Predictors of persistent opioid use in Australian primary care: A retrospective cohort study, 2018-2022.

OBJECTIVE: To examine the predictors of persistent opioid use ('persistence') in people initiating opioids for non-cancer pain in Australian primary care. DESIGN: A retrospective cohort study. SETTING: Australian primary care. SUBJECTS: People prescribed opioid analgesics between 2018-2022, identified through the Population Level Analysis and Reporting (POLAR) database. METHODS: Persistence was defined as receiving opioid prescriptions for at least 90 days with a gap of less than 60 days between subsequent prescriptions. Multivariable logistic regression was used to examine the predictors of persistent opioid use. RESULTS: The sample consisted of 343,023 people initiating opioids for non-cancer pain; of these, 16,527 (4.8%) developed persistent opioid use. Predictors of persistence included older age (≥75 vs 15-44 years: Adjusted odds ratio: 1.67, 95% CI: 1.58-1.78), concessional beneficiary status (1.78, 1.71-1.86), diagnosis of substance use disorder (1.44, 1.22-1.71) and chronic pain (2.05, 1.85-2.27), initiation of opioid therapy with buprenorphine (1.95, 1.73-2.20) and long-acting opioids (2.07, 1.90-2.25), provision of higher quantity of opioids prescribed at initiation (total OME of ≥ 750mg vs < 100mg: 7.75, 6.89-8.72), provision of repeat/refill opioid prescriptions at initiation (2.94, 2.77-3.12), and prescription of gabapentinoids (1.59, 1.50-1.68), benzodiazepines (1.43, 1.38-1.50) and z-drugs (e.g., zopiclone, zolpidem; 1.61, 1.46-1.78). CONCLUSIONS: These findings add to the limited evidence of individual-level factors associated with persistent opioid use. Further research is needed to understand the clinical outcomes of persistent opioid use in people with these risk factors to support the safe and effective prescribing of opioids.

Prevalence of problematic pharmaceutical opioid use in patients with chronic non-cancer pain: A systematic review and meta-analysis.

BACKGROUND AND AIMS: Chronic non-cancer pain (CNCP) is one of the most common causes of disability globally. Opioid prescribing to treat CNCP remains widespread, despite limited evidence of long-term clinical benefit and evidence of harm such as problematic pharmaceutical opioid use (POU) and overdose. The study aimed to measure the prevalence of POU in CNCP patients treated with opioid analgesics. METHOD: A comprehensive systematic literature review and meta-analysis was undertaken using MEDLINE, Embase and PsycINFO databases from inception to 27 January 2021. We included studies from all settings with participants aged ≥ 12 with non-cancer pain of ≥ 3 months duration, treated with opioid analgesics. We excluded case-control studies, as they cannot be used to generate prevalence estimates. POU was defined using four categories: dependence and opioid use disorder (D&OUD), signs and symptoms of D&OUD (S&S), aberrant behaviour (AB) and at risk of D&OUD. We used a random-effects multi-level meta-analytical model. We evaluated inconsistency using the I2 statistic and explored heterogeneity using subgroup analyses and meta-regressions. RESULTS: A total of 148 studies were included with > 4.3 million participants; 1% of studies were classified as high risk of bias. The pooled prevalence was 9.3% [95% confidence interval (CI) = 5.7-14.8%; I2 = 99.9%] for D&OUD, 29.6% (95% CI = 22.1-38.3%, I2 = 99.3%) for S&S and 22% (95% CI = 17.4-27.3%, I2 = 99.8%) for AB. The prevalence of those at risk of D&OUD was 12.4% (95% CI = 4.3-30.7%, I2 = 99.6%). Prevalence was affected by study setting, study design and diagnostic tool. Due to the high heterogeneity, the findings should be interpreted with caution. CONCLUSIONS: Problematic pharmaceutical opioid use appears to be common in chronic pain patients treated with opioid analgesics, with nearly one in 10 experiencing dependence and opioid use disorder, one in three showing signs and symptoms of dependence and opioid use disorder and one in five showing aberrant behaviour.

Opioid prescription following radical orchiectomy associated with new persistent opioid use.

