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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 -
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 -
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 -
British Journal of Clinical Pharmacology Feb 2021Analgesics are the most widely used medicines worldwide. In parallel, opioid abuse has increased and is of major concern. The accessibility of pharmacologically powerful...
AIMS
Analgesics are the most widely used medicines worldwide. In parallel, opioid abuse has increased and is of major concern. The accessibility of pharmacologically powerful medicines and the addictovigilance signals in France about the risk of opiates addiction call for an overview of analgesic use. The objective of this study was to investigate the use of analgesics reimbursed in France over a 10-year period through its prevalence.
METHODS
A cross-sectional study repeated yearly was conducted by using data from the French reimbursement database from 2006 to 2015. Analgesics were classified according to their pharmacological potency: prevalence of use for each category and sociodemographic characteristics of patients treated were analysed.
RESULTS
The annual prevalence of analgesic use was high and increased during the study period (59.8%, 253 976 users in 2015). In 2015, prevalence was always higher in women and increased with age, except for those older than 84 years. Peripheral analgesics were the most used (55.3%, 234 739 users). The prevalence of weak analgesic use decreased (21.3%, 90 257 users), mainly due to the definitive withdrawal of dextropropoxyphene in France in 2011, which was not offset by an increase in the consumption of other weak analgesics. For strong analgesics (1.2%, 5129 users), morphine was the most widely used, with a dramatic increase in oxycodone use, especially in the elderly.
CONCLUSION
The prevalence of analgesic use is high: approximately 31 million adults had at least 1 analgesic reimbursed in 2015. The most widely used analgesics were peripheral analgesics, far ahead of opioid analgesics.
Topics: Adult; Aged; Aged, 80 and over; Analgesics, Non-Narcotic; Analgesics, Opioid; Cross-Sectional Studies; Female; France; Humans; Opioid-Related Disorders
PubMed: 32496599
DOI: 10.1111/bcp.14415 -
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 -
The Cochrane Database of Systematic... Aug 2020Acute soft tissue injuries are common and costly. The best drug treatment for such injuries is not certain, although non-steroidal anti-inflammatory drugs (NSAIDs) are... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Acute soft tissue injuries are common and costly. The best drug treatment for such injuries is not certain, although non-steroidal anti-inflammatory drugs (NSAIDs) are often recommended. There is concern about the use of oral opioids for acute pain leading to dependence. This is an update of a Cochrane Review published in 2015.
OBJECTIVES
To assess the benefits or harms of NSAIDs compared with other oral analgesics for treating acute soft tissue injuries.
SEARCH METHODS
We searched the CENTRAL, 2020 Issue 1, MEDLINE (from 1946), and Embase (from 1980) to January 2020; other databases were searched to February 2019.
SELECTION CRITERIA
We included randomised or quasi-randomised controlled trials involving people with acute soft tissue injury (sprain, strain, or contusion of a joint, ligament, tendon, or muscle occurring within 48 hours of inclusion in the study), and comparing oral NSAIDs versus paracetamol (acetaminophen), opioid, paracetamol plus opioid, or complementary and alternative medicine. The outcomes were pain, swelling, function, adverse effects, and early re-injury.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed studies for eligibility, extracted data, and assessed risk of bias. We assessed the quality of the evidence using GRADE methodology.
MAIN RESULTS
We included 20 studies, with 3305 participants. Three studies included children only. The others included predominantly young adults; approximately 60% were male. Seven studies recruited people with ankle sprains only. Most studies were at low or unclear risk of bias; however, two were at high risk of selection bias, three were at high risk of bias from lack of blinding, and five were at high risk of selective outcome reporting bias. Some evidence relating to pain relief was high certainty. Other evidence was either moderate, low or very low certainty, reflecting study limitations, indirectness, imprecision, or combinations of these. Thus, we are certain or moderately certain about some of the estimates, and uncertain or very uncertain of others. Eleven studies, involving 1853 participants compared NSAIDs with paracetamol. There were no differences between the two groups in pain at one to two hours (1178 participants, 6 studies; high-certainty evidence), at days one to three (1232 participants, 6 studies; high-certainty evidence), and at day seven or later (467 participants, 4 studies; low-certainty evidence). There was little difference between the groups in numbers of participants with minimal swelling at day seven or later (77 participants, 1 study; low-certainty evidence). Very low-certainty evidence from three studies (386 participants) means we are uncertain of the finding of little difference between the two groups in return to function at day seven or later. There was low-certainty evidence from 10 studies (1504 participants) that NSAIDs may slightly increase the risk of gastrointestinal adverse events compared with paracetamol. There was low-certainty evidence from nine studies (1679 participants) of little difference in neurological adverse events between the NSAID and paracetamol groups. Six studies, involving 1212 participants compared NSAIDs with opioids. There was moderate-certainty evidence of no difference between the groups in pain at one hour (1058 participants, 4 studies), and low-certainty evidence for no difference in pain at days four or seven (706 participants, 1 study). There was very low-certainty evidence of no important difference between the groups in swelling (84 participants, 1 study). Participants in the NSAIDs group were more likely to return to function in 7 to 10 days (542 participants, 2 studies; low-certainty evidence). There was moderate-certainty evidence (1143 participants, 5 studies) that NSAIDs were less likely to result in gastrointestinal or neurological adverse events compared with opioids. Four studies, involving 240 participants, compared NSAIDs with the combination of paracetamol and an opioid. The applicability of findings from these studies is in question because the dextropropoxyphene combination analgesic agents used are no longer in general use. Very low-certainty evidence means we are uncertain of the findings of no differences between the two interventions in the numbers with little or no pain at day one (51 participants, 1 study), day three (149 participants, 2 studies), or day seven (138 participants, 2 studies); swelling (230 participants, 3 studies); return to function at day seven (89 participants, 1 study); and the risk of gastrointestinal or neurological adverse events (141 participants, 3 studies). No studies reported re-injury rates. No studies compared NSAIDs with oral complementary and alternative medicines, AUTHORS' CONCLUSIONS: Compared with paracetamol, NSAIDs make no difference to pain at one to two hours and at two to three days, and may make no difference at day seven or beyond. NSAIDs may result in a small increase in gastrointestinal adverse events and may make no difference in neurological adverse events compared with paracetamol. Compared with opioids, NSAIDs probably make no difference to pain at one hour, and may make no difference at days four or seven. NSAIDs probably result in fewer gastrointestinal and neurological adverse effects compared with opioids. The very low-certainly evidence for all outcomes for the NSAIDs versus paracetamol with opioid combination analgesics means we are uncertain of the findings of no differences in pain or adverse effects. The current evidence should not be extrapolated to adults older than 65 years, as this group was not well represented in the studies.
