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Scandinavian Journal of Pain Jan 2024Opioids are important for postoperative analgesia but their use can be associated with numerous side effects. Transcutaneous electrical nerve stimulation (TENS) has been... (Meta-Analysis)
Meta-Analysis
High-frequency, high-intensity transcutaneous electrical nerve stimulation compared with opioids for pain relief after gynecological surgery: a systematic review and meta-analysis.
OBJECTIVES
Opioids are important for postoperative analgesia but their use can be associated with numerous side effects. Transcutaneous electrical nerve stimulation (TENS) has been used for acute pain treatment and has dose-dependent analgesic effects, and therefore presents an alternative to intravenous (iv) opioids for postoperative pain relief. The aim of this meta-analysis was to compare high-frequency, high-intensity (HFHI or intense) TENS to iv opioids with regard to postoperative pain intensity, recovery time in the Post Anesthesia Care Unit (PACU) and opioid consumption after elective gynecological surgery.
METHODS
We searched Medline, Embase, Web of Science, Cochrane, Amed and Cinahl for RCTs and quasi-experimental studies (2010-2022), and WHO and ClinicalTrials.gov for ongoing/unpublished studies. Meta-analysis and subsequent Trial Sequential Analysis (TSA) was performed for all stated outcomes. Quality of evidence was assessed according to GRADE.
RESULTS
Only three RCTs met the inclusion criteria (362 participants). The surgical procedures involved surgical abortion, gynecologic laparoscopy and hysteroscopy. The applied TENS frequency was 80 Hz and intensity 40-60 mA. There was no difference in pain intensity according to Visual Analogue Scale (VAS) at discharge from PACU between the TENS and opioid group (MD VAS -0.15, 95 % CI -0.38 to 0.09) (moderate level of evidence). Time in PACU was significantly shorter in the TENS group (MD -15.2, 95 % -22.75 to -7.67), and this finding was manifested by TSA (high-level of evidence). Opioid consumption in PACU was lower in the TENS group (MD Morphine equivalents per patient mg -3.42, 95 % -4.67 to -2.17) (high-level of evidence).
CONCLUSIONS
There was no detectable difference in postoperative pain relief between HFHI TENS and iv opioids after gynecological surgery. Moreover, HFHI TENS decreases recovery time and opioid consumption in PACU. HFHI TENS may be considered an opioid-sparing alternative for postoperative pain relief after gynecological surgery.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42021231048.
Topics: Pregnancy; Female; Humans; Analgesics, Opioid; Transcutaneous Electric Nerve Stimulation; Gynecologic Surgical Procedures; Morphine; Pain, Postoperative
PubMed: 37819201
DOI: 10.1515/sjpain-2023-0068 -
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 -
Pain Physician Jul 2023Intrathecal opioids have long been used as analgesia for intractable cancer pain or as part of spinal anesthesia during obstetric operations. More recently, they have... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Intrathecal opioids have long been used as analgesia for intractable cancer pain or as part of spinal anesthesia during obstetric operations. More recently, they have been used preoperatively as a pain management adjuvant for open cardiac and thoracic procedures.
OBJECTIVE
This study aims to analyze the impact of administering intrathecal opioids before cardiac and thoracic surgeries on postoperative pain and mechanical ventilation.
STUDY DESIGN
Systematic review and meta-analysis.
SETTING
University, School of Medicine, and several university-affiliated hospitals.
METHODS
Five outcomes were studied, including the primary outcome of time to extubation, secondary outcomes of analgesia requirements at 24 and 48 hours, resting pain scores at 1 and 24 hours post-extubation, ICU length of stay in hours, and hospital length of stay in days. A search of multiple databases provided 28 studies reporting 4,000 total patients. Outcomes were measured using continuous mean difference with a 95% confidence interval, and the studies were examined for heterogeneity and sensitivity analysis.
