Safety Of Opioids Research Articles

Comparative risk of mortality in new users of prescription opioids for noncancer pain: results from the International Pharmacosurveillance Study.

Although opioids continue to be used internationally for noncancer pain, evidence to date on the comparative safety of different opioids is sparse and conflicting. The aim of this study was to examine the comparative risk of all-cause mortality in patients newly initiated on opioids for noncancer pain, across 3 jurisdictions in the United Kingdom (UK), United States, and Canada. A multicentre retrospective, population-based cohort study was conducted. Data sources included UK national primary care electronic health records (Clinical Practice Research Datalink), The Partners HealthCare Research Patient Data in Boston (US), and The Montreal Population Health Record data (Canada). New users of opioids aged ≥18 years without cancer were included. Patients with a diagnosis of a pain condition and with known back pain were analysed separately. Fully adjusted hazard ratios (HRs) were calculated using Cox-proportional models and adjusted for confounders. In total, 1,066,216 patients were included (UK: n = 993,294; Boston, US: n = 43,243; Montreal, Canada: n = 26,116). Compared with codeine, patients using morphine had a significantly higher adjusted risk in the UK {HR: 12.58 [95% confidence interval (CI), 11.87-13.32]}, US (HR: 8.62 [95% CI, 3.34-22.27]), and Canadian cohorts (HR: 6.69; [95% CI, 1.35-32.22]). In addition, other factors associated with higher mortality were being on combination opioids, fentanyl, buprenorphine, and oxycodone. Compared with those on <50 morphine milligram equivalents/day, patients on higher-doses experience an incremental increase in risk. In new users of opioids, compared with codeine, strong opioids, including morphine, fentanyl, buprenorphine, oxycodone, and combination opioids, and those on ≥50 morphine milligram equivalent/day were associated with a higher subsequent risk of all-cause mortality.

Effects of Intraoperative Opioid Use and a Combined Anesthesia Protocol in Patients Undergoing Radical Cystectomy for Urothelial Carcinoma of the Bladder—A Single-Center Experience

Background: An increased intraoperative opioid dose seems to lead to worse outcomes in several types of cancer. We assessed the effect of intraoperatively administered opioids as well as the type of anesthesia on survival, recurrence rates and major perioperative outcomes in patients who underwent radical cystectomy (RC) for urothelial carcinoma of the urinary bladder. Methods: We included patients who underwent open RC at our center between 2015 and 2022. The role of the type and dosage of intraoperative opioid agents, such as remifentanil, sufentanil and morphine milligram equivalents (MME), as well as the type of anesthesia (intravenous only versus intravenous/epidural), was assessed regarding perioperative and long-term outcomes after RC. Results: A total of 508 patients with a median age of 73 years (IQR: 64–78) were included. Overall, 92 (18%) patients received intravenous anesthesia, whereas 416 (82%) received combined anesthesia. At a median follow-up of 270 days (IQR: 98–808), 108 (21%) deaths and 106 (21%) recurrences occurred. Combined anesthesia was associated with better survival (HR:0.63, 95% CI: 0.4–0.97, p = 0.037) and lower intensive care unit admission rates (OR: 0.49, 95% CI: 0.31–0.77, p = 0.002) in the univariate analysis (unadjusted). The type and dosage of intraoperative opioid agents did not affect long-term survival and recurrence rates, as well as major perioperative outcomes. Nevertheless, the findings of our study were limited by its single-center, retrospective design. Conclusion: The use of intraoperative opioids was not associated with worse outcomes in our cohort, while the use of additional epidural anesthesia seems to be beneficial in terms of overall survival and intensive care unit admissions. Nevertheless, further research is mandatory to validate the safety of opioids in patients undergoing RC.

