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The Cochrane Database of Systematic... Jun 2021Postoperative pain is a common consequence of surgery and can have many negative perioperative effects. It has been suggested that the administration of analgesia before... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Postoperative pain is a common consequence of surgery and can have many negative perioperative effects. It has been suggested that the administration of analgesia before a painful stimulus may improve pain control. We defined pre-emptive nonsteroidal anti-inflammatories (NSAIDs) as those given before surgery but not continued afterwards and preventive NSAIDs as those given before surgery and continued afterwards. These were compared to a control group given the NSAIDs after surgery instead of before surgery.
OBJECTIVES
To assess the efficacy of preventive and pre-emptive NSAIDs for reducing postoperative pain in adults undergoing all types of surgery.
SEARCH METHODS
We searched the following electronic databases: CENTRAL, MEDLINE, Embase, AMED and CINAHL (up to June 2020). In addition, we searched for unpublished studies in three clinical trial databases, conference proceedings, grey literature databases, and reference lists of retrieved articles. We did not apply any restrictions on language or date of publication.
SELECTION CRITERIA
We included parallel-group randomized controlled trials (RCTs) only. We included adult participants undergoing any type of surgery. We defined pre-emptive NSAIDs as those given before surgery but not continued afterwards and preventive NSAIDs as those given before surgery and continued afterwards. These were compared to a control group given the NSAIDs after surgery instead of before surgery. We included studies that gave the medication by any route but not given on the skin.
DATA COLLECTION AND ANALYSIS
We used the standard methods expected by Cochrane, as well as a novel publication bias test developed by our research group. We used GRADE to assess the certainty of the evidence for each outcome. Outcomes included acute postoperative pain (minimal clinically important difference (MCID): 1.5 on a 0-10 scale), adverse events of NSAIDs, nausea and vomiting, 24-hour morphine consumption (MCID: 10 mg reduction), time to analgesic request (MCID: one hour), pruritus, sedation, patient satisfaction, chronic pain and time to first bowel movement (MCID: 12 hours).
MAIN RESULTS
We included 71 RCTs. Seven studies are awaiting classification. We included 45 studies that evaluated pre-emptive NSAIDs and 26 studies that evaluated preventive NSAIDs. We considered only four studies to be at low risk of bias for most domains. The operations and NSAIDs used varied, although most studies were conducted in abdominal, orthopaedic and dental surgery. Most studies were conducted in secondary care and in low-risk participants. Common exclusions were participants on analgesic medications prior to surgery and those with chronic pain. Pre-emptive NSAIDs compared to post-incision NSAIDs For pre-emptive NSAIDs, there is probably a decrease in early acute postoperative pain (MD -0.69, 95% CI -0.97 to -0.41; studies = 36; participants = 2032; I = 96%; moderate-certainty evidence). None of the included studies that reported on acute postoperative pain reported adverse events as an outcome. There may be little or no difference between the groups in short-term (RR 1.00, 95% CI 0.34 to 2.94; studies = 2; participants = 100; I = 0%; low-certainty evidence) or long-term nausea and vomiting (RR 0.85, 95% CI 0.52 to 1.38; studies = 5; participants = 228; I = 29%; low-certainty evidence). There may be a reduction in late acute postoperative pain (MD -0.22, 95% CI -0.44 to 0.00; studies = 28; participants = 1645; I = 97%; low-certainty evidence). There may be a reduction in 24-hour morphine consumption with pre-emptive NSAIDs (MD -5.62 mg, 95% CI -9.00 mg to -2.24 mg; studies = 16; participants = 854; I = 99%; low-certainty evidence) and an increase in the time to analgesic request (MD 17.04 minutes, 95% CI 3.77 minutes to 30.31 minutes; studies = 18; participants = 975; I = 95%; low-certainty evidence). There may be little or no difference in opioid adverse events such as pruritus (RR 0.40, 95% CI 0.09 to 1.76; studies = 4; participants = 254; I = 0%; low-certainty evidence) or sedation (RR 0.51, 95% CI 0.16 to 1.68; studies = 4; participants = 281; I = 0%; low-certainty evidence), although the number of included studies for these outcomes was small. No study reported patient satisfaction, chronic pain or time to first bowel movement for pre-emptive NSAIDs. Preventive NSAIDs compared to post-incision NSAIDs For preventive NSAIDs, there may be