INTRODUCTION: Opioid dependence represents a public health crisis and can be observed after outpatient urologic procedures. The purpose of this study was to evaluate the risk of persistent opioid usage after radical orchiectomy for testicular cancer. MATERIALS AND METHODS: The TriNetX Research network database was queried for men between 15 and 45 years undergoing radical orchiectomy for a diagnosis of testicular cancer. All patients with N+ or M+ disease, prior opioid use, and patients who underwent chemotherapy, radiotherapy, or retroperitoneal lymph node dissection were excluded. Patients were stratified whether they were prescribed opioids or not at time of orchiectomy. The incidence of new, persistent opioid use, defined as a prescription for opioids between 3 and 15 months after orchiectomy, was evaluated. RESULTS: A total of 2,911 men underwent radical orchiectomy for testicular cancer, of which 89.8% were prescribed opioids at time of orchiectomy. After propensity score matching for age, race, and history of psychiatric diagnosis, 592 patients were included (296 received opioids, 296 did not). Overall, 0% of patients who did not receive postoperative opioids developed new persistent opioid use, whereas 10.5% of patients who received postoperative opioids developed new persistent opioid use. Patients prescribed postoperative opioids for orchiectomy had statistically higher risk difference of developing new persistent opioid use (Risk Difference: 10.5%; 95% CI: 7.0-14.0; Z: 5.7; P < 0.01). CONCLUSIONS: Postoperative opioid prescription following radical orchiectomy is significantly associated with developing new persistent opioid use, with 1 in 10 young men who received postoperative opioids obtaining a new prescription for opioids well beyond the postoperative period. Future efforts should emphasize nonopioid pathways for pain control following this generally minor procedure.

Analgesic efficacy and safety of erector spinae plane block in pediatric patients undergoing elective surgery: A systematic review and Meta-analysis of randomized controlled trials.

STUDY OBJECTIVE: Ultrasound-guided erector spinae plane block (ESPB) is commonly used for perioperative analgesia in adults; however, its analgesic efficacy and safety in pediatric patients remain uncertain. This review aimed to determine whether ultrasound-guided ESPB can improve analgesic efficacy and safety in pediatric surgery. DESIGN: Meta-analysis of randomized controlled trials. SETTING: Perioperative setting. PATIENTS: Pediatric patients undergoing elective surgery under general anesthesia. INTERVENTIONS: We searched PubMed, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, KoreaMed, Web of Science, Scopus, and ClinicalTrials.gov databases for eligible published randomized controlled studies (RCTs) comparing ESPB with controls (no block or other block) in pediatric patients undergoing elective surgery under general anesthesia. MEASUREMENTS: The primary outcome was cumulative opioid consumption after surgery. Other outcomes included intraoperative opioid consumption, time to first request for rescue analgesia, number of patients requiring rescue analgesics, and pain scores after surgery. The safety outcomes were the incidences of bradycardia, hypotension, and postoperative vomiting. MAIN RESULTS: The analysis included 17 RCTs comprising 919 participants: 461 in the ESPB group, 269 in the no-block group (no block/sham block), and 189 in the other block group. Compared with the control group (no block and other blocks), ESPB significantly reduced the cumulative opioid consumption (intravenous morphine milligram equivalents) after surgery (standardized mean difference = -1.51; 95% confidence interval, -2.39 to -0.64; P = 0.0002; I2 = 92.9%) and intraoperative opioid consumption, and lowered average pain scores up to 24 h after surgery. ESPB extended the time to the first request for rescue analgesia and decreased the number of patients requiring rescue analgesics. Furthermore, ESPB lowered the pain score at most time points for 24 h after surgery, improved parental satisfaction, and reduced the incidence of postoperative vomiting compared with that in no block/sham block. CONCLUSIONS: ESPB provides effective and safe perioperative analgesia in pediatric patients undergoing elective surgery under general anesthesia.

Rationale and Design for the BLOCK-SAH Study (Pterygopalatine Fossa Block as an Opioid-Sparing Treatment for Acute Headache in Aneurysmal Subarachnoid Hemorrhage): A Phase II, Multicenter, Randomized, Double-Blinded, Placebo-Controlled Clinical Trial with a Sequential Parallel Comparison Design.