RESULTS
The primary outcome analysis suggested that time to extubation was 42 minutes shorter in the intrathecal opioid group (ranging from 82 to 1 minute, P = 0.04). There was also a decrease in postoperative analgesia requirements at both 24 hours (mean difference (MD) = -8.95 mg morphine equivalent doses (MED) [-9.4, -8.5], P < 0.001) and 48 hours (MD = -17.7 mg MED [-23.1, -12.4], P < 0.001) with I2 of 94% and 85% respectively, an improvement of pain scores at both 1 hour (MD = -2.24 [-3.16, -1.32], P < 0.001) and 24-hours (MD = -1.64 [-2.48, -0.80], P =< 0.001) I2 of 94% and 85%, no change in both ICU length of stay (MD = -0.27 hours [-0.55, 0.01], P = 0.06) I2 = 77% and hospital length of stay (MD = -0.30 days [-0.66, 0.06], P = 0.11) I2 = 32%.
LIMITATIONS
The major limitation of this meta-analysis was the inconsistent dosages of intrathecal opioids utilized. Some used the same dose for each patient, while other studies used weight-based doses. The differences in the outcomes observed may then be a result of the different amounts of opioids administered rather than the technique itself. Another limitation was the inconsistent timing of reports for pain scores and postoperative analgesic requirements. Further studies were analyzed at the 2 time periods for both secondary outcomes, making it difficult to attribute the 2 effects solely to the intervention.
CONCLUSIONS
We conclude that preoperative injection of intrathecal opioids is significantly associated with decreased time to extubation, decreased postoperative analgesia requirement, and improved pain scores. In controlled conditions with adequate staff education, this method of analgesia may make it possible to extubate the patients after the surgery in the operating room and fast-track their discharge from the hospital.
Topics: Humans; Analgesics, Opioid; Injections, Spinal; Morphine; Coronary Artery Bypass; Pain, Postoperative; Treatment Outcome
PubMed: 37535770
DOI: No ID Found -
Sleep Medicine Sep 2023Narcolepsy type 1 is a primary sleep disorder caused by deficient hypocretin transmission leading to excessive daytime sleepiness and cataplexy. Opioids have been...
OBJECTIVE
Narcolepsy type 1 is a primary sleep disorder caused by deficient hypocretin transmission leading to excessive daytime sleepiness and cataplexy. Opioids have been suggested to increase the number of hypocretin-producing neurons. We aimed to assess opioid use and its self-reported effect on narcolepsy type 1 symptom severity through a literature review and questionnaire study.
METHODS
We systematically reviewed literature on opioid use in narcolepsy. We also recruited 100 people with narcolepsy type 1 who completed an online questionnaire on opioid use in the previous three years. The main questionnaire topics were the indication for use, and the possible effects on narcolepsy symptom severity. Structured follow-up interviews were conducted when opioid use was reported.
RESULTS
The systematic literature review mainly showed improvements in narcolepsy symptom severity. Recent opioid use was reported by 16/100 questionnaire respondents, who had used 20 opioids (codeine: 7/20, tramadol: 6/20, oxycodone: 6/20, fentanyl: 1/20). Narcolepsy symptom changes were reported in 11/20. Positive effects on disturbed nocturnal sleep (9/20), excessive daytime sleepiness (4/20), hypnagogic hallucinations (3/17), cataplexy (2/18), and sleep paralysis (1/13) were most pronounced for oxycodone (4/6) and codeine (4/7).
CONCLUSIONS
Opioids were relatively frequently used compared to a similarly young general Dutch sample. Oxycodone and, to a lesser extent, codeine were associated with self-reported narcolepsy symptom severity improvements. Positive changes in disturbed nocturnal sleep and daytime sleepiness were most frequently reported, while cataplexy effects were less pronounced. Randomised controlled trials are now needed to verify the potential of opioids as therapeutic agents for narcolepsy.