Comparative safety of tramadol and other opioids following total hip and knee arthroplasty

BackgroundTramadol is increasingly used to treat acute postoperative pain among older adults following total hip and knee arthroplasty (THA/TKA). However, tramadol has a complex pharmacology and may be no safer than full opioid agonists. We compared the safety of tramadol, oxycodone, and hydrocodone among opioid-naïve older adults following elective THA/TKA.MethodsThis retrospective cohort included Medicare Fee-for-Service beneficiaries ≥ 65 years with elective THA/TKA between January 1, 2010 and September 30, 2015, 12 months of continuous Parts A and B enrollment, 6 months of continuous Part D enrollment, and no opioid use in the 6 months prior to THA/TKA. Participants initiated single-opioid therapy with tramadol, oxycodone, or hydrocodone within 7 days of discharge from THA/TKA hospitalization, regardless of concurrently administered nonopioid analgesics. Outcomes of interest included all-cause hospitalizations or emergency department visits (serious adverse events (SAEs)) and a composite of 10 surgical- and opioid-related SAEs within 90-days of THA/TKA. The intention-to-treat (ITT) and per-protocol (PP) hazard ratios (HRs) for tramadol versus other opioids were estimated using inverse-probability-of-treatment-weighted pooled logistic regression models.ResultsThe study population included 2,697 tramadol, 11,407 oxycodone, and 14,665 hydrocodone initiators. Compared to oxycodone, tramadol increased the rate of all-cause SAEs in ITT analyses only (ITT HR 1.19, 95%CLs, 1.02, 1.41; PP HR 1.05, 95%CLs, 0.86, 1.29). Rates of composite SAEs were not significant across comparisons. Compared to hydrocodone, tramadol increased the rate of all-cause SAEs in the ITT and PP analyses (ITT HR 1.40, 95%CLs, 1.10, 1.76; PP HR 1.34, 95%CLs, 1.03, 1.75), but rates of composite SAEs were not significant across comparisons.ConclusionsPostoperative tramadol was associated with increased rates of all-cause SAEs, but not composite SAEs, compared to oxycodone and hydrocodone. Tramadol does not appear to have a superior safety profile and should not be preferentially prescribed to opioid-naïve older adults following THA/TKA.

Safety, Tolerability, and Dose-Limiting Toxicity of Lacosamide in Patients With Painful Chronic Pancreatitis: Protocol for a Phase 1 Clinical Trial to Determine Safety and Identify Side Effects.

Chronic abdominal pain is the hallmark symptom of chronic pancreatitis (CP), with 50% to 80% of patients seeking medical attention for pain control. Although several management options are available, outcomes are often disappointing, and opioids remain a mainstay of therapy. Opioid-induced hyperalgesia is a phenomenon resulting in dose escalation, which may occur partly because of the effects of opioids on voltage-gated sodium channels associated with pain. Preclinical observations demonstrate that the combination of an opioid and the antiseizure drug lacosamide diminishes opioid-induced hyperalgesia and improves pain control. In this phase 1 trial, we aim to determine the safety, tolerability, and dose-limiting toxicity of adding lacosamide to opioids for the treatment of painful CP and assess the feasibility of performance of a pilot study of adding lacosamide to opioid therapy in patients with CP. As an exploratory aim, we will assess the efficacy of adding lacosamide to opioid therapy in patients with painful CP. Using the Bayesian optimal interval design, we will conduct a dose-escalation trial of adding lacosamide to opioid therapy in patients with painful CP enrolled in cohorts of size 3. The initial dose will be 50 mg taken orally twice a day, followed by incremental increases to a maximum dose of 400 mg/day, with lacosamide administered for 7 days at each dose level. Adverse events will be documented according to Common Terminology Criteria for Adverse Events (version 5.0). As of December 2023, we have currently enrolled 6 participants. The minimum number of participants to be enrolled is 12 with a maximum of 24. We expect to publish the results by March 2025. This trial will test the feasibility of the study design and provide reassurance regarding the tolerability and safety of opioids in treating painful CP. It is anticipated that lacosamide will prove to be safe and well tolerated, supporting a subsequent phase 2 trial assessing the efficacy of lacosamide+opioid therapy in patients with painful CP, and that lacosamide combined with opiates will lower the opioid dose necessary for pain relief and improve the safety profile of opioid use in treating painful CP. Clinicaltrials.gov NCT05603702; https://clinicaltrials.gov/study/NCT05603702. PRR1-10.2196/50513.

Antinociceptive and adverse effects of morphine:ketamine mixtures in rats.