BACKGROUND: Acute post-subarachnoid hemorrhage (SAH) headaches are common and severe. Management strategies for post-SAH headaches are limited, with heavy reliance on opioids, and pain control is overall poor. Pterygopalatine fossa (PPF) nerve blocks have shown promising results in treatment of acute headache, including our preliminary and published experience with PPF-blocks for refractory post-SAH headache during hospitalization. The BLOCK-SAH trial was designed to assess the efficacy and safety of bilateral PPF-blocks in awake patients with severe headaches from aneurysmal SAH who require opioids for pain control and are able to verbalize pain scores. METHODS: BLOCK-SAH is a phase II, multicenter, randomized, double-blinded, placebo-controlled clinical trial using the sequential parallel comparison design (SPCD), followed by an open-label phase. RESULTS: Across 12 sites in the United States, 195 eligible study participants will be randomized into three groups to receive bilateral active or placebo PPF-injections for 2 consecutive days with periprocedural monitoring of intracranial arterial mean flow velocities with transcranial Doppler, according to SPCD (group 1: active block followed by placebo; group 2: placebo followed by active block; group 3: placebo followed by placebo). PPF-injections will be delivered under ultrasound guidance and will comprise 5-mL injectates of 20 mg of ropivacaine plus 4 mg of dexamethasone (active PPF-block) or saline solution (placebo PPF-injection). CONCLUSIONS: The trial has a primary efficacy end point (oral morphine equivalent/day use within 24 h after each PPF-injection), a primary safety end point (incidence of radiographic vasospasm at 48 h from first PPF-injection), and a primary tolerability end point (rate of acceptance of second PPF-injection following the first PPF-injection). BLOCK-SAH will inform the design of a phase III trial to establish the efficacy of PPF-block, accounting for different headache phenotypes.

Awareness of the potential consequences of alcohol consumption in the context of chronic pain and prescription opioid use.

Background: Alcohol and prescription opioid use are highly prevalent among chronic pain populations. One-fifth of individuals prescribed opioids report same-day use of alcohol and opioids. Alcohol use and alcohol/opioid co-use can have deleterious pain management and health outcomes. The extent to which individuals with chronic pain are aware of these deleterious outcomes is considerably understudied.Objectives: To explore individuals' understanding of seven health- and pain-related risks of alcohol/alcohol-opioid use. An exploratory aim was to examine whether greater risk awareness was associated with alcohol/opioid use patterns.Methods: Participants included 261 adults age ≥21(36.4% women) endorsing current alcohol use, chronic musculoskeletal pain, and opioid prescription who completed an online survey via Amazon Mechanical Turk.Results: Distribution of the total number of items for which a participant endorsed awareness was as follows: zero (10.7%), one (5.0%), two (13.0%), three (13.8%), four (13.8%), five (11.5%), six (10.0%), and seven items (22.2%). Awareness of the health consequences of alcohol/alcohol-opioid use was positively associated with opioid misuse behaviors (ß = .525, ΔR2 = .251, p < .001), and higher-risk alcohol consumption (ß = .152, ΔR2 = .021, p = .011).Conclusion: Many adults with chronic pain are unaware of the health consequences of alcohol/alcohol-opioid use. Findings of positive covariation between risk awareness and higher-risk alcohol/opioid use suggest that future interventions among this population should go beyond simple risk education and utilize motivational enhancement to help change decisional balance.

Opioid exit plans for tapering postoperative pain control in noncancer patients: a systematic review.

BACKGROUND: A growing number of countries have reported sharp increases in the use and harm of opioid analgesics. High rates of new opioid initiation are observed in postoperative patients. In response, various tertiary care institutions have developed opioid exit plans (OEPs) to curb potential opioid-related harm. METHODS: PubMed and Embase were systematically searched to identify, summarize, and compare the interventional elements of OEPs for postoperative patient populations published from January 1, 2000, to June 4, 2024. Two researchers independently screened the articles for eligibility following the PRISMA 2020 guidelines, extracted the data, and assessed the study quality and risk of bias. Data synthesis was performed for study characteristics, intervention details, efficacy, and development. RESULTS: A total of 2,585 articles were screened, eight of which met the eligibility criteria. All studies were conducted in North America and focused on orthopedic surgery patients following total hip or knee arthroplasty (n = 5) or neurosurgery (n = 3). Most studies (n = 7) included a pre-post (n = 4) or randomized clinical design (n = 3). Three studies were of good quality, and none had a low risk of bias. The interventions varied and ranged from educational sessions (n = 1) to individualized tapering protocols (n = 4) or a combination of the two (n = 2). Key elements were instructions on how to anticipate patients' postoperative need for opioid analgesics and tapering strategies based on 24-h predischarge opioid consumption. Six studies included efficacy as an endpoint in their analysis, of which four assessed statistical significance, with all four identifying that the OEPs were successful in reducing postoperative opioid use. CONCLUSION: Despite differences in design and implementation, the identified OEPs suggest that they are efficacious in reducing outpatient opioid consumption. They provide a robust estimate of postoperative analgesic requirements and a rationale for tapering duration and rate. However, more rigorous studies are needed to evaluate their real-world effectiveness.