little or no difference in early acute postoperative pain (MD -0.14, 95% CI -0.39 to 0.12; studies = 18; participants = 1140; I = 75%; low-certainty evidence). One study reported adverse events from NSAIDs (reoperation for bleeding) although the events were low which did not allow any meaningful conclusions to be drawn (RR 1.95; 95% CI 0.18 to 20.68). There may be little or no difference in rates of short-term (RR 1.26, 95% CI 0.49 to 3.30; studies = 1; participants = 76; low-certainty evidence) or long-term (RR 0.85, 95% CI 0.52 to 1.38; studies = 5; participants = 456; I = 29%; low-certainty evidence) nausea and vomiting. There may be a reduction in late acute postoperative pain (MD -0.33, 95% CI -0.59 to -0.07; studies = 21; participants = 1441; I = 81%; low-certainty evidence). There is probably a reduction in 24-hour morphine consumption (MD -1.93 mg, 95% CI -3.55 mg to -0.32 mg; studies = 16; participants = 1323; I = 49%; moderate-certainty evidence). It is uncertain if there is any difference in time to analgesic request (MD 8.51 minutes, 95% CI -31.24 minutes to 48.27 minutes; studies = 8; participants = 410; I = 98%; very low-certainty evidence). As with pre-emptive NSAIDs, there may be little or no difference in other opioid adverse events such as pruritus (RR 0.56, 95% CI 0.09 to 3.35; studies = 3; participants = 211; I = 0%; low-certainty evidence) and sedation (RR 0.84, 95% CI 0.44 to 1.63; studies = 5; participants = 497; I = 0%; low-certainty evidence). There is probably little or no difference in patient satisfaction (MD -0.42; 95% CI -1.09 to 0.25; studies = 1; participants = 72; moderate-certainty evidence). No study reported on chronic pain. There is probably little or no difference in time to first bowel movement (MD 0.00; 95% CI -15.99 to 15.99; studies = 1; participants = 76; moderate-certainty evidence).
AUTHORS' CONCLUSIONS
There was some evidence that pre-emptive and preventive NSAIDs reduce both pain and morphine consumption, although this was not universal for all pain and morphine consumption outcomes. Any differences found were not clinically significant, although we cannot exclude this in more painful operations. Moreover, without any evidence of reductions in opioid adverse effects, the clinical significance of these results is questionable although few studies reported these outcomes. Only one study reported clinically significant adverse events from NSAIDs administered before surgery and, therefore, we have very few data to assess the safety of either pre-emptive or preventive NSAIDs. Therefore, future research should aim to adhere to the highest methodology and be adequately powered to assess serious adverse events of NSAIDs and reductions in opioid adverse events.
Topics: Acute Pain; Adult; Analgesics, Opioid; Anti-Inflammatory Agents, Non-Steroidal; Bias; Confidence Intervals; Cyclooxygenase 2 Inhibitors; Humans; Morphine; Pain, Postoperative; Patient Satisfaction; Postoperative Hemorrhage; Postoperative Nausea and Vomiting; Pruritus; Randomized Controlled Trials as Topic; Reoperation; Surgical Procedures, Operative
PubMed: 34125958
DOI: 10.1002/14651858.CD012978.pub2 -
JAMA Network Open Aug 2023Concerns that take-home naloxone (THN) training may lead to riskier drug use (as a form of overdose risk compensation) remain a substantial barrier to training...
IMPORTANCE
Concerns that take-home naloxone (THN) training may lead to riskier drug use (as a form of overdose risk compensation) remain a substantial barrier to training implementation. However, there was limited good-quality evidence in a systematic review of the association between THN access and subsequent risk compensation behaviors.
OBJECTIVE
To assess whether THN training is associated with changes in overdose risk behaviors, indexed through injecting frequency, in a cohort of people who inject drugs.
DESIGN, SETTING, AND PARTICIPANTS
This cohort study used prospectively collected self-reported behavioral data before and after THN training of participants in The Melbourne Injecting Drug User Cohort Study (SuperMIX). Annual interviews were conducted in and around Melbourne, Victoria, Australia, from 2008 to 2021. SuperMIX participants were adults who regularly injected heroin or methamphetamine in the 6 months preceding their baseline interview. The current study included only people who inject drugs who reported THN training and had participated in at least 1 interview before THN training.
EXPOSURE
In 2017, the SuperMIX baseline or follow-up survey began asking participants if and when they had received THN training. The first THN training date that was recorded was included as the exposure variable. Subsequent participant interviews were excluded from analysis.