Topics: Acetaminophen; Acute Disease; Administration, Oral; Adult; Analgesics; Analgesics, Opioid; Anti-Inflammatory Agents, Non-Steroidal; Bias; Child; Contusions; Female; Humans; Male; Middle Aged; Pain; Randomized Controlled Trials as Topic; Soft Tissue Injuries; Sprains and Strains; Time-to-Treatment; Young Adult
PubMed: 32797734
DOI: 10.1002/14651858.CD007789.pub3 -
Frontiers in Pharmacology 2019Wnt/β-catenin signaling is involved in various biological processes, including the development of the central nervous system. The dysfunction of mitochondria has been...
Wnt/β-catenin signaling is involved in various biological processes, including the development of the central nervous system. The dysfunction of mitochondria has been shown to participate in the progress of subarachnoid hemorrhage (SAH). Traumatic subarachnoid hemorrhage (tSAH) is a serious complication in acute craniocerebral trauma. Opioids can activate the canonical Wnt/β-catenin signaling pathway. c-Myc, a downstream protein of Wnt/β-catenin signaling, contributes to the fusion of mitochondria. Here, we investigated the protective roles of Propoxyphene (Pro) against Oxyhemoglobin (OxyHb)-induced primary cultured neuron apoptosis. The data indicated that Pro rescued active-β-catenin from OxyHb-induced decline. Furthermore, Pro attenuated OxyHb-induced apoptosis and fission of mitochondria in primary cortical neurons. However, the protective effects were abrogated under active-β-catenin-deficient conditions. Together, the data presented here showed that Pro, a weak opioid analgesic drug, attenuates OxyHb-induced mitochondria-dependent apoptosis in an active-β-catenin-c-Myc-dependent manner.
PubMed: 32082150
DOI: 10.3389/fphar.2019.01616 -
European Journal of Hospital Pharmacy :... Sep 2020Pain management in the emergency department (ED) is a key issue that must be regularly evaluated. Practice evaluation gold standard remains patient file analysis, but is...
OBJECTIVE
Pain management in the emergency department (ED) is a key issue that must be regularly evaluated. Practice evaluation gold standard remains patient file analysis, but is highly time consuming. The aim of this study is to evaluate the interest of a defined daily dose (DDD) based analysis in the evaluation of pain management in the ED.
METHODS
A local indicator was elaborated based on the DDD concept: the defined dose per admission (DDA). Unlike the DDD that corresponds to a standardised total dose administered over a day, the DDA represents the average total dose administrated to a patient throughout the stay in the ED. A DDA was assigned to every analgesic, from step 1 to step 3. Oral and injectable forms were studied, but transdermal forms were not considered. DDA values were assimilated to the existing DDDs when these were officially established by the WHO. When values were not defined by the WHO, mean values observed in local practice were selected. Annual numbers of patients admitted to the ED and quantities of each analgesic supplied by the pharmacy ward were annually extracted from respective data files. Paediatric patients being treated at a specific separate ED, only adults were considered throughout the study. Raw quantities of analgesics used each year were converted to their equivalent amounts in DDA, and then expressed in numbers of DDA per 100 admissions (DDA/100A). This indicator allowed us to describe relative evolutions of analgesics prescriptions from 2006 to 2017.
RESULTS
Analgesic overall use rose from 18.4 to 30.2 DDA/100A between 2006 and 2017, representing a prescription increase of 64%. Throughout the study, step 1 analgesics rose from 10.8 to 19.3 DDA/100A (+79%), step 3 from 1.8 to 5.4 (+200%) and step 2 remained stable around 5.6 DDA/100A. The integration of orodispersible paracetamol tablets in 2013 allowed us to halve the consumption of injectable paracetamol in the long term and had no effect on classic paracetamol oral forms such as tablets or capsules. Tramadol increased from 41% to 78% among step 2 analgesics after the withdrawal of dextropropoxyphene in 2011. Codeine use shows a steady decline from 1.9 DDA/100A in 2011 to 0.72 in 2017.
DISCUSSION/CONCLUSION
The DDA concept appears to be an effective tool for assessing long-term analgesic-use trends at hospital EDs. This tool can also mitigate one major bias at EDs, that is the lack of traceability of analgesic administration in emergency contexts. This tool could be adjusted by integrating the average length of stay in the ED.
Topics: Analgesics; Analgesics, Non-Narcotic; Analgesics, Opioid; Dose-Response Relationship, Drug; Drug Administration Schedule; Emergency Service, Hospital; Hospitals, University; Humans; Pain Management; Pain Measurement
PubMed: 32839258
DOI: 10.1136/ejhpharm-2018-001749