Opioid-Related Emergency Department Visits Before and During COVID-19: Association with Community-Level Factors.

Background: The purpose of the study was to investigate the relationship between community-level variables and emergency department (ED) visit rates before and during COVID-19. The focus was on opioid-related ED visits. Despite large declines in overall ED visits during COVID-19, opioid-related visits increased. While visits for avoidable conditions decreased, the opposite was true for opioid-related visits. Methods: We combined data from Florida EDs with community-level variables from the 2020 American Community Survey. The outcome measures of the study were quarterly ZIP code tabulation-area-level ED visit rates for opioid-related ED visits as well as visit rates for all other causes. Associations with opioid-related visit rates were estimated before and during COVID-19. Results: The associations between community-level variables and opioid-related visit rates did not match those found when analyzing overall ED visit rates. The increase in opioid-related visits during COVID-19 was not unique to or more prevalent in areas with a larger percentage of racial/ethnic minority populations. However, socioeconomic status was important, as areas with higher unemployment, lower income, lower home ownership, and higher uninsured had higher overall ED visit rates and opioid visit rates during the pandemic. In addition, the negative association with income increased during the pandemic. Conclusion: These results suggest socioeconomic status should be the focus of prevention and treatment efforts to reduce opioid-related visits in future pandemics. Healthcare organizations can use these results to target their prevention and treatment efforts during future pandemics.

Outcomes After a Statewide Policy to Improve Evidence-Based Treatment of Back Pain Among Medicaid Enrollees in Oregon.

BACKGROUND: A novel Oregon Medicaid policy guiding back pain management combined opioid restrictions with emphasis on non-opioid and non-pharmacologic therapies. OBJECTIVE: To examine the effect of the policy on prescribing, health outcomes, and health service utilization. DESIGN: Using Medicaid enrollment, medical and prescription claims, prescription drug monitoring program, and vital statistics files, we analyzed the policy's association with selected outcomes using interrupted time series models. SUBJECTS: Adult Medicaid patients with back pain enrolled between 2014 and 2018. INTERVENTION: The Oregon Medicaid back pain policy. MAIN MEASURES: Opioid and non-opioid medication prescribing, procedural care, substance use and mental health conditions, and outpatient and inpatient healthcare utilization. KEY RESULTS: The policy was associated with decreases in the percentage of Medicaid enrollees with back pain receiving any opioids (- 2.68 percentage points [95% CI - 3.14, - 2.23] level, - 1.01 pp [95% CI - 1.1, - 0.92] slope), days of short-acting opioid use (- 0.4 days [95% CI - 0.53, - 0.26] slope), receipt of more than 7 days of short-acting opioids (- 2.36 pp [95% CI - 2.76, - 1.95] level, - 0.91 pp [95% CI - 1, - 0.83] slope), chronic opioid use (- 1.27 pp [95% CI - 1.59, - 0.94] level, - 0.46 [95% CI - 0.53, - 0.39 slope), and spinal surgeries and procedures. Among secondary outcomes, we found no increase in opioid overdose and a small, statistically significant trend decrease in opioid use disorders. There were small increases in non-opioid substance use and mental health diagnoses and visits but no increase in self-harm. CONCLUSIONS: A state Medicaid policy emphasizing evidence-based back pain management was associated with decreases in opioid prescribing, spinal surgeries, and opioid use disorder trends, but also short-term increases in mental health encounters and an increase in non-opioid substance use disorder trends. Such policies may help reinforce evidence-based care, but must be designed with consideration of potential harms.

Attenuation of acute postoperative pain and opioid requirement with the use of magnesium sulfate in patients undergoing limb amputations.