Prescription opioids are the gold standard for treating moderate to severe pain despite their well-documented adverse effects. Of all prescription medications, opioids are abused most widely, and fatal overdoses have reached epidemic levels. One strategy for improving the margin of safety of opioids is combining them with non-opioid drugs to decrease the opioid dose needed for pain relief, thereby reducing adverse effects that occur with larger doses. The N-methyl-D-aspartate receptor antagonist ketamine has been used safely as an analgesic but only under a very limited range of conditions. The current studies characterized the antinociceptive, behavioral suppressant, and gastrointestinal effects of morphine and ketamine alone and in mixtures to determine their interaction in 24 adult male Sprague-Dawley rats (n = 8 per assay). Given alone, both morphine and ketamine produced antinociception, decreased responding for food, and reduced gastrointestinal transit (i.e. produced constipation). The effects of morphine:ketamine mixtures generally were additive, except for the antinociceptive effects of 1:1 mixtures for which the difference in slope (i.e. non-parallel shift) between the observed and predicted effects suggested synergy at smaller doses and additivity at larger doses. The potency of morphine to produce constipation was not enhanced by administration of morphine:ketamine mixtures with antinociceptive effects. The nature of the interaction between morphine and ketamine for adverse effects such as dependence, withdrawal, abuse, or respiratory depression remains unknown but also might be related to the ratio of each drug in mixtures. It will be important to identify conditions that produce the largest potential therapeutic window in humans.

Opioid Prescription in Patients With Chronic Kidney Disease: A Systematic Review of Comparing Safety and Efficacy of Opioid Use in Chronic Kidney Disease Patients.

Patients with diminished renal function necessitate special care. In patients with chronic kidney disease (CKD), opioid analgesics should be prescribed based on the severity of renal insufficiency; this will determine treatment options at the beginning and throughout the management of pain in CKD patients. The dosage of hydrophilic drugs and drugs with active metabolites should be adjusted according to the severity of CKD, and the process of treatment should be monitored by modifying drug dosages as necessary for background and breakthrough pain. Patients with CKD may benefit from opioid analgesics that are lipophilic, such as methadone, fentanyl, and buprenorphine, as the first line; however, fentanyl is inappropriate for patients undergoing hemodialysis. Opioid prescription in CKD patients is the subject of this systematic review, which aims to compare their safety and efficacy. This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 recommendations. Using three databases (PubMed, ScienceDirect, and Google Scholar), we collected and reviewed articles, including literature reviews, randomized control trials (RCTs), and systematic reviews published between 1980 and 2022, to enable us to gather enough valuable data on this rare topic. After applying appropriate filters, a total of 109 results were obtained. They were further screened and subjected to quality assessment tools, which finally yielded 11 studies included in this systematic review. This consisted of two RCTs, two systematic reviews, and seven narrative reviews. This review focused on the safety and appropriate use of opioids in patients with CKD. The accumulation of morphine and codeine metabolites may result in neurotoxic side effects. Hydromorphone and oxycodone are considered safe to administer but require careful adjustments in dosage. Common comorbidities among patients with CKD may amplify opioid-related adverse effects.

Effectiveness and safety of opioids on breathlessness and exercise endurance in patients with chronic obstructive pulmonary disease: A systematic review and meta-analysis of randomised controlled trials.

Opioids are recommended to treat advanced refractory dyspnoea despite optimal therapy by the American Thoracic Society clinical practice guidelines, while newly published randomised controlled trials of opioids in chronic obstructive pulmonary disease yield conflicting results. This study aimed to evaluate the effectiveness and safety of opioids for patients with chronic obstructive pulmonary disease. Systematic review and meta-analysis (PROSPERO CRD42021272556). Databases of PubMed, EMBASE and CENTRAL were searched from inception to 2022 for eligible randomised controlled trials. Twenty-four studies including 975 patients, were included. In cross-over studies, opioids improved breathlessness (standardised mean difference, -0.43; 95% CI, -0.55 to -0.30; I2 = 18%) and exercise endurance (standardised mean difference, 0.22; 95% CI, 0.02-0.41; I2 = 70%). However, opioids failed to improve dyspnoea (standardised mean difference, -0.02; 95% CI, -0.22 to 0.19; I2 = 39%) and exercise endurance (standardised mean difference, 0.00; 95% CI, -0.27 to 0.27; I2 = 0%) in parallel control studies that administered sustained-release opioids for more than 1 week. The opioids used in most crossover studies were short-acting and rarely associated with serious adverse effects. Only minor side effects such as dizziness, nausea, constipation and vomiting were identified for short-acting opioids. Sustained-release opioids did not improve dyspnoea and exercise endurance. Short-acting opioids appeared to be safe, have potential to lessen dyspnoea and improve exercise endurance, supporting benefit in managing episodes of breathlessness and providing prophylactic treatment for exertional dyspnoea.

