Opioid Dose Research Articles

Interventions to reduce opioid use for patients with chronic non-cancer pain in primary care settings: A systematic review and meta-analysis.

This systematic review and meta-analysis aimed to assess interventions to reduce opioid use for patients with chronic non-cancer pain (CNCP) versus usual care or active controls in primary care settings. In this registered study (PROSPERO: CRD42022338458), we searched MEDLINE, Embase PsycInfo, CINAHL, and Cochrane Library from inception to December 28th 2021, and updated on Dec 14th 2023 for randomized controlled trials (RCTs) and cohort studies with no restrictions. Methodological quality was assessed using the Cochrane Risk of Bias tool for RCTs and Newcastle Ottawa Scale for cohort studies. Primary outcomes included mean reduction in morphine equivalent daily dose (reported as mean differences [MDs] mg/day; 95% confidence intervals [95%CIs]) and/or opioid cessation proportion. Secondary outcomes were mean changes in pain severity (reported as standardized mean difference [SMDs]; 95%CIs) and (serious) adverse events. Meta-analyses were performed using random-effects models. We identified 3,826 records, of which five RCTs (953 participants) and five cohort studies (901 participants) were included. Overall, opioid dosage was significantly reduced in intervention groups compared to controls (MD: -28.63 mg/day, 95%CI: -39.77 to -17.49; I2 = 31.25%; eight studies). Subgroup analyses revealed significant opioid dose reductions with mindfulness (MD: -29.36 mg/day 95%CI: -40.55 to -18.17; I2 = 0.00%; two trials) and CBT-based multimodalities (MD: -41.68 mg/day; 95%CI: -58.47 to -24.89; I2 = 0.00%; two cohort studies), respectively, compared to usual care. No significant differences were observed in opioid cessation (Odds ratio: 1.10, 95%CI: -0.48 to 2.67, I2 = 58.59%; two trials) or pain severity (SMD: -0.13, 95%CI: -0.37 to 0.11; I2 = 33.51%; three trials). Adverse events were infrequently examined, with withdrawal symptoms commonly reported. The studied interventions were effective in reducing opioid dosage for people with CNCP in primary care. They highlighted the importance of multidisciplinary collaboration. Large-scale RCTs measuring the long-term effects and cost of these interventions are needed before their implementation.

Pharmacological treatment of pain, dyspnea, death rattle, fever, nausea, and vomiting in the last days of life in older people: A systematic review.

Evidence based guidelines for treatment of physical symptoms during the last days of life in older people are not available. We wanted to synthesize the existing evidence on the pharmacological treatment of pain, dyspnea, death rattle, fever, nausea, and vomiting during the last days of life in older people to develop recommendations that can help guide clinical practice. A systematic review was conducted (PROSPERO #CRD42023406100) and reported in accordance with PRISMA guidelines. MEDLINE and EMBASE were searched from inception till March 2023, together with national and international guideline databases. Four predominantly descriptive studies on opioid use were included for the treatment of pain and four for dyspnea, without clear evidence for the choice of one specific opioid, nor a specific opioid dose. For death rattle, five randomized controlled trials and two retrospective studies were included. These provide evidence for the prophylactic treatment of death rattle with hyoscine butylbromide. For fever, nausea, and vomiting, no articles met the inclusion criteria. Limited evidence exists to guide the pharmacological treatment of pain, dyspnea, death rattle, fever, nausea, and vomiting in the last days of life of older people. Other than the use of opioids for treatment of pain and dyspnea and prophylactic administration of hyoscine butylbromide to decrease the likelihood of developing death rattle, no specific recommendations can be formulated for use in clinical practice. This demonstrates the challenging nature of research in the last days of life of older people, despite its pressing need.

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.