OBJECTIVE: To compare the effects of magnesium sulphate on the total dose of intravenous morphine consumption postoperatively following limb amputations along with rescue analgesia requirement, pain scores and side effects. METHODS: This prospective, triple-blinded, randomised controlled study was conducted from October 2021 to May 2022 at the Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan, and comprised of patients scheduled for limb amputations. They were randomised into 2 equal groups. The anaesthesia protocol was uniform for all patients. Intervention group A was administered 30mg/kg loading dose and 10mg/kg/hr maintenance dose of magnesium sulphate intravenously, while patients in control group B received the same amount of plain isotonic saline. Morphine consumption, including that used for rescue analgesia and patient-controlled analgesia, was measured for 24 hours postoperatively. Numeric rating scale was used for the evaluation of postoperative pain in both groups at 15min, 1h, 2h, at discharge from the post-anaesthesia care unit and at 12h and 24h in the ward. Data was analysed using SPSS 23. RESULTS: Of the 24 patients enrolled, the study was completed by 20(83.33%). There were 10(50%) patients in group A; 8(40%) males and 2(20%) females with mean age 24.8±14.14 years and mean surgery time 130.5±47.86 minutes. There were 10(50%) patients in group B; 8(40%) males and 2(20%) females with mean age 23.2±7.4 years and mean surgery time 117±23.85 minutes (p>0.05). Total morphine used over 24 hours in group A was 16±3.1 mg compared to 29.6±11.2 mg in group B (p<0.05). The time for first use of patient-controlled analgesia after arriving in the postanaesthesia care unit was significantly delayed in group A (72.2±24.95 minutes) compared to that in group B (25±26.68 minutes) (p<0.05). Pain scores were significantly higher in the group B at 15min compared to group A (p<0.05), but not at the rest of the time points (p>0.05). CONCLUSIONS: Intravenous magnesium sulphate proved to be effective in lowering postoperative opioid requirement following limb amputations.

Review of Opioid Abuse-Deterrent Formulations: Impact and Barriers to Access.

The misuse and abuse of opioid analgesics continue to pose a serious public health concern, but for some patients, opioids remain an important analgesic option. Extended-release (ER) opioid formulations are effective for treating chronic pain and are supported by multiple 12-week efficacy studies. ER opioids often contain a high opioid content, and similar to immediate-release (IR) formulations, are subject to abuse, misuse, and diversion. Unintentional misuse may also occur when ER formulations are manipulated for medicinal administration, such as crushing a dose for easier oral intake. As part of a multipronged strategy designed to fight the opioid epidemic, abuse-deterrent formulations (ADFs) were developed to deter misuse, abuse, and diversion of opioids by making manipulation more difficult and nonoral routes of administration less rewarding. Although ADF opioids have been shown to decrease rates of abuse and diversion, they are not equally effective in terms of deterring manipulation for abuse or misuse. Xtampza ER utilizes DETERx technology, which allows it to retain ER characteristics when chewed or crushed, making it the only ER opioid without a boxed warning against these types of manipulation. OxyContin was also developed as an ADF but uses RESISTEC technology, making the tablet hard to crush and viscous in aqueous solutions. ADF utilization has been hampered by patient access issues, including high prices due to lack of insurance coverage. Postmarket real-world studies demonstrate lower rates of abuse, misuse, and diversion for ADF ER opioids compared with non-ADF formulations. However, similar studies comparing abuse-related effectiveness and health care costs for ADF opioids are warranted if clinicians are expected to utilize these potentially safer opioid formulations. These studies would support further education surrounding the benefits and utilization of ADFs and manipulation potential of different ADFs.

Data-Driven Identification of Potentially Successful Intervention Implementations Using 5 Years of Opioid Prescribing Data: Retrospective Database Study.