Topics: Humans; Cataplexy; Analgesics, Opioid; Orexins; Oxycodone; Narcolepsy; Disorders of Excessive Somnolence; Surveys and Questionnaires
PubMed: 37437491
DOI: 10.1016/j.sleep.2023.06.008 -
The Cochrane Database of Systematic... Jun 2023Neonates might be exposed to numerous painful procedures due to diagnostic reasons, therapeutic interventions, or surgical procedures. Options for pain management... (Review)
Review
BACKGROUND
Neonates might be exposed to numerous painful procedures due to diagnostic reasons, therapeutic interventions, or surgical procedures. Options for pain management include opioids, non-pharmacological interventions, and other drugs. Morphine, fentanyl, and remifentanil are the opioids most often used in neonates. However, negative impact of opioids on the structure and function of the developing brain has been reported.
OBJECTIVES
To evaluate the benefits and harms of opioids in term or preterm neonates exposed to procedural pain, compared to placebo or no drug, non-pharmacological intervention, other analgesics or sedatives, other opioids, or the same opioid administered by a different route.
SEARCH METHODS
We used standard, extensive Cochrane search methods. The latest search date was December 2021.
SELECTION CRITERIA
We included randomized controlled trials conducted in preterm and term infants of a postmenstrual age (PMA) up to 46 weeks and 0 days exposed to procedural pain where opioids were compared to 1) placebo or no drug; 2) non-pharmacological intervention; 3) other analgesics or sedatives; 4) other opioids; or 5) the same opioid administered by a different route.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. Our primary outcomes were pain assessed with validated methods and any harms. We used a fixed-effect model with risk ratio (RR) for dichotomous data and mean difference (MD) for continuous data, and their confidence intervals (CI). We used GRADE to assess the certainty of the evidence for each outcome.
MAIN RESULTS
We included 13 independent studies (enrolling 823 newborn infants): seven studies compared opioids to no treatment or placebo (the main comparison in this review), two studies to oral sweet solution or non-pharmacological intervention, and five studies (of which two were part of the same study) to other analgesics and sedatives. All studies were performed in a hospital setting. Opioids compared to placebo or no drug Compared to placebo, opioids probably reduce pain score assessed with the Premature Infant Pain Profile (PIPP)/PIPP-Revised (PIPP-R) scale during the procedure (MD -2.58, 95% CI -3.12 to -2.03; 199 participants, 3 studies; moderate-certainty evidence); may reduce Neonatal Infant Pain Scale (NIPS) during the procedure (MD -1.97, 95% CI -2.46 to -1.48; 102 participants, 2 studies; low-certainty evidence); and may result in little to no difference in pain score assessed with the Douleur Aiguë du Nouveau-né (DAN) scale one to two hours after the procedure (MD -0.20, 95% CI -2.21 to 1.81; 42 participants, 1 study; low-certainty evidence). The evidence is very uncertain about the effect of opioids on pain score assessed with the PIPP/PIPP-R scale up to 30 minutes after the procedure (MD 0.14, 95% CI -0.17 to 0.45; 123 participants, 2 studies; very low-certainty evidence) or one to two hours after the procedure (MD -0.83, 95% CI -2.42 to 0.75; 54 participants, 2 studies; very low-certainty evidence). The evidence is very uncertain about the effect of opioids on episodes of bradycardia (RR 3.19, 95% CI 0.14 to 72.69; 172 participants, 3 studies; very low-certainty evidence). Opioids may result in an increase in episodes of apnea compared to placebo (RR 3.15, 95% CI 1.08 to 9.16; 199 participants, 3 studies; low-certainty evidence): with one study reporting a concerning increase in severe apnea (RR 7.44, 95% CI 0.42 to 132.95; 31 participants, 1 study; very low-certainty). The evidence is very uncertain about the effect of opioids on episodes of hypotension (RR not estimable, risk difference 0.00, 95% CI -0.06 to 0.06; 88 participants, 2 studies; very low-certainty evidence). No studies reported