MAIN OUTCOMES AND MEASURES
Injecting frequency was the primary outcome and was used as an indicator of overdose risk. Secondary outcomes were opioid injecting frequency, benzodiazepine use frequency, and the proportion of the time drugs were used alone. Fixed-effects generalized linear (Poisson) multilevel modeling was used to estimate the association between THN training and the primary and secondary outcomes. Time-varying covariates included housing status, income, time in study, recent opioid overdose, recent drug treatment, and needle and syringe coverage. Findings were expressed as incidence rate ratios (IRRs) with 95% CIs.
RESULTS
There were 1328 participants (mean [SD] age, 32.4 [9.0] years; 893 men [67.2%]) who completed a baseline interview in the SuperMIX cohort, and 965 participants completed either a baseline or follow-up interview in or after 2017. Of these 965 participants, 390 (40.4%) reported THN training. A total of 189 people who inject drugs had pretraining participant interviews with data on injecting frequency and were included in the final analysis (mean [SD] number of interviews over the study period, 6.2 [2.2]). In fixed-effects regression analyses adjusted for covariates, there was no change in the frequency of injecting (IRR, 0.91; 95% CI, 0.69-1.20; P = .51), opioid injecting (IRR, 0.95; 95% CI, 0.74-1.23; P = .71), benzodiazepine use (IRR, 0.96; 95% CI, 0.69-1.33; P = .80), or the proportion of reported time of using drugs alone (IRR, 1.04; 95% CI, 0.86-1.26; P = .67) before and after THN training.
CONCLUSIONS AND RELEVANCE
This cohort study of people who inject drugs found no evidence of an increase in injecting frequency, along with other markers of overdose risk, after THN training and supply. The findings suggest that THN training should not be withheld because of concerns about risk compensation and that advocacy for availability and uptake of THN is required to address unprecedented opioid-associated mortality.
Topics: Male; Adult; Humans; Naloxone; Narcotic Antagonists; Analgesics, Opioid; Cohort Studies; Drug Overdose; Victoria
PubMed: 37540514
DOI: 10.1001/jamanetworkopen.2023.27319 -
Clinical Cardiology Sep 2021While morphine has long been widely used in treating acute heart failure (AHF) due to its vasodilatory properties and anticipated anxiolysis, it remains unclear whether... (Meta-Analysis)
Meta-Analysis Review
While morphine has long been widely used in treating acute heart failure (AHF) due to its vasodilatory properties and anticipated anxiolysis, it remains unclear whether the application of morphine to those patients is reasonable. We aim to conduct a systematic review and meta-analysis to assess the safety of morphine in patients with AHF. We searched PubMed, Cochrane Library, and Embase electronic databases from inception through March 2020. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to estimate the outcomes. Seven studies with 172, 226 patients were included. The results showed that morphine usage was not associated with increased in-hospital mortality (OR: 1.94; 95% CI 0.93 to 4.03; p = 0.08). However, the use of morphine significantly increased the risk of invasive ventilation (OR: 2.72; 95% CI 1.09 to 6.80; p = 0.03). Furthermore, the subgroup analysis indicated that the application of morphine was not associated with increased 7-day all-cause mortality in patients with AHF (OR: 1.69; 95% CI 0.80 to 3.22; p = 0.11) but significantly increased the risk of 30-day all-cause mortality (OR: 1.59; 95% CI 1.16 to 2.17; p = 0.004). Based on current evidence, our results suggested that although morphine therapy did not significantly increase the risk of short-term death (in the hospital or within 7 days) in patients with AHF, the risk of long-term death and invasive ventilation were significantly increased. This result needs to be further confirmed by an ongoing randomized control trial.
Topics: Heart Failure; Hospital Mortality; Humans; Morphine
PubMed: 34236089
DOI: 10.1002/clc.23691 -
The Cochrane Database of Systematic... Dec 2019This review represents one in a family of three reviews focusing on the effectiveness of interventions in reducing drug use and criminal activity for offenders. (Meta-Analysis)
Meta-Analysis
BACKGROUND
This review represents one in a family of three reviews focusing on the effectiveness of interventions in reducing drug use and criminal activity for offenders.
OBJECTIVES
To assess the effectiveness of interventions for female drug-using offenders in reducing criminal activity, or drug use, or both.
SEARCH METHODS
We searched 12 electronic bibliographic databases up to February 2019.