A COMPARISON OF EFFICACY OF EPIDURAL BUTORPHANOL AND FENTANYL FOR POST-OPERATIVE PAIN ANALGESIA IN LOWER ABDOMINAL AND LOWER LIMB SURGERIES UNDER EPIDURAL ANESTHESIA: A PROSPECTIVE RANDOMIZED DOUBLE-BLINDED STUDY

Objective: Lower doses of epidural opioids can achieve post-operative analgesia for infraumbilical surgeries. A study was conducted to compare the efficacy of epidural butorphanol and fentanyl for post-operative analgesia, onset, duration, and side effects in infraumbilical surgeries. Methods: A study was conducted on 80 adult patients, both male and female, aged between 20 and 60 years, having American Society of Anesthesiologists Physical Status I and II, who were undergoing lower abdominal and lower limb surgeries under epidural anesthesia. The patients were randomly divided into two groups: Group A and Group B. Both groups were given injections of bupivacaine 20 mL of 0.5% epidurally. In the post-operative period, when the patient’s Visual Analog Scale score was more than 4, Group A was administered butorphanol 2 mg followed by top-up doses of 0.5 mg, and Group B was administered fentanyl 50 μg followed by top-up doses of 15 μg, which were diluted to 10 mL in normal saline. Along with cardiorespiratory parameters, the study also noted onset, duration, quality of analgesia, and the number of epidural doses in 24 h. The statistical analysis was done using Student’s t-test and two-tailed Fisher’s exact test or Chi-square (χ2) test, and a significant value of p<0.05 was considered. Results: In comparing the post-operative analgesia between both groups, it was found that Group B had significant early onset of analgesia (2.600±0.4557 vs. 6.087±0.7501), shorter duration of analgesia (200.08±26.257 vs. 366.25±42.829), a higher number of epidural doses administered (3.75±1.171 vs. 2.98±0.733), lower quality of analgesia (2.55±0.504 vs. 3.18±0.636), and a greater incidence of vomiting (30.0% vs. 2.5%) when compared to group A. Conclusion: Superior analgesia with higher sedation can be achieved through epidural butorphanol, while fentanyl has a quicker onset of analgesia but a higher tendency for vomiting. Our conclusion is that both options, fentanyl and epidural butorphanol, are safe and effective for achieving post-operative pain relief.

The opioid industry's use of scientific evidence to advance claims about prescription opioid safety and effectiveness

Abstract It is widely recognized that pharmaceutical marketing contributed to the ongoing US opioid epidemic, but less is understood about how the opioid industry used scientific evidence to generate product demand, shape opioid regulation, and change clinician behavior. In this qualitative study, we characterize select scientific articles used by industry to support safety and effectiveness claims and use a novel database, the Opioid Industry Documents Archive, to determine notable elements of industry and non-industry documents citing the scientific articles to advance each claim. We found that 15 scientific articles were collectively mentioned in 3666 documents supporting 5 common, inaccurate claims: opioids are effective for treatment of chronic, non-cancer pain; opioids are “rarely” addictive; “pseudo-addiction” is due to inadequate pain management; no opioid dose is too high; and screening tools can identify those at risk of developing addiction. The articles contributed to the eventual normalization of these claims by symbolically associating the claims with scientific evidence, building credibility, expanding and diversifying audiences and the parties asserting the claims, and obfuscating conflicts of interest. These findings have implications for regulators of industry products and corporate activity and can inform efforts to prevent similar public health crises.

Phenotypes based on respiratory drive and effort to identify the risk factors when P0.1 fails to estimate ∆PES in ventilated children.