Clinical Use of Oral Opioid Therapy for Dyspnea in Patients With Advanced Heart Failure - A Single-Center Retrospective Study.

Background: For patients with advanced heart failure, palliative care, including opioids, is needed as a treatment for refractory dyspnea. However, little evidence has been reported on the efficacy and safety of opioids, and their use is not well established. Methods and Results: We have introduced a protocol for the use of opioids for dyspnea in patients with advanced heart failure admitted to Saitama Citizens Medical Center. Following this protocol, differences in clinical variables and outcome were investigated between patients in whom opioids were initiated intravenously or subcutaneously (i.v./s.c. group; n=13) and patients in whom they were initiated orally (oral group; n=18). In a comparison of baseline characteristics, significantly more patients in the oral group had a history of hospitalization for heart failure within the past year, and significantly more patients were treated with dobutamine and tolvaptan. After initiation of opioid treatment, both groups showed improvement in dyspnea; however, serial changes in vital signs were significantly greater in the i.v./s.c. group. The survival rate was significantly higher in the oral group (P<0.0001), with 33% of patients discharged alive. Conclusions: The clinical use of oral opioids using a single-center protocol is reported, suggesting that oral opioids may be practical and effective for dyspnea in patients with advanced heart failure.

Maximizing patient safety when prescribing opioids for pain management.

Cytochrome P450 enzyme metabolism is altered by environmental and genetic factors, which can affect the efficacy and safety of opioids. This article describes CYP polymorphisms and how pharmacogenetic testing could be used to help clinicians make safer decisions about opioid use in patients.

Breakthrough pain and rapid-onset opioids in patients with cancer pain: a narrative review.

Breakthrough pain is transitory pain that occurs despite the use of opioids for background pain control. Breakthrough pain occurs in 40% to 80% of patients with cancer pain. Despite effective analgesic therapy, patients and their caregivers often feel that their pain is not sufficiently controlled. Therefore, an improved understanding of breakthrough pain and its management is essential for all physicians caring for patients with cancer. This article reviews the definition, clinical manifestations, accurate diagnostic strategies, and optimal treatment options for breakthrough pain in patients with cancer. This review focuses on the efficacy and safety of rapid-onset opioids, which are the primary rescue drugs for breakthrough pain.

Opioids for the management of dyspnea in cancer patients: a systematic review and meta-analysis.

Dyspnea is a prevalent symptom that significantly reduces quality of life of cancer patients. Palliative treatment is necessary when the symptoms do not respond to treatment for their cause. Opioids are widely used as pharmacological therapy, but evidence for individual agents is inconsistent. The purpose of this study was to evaluate the efficacy and safety of opioids for dyspnea in cancer patients. We searched the CENTRAL, MEDLINE, EMBASE, and ICHUSHI for studies using opioids for dyspnea in adult cancer patients reported by September 2019. Screening of the retrieved literature and assessment of risk of bias and outcomes were performed by two independent authors. A meta-analysis was performed on the primary endpoint, relief of dyspnea, and secondary endpoints including quality of life, somnolence as a side effect, and serious adverse events. Twelve randomized controlled trials were evaluated regarding relief of dyspnea. Somnolence and serious adverse events were evaluated in seven and four randomized controlled trials, respectively, but no randomized controlled trials were evaluable for quality of life. Overall, opioids were more effective than placebo for dyspnea (standardized mean difference -0.43, 95% confidence interval [CI] -0.75 to -0.12). Although significant difference was found between systemic morphine and placebo in the drug-specific analysis, no significant difference could be detected in the other analyses. Systemic administration of opioids is more effective than placebo in relieving dyspnea in cancer patients. Robust evidence on the efficacy and safety of opioids on dyspnea in cancer patients is lacking, and further studies are needed.