parent satisfaction with care provided in the neonatal intensive care unit (NICU). Opioids compared to non-pharmacological intervention The evidence is very uncertain about the effect of opioids on pain score assessed with the Crying Requires oxygen Increased vital signs Expression Sleep (CRIES) scale during the procedure when compared to facilitated tucking (MD -4.62, 95% CI -6.38 to -2.86; 100 participants, 1 study; very low-certainty evidence) or sensorial stimulation (MD 0.32, 95% CI -1.13 to 1.77; 100 participants, 1 study; very low-certainty evidence). The other main outcomes were not reported. Opioids compared to other analgesics or sedatives The evidence is very uncertain about the effect of opioids on pain score assessed with the PIPP/PIPP-R during the procedure (MD -0.29, 95% CI -1.58 to 1.01; 124 participants, 2 studies; very low-certainty evidence); up to 30 minutes after the procedure (MD -1.10, 95% CI -2.82 to 0.62; 12 participants, 1 study; very low-certainty evidence); and one to two hours after the procedure (MD -0.17, 95% CI -2.22 to 1.88; 12 participants, 1 study; very low-certainty evidence). No studies reported any harms. The evidence is very uncertain about the effect of opioids on episodes of apnea during (RR 3.27, 95% CI 0.85 to 12.58; 124 participants, 2 studies; very low-certainty evidence) and after the procedure (RR 2.71, 95% CI 0.11 to 64.96; 124 participants, 2 studies; very low-certainty evidence) and on hypotension (RR 1.34, 95% CI 0.32 to 5.59; 204 participants, 3 studies; very low-certainty evidence). The other main outcomes were not reported. We identified no studies comparing different opioids (e.g. morphine versus fentanyl) or different routes for administration of the same opioid (e.g. morphine enterally versus morphine intravenously).
AUTHORS' CONCLUSIONS
Compared to placebo, opioids probably reduce pain score assessed with PIPP/PIPP-R scale during the procedure; may reduce NIPS during the procedure; and may result in little to no difference in DAN one to two hours after the procedure. The evidence is very uncertain about the effect of opioids on pain assessed with other pain scores or at different time points. The evidence is very uncertain about the effect of opioids on episodes of bradycardia, hypotension or severe apnea. Opioids may result in an increase in episodes of apnea. No studies reported parent satisfaction with care provided in the NICU. The evidence is very uncertain about the effect of opioids on any outcome when compared to non-pharmacological interventions or to other analgesics. We identified no studies comparing opioids to other opioids or comparing different routes of administration of the same opioid.
Topics: Humans; Infant, Newborn; Analgesics; Analgesics, Opioid; Apnea; Bradycardia; Fentanyl; Hypotension; Morphine; Pain; Pain, Procedural
PubMed: 37350685
DOI: 10.1002/14651858.CD015056.pub3 -
The Cochrane Database of Systematic... Jun 2023Pain is a common symptom in people with cancer; 30% to 50% of people with cancer will experience moderate-to-severe pain. This can have a major negative impact on their... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Pain is a common symptom in people with cancer; 30% to 50% of people with cancer will experience moderate-to-severe pain. This can have a major negative impact on their quality of life. Opioid (morphine-like) medications are commonly used to treat moderate or severe cancer pain, and are recommended for this purpose in the World Health Organization (WHO) pain treatment ladder. Pain is not sufficiently relieved by opioid medications in 10% to 15% of people with cancer. In people with insufficient relief of cancer pain, new analgesics are needed to effectively and safely supplement or replace opioids.
OBJECTIVES
To evaluate the benefits and harms of cannabis-based medicines, including medical cannabis, for treating pain and other symptoms in adults with cancer compared to placebo or any other established analgesic for cancer pain.
SEARCH METHODS
We used standard, extensive Cochrane search methods. The latest search date was 26 January 2023.