Monitoring respiratory effort and drive during mechanical ventilation is needed to deliver lung and diaphragm protection. Esophageal pressure (∆PES) is the gold standard measure of respiratory effort but is not routinely available. Airway occlusion pressure in the first 100ms of the breath (P0.1) is a readily available surrogate for both respiratory effort and drive but is only modestly correlated with ∆PES in children. We sought to identify risk factors for P0.1 over or underestimating ∆PES in ventilated children. Secondary analysis of physiological data from children and young adults enrolled in a randomized controlled trial testing lung and diaphragm protective ventilation in pediatric acute respiratory distress syndrome (PARDS) (NCT03266016). ∆PES (∆PES-REAL), P0.1 and predicted ∆PES (∆PES-PRED = 5.91*P0.1) were measured daily to identify phenotypes based upon the level of respiratory effort and drive: one passive (no spontaneous breathing), three where ∆PES-REAL and ∆PES-PRED were aligned (low, normal, and high effort and drive), two where ∆PES-REAL and ∆PES-PRED were mismatched (high underestimated effort, and overestimated effort). Logistic regression models were used to identify factors associated with each mismatch phenotype (High underestimated effort, or overestimated effort) as compared to all other spontaneous breathing phenotypes. We analyzed 953 patient days (222 patients). ∆PES-REAL and ∆PES-PRED were aligned in 536 (77%) of the active patient days. High underestimated effort (n = 119 (12%)) was associated with higher airway resistance (adjusted OR 5.62 (95%CI 2.58, 12.26) per log unit increase, p < 0.001), higher tidal volume (adjusted OR 1.53 (95%CI 1.04, 2.24) per cubic unit increase, p = 0.03), higher opioid use (adjusted OR 2.4 (95%CI 1.12, 5.13, p = 0.024), and lower set ventilator rate (adjusted OR 0.96 (95%CI 0.93, 0.99), p = 0.005). Overestimated effort was rare (n = 37 (4%)) and associated with higher alveolar dead space (adjusted OR 1.05 (95%CI 1.01, 1.09), p = 0.007) and lower respiratory resistance (adjusted OR 0.32 (95%CI 0.13, 0.81), p = 0.017). In patients with PARDS, P0.1 commonly underestimated high respiratory effort particularly with high airway resistance, high tidal volume, and high doses of opioids. Future studies are needed to investigate the impact of measures of respiratory effort, drive, and the presence of a mismatch phenotype on clinical outcome. NCT03266016; August 23, 2017.

A retrospective study of duloxetine for phantom limb pain post lower‐limb amputation

AbstractBackgroundPhantom limb pain (PLP) refers to the painful sensory perception of a missing limb after amputation, which can have physical and psychological impacts.AimTo determine the effectiveness of duloxetine for pain management in PLP by the reduction of opioid doses and other neuropathic analgesics when introduced into multimodal pain management strategies in the subacute rehabilitation setting.MethodThis was a retrospective observational case‐matched cohort study of patients who were admitted to a geriatric and rehabilitation unit at a tertiary Australian hospital from January 2005–December 2017 with PLP after lower‐limb amputation. Patients were included if they had a new amputation and experienced PLP. The primary outcome was a difference in oxycodone dose equivalents at discharge between the two cohorts. Univariable analysis was used to compare groups. Ethical approval was granted by the Metro South Low Negligible Risk Ethics Committee (Reference no: LNR/2018/QMS/47370) and the study conforms with the National statement on ethical conduct in human research.ResultsThirty patients from the duloxetine treatment cohort and 57 patients from the non‐duloxetine cohort were identified. Participants were predominantly male (81%) and had a median age of 63 years (interquartile range = 10.7). Both populations showed a similar rate of opioid dose reduction comparing doses at admission with those at discharge. There were no significant differences in absolute oxycodone equivalent doses at the two observed check points: admission and discharge.ConclusionThis study demonstrated that opioid consumption in post‐surgical lower‐limb amputees reporting PLP was not significantly different between populations that used and did not use duloxetine. Future research should evaluate the efficacy of duloxetine in PLP pain management using a multisite prospective study design.

Opioid tapering and discontinuation for head and neck cancer (HNC) survivors.