BACKGROUND: We have previously demonstrated that opioid prescribing increased by 127% between 1998 and 2016. New policies aimed at tackling this increasing trend have been recommended by public health bodies, and there is some evidence that progress is being made. OBJECTIVE: We sought to extend our previous work and develop a data-driven approach to identify general practices and clinical commissioning groups (CCGs) whose prescribing data suggest that interventions to reduce the prescribing of opioids may have been successfully implemented. METHODS: We analyzed 5 years of prescribing data (December 2014 to November 2019) for 3 opioid prescribing measures-total opioid prescribing as oral morphine equivalent per 1000 registered population, the number of high-dose opioids prescribed per 1000 registered population, and the number of high-dose opioids as a percentage of total opioids prescribed. Using a data-driven approach, we applied a modified version of our change detection Python library to identify reductions in these measures over time, which may be consistent with the successful implementation of an intervention to reduce opioid prescribing. This analysis was carried out for general practices and CCGs, and organizations were ranked according to the change in prescribing rate. RESULTS: We identified a reduction in total opioid prescribing in 94 (49.2%) out of 191 CCGs, with a median reduction of 15.1 (IQR 11.8-18.7; range 9.0-32.8) in total oral morphine equivalence per 1000 patients. We present data for the 3 CCGs and practices demonstrating the biggest reduction in opioid prescribing for each of the 3 opioid prescribing measures. We observed a 40% proportional drop (8.9% absolute reduction) in the regular prescribing of high-dose opioids (measured as a percentage of regular opioids) in the highest-ranked CCG (North Tyneside); a 99% drop in this same measure was found in several practices (44%-95% absolute reduction). Decile plots demonstrate that CCGs exhibiting large reductions in opioid prescribing do so via slow and gradual reductions over a long period of time (typically over a period of 2 years); in contrast, practices exhibiting large reductions do so rapidly over a much shorter period of time. CONCLUSIONS: By applying 1 of our existing analysis tools to a national data set, we were able to identify rapid and maintained changes in opioid prescribing within practices and CCGs and rank organizations by the magnitude of reduction. Highly ranked organizations are candidates for further qualitative research into intervention design and implementation.

Impact of opioid analgesics on survival in cancer patients receiving immune checkpoint inhibitors.

PURPOSE: This study aimed to assess the effects of concurrent opioid analgesic (OA) use with immune checkpoint inhibitors (ICIs) on progression-free survival (PFS) and overall survival (OS). METHODS: In this observational retrospective study, we included advanced cancer patients who received ICIs at Hacettepe University Hospital's Department of Medical Oncology between June 2018 and January 2023. RESULTS: Our study included 375 recurrent or metastatic cancer patients treated with ICIs in the first, second line, or beyond. There were no significant differences between the OA-treated and OA-untreated groups regarding median age, age group, gender, primary tumor location, ICI type, or the presence of baseline liver and lung metastases. However, the OA-treated group exhibited a significantly higher proportion of patients who had received three or more prior treatments before initiating ICIs (p = 0.015). OA-Untreatment was significantly correlated with prolonged mPFS (6.83 vs. 4.30 months, HR 0.59, 95% CI 0.44-0.79, p < 0.001) and mOS (17.05 vs. 7.68 months, HR 0.60, 95% CI 0.45-0.80, p < 0.001). CONCLUSIONS: Our study demonstrates an association between the concurrent use of OAs and reduced OS and PFS in patients treated with ICIs. While OA treatment serves as a surrogate marker for higher disease burden, it may also suggest a potential biological relationship between opioids and immunotherapy efficacy.

Adverse Effects of Opioid Analgesics in Osteoarthritis Treatment: A Global Meta-Analysis, 2000-2022.

Osteoarthritis (OA) treatment commonly depends on nonsteroidal anti-inflammatory drugs and opioid medications. Nevertheless, the clinical use of opioids is controversial due to their adverse effects and addiction potential. This study, drawing on 24 randomized controlled trials (RCTs) with a total of 9,586 patients, thoroughly explored the various side effects associated with opioid use in OA treatment. The results provide additional insight into the non-addictive risks of opioids and may assist clinicians in their judicious use, potentially fostering the advancement of safer treatment options. By reducing the risks of misuse and addiction, public health and safety can be enhanced.

Access to care for patients with chronic pain receiving prescription opioids, cannabis, or other treatments.

Changes in chronic noncancer pain treatment have led to decreases in prescribing of opioids and increases in the availability of medical cannabis, despite its federal prohibition. Patients may face barriers to establishing new care with a physician based on use of these treatments. We compared physician willingness to accept patients based on prescription opioid, cannabis, or other pain treatment use. This study of 36 states and Washington, DC, with active medical cannabis programs surveyed physicians who treat patients with chronic noncancer pain between July 13 and August 4, 2023. Of 1000 physician respondents (34.5% female, 63.2% White, 78.1% primary care), 852 reported accepting new patients with chronic pain. Among those accepting new patients with chronic pain, more physicians reported that they would not accept new patients taking prescription opioids (20.0%) or cannabis (12.7%) than those taking nonopioid prescription analgesics (0.1%). In contrast, 68.1% reported willingness to accept new patients using prescribed opioids on a daily basis. For cannabis, physicians were more likely to accept new patients accessing cannabis through medical programs (81.6%) than from other sources (60.2%). Access to care for persons with chronic noncancer pain appears to be the most restricted among those taking prescription opioids, although patients taking cannabis may also encounter reduced access.