SELECTION CRITERIA
We selected double-blind randomised, controlled trials (RCT) of medical cannabis, plant-derived and synthetic cannabis-based medicines against placebo or any other active treatment for cancer pain in adults, with any treatment duration and at least 10 participants per treatment arm.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. The primary outcomes were 1. proportions of participants reporting no worse than mild pain; 2. Patient Global Impression of Change (PGIC) of much improved or very much improved and 3. withdrawals due to adverse events. Secondary outcomes were 4. number of participants who reported pain relief of 30% or greater and overall opioid use reduced or stable; 5. number of participants who reported pain relief of 30% or greater, or 50% or greater; 6. pain intensity; 7. sleep problems; 8. depression and anxiety; 9. daily maintenance and breakthrough opioid dosage; 10. dropouts due to lack of efficacy; 11. all central nervous system adverse events. We used GRADE to assess certainty of evidence for each outcome.
MAIN RESULTS
We identified 14 studies involving 1823 participants. No study assessed the proportions of participants reporting no worse than mild pain on treatment by 14 days after start of treatment. We found five RCTs assessing oromucosal nabiximols (tetrahydrocannabinol (THC) and cannabidiol (CBD)) or THC alone involving 1539 participants with moderate or severe pain despite opioid therapy. The double-blind periods of the RCTs ranged between two and five weeks. Four studies with a parallel design and 1333 participants were available for meta-analysis. There was moderate-certainty evidence that there was no clinically relevant benefit for proportions of PGIC much or very much improved (risk difference (RD) 0.06, 95% confidence interval (CI) 0.01 to 0.12; number needed to treat for an additional beneficial outcome (NNTB) 16, 95% CI 8 to 100). There was moderate-certainty evidence for no clinically relevant difference in the proportion of withdrawals due to adverse events (RD 0.04, 95% CI 0 to 0.08; number needed to treat for an additional harmful outcome (NNTH) 25, 95% CI 16 to endless). There was moderate-certainty evidence for no difference between nabiximols or THC and placebo in the frequency of serious adverse events (RD 0.02, 95% CI -0.03 to 0.07). There was moderate-certainty evidence that nabiximols and THC used as add-on treatment for opioid-refractory cancer pain did not differ from placebo in reducing mean pain intensity (standardised mean difference (SMD) -0.19, 95% CI -0.40 to 0.02). There was low-certainty evidence that a synthetic THC analogue (nabilone) delivered over eight weeks was not superior to placebo in reducing pain associated with chemotherapy or radiochemotherapy in people with head and neck cancer and non-small cell lung cancer (2 studies, 89 participants, qualitative analysis). Analyses of tolerability and safety were not possible for these studies. There was low-certainty evidence that synthetic THC analogues were superior to placebo (SMD -0.98, 95% CI -1.36 to -0.60), but not superior to low-dose codeine (SMD 0.03, 95% CI -0.25 to 0.32; 5 single-dose trials; 126 participants) in reducing moderate-to-severe cancer pain after cessation of previous analgesic treatment for three to four and a half hours (2 single-dose trials; 66 participants). Analyses of tolerability and safety were not possible for these studies. There was low-certainty evidence that CBD oil did not add value to specialist palliative care alone in the reduction of pain intensity in people with advanced cancer. There was no difference in the number of dropouts due to adverse events and serious adverse events (1 study, 144 participants, qualitative analysis). We found no studies using herbal cannabis.
AUTHORS' CONCLUSIONS
There is moderate-certainty evidence that oromucosal nabiximols and THC are ineffective in relieving moderate-to-severe opioid-refractory cancer pain. There is low-certainty evidence that nabilone is ineffective in reducing pain associated with (radio-) chemotherapy in people with head and neck cancer and non-small cell lung cancer. There is low-certainty evidence that a single dose of synthetic THC analogues is not superior to a single low-dose morphine equivalent in reducing moderate-to-severe cancer pain. There is low-certainty evidence that CBD does not add value to specialist palliative care alone in the reduction of pain in people with advanced cancer.