366 Background: Older HNC survivors often experience post-treatment pain, and they fill opioid prescriptions more often than similar cancer-free adults for the first 5 years after HNC diagnosis. To better understand whether ongoing opioid use is likely explained by continued opioid prescribing from the time of cancer treatment, we aimed to quantify the extent to which opioids prescribed near the end of treatment are reduced in dose (tapered) and discontinued after treatment completion. Methods: Using linked Surveillance, Epidemiology, and End Results (SEER) registry and Medicare claims data, we identified adults age &gt;65 diagnosed 2014-2017 with stage I-III HNC with ≥6 months treatment-free follow-up prior to censoring at further treatment, new cancer, hospice, 3 months prior to death, or end 2019. We evaluated the presence of a new or ongoing opioid prescription 2 weeks following treatment completion (baseline) and calculated daily baseline dose in morphine milligram equivalents (MME). Among those with an opioid prescription (“on opioids”) at baseline, we described cross-sectional metrics of opioid receipt and dose every 30 days: proportion of survivors on opioids (who were also on opioids the prior month), initial and current dose of opioids for those currently on opioids, and proportion of survivors on opioids whose dose declined ≥50% from baseline. Results: Among 5135 HNC survivors, 894 were on opioids at baseline (average daily dose 44 MME). By 1 month, 29% of survivors on opioids at baseline (N=260) had a current opioid fill, and 7% had an opioid dose &lt;50% of the baseline dose. Discontinuation of opioids increased each month; median daily dose each month ranged from 44 MME at 30 days to 60 MME at 180 days. Those who remained on opioids over 6 months had the highest opioid dose than those who discontinued earlier (median 45 MME at 90 days; Table). Conclusions: About 1 in 6 HNC survivors had an opioid prescription filled at the end of cancer treatment, and opioids were generally discontinued within a few months. Given the low median dose at baseline, the limited evidence of tapering likely results from low initial opioid doses rather than a failure to taper from long-term or high-dose use. Opioid use among older treatment-free HNC survivors that is apparent years after treatment completion is unlikely to result from inadequate tapering. Instead, it may be due to new or worsening cancer-related pain, as well as to non-cancer pain. Dose reduction and discontinuation (N=894). Days after baseline Off opioids On opioids Starting dose in MME among those on opioids Current dose in MME among those on opioids Tapered to &lt;50% starting dose N (%) N (%) Median (IQR) Median (IQR) N (%) 30 634 (71) 260 (29) 53 (30, 80) 44 (29, 60) 61 (7) 60 772 (86) 122 (14) 45 (30, 67.5) 44 (29, 60) 15 (2) 90 820 (92) 74 (8) 58 (30, 90) 45 (29, 60) 7 (1) 120 838 (94) 56 (6) 60 (30, 90) 45 (25, 60) 7 (1) 150 849 (95) 45 (5) 56 (30, 65) 48 (29, 60) 2 (&lt;1) 180 856 (96) 38 (4) 51 (30, 65) 60 (30, 90) 1 (&lt;1)

Clinical Trial Study Protocol: A Prospective Blinded, Randomized, Controlled Clinical Trial Protocol to Assess the Efficacy of Ultrasound-Guided Transversus Abdominis Plane Block on Postoperative Analgesia and Recovery Quality in Laparoscopic Donor Hepatectomy.

Liver transplantation is considered an effective treatment for end-stage liver disease. Laparoscopic donor hepatectomy (LDH) has become a new standard procedure. And it is important to minimize the pain of the donor. Good postoperative analgesia can reduce the occurrence of postoperative complications and promote the early recovery of the donor. Ultrasound-guided transversus abdominis plane (TAP) block can provide effective analgesia for liver donors and reduce postoperative opioid consumption. This study aims to use ultrasound-guided TAP block for LDH to improve postoperative analgesia for donors while reducing opioid consumption and improving patient rehabilitation quality. This study is a prospective blinded, randomized, controlled clinical trial with a concealed allocation of patients (living liver donors) scheduled to receive laparoscopic partial hepatectomy 1:1 to receive local infiltration anesthesia or TAP block. This study will recruit a total of 80 patients. The primary outcome is the dosage of opioids within 24hours after surgery. This trial has been approved by the Institutional Review Board of Beijing Friendship Hospital of China Capital University. This trial study protocol was approved on 8 May 2023. The trial will start recruiting patients after being registered on the Chinese Clinical Trial Registry. ChiCTR2300071694.

The effects of opioid tapering on select endocrine measures in men and women with head and neck cancer-a longitudinal 12-month study.