Efficacy and Safety of Ketamine Versus Opiates in the Treatment of Patients with Renal Colic: A Systematic Review and Meta-analysis.

Renal colic is one of the most common urological emergencies, and is usually caused by ureteral colic spasms. Pain management in renal colic remains the central focus of emergency treatment. The purpose of this meta-analysis is to identify the efficacy and safety of ketamine versus opioids in the treatment of patients with renal colic. We searched PubMed, EMBASE, Cochrane Library, and Web of Science databases for published randomized controlled trials (RCTs) that referred to the use of ketamine and opioids for patients with renal colic. The methodology was based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The mean difference (MD) or odds ratio (OR) with a 95% confidence interval (CI) was used to analyze the data. The results were pooled using a fixed-effects model or random-effects model. The primary outcome measure was patient-reported pain scores 5, 15, 30, and 60min after drug administration. The secondary outcome measure was side effects. The data analysis revealed that ketamine was similar to opioids in pain intensity at the time of 5min post-dose (MD = - 0.40, 95% CI - 1.82 to 1.01, P = 0.57), 15min post-dose (MD = - 0.15, 95% CI - 0.82 to 0.52, P = 0.67), 30min post-dose (MD = 0.38, 95% CI - 0.25 to 1.01, P = 0.24). Also, the pain score of ketamine was better than that of opioids at 60min after administration (MD = - 0.12, 95% CI - 0.22 to - 0.02, P = 0.02). As for safety, the ketamine group was linked to a significant decrease in the incidence of hypotensive (OR = 0.08, 95% CI 0.01-0.65, P = 0.02). The two groups did not statistically differ in the incidence of nausea, vomiting, and dizziness. Compared with opioids, ketamine showed a longer duration of analgesia in renal colic, with satisfactory safety. The PROSPERO registration number is CRD42022355246.

Executive functioning, behavioural, emotional, andcognitive difficulties in school-aged children prenatally exposed to methadone.

The aim of this study was to examine executive function and emotional and behavioural difficulties of children aged between 8 and 10 years who had been prenatally exposed to methadone, compared to non-exposed peers. Prospective study: third follow-up of an original cohort of 153 children born to methadone-maintained opioid-dependent mothers 2008-2010: previous investigations were at 1-3 days and at 6-7 months of age. Carers completed the Strength and Difficulties Questionnaire (SDQ) and the Behaviour Rating Inventory of Executive Function, Second Edition (BRIEF®2). Results were compared between exposed and non-exposed groups. Carers of 33 of 144 traceable children completed the measures. SDQ responses showed no group differences on subscales of emotional symptoms, conduct problems, or peer relationship problems. A marginally higher proportion of exposed children had a high or very high hyperactivity subscale score. Exposed children scored significantly higher on BRIEF®2 behavioural, emotional, and cognitive regulation indices, and on the global executive composite. After controlling for potentially confounding higher reported maternal tobacco use in the exposed group via regression modelling, the effect of methadone exposure reduced. This study supports evidence that methadone exposure in utero is associated with adverse neurodevelopmental outcomes in childhood. Challenges in studying this population include difficulties with long-term follow-up and controlling for potentially confounding factors. Further investigation of the safety of methadone and other opioids in pregnancy must include consideration of maternal tobacco use.

High-dose opioids for chronic non-cancer pain: an overview of Cochrane Reviews.

This overview was originally published in 2017, and is being updated in 2022. Chronic pain is typically described as pain on most days for at least three months. Chronic non-cancer pain (CNCP) is any chronic pain that is not due to a malignancy. Chronic non-cancer pain in adults is a common and complex clinical issue, for which opioids are prescribed by some physicians for pain management. There are concerns that the use of high doses of opioids for CNCP lacks evidence of effectiveness, and may increase the risk of adverse events. To describe the evidence from Cochrane Reviews and overviews regarding the efficacy and safety of high-dose opioids (defined as 200 mg morphine equivalent or more per day) for CNCP. We identified Cochrane Reviews and overviews by searching the Cochrane Database of Systematic Reviews in The Cochrane Library. The date of the last search was 21 July 2022. Two overview authors independently assessed the search results. We planned to analyse data on any opioid agent used at a high dose for two weeks or more for the treatment of CNCP in adults. We did not identify any reviews or overviews that met the inclusion criteria. The excluded reviews largely reflected low doses or titrated doses, where all doses were analysed as a single group; we were unable to extract any data for high-dose use only. There is a critical lack of high-quality evidence, in the form of Cochrane Reviews, about how well high-dose opioids work for the management of CNCP in adults, and regarding the presence and severity of adverse events. No evidence-based argument can be made on the use of high-dose opioids, i.e. 200 mg morphine equivalent or more daily, in clinical practice. Considering that high-dose opioids have been, and are still being used in clinical practice to treat CNCP, knowing about the efficacy and safety of these higher doses is imperative.