Opioid analgesic exposure during the first trimester of pregnancy and the risk of major congenital malformations in infants: a systematic review and meta-analysis†.

BACKGROUND: Prescribed opioid analgesics are frequently used to manage pain in pregnancy. However, the available literature regarding the teratogenic potential of opioid use during pregnancy has not been systematically summarised. This systematic review and meta-analysis aimed to assess the quality of the evidence on these potential risks and calculate a pooled estimate of risk for any opioid analgesic and individual opioids. METHODS: We searched PubMed, Embase and CINAHL for published studies assessing the risk of major congenital malformations in infants following first-trimester exposure to opioid analgesics compared with a reference group, excluding studies examining opioid agonist therapy or illicit opioid use. We assessed the risk of bias using the Risk of Bias in Non-Randomised Studies of Intervention tool. We pooled adjusted risk estimates from studies rated at serious risk of bias or better in a random-effects meta-analysis. RESULTS: Of 12 identified studies, 11 were at high risk of bias (eight serious; three critical). Relative to unexposed infants, those exposed to any opioid use during the first trimester of pregnancy were not at an increased risk of major congenital malformations overall (relative risk 1.04, 95%CI 0.98-1.11); cardiovascular malformations (relative risk 1.07, 95%CI 0.96-1.20); or central nervous system malformations (relative risk 1.06, 95%CI 0.92-1.21). Raised risk estimates were observed for gastrointestinal malformations (relative risk 1.40, 95%CI 0.38-5.16) and cleft palate (relative risk 1.57, 95%CI 0.48-5.13) following any opioid exposure and atrial septal defects (relative risk 1.20, 95%CI 1.05-1.36) following codeine exposure. CONCLUSIONS: Although the meta-analysis did not indicate substantial increased risk for most malformations examined, this risk remains uncertain due to the methodological limitations of the included studies. Healthcare professionals and pharmaceutical regulators should be aware of the issues related to the quality of research in this field.

Maternal opioid use during pregnancy and the risk of neonatal opioid withdrawal syndrome in the offspring.

INTRODUCTION: Neonatal opioid withdrawal syndrome (NOWS) is caused by sudden cessation from in utero exposure to opioids. The indications for opioid use during pregnancy are diverse including medication for opioid use disorder and analgesia. The opioid dose typically depends on the indication, with higher doses used for medication for opioid use disorder and lower doses used for analgesia. The aim of this study was to investigate the relationship between maternal opioid dose during pregnancy and the risk of NOWS. MATERIAL AND METHODS: We conducted a historical multicenter cohort study of neonates prenatally exposed to opioids in Eastern Denmark during a six-year period from 2013 to 2018. The data was extracted from reviewing the individual's medical record(s), which were identified through a search of the Danish National Patient Register. Four groups (quartiles) according to maternal opioid dose during the last four weeks prior to delivery were compared. Unadjusted and adjusted logistic regression analyses were conducted to examine the risk of NOWS while controlling for relevant covariates. RESULTS: A total of 130 in utero opioid exposed neonates were included. The majority of the pregnant patients (88%) were treated with opioids for analgesic purposes. Overall, 52% of neonates developed NOWS. The cumulative incidence of NOWS was 21%, 28%, 67% and 91% at maternal average daily dose of morphine milligram equivalent during the last four weeks prior to delivery of 0.7-14 (group I), 14.3-38.6 (group II), 40-90 (group III) and 90.9-1440 (group IV), respectively. Compared to group I the adjusted odds (aOR) of NOWS increased significantly in group III (aOR 10.6 [2.9-39.1]) and group IV (aOR 37.8 [7.6-188.2]) but not in group II (aOR 1.5 [0.4-5.2]). No cases of NOWS were reported at maternal dose less than an average daily dose of five morphine milligram equivalent during the last four weeks prior to delivery. No significant changes in the incidence of NOWS were observed between 2013 and 2018. CONCLUSIONS: The odds of neonatal opioid withdrawal syndrome increased significantly as the maternal average daily dose of morphine milligram equivalent during the last four weeks prior to delivery surpassed 40.