Topics: Adult; Humans; Analgesics, Opioid; Cancer Pain; Cannabis; Carcinoma, Non-Small-Cell Lung; Codeine; Lung Neoplasms; Medical Marijuana; Morphine; Randomized Controlled Trials as Topic
PubMed: 37283486
DOI: 10.1002/14651858.CD014915.pub2 -
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 -
The Cochrane Database of Systematic... May 2023Harmful alcohol use is defined as unhealthy alcohol use that results in adverse physical, psychological, social, or societal consequences and is among the leading risk... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Harmful alcohol use is defined as unhealthy alcohol use that results in adverse physical, psychological, social, or societal consequences and is among the leading risk factors for disease, disability and premature mortality globally. The burden of harmful alcohol use is increasing in low- and middle-income countries (LMICs) and there remains a large unmet need for indicated prevention and treatment interventions to reduce harmful alcohol use in these settings. Evidence regarding which interventions are effective and feasible for addressing harmful and other patterns of unhealthy alcohol use in LMICs is limited, which contributes to this gap in services.
OBJECTIVES
To assess the efficacy and safety of psychosocial and pharmacologic treatment and indicated prevention interventions compared with control conditions (wait list, placebo, no treatment, standard care, or active control condition) aimed at reducing harmful alcohol use in LMICs.
SEARCH METHODS
We searched for randomized controlled trials (RCTs) indexed in the Cochrane Drugs and Alcohol Group (CDAG) Specialized Register, the Cochrane Clinical Register of Controlled Trials (CENTRAL) in the Cochrane Library, PubMed, Embase, PsycINFO, CINAHL, and the Latin American and Caribbean Health Sciences Literature (LILACS) through 12 December 2021. We searched clinicaltrials.gov, the World Health Organization International Clinical Trials Registry Platform, Web of Science, and Opengrey database to identify unpublished or ongoing studies. We searched the reference lists of included studies and relevant review articles for eligible studies.
SELECTION CRITERIA
All RCTs comparing an indicated prevention or treatment intervention (pharmacologic or psychosocial) versus a control condition for people with harmful alcohol use in LMICs were included.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane.
MAIN RESULTS
We included 66 RCTs with 17,626 participants. Sixty-two of these trials contributed to the meta-analysis. Sixty-three studies were conducted in middle-income countries (MICs), and the remaining three studies were conducted in low-income countries (LICs). Twenty-five trials exclusively enrolled participants with alcohol use disorder. The remaining 51 trials enrolled participants with harmful alcohol use, some of which included both cases of alcohol use disorder and people reporting hazardous alcohol use patterns that did not meet criteria for disorder. Fifty-two RCTs assessed the efficacy of psychosocial interventions; 27 were brief interventions primarily based on motivational interviewing and were compared to brief advice, information, or assessment only. We are uncertain whether a reduction in harmful alcohol use is attributable to brief interventions given the high levels of heterogeneity among included studies (Studies reporting continuous outcomes: Tau² = 0.15, Q =139.64, df =16, P<.001, I² = 89%, 3913 participants, 17 trials, very low certainty; Studies reporting dichotomous outcomes: Tau²=0.18, Q=58.26, df=3, P<.001, I² =95%, 1349 participants, 4 trials, very low certainty). The other types of psychosocial interventions included a range of therapeutic approaches such as behavioral risk reduction, cognitive-behavioral therapy, contingency management, rational emotive therapy, and relapse prevention. These interventions were most commonly compared to usual care involving varying combinations of psychoeducation, counseling, and pharmacotherapy. We are uncertain whether a reduction in harmful alcohol use is attributable to psychosocial treatments due to high levels of heterogeneity among included studies (Heterogeneity: Tau² = 1.15; Q = 444.32, df = 11, P<.001; I²=98%, 2106 participants, 12 trials, very low certainty). Eight trials compared combined pharmacologic and psychosocial interventions with placebo, psychosocial