Systematic assessment of opioid advertisements in general medical journals.

To systematically examine the content of opioid-related advertisements. Content analysis and quantitative assessment. North America. Researchers examined advertisements in 2 issues per year from 1996 to 2016 of American Family Physician, Canadian Family Physician, the Canadian Medical Association Journal, JAMA, and the New England Journal of Medicine. Number of advertisements, nature of the claims made, and quality of cited evidence in the advertisements. Opioid advertisements composed 89 of the 3173 pharmaceutical advertisements in 210 journal issues searched. Seventy-three advertisements were able to be obtained for analysis. Thirty-four (46.6%) did not mention the addictive potential of opioids, and 54 of 73 (74.0%) did not mention the possibility of death. All referenced studies in advertisements were funded by pharmaceutical organizations or had pharmaceutical company employees as authors. No advertisements cited high-quality evidence. Many claims of the effectiveness and safety of opioids were published in medical journals through advertisements. Advertisements did not usually mention key negative information about opioids. Although the extent to which these advertisements directly influenced the development of the opioid crisis in North America is unknown, the marked omission of important detrimental effects of opioids may have played a role. Further efforts to restrict opioid marketing may be warranted.

Opioids and restless legs syndrome: a double-edged sword.

Opioids and restless legs syndrome: a double-edged sword.

Long-term Safety, Dose Stability, and Efficacy of Opioids for Patients With Restless Legs Syndrome in the National RLS Opioid Registry.

Restless legs syndrome (RLS) is a sensory-motor neurologic disorder. Low-dose opioids are prescribed for patients with refractory or augmented RLS. The long-term safety, dose stability, and efficacy of these medications for RLS treatment is still unclear. In this study, we report the 2-year longitudinal data in a sample of patients treated with opioids for RLS in the community. The National RLS Opioid Registry is an observational longitudinal study consisting of individuals taking a prescribed opioid for diagnosed and confirmed RLS, most of whom experienced augmented symptoms from dopamine agonists. Information on opioid dosages, side effects, past and current concomitant RLS treatments, RLS severity, psychiatric symptoms, and opioid abuse risk factors was collected at initial Registry entry and every 6 months thereafter by surveys on REDCap. No feedback or intervention was provided by the study staff to local providers. Registry participants (n = 448) with 2-year longitudinal data available were mostly White, female, older than 60 years, and, at Registry entry, had been on opioids for a median of 1-3 years at a mean morphine milligram equivalent (MME) of 38.4 (SD = 43.5). No change in RLS severity in the overall cohort was observed over the 2-year follow-up period. The median change in daily opioid dose from baseline to 2 years was 0 MME (interquartile range = 0-10). While 41.1% of participants increased their dose during the follow-up period (median increase = 10 MME), 58.9% decreased their dose or saw no change. Only 8% and 4% saw increases of >25 MME and >50 MME, respectively. Ninety-five percent of those who increased opioid dose >25 or >50 MME had one of the following features: switching opioids, discontinuation of nonopioid RLS treatment medications, at least mild insomnia at baseline, a history of depression, male sex, younger than 45 years, and opioid use for comorbid pain. Low-dose opioid medications continue to adequately control symptoms of refractory RLS over 2 years of follow-up in most of the participants. A minority of patients did see larger dose increases, which were invariably associated with a limited number of factors, most notably changes in opioid and nonopioid RLS medications and opioid use for a non-RLS condition. Continued longitudinal observations will provide insight into the long-term safety and efficacy of opioid treatment of severe, augmented RLS. This study provides Class IV evidence that opioid doses increase in roughly 40% of patients, in most by small amounts, over a 2-year period when prescribed for adult refractory restless leg syndrome.