SELECTION CRITERIA
We included randomised controlled trials (RCTs).
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane.
MAIN RESULTS
We included 13 trials with 2560 participants. Interventions were delivered in prison (7/13 studies, 53%) and community (6/13 studies, 47%) settings. The rating of bias was affected by the lack of clear reporting by authors, and we rated many items as 'unclear'. In two studies (190 participants) collaborative case management in comparison to treatment as usual did not reduce drug use (risk ratio (RR) 0.65, 95% confidence interval (CI) 0.20 to 2.12; 1 study, 77 participants; low-certainty evidence), reincarceration at nine months (RR 0.71, 95% CI 0.32 to 1.57; 1 study, 77 participants; low-certainty evidence), and number of subsequent arrests at 12 months (RR 1.11, 95% CI 0.83 to 1.49; 1 study, 113 participants; low-certainty evidence). One study (36 participants) comparing buprenorphine to placebo showed no significant reduction in self-reported drug use at end of treatment (RR 0.57, 95% CI 0.27 to 1.20) and three months (RR 0.58, 95% CI 0.25 to 1.35); very low-certainty evidence. No adverse events were reported. One study (38 participants) comparing interpersonal psychotherapy to a psychoeducational intervention did not find reduction in drug use at three months (RR 0.67, 95% CI 0.30 to 1.50; low-certainty evidence). One study (31 participants) comparing acceptance and commitment therapy (ACT) to a waiting list showed no significant reduction in self-reported drug use using the Addiction Severity Index (mean difference (MD) -0.04, 95% CI -0.37 to 0.29) and abstinence from drug use at six months (RR 2.89, 95% CI 0.73 to 11.43); low-certainty evidence. One study (314 participants) comparing cognitive behavioural skills to a therapeutic community programme and aftercare showed no significant reduction in self-reported drug use (RR 0.86, 95% CI 0.58 to 1.27), re-arrest for any type of crime (RR 0.73, 95% CI 0.52 to 1.03); criminal activity (RR 0.80, 95% CI 0.63 to 1.03), or drug-related crime (RR 0.95, 95% CI 0.68 to 1.32). A significant reduction for arrested (not for parole) violations at six months follow-up was significantly in favour of cognitive behavioural skills (RR 0.43, 95% CI 0.25 to 0.77; very low-certainty evidence). A second study with 115 participants comparing cognitive behavioural skills to an alternative substance abuse treatment showed no significant reduction in reincarceration at 12 months (RR 0.70, 95% CI 0.43 to 1.12; low certainty-evidence. One study (44 participants) comparing cognitive behavioural skills and standard therapy versus treatment as usual showed no significant reduction in Addiction Severity Index (ASI) drug score at three months (MD 0.02, 95% CI -0.05 to 0.09) and six months (MD -0.02, 95% CI -0.09 to 0.05), and incarceration at three months (RR 0.46, 95% CI 0.04 to 4.68) and six months (RR 0.51, 95% CI 0.20 to 1.27); very low-certainty evidence. One study (171 participants) comparing a single computerised intervention versus case management showed no significant reduction in the number of days not using drugs at three months (MD -0.89, 95% CI -4.83 to 3.05; low certainty-evidence). One study (116 participants) comparing dialectic behavioural therapy and case management (DBT-CM) versus a health promotion intervention showed no significant reduction at six months follow-up in positive drug testing (RR 0.67, 95% CI 0.43 to 1.03), number of people not using marijuana (RR 1.23, 95% CI 0.95 to 1.59), crack (RR 1.00, 95% CI 0.87 to 1.14), cocaine (RR 1.02, 95% CI 0.93 to 1.12), heroin (RR 1.05, 95% CI 0.98 to 1.13), methamphetamine (RR 1.02, 95% CI 0.87 to 1.20), and self-reported drug use for any drug (RR 1.20, 95% CI 0.92 to 1.56); very low-certainty evidence. One study (211 participants) comparing a therapeutic community programme versus work release showed no significant reduction in marijuana use at six months (RR 1.03, 95% CI 0.19 to 5.65), nor 18 months (RR 1.00, 95% CI 0.07 to 14.45), heroin use at six months (RR 1.59, 95% CI 0.49 to 5.14), nor 18 months (RR 1.92, 95% CI 0.24 to 15.37), crack use at six months (RR 2.07, 95% CI 0.41 to 10.41), nor 18 months (RR 1.64, 95% CI 0.19 to 14.06), cocaine use at six months (RR 1.09, 95% CI 0.79 to 1.50), nor 18 months (RR 0.93, 95% CI 0.64 to 1.35). It also showed no significant reduction in incarceration for drug offences at 18 months (RR 1.45, 95% CI 0.87 to 2.42); with overall very low- to low-certainty evidence. One study (511 participants) comparing intensive discharge planning and case management versus prison only showed no significant reduction in use of marijuana (RR 0.79, 95% CI 0.53 to 1.16), hard drugs (RR 1.12, 95% CI 0.88 to 1.43), crack cocaine (RR 1.08, 95% CI 0.75 to 1.54), nor positive hair testing for marijuana (RR 0.75, 95% CI 0.55 to 1.03); it found a significant reduction in arrests (RR 0.19, 95% CI 0.04 to 0.87), but no significant reduction in drug charges (RR 1.07, 95% CI 0.75 to 1.53) nor incarceration (RR 1.09, 95% CI 0.86 to 1.39); moderate-certainty evidence. One narrative study summary (211 participants) comparing buprenorphine pre- and post-release from prison showed no significant reduction in drug use at 12 months post-release; low certainty-evidence. No adverse effects were reported.