Effect of perioperative intravenous ibuprofen versus acetaminophen on postoperative opioid consumption and pain after general anesthesia: a systematic review and meta-analysis with trial sequential analysis of randomized controlled trials.

BACKGROUND: Ibuprofen and acetaminophen are widely used as adjuvant analgesics for postoperative pain. This meta-analysis compared the effects of intravenous (IV) ibuprofen and acetaminophen on postoperative opioid consumption and pain intensity after general anesthesia. METHODS: PubMed/MEDLINE, EMBASE, and Cochrane Library databases were searched to identify relevant studies published up to May 2023. Randomized controlled trials comparing the effects of perioperative IV ibuprofen and acetaminophen on postoperative opioid consumption and pain after general anesthesia were included in the meta-analysis and trial sequential analysis (TSA). RESULTS: Eight studies with 494 participants were included. Compared to IV acetaminophen, IV ibuprofen significantly reduced 24 h opioid consumption, presented as morphine equivalents (mean difference [MD]: -6.01 mg, 95% CI [-8.60, -3.42], P < 0.00001, I2 = 55%), and pain scores (on a scale of 0-10) at 4-6 h (MD: -0.83, 95% CI [-1.29, -0.37], P = 0.0004, I2 = 65%) and 12 h (MD: -0.38, 95% CI [-0.68, -0.08], P = 0.01, I2 = 11%) postoperatively. These results were statistically significant in TSA. Pain scores at 24 h postoperatively and side effects were not significantly different between the two groups in the meta-analysis, and TSA revealed that the sample size was too small to adequately evaluate the effects, requiring further studies for conclusive results. CONCLUSIONS: Perioperative IV ibuprofen reduced 24 h opioid consumption and pain severity up to 12 h postoperatively compared to acetaminophen. Additional research is required to assess pain intensity beyond 12 h and side effects.

Opioid-free anesthesia using a combination of ketamine and dexmedetomidine in patients undergoing laparoscopic cholecystectomy: a randomized controlled trial.

BACKGROUND: Opioids administered as bolus doses or continuous infusions are widely used for major and daycare surgeries. Opioid-free anesthesia is multimodal anesthesia and analgesia that does not use opioids, benefiting patients from opioid-related adverse effects. We compared the postoperative analgesic requirements of patients scheduled for elective laparoscopic cholecystectomy under opioid-free and opioid-based anesthesia. METHODS: Study included 88 patients aged 18-60 years with American Society of Anesthesiologists physical status 1 and 2 who underwent elective laparoscopic cholecystectomy. Participants were randomly divided into two groups with 44 in each. The opioid-free group was administered an intravenous bolus of ketamine and dexmedetomidine, whereas fentanyl was used in opioid group. Primary outcome was to compare the total amount of fentanyl consumed by both groups during 6 h postoperative period. Episodes of postoperative nausea and vomiting (PONV) and vital signs were noted throughout the postoperative period to analyze the secondary outcomes. RESULTS: Both groups had similar demographic characteristics. The opioid-free group required lesser analgesia within the first 2 h (61.4 ± 17.4 vs. 79.0 ± 19.4 of fentanyl, P < 0.001), which was statistically significant. However, fentanyl consumption was comparable between the groups at 6 h (152 ± 28.2 vs. 164 ± 33.4, P = 0.061). Compared with 4.5% of the participants in the opioid-free group, 34% of those in the opioid-based group developed moderate PONV. CONCLUSIONS: Opioid-free anesthesia in patients undergoing laparoscopic cholecystectomy reduced the requirement of analgesia in first two-hour postoperative period and was associated with decreased PONV.

[Pain therapy in urology-overview of current S3 guideline recommendations]. / Schmerztherapie in der Urologie ­ Überblick zu aktuellen Empfehlungen der S3-Leitlinen.

Dealing efficiently with patients suffering from pain is a central medical task. Pain, as an important function in developmental physiology, warns against damage to the body caused by external noxious agents as well as internal malfunctions and requires special attention in modern medicine. Peri- and postoperative pain is known to have a negative influence on postoperative convalescence. Treatment of tumor-related pain represents another relevant challenge in uro-oncology and palliative medicine. The updated guideline on perioperative pain therapy and palliative medicine for patients with incurable diseases or cancer is dedicated to these two topics.