Effectiveness and safety of opioids for dyspnea in patients with lung cancer: secondary analysis of multicenter prospective observational study

Patients with lung cancer are more likely to have comorbidities [e.g., interstitial lung disease (ILD)], chronic obstructive pulmonary disease) and metastases that may affect dyspnea and the effectiveness and safety of opioids for dyspnea than other cancer types. Therefore, this study examined the effectiveness and safety of opioids for dyspnea, among the patients with lung cancer. The present study is a secondary analysis of a multicenter prospective observational study examining the effectiveness and safety of opioids for dyspnea in patients with cancer in Japan. For this secondary analysis, patients with lung cancer with a documented dyspnea Numerical Rating Scale (NRS) at baseline were included. The primary outcome was dyspnea NRS, and Integrated Palliative care Outcome Scale/Support Team Assessment Schedule (IPOS/STAS) scores change between baseline and 24 hours after baseline. As secondary outcomes, we investigated the predictors of opioid effectiveness for dyspnea improvement and adverse events (nausea, somnolence, and delirium). This study analyzed 124 patients with lung cancer with known dyspnea NRS at baseline. The median age was 74, and the Eastern Cooperative Oncology Group performance status of 107 patients were 3-4. Both NRS and IPOS/STAS score of dyspnea significantly improved 24 hours after opioid initiation [-1.64, 95% confidence interval (CI): -2.12 to -1.17, P<0.001; -1.03; 95% CI: -1.21 to -0.85, P<0.001; respectively]. Moreover, the improvement of NRS score was greater than the minimal clinically important difference of 1 point. In the multivariate logistic regression analysis, ILD was significantly associated with a better improvement [(hazard ratio (HR): 3.39, 95% CI: 1.34-11.09, P=0.043]. Somnolence was the most common grade 3-4 adverse event (n=16), followed by delirium (n=9). Opioids were effective and safe for treating dyspnea in patients with lung cancer. Furthermore, lung cancer patients with ILD may benefit more from opioids.

Are opioids safe for use in obstetric general anaesthesia?

The use of opioids during caesarean section has historically been avoided because of concerns regarding neonatal compromise. There is now more evidence regarding the safety and benefits of opioids in obstetric general anaesthesia, so should opioids be used during induction of anaesthesia for caesarean section?

Healthcare professionals' perspectives on the use of medicinal cannabis to manage chronic pain: A systematic search and narrative review.

Chronic pain is a global public health problem that negatively impacts individuals' quality of life and imposes a substantial economic burden on societies. The use of medicinal cannabis (MC) is often considered by patients to help manage chronic pain as an alternative or supplement to more conventional treatments, given enabling legalization in a number of countries. However, healthcare professionals involved in providing guidance for patients related to MC are often doing so in the absence of strong evidence and clinical guidelines. Therefore, it is crucial to understand their perspectives regarding the clinical use and relevance of MC for chronic pain. As little is known about attitudes of HCPs with regard to MC use for chronic pain specifically, the aim of this review was to identify and synthesize the published evidence on this topic. A systematic search was conducted across six databases: MEDLINE, EMBASE, CINAHL, Scopus, Web of Science, and PubMed from 2001 to March 26, 2021. Three authors independently performed the study selection and data extraction. Thematic analysis was undertaken to identify key themes. A total of 26 studies were included, involving the United States, Israel, Canada, Australia, Ireland, and Norway, and the perspectives of physicians, nurses, and pharmacists. Seven key themes were identified: MC as a treatment option for chronic pain, and perceived indicated uses; willingness to prescribe MC; legal issues; low perceived knowledge and the need for education; comparative safety of MC versus opioids; addiction and abuse; and perceived adverse effects; CONCLUSION: To support best practice in the use of MC for chronic pain, healthcare professionals require education and training, as well as clinical guidelines that provide evidence-based information about efficacy, safety, and appropriate dosage of products for this indication. Until these gaps are addressed, healthcare professionals will be limited in their capacity to make treatment recommendations about MC for people/patients with chronic pain.