, designed for whole blood, for the near-body analysis of drugs in a range of post-mortem body specimens.
BACKGROUND
This paper describes the performance of four Randox drug arrays, designed for whole blood, for the near-body analysis of drugs in a range of post-mortem body specimens.
METHODS
Liver, psoas muscle, femoral blood, vitreous humor and urine from 261 post-mortem cases were screened in the mortuary and results were obtained within the time taken to complete a post-mortem. Specimens were screened for the presence of amfetamine, barbiturates, benzodiazepines, benzoylecgonine, buprenorphine, cannabinoids, dextropropoxyphene, fentanyl, ketamine, lysergide, methadone, metamfetamine, methaqualone, 3,4-methylenedioxymetamfetamine, opioids, paracetamol, phencyclidine, salicylate, salicylic acid, zaleplon, zopiclone and zolpidem using the DOA I, DOA I+, DOA II and Custom arrays.
RESULTS
Liver and muscle specimens were obtained from each of the 261 post-mortem cases; femoral blood, vitreous humor and urine were available in 98%, 92% and 72% of the cases, respectively. As such, the equivalent of 12,978 individual drug-specific, or drug-group, immunoassay tests were undertaken. Overall >98% of the 12,978 screening tests undertaken agreed with laboratory confirmatory tests performed on femoral blood.
CONCLUSIONS
There is growing interest in the development of non-invasive procedures for determining the cause of death using MRI and CT scanning however these procedures are, in most cases, unable to determine whether death may have been associated with drug use. The Randox arrays can provide qualitative and semi-quantitative results in a mortuary environment enabling pathologists to decide whether to remove specimens from the body and submit them for laboratory analysis. Analysis can be undertaken on a range of autopsy specimens which is particularly useful when conventional specimens such as blood are unavailable.
Topics: Forensic Toxicology; Humans; Illicit Drugs; Immunoassay; Liver; Luminescence; Pharmaceutical Preparations; Psoas Muscles; Substance Abuse Detection; Substance-Related Disorders; Vitreous Body
PubMed: 30544085
DOI: 10.1016/j.forsciint.2018.11.018