intervention alone, or another pharmacologic treatment. The active pharmacologic study conditions included disulfiram, naltrexone, ondansetron, or topiramate. The psychosocial components of these interventions included counseling, encouragement to attend Alcoholics Anonymous, motivational interviewing, brief cognitive-behavioral therapy, or other psychotherapy (not specified). Analysis of studies comparing a combined pharmacologic and psychosocial intervention to psychosocial intervention alone found that the combined approach may be associated with a greater reduction in harmful alcohol use (standardized mean difference (standardized mean difference (SMD))=-0.43, 95% confidence interval (CI): -0.61 to -0.24; 475 participants; 4 trials; low certainty). Four trials compared pharmacologic intervention alone with placebo and three with another pharmacotherapy. Drugs assessed were: acamprosate, amitriptyline, baclofen disulfiram, gabapentin, mirtazapine, and naltrexone. None of these trials evaluated the primary clinical outcome of interest, harmful alcohol use. Thirty-one trials reported rates of retention in the intervention. Meta-analyses revealed that rates of retention between study conditions did not differ in any of the comparisons (pharmacologic risk ratio (RR) = 1.13, 95% CI: 0.89 to 1.44, 247 participants, 3 trials, low certainty; pharmacologic in addition to psychosocial intervention: RR = 1.15, 95% CI: 0.95 to 1.40, 363 participants, 3 trials, moderate certainty). Due to high levels of heterogeneity, we did not calculate pooled estimates comparing retention in brief (Heterogeneity: Tau² = 0.00; Q = 172.59, df = 11, P<.001; I = 94%; 5380 participants; 12 trials, very low certainty) or other psychosocial interventions (Heterogeneity: Tau² = 0.01; Q = 34.07, df = 8, P<.001; I = 77%; 1664 participants; 9 trials, very low certainty). Two pharmacologic trials and three combined pharmacologic and psychosocial trials reported on side effects. These studies found more side effects attributable to amitriptyline relative to mirtazapine, naltrexone and topiramate relative to placebo, yet no differences in side effects between placebo and either acamprosate or ondansetron. Across all intervention types there was substantial risk of bias. Primary threats to validity included lack of blinding and differential/high rates of attrition.
AUTHORS' CONCLUSIONS
In LMICs there is low-certainty evidence supporting the efficacy of combined psychosocial and pharmacologic interventions on reducing harmful alcohol use relative to psychosocial interventions alone. There is insufficient evidence to determine the efficacy of pharmacologic or psychosocial interventions on reducing harmful alcohol use largely due to the substantial heterogeneity in outcomes, comparisons, and interventions that precluded pooling of these data in meta-analyses. The majority of studies are brief interventions, primarily among men, and using measures that have not been validated in the target population. Confidence in these results is reduced by the risk of bias and significant heterogeneity among studies as well as the heterogeneity of results on different outcome measures within studies. More evidence on the efficacy of pharmacologic interventions, specific types of psychosocial interventions are needed to increase the certainty of these results.
Topics: Humans; Male; Acamprosate; Alcoholism; Amitriptyline; Developing Countries; Disulfiram; Mirtazapine; Naltrexone; Ondansetron; Topiramate
PubMed: 37158538
DOI: 10.1002/14651858.CD013350.pub2 -
Harm Reduction Journal Apr 2023Preliminary evidence suggests that people who inject drugs (PWID) may be at an increased risk of developing infective endocarditis (IE), hepatitis C virus (HCV)... (Review)
Review
BACKGROUND
Preliminary evidence suggests that people who inject drugs (PWID) may be at an increased risk of developing infective endocarditis (IE), hepatitis C virus (HCV) infection, and/or human immunodeficiency virus (HIV) infection from hydromorphone controlled-release formulation. The hypothesized mechanism is related to insolubility of the drug, which promotes reuse, leading to contamination of injecting equipment. However, this relationship has not been confirmed. We aimed to conduct a systematic review including adult PWID exposed to controlled-release hydromorphone and the risk of acquiring IE, HCV, and HIV.