AUTHORS' CONCLUSIONS
The studies showed a high degree of heterogeneity for types of comparisons, outcome measures and small samples. Descriptions of treatment modalities are required. On one outcome of arrest (no parole violations), we identified a significant reduction when cognitive behavioural therapy (CBT) was compared to a therapeutic community programme. But for all other outcomes, none of the interventions were effective. Larger trials are required to increase the precision of confidence about the certainty of evidence.
Topics: Acceptance and Commitment Therapy; Buprenorphine; Case Management; Cognitive Behavioral Therapy; Criminals; Female; Humans; Law Enforcement; Randomized Controlled Trials as Topic; Substance-Related Disorders
PubMed: 31834635
DOI: 10.1002/14651858.CD010910.pub3 -
PLoS Medicine Dec 2019Worldwide opioid-related overdose has become a major public health crisis. People with opioid use disorder (OUD) are overrepresented in the criminal justice system and...
BACKGROUND
Worldwide opioid-related overdose has become a major public health crisis. People with opioid use disorder (OUD) are overrepresented in the criminal justice system and at higher risk for opioid-related mortality. However, correctional facilities frequently adopt an abstinence-only approach, seldom offering the gold standard opioid agonist treatment (OAT) to incarcerated persons with OUD. In an attempt to inform adequate management of OUD among incarcerated persons, we conducted a systematic review of opioid-related interventions delivered before, during, and after incarceration.
METHODS AND FINDINGS
We systematically reviewed 8 electronic databases for original, peer-reviewed literature published between January 2008 and October 2019. Our review included studies conducted among adult participants with OUD who were incarcerated or recently released into the community (≤90 days post-incarceration). The search identified 2,356 articles, 46 of which met the inclusion criteria based on assessments by 2 independent reviewers. Thirty studies were conducted in North America, 9 in Europe, and 7 in Asia/Oceania. The systematic review included 22 randomized control trials (RCTs), 3 non-randomized clinical trials, and 21 observational studies. Eight observational studies utilized administrative data and included large sample sizes (median of 10,419 [range 2273-131,472] participants), and 13 observational studies utilized primary data, with a median of 140 (range 27-960) participants. RCTs and non-randomized clinical trials included a median of 198 (range 15-1,557) and 44 (range 27-382) participants, respectively. Twelve studies included only men, 1 study included only women, and in the remaining 33 studies, the percentage of women was below 30%. The majority of study participants were middle-aged adults (36-55 years). Participants treated at a correctional facility with methadone maintenance treatment (MMT) or buprenorphine (BPN)/naloxone (NLX) had lower rates of illicit opioid use, had higher adherence to OUD treatment, were less likely to be re-incarcerated, and were more likely to be working 1 year post-incarceration. Participants who received MMT or BPN/NLX while incarcerated had fewer nonfatal overdoses and lower mortality. The main limitation of our systematic review is the high heterogeneity of studies (different designs, settings, populations, treatments, and outcomes), precluding a meta-analysis. Other study limitations include the insufficient data about incarcerated women with OUD, and the lack of information about incarcerated populations with OUD who are not included in published research.
CONCLUSIONS
In this carefully conducted systematic review, we found that correctional facilities should scale up OAT among incarcerated persons with OUD. The strategy is likely to decrease opioid-related overdose and mortality, reduce opioid use and other risky behaviors during and after incarceration, and improve retention in addiction treatment after prison release. Immediate OAT after prison release and additional preventive strategies such as the distribution of NLX kits to at-risk individuals upon release greatly decrease the occurrence of opioid-related overdose and mortality. In an effort to mitigate the impact of the opioid-related overdose crisis, it is crucial to scale up OAT and opioid-related overdose prevention strategies (e.g., NLX) within a continuum of treatment before, during, and after incarceration.
Topics: Adult; Analgesics, Opioid; Asia; Drug Overdose; Europe; Female; Humans; Male; Middle Aged; North America; Opiate Substitution Treatment; Opioid-Related Disorders; Prisoners
PubMed: 31891578
DOI: 10.1371/journal.pmed.1003002 -
Pain Physician May 2023Thoracotomy is associated with severe postoperative pain. Effective management of acute pain after thoracotomy may reduce complications and chronic pain. Epidural... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Thoracotomy is associated with severe postoperative pain. Effective management of acute pain after thoracotomy may reduce complications and chronic pain. Epidural analgesia (EPI) is considered the gold standard for postthoracotomy analgesia; however, it is associated with complications and limitations. Emerging evidence suggests that an intercostal nerve block (ICB) has a low risk of severe complications. Anesthetists will benefit from a review that assesses the advantages and disadvantages associated with ICB and EPI in thoracotomy.
OBJECTIVES
This meta-analysis aimed to evaluate the analgesic efficacy and adverse effects of ICB and EPI for pain treatment after thoracotomy.
STUDY DESIGN
Systematic review.
METHODS
This study was registered in the International Prospective Register of Systematic Reviews (CRD42021255127). Relevant studies were searched for in PubMed, Embase, Cochrane, and Ovid databases. Primary (postoperative pain at rest and during cough) and secondary (nausea and vomiting, morphine consumption, and length of hospital stay) outcomes were analyzed. The standard mean difference for continuous variables and the risk ratio for dichotomous variables were calculated.
RESULTS
Nine randomized controlled studies with a total of 498 patients who underwent thoracotomy were included. The results of the meta-analysis demonstrated no statistically significant differences between the 2 methods in terms of the Visual Analog Scale scores for pain at 6-8, 12-15, 24-25, and 48-50 hours at rest and at 24 hours during coughing after surgery. There were no significant differences in nausea and vomiting, morphine consumption, or length of hospital stay between the ICB and EPI groups.
LIMITATIONS
The number of included studies was small, and the quality of evidence was low.
CONCLUSIONS
ICB may be as effective as EPI for pain relief after thoracotomy.
Topics: Humans; Analgesia, Epidural; Thoracotomy; Nerve Block; Randomized Controlled Trials as Topic; Pain, Postoperative; Morphine; Nausea; Vomiting; Analgesics, Opioid
PubMed: 37192224
DOI: No ID Found -
Metabolites Oct 2021After ingestion, consumed drugs and their metabolites are incorporated into hair, which has a long detection window, ranging up to months. Therefore, in addition to... (Review)
Review
After ingestion, consumed drugs and their metabolites are incorporated into hair, which has a long detection window, ranging up to months. Therefore, in addition to conventional blood and urine analyses, hair analysis can provide useful information on long-term drug exposure. Meta-bolite-to-drug (MD) ratios are helpful in interpreting hair results, as they provide useful information on drug metabolism and can be used to distinguish drug use from external contamination, which is otherwise a limitation in hair analysis. Despite this, the MD ratios of a wide range of pharmaceuticals have scarcely been explored. This review aims to provide an overview of MD ratios in hair in a range of pharmaceuticals of interest to forensic toxicology, such as antipsychotic drugs, antidepressant drugs, benzodiazepines, common opiates/opioids, etc. The factors influencing the ratio were evaluated. MD ratios of 41 pharmaceuticals were reported from almost 100 studies. MD ratios below 1 were frequently reported, indicating higher concentrations of the parent pharmaceutical than of its metabolite in hair, but wide-ranging MD ratios of the majority of pharmaceuticals were found. Intra- and interindividual differences and compound properties were variables possibly contributing to this. This overview presents guidance for future comparison and evaluation of MD ratios of pharmaceuticals.