METHODS
We searched MEDLINE, EMBASE, and Evidence Based Medicine reviews from inception until September 2021. Following pilot testing, two reviewers conducted all screening of citations and full-text articles, as well as abstracted data, and appraised risk of bias using the Newcastle-Ottawa scale and Effective Practice and Organization of Care tool. Equity issues were examined using the PROGRESS-PLUS framework. Discrepancies were resolved consistently by a third reviewer. Meta-analysis was not feasible due to heterogeneity across the studies.
RESULTS
After screening 3,231 citations from electronic databases, 722 citations from unpublished sources/reference scanning, and 626 full-text articles, five studies were included. Five were cohort studies, and one was a case-control study. The risk of bias varied across the studies. Two studies reported on gender, as well as other PROGRESS-PLUS criteria (race, housing, and employment). Three studies focused specifically on the controlled-release formulation of hydromorphone, whereas two studies focused on all formulations of hydromorphone. One retrospective cohort study found an association between controlled-release hydromorphone and IE, whereas a case-control study found no evidence of an association. One retrospective cohort study found an association between the number of hydromorphone controlled-release prescriptions and prevalence of HCV. None of the studies specifically reported on associations with HIV.
DISCUSSION
Very few studies have examined the risk of IE, HCV, and HIV infection after exposure to controlled-release hydromorphone. Very low-quality and scant evidence suggests uncertainty around the risks of blood-borne infections, such as HCV and IE to PWID using this medication.
Topics: Humans; Adult; Hydromorphone; HIV Infections; Substance Abuse, Intravenous; Delayed-Action Preparations; Retrospective Studies; Case-Control Studies; Hepatitis C; Hepacivirus; Endocarditis; Endocarditis, Bacterial
PubMed: 37118805
DOI: 10.1186/s12954-023-00788-9 -
Drug and Alcohol Dependence Jun 2023Randomised controlled trials in Europe and Canada have shown that supervised heroin assisted treatment (HAT) is an effective treatment option for people with long-term... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND AIMS
Randomised controlled trials in Europe and Canada have shown that supervised heroin assisted treatment (HAT) is an effective treatment option for people with long-term heroin addictions for whom the standard opioid substitution treatments (OST) have not been effective. This review aims to evaluate the effectiveness of supervised HAT and analyse the significance of context and implementation in the design of successful HAT programmes.
METHODS
PubMed, CENTRAL, Embase, and Web of Science were searched to identify randomised controlled trials (RCT) and systematic reviews evaluating supervised HAT compared to any other OST. Studies were eligible for inclusion if they were published in English, evaluated a supervised form of HAT, and included illegal drug use and/or health as a primary outcome measure. There were no restrictions on publication date. The following outcomes of the included studies were analysed using narrative synthesis and meta-analysis where possible: retention, street drug use, health, and social functioning.
RESULTS
Nine randomised controlled trials spanning eight studies (n = 2331) and three systematic reviews met the inclusion criteria. Seven of the eight studies compared HAT to methadone maintenance treatment (MMT). One study compared HAT to injectable hydromorphone in a double-blind non-inferiority trial. Meta-analysis was performed on pooled results of retention across all included studies and found that HAT has a statistically significant effect on retention [Z = 7.65 (P > 0.0001)]. Five of the eight included studies found that supervised HAT reduces participants' use of illegal drugs more significantly than MMT. Evidence of improved health in participants receiving supervised HAT compared to other OSTs was inconsistent; positive effects were observed in three of the included studies (n = 1626).
CONCLUSION
When compared to methadone maintenance treatment (MMT), heroin assisted treatment (HAT) more consistently retains people with heroin addictions in treatment and reduces their consumption of illicit drugs.
TRIAL REGISTRATION
PROSPERO registration: CRD42022341306.
Topics: Humans; Heroin; Heroin Dependence; Opiate Substitution Treatment; Treatment Outcome; Illicit Drugs; Methadone; Narcotics; Randomized Controlled Trials as Topic
PubMed: 37086659
DOI: 10.1016/j.drugalcdep.2023.109869