PubMed: 34677401
DOI: 10.3390/metabo11100686 -
The Cochrane Database of Systematic... Sep 2022There are ongoing concerns regarding pharmaceutical opioid-related harms, including overdose and dependence, with an associated increase in treatment demand. People... (Review)
Review
BACKGROUND
There are ongoing concerns regarding pharmaceutical opioid-related harms, including overdose and dependence, with an associated increase in treatment demand. People dependent on pharmaceutical opioids appear to differ in important ways from people who use heroin, yet most opioid agonist treatment research has been conducted in people who use heroin. OBJECTIVES: To assess the effects of maintenance opioid agonist pharmacotherapy for the treatment of pharmaceutical opioid dependence.
SEARCH METHODS
We updated our searches of the following databases to January 2022: the Cochrane Drugs and Alcohol Group Specialised Register, CENTRAL, MEDLINE, four other databases, and two trial registers. We checked the reference lists of included studies for further references to relevant randomised controlled trials (RCTs).
SELECTION CRITERIA
We included RCTs with adults and adolescents examining maintenance opioid agonist treatments that made the following two comparisons. 1. Full opioid agonists (methadone, morphine, oxycodone, levo-alpha-acetylmethadol (LAAM), or codeine) versus different full opioid agonists or partial opioid agonists (buprenorphine) for maintenance treatment. 2. Full or partial opioid agonist maintenance versus non-opioid agonist treatments (detoxification, opioid antagonist, or psychological treatment without opioid agonist treatment).
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods.
MAIN RESULTS
We identified eight RCTs that met inclusion criteria (709 participants). We found four studies that compared methadone and buprenorphine maintenance treatment, and four studies that compared buprenorphine maintenance to either buprenorphine taper (in addition to psychological treatment) or a non-opioid maintenance treatment comparison. We found low-certainty evidence from three studies of a difference between methadone and buprenorphine in favour of methadone on self-reported opioid use at end of treatment (risk ratio (RR) 0.49, 95% confidence interval (CI) 0.28 to 0.86; 165 participants), and low-certainty evidence from four studies finding a difference in favour of methadone for retention in treatment (RR 1.21, 95% CI 1.02 to 1.43; 379 participants). We found low-certainty evidence from three studies showing no difference between methadone and buprenorphine on substance use measured with urine drug screens at end of treatment (RR 0.81, 95% CI 0.57 to 1.17; 206 participants), and moderate-certainty evidence from one study of no difference in days of self-reported opioid use (mean difference 1.41 days, 95% CI 3.37 lower to 0.55 days higher; 129 participants). There was low-certainty evidence from three studies of no difference between methadone and buprenorphine on adverse events (RR 1.13, 95% CI 0.66 to 1.93; 206 participants). We found low-certainty evidence from four studies favouring maintenance buprenorphine treatment over non-opioid treatments in terms of fewer opioid positive urine drug tests at end of treatment (RR 0.66, 95% CI 0.52 to 0.84; 270 participants), and very low-certainty evidence from four studies finding no difference on self-reported opioid use in the past 30 days at end of treatment (RR 0.63, 95% CI 0.39 to 1.01; 276 participants). There was low-certainty evidence from three studies of no difference in the number of days of unsanctioned opioid use (standardised mean difference (SMD) -0.19, 95% CI -0.47 to 0.09; 205 participants). There was moderate-certainty evidence from four studies favouring buprenorphine maintenance over non-opioid treatments on retention in treatment (RR 3.02, 95% CI 1.73 to 5.27; 333 participants). There was moderate-certainty evidence from three studies of no difference in adverse effects between buprenorphine maintenance and non-opioid treatments (RR 0.50, 95% CI 0.07 to 3.48; 252 participants). The main weaknesses in the quality of the data was the use of open-label study designs, and difference in follow-up rates between treatment arms.
AUTHORS' CONCLUSIONS
There is very low- to moderate-certainty evidence supporting the use of maintenance agonist pharmacotherapy for pharmaceutical opioid dependence. Methadone or buprenorphine did not differ on some outcomes, although on the outcomes of retention and self-reported substance use some results favoured methadone. Maintenance treatment with buprenorphine appears more effective than non-opioid treatments. Due to the overall very low- to moderate-certainty evidence and small sample sizes, there is the possibility that the further research may change these findings.
Topics: Adolescent; Analgesics, Opioid; Buprenorphine; Heroin; Humans; Methadone; Opioid-Related Disorders; Pharmaceutical Preparations
PubMed: 36063082
DOI: 10.1002/14651858.CD011117.pub3 -
World Journal of Clinical Cases Dec 2019The literature suggests that there is a high degree of co-occurrence between chronic pain and posttraumatic stress disorder (PTSD). An association has been found between...
BACKGROUND
The literature suggests that there is a high degree of co-occurrence between chronic pain and posttraumatic stress disorder (PTSD). An association has been found between PTSD and substance abuse. PTSD is a severe disorder that should be taken into account when opioids are prescribed. It has been found that the prevalence of opioid use disorder (OUD) in chronic pain patients is higher among those with PTSD than those without this disorder.
AIM
To perform a systematic review on the association between PTSD, chronic non-cancer pain (CNCP), and opioid intake (., prescription, misuse, and abuse).
METHODS
We conducted a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The Patient, Intervention, Comparator, and Outcomes (PICOS) criteria were formulated a priori in the protocol of the systematic review. A search was conducted of the PROSPERO database. In March 2019, searches were also conducted of 5 other databases: PubMed, MEDLINE, PsycINFO, Web of Science, and PILOTS. The Scottish Intercollegiate Guidelines Network checklist for cohort studies was used to assess the selected studies for their methodological quality and risk of bias. Each study was evaluated according to its internal validity, participant sampling, confounding variables, and the statistical analysis.
RESULTS
A total of 151 potentially eligible studies were identified of which 17 were retained for analysis. Only 10 met the selection criteria. All the studies were published between 2008 and 2018 and were conducted in the United States. The eligible studies included a total of 1622785 unique participants. Of these, 196516 had comorbid CNCP and PTSD and were consuming opiates. The participants had a cross-study mean age of 35.2 years. The majority of participants were men (81.6%). The most common chronic pain condition was musculoskeletal pain: back pain (47.14% across studies; range: 16%-60.6%), arthritis and joint pain (31.1%; range: 18%-67.5%), and neck pain (28.7%; range: 3.6%-63%). In total, 42.4% of the participants across studies had a diagnosis of PTSD (range: 4.7%-95%). In relation to opioid intake, we identified 2 different outcomes: opioid prescription and OUD. All the studies reported evidence of a greater prevalence of PTSD in CNCP patients who were receiving prescribed opioids and that PTSD was associated with OUD in CNCP patients.
CONCLUSION
Opioid analgesic prescription as the treatment of choice for CNCP patients should include screening for baseline PTSD to ensure that these drugs are safely consumed.
PubMed: 31911906
DOI: 10.12998/wjcc.v7.i24.4254 -
Japanese Journal of Clinical Oncology Mar 2023the role of benzodiazepines in relieving dyspnea in patients with cancer has not yet been established. This systematic review and meta-analysis aimed to determine the... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
the role of benzodiazepines in relieving dyspnea in patients with cancer has not yet been established. This systematic review and meta-analysis aimed to determine the efficacy and safety of benzodiazepines alone or in combination with opioids for dyspnea in patients with cancer.
METHODS
Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and Ichushi-Web were searched for articles published from database inception to 23 September 2019. Studies of benzodiazepines alone or in combination with opioids for dyspnea were included. The primary outcome measure was the relief of dyspnea. The secondary outcome measures were anxiety, somnolence and severe adverse events.
RESULTS
of 505 publications initially identified, two trials and one trial were included in the meta-analysis of midazolam alone and in combination with morphine, respectively. With regard to the relief of dyspnea, midazolam alone showed no significant difference compared with morphine alone, with a relative risk of 0.95 (95% confidence interval: 0.47-1.89). Meanwhile, midazolam plus morphine was significantly more effective than morphine alone, with a relative risk of 1.33 (95% confidence interval: 1.02-1.75). For anxiety relief, a meta-analysis could not be performed because of insufficient data. The incidence of somnolence and severe adverse events was not significantly different between the experimental and control groups for either midazolam alone or in combination with morphine.
CONCLUSIONS
benzodiazepines alone do not significantly improve dyspnea compared with opioids alone, but a combination of benzodiazepines and opioids may be more effective. Evidence from randomized controlled trials focusing on patients with cancer has not been generated in recent years. Further appropriately designed randomized controlled trials are required.
Topics: Humans; Benzodiazepines; Midazolam; Sleepiness; Dyspnea; Neoplasms; Morphine; Analgesics, Opioid
PubMed: 36636762
DOI: 10.1093/jjco/hyac206