Opioid treatment may affect endocrine measures in humans either through centrally or peripherally mediated mechanisms. There is a general lack of longitudinal studies examining endocrine measures in opioid-treated patients. To longitudinally follow the levels of select endocrine measures in men and women with head and neck cancer for 1 year, who after having completed radiotherapy began tapering opioids. This was a prospective, longitudinal, observational study. Testosterone and estradiol were measured in men and women, respectively. Follicle-stimulating hormone (FSH), luteinizing hormone (LH), dehydroepiandrosterone sulfate (DHEAS), and prolactin were measured in both sexes. Women were grouped based on if premenopausal or postmenopausal. Samples were collected when opioid tapering started and at 1, 3, 6, and 12 months after tapering start. Daily opioid doses at the same time points were registered. Twenty-five men and 12 women were followed for 12 months. In men, testosterone levels increased significantly during the first month after opioid tapering started (P < 0.001). Levels of testosterone, FSH, DHEAS, and prolactin changed significantly in men during the study period. A moderate correlation between opioid dose reduction and testosterone level increase in men aged ≤60 years was found (r s = -0.577, 95% CI -0.854 to -0.044, P = 0.039). In postmenopausal women (n = 10), levels of FSH and LH changed significantly during the study period. Previously known effects of opioids on endocrine measures in humans seem to be reversible as select endocrine measures changed significantly in men and postmenopausal women after opioid tapering was initiated.

A Framework for a New Paradigm of Opioid Drug Tapering Using Adjunct Drugs.

The misuse of and dependency on prescription opioids represents a significant crisis at the national level, impacting not only the health of the public but also the societal and economic well-being. There is a critical need for strategies to reduce the dosage of prescribed opioids to limit opioid-associated adverse effects and lower the risk of addiction development in patients experiencing chronic pain. Opioid-sparing medications, when co-administered with opioids, enable a reduced opioid dose without loss of efficacy. This suggests the potential for using opioid adjunct drugs in opioid tapering, whereby opioid doses are lowered incrementally in a systematic manner to improve a patient's safety profile or quality of life. The objective of this report is two-fold: 1) to illustrate the potential for adjunct drugs in opioid tapering, and 2) to describe the steps needed to be taken to develop a framework for the use of adjunct drugs in opioid tapering. This can provide the impetus for further investigation into opioid tapering and the development of improved clinical care. The proposed project implements knowledge synthesis methods to develop the framework for a new paradigm of opioid drug tapering that incorporates opioid dosage reductions with adjunct drugs. Framework development is organized into three major phases: 1) Adjunct drug characterization, 2) Assessment of the opioid-sparing effect, and 3) Usability of data for clinicians. The knowledge gained from this project can provide a foundation for improved analgesia protocols for opioids and adjunctive drug therapy.

Effect of Neuromuscular Blockade Reversal on Postoperative Gastrointestinal Motility after Laparoscopic Cholecystectomy: Neostigmine / Atropine versus Sugammadex.

To compare sugammadex with neostigmine / atropine combination for reversal of neuromuscular blocker agents in terms of postoperative gastrointestinal motility in patients who underwent laparoscopic cholecystectomy. Experimental study. Place and Duration of the Study: University of Health Sciences, Izmir Bozyaka Training and Research Hospital, Izmir, Turkiye, between December 2020 and June 2021. Seventy-two patients undergoing laparoscopic cholecystectomy were included. At the end of the surgery, patients were antagonised for neuromuscular blockers either by atropine / neostigmine or sugammadex by an anaesthesiologist who was not involved in the study. Total anaesthesia time, pneumoperitoneum time, surgery time, number of postoperative opioid dose requirements and total opioid dose administered, number of medication requirements for postoperative nausea and vomiting, postoperative hospital stay, and first gas and stool output time of all the cases were evaluated by the researcher who was unaware of the medicines used for antagonisation. There were no statistically significant differences between the two groups in terms of their effects on postoperative gastrointestinal motility (first gas and stool output time), duration of anaesthesia, duration of surgery, duration of pneumoperitoneum, the number of postoperative opioid dose requirements, the number of drug requirements for postoperative nausea / vomiting, and the postoperative hospitalisation duration of the cases. Effects of reversal agents on postoperative gastrointestinal motility are still debated. Studies on this subject in the literature are both limited in number and have been conducted with different medicine combinations in a wide variety of patient populations. The authors thought that further prospective randomised studies are needed to interpret this effect more clearly. Sugammadex, Neostigmine / atropine, Gastrointestinal motility, Laparoscopic cholecystectomy.

Chronic Opioid Use Following Implementation of Oregon's Medicaid Back Pain Policy

IntroductionIn 2016, Oregon developed an innovative policy to improve care for Medicaid patients with back pain. The objective of this study was to identify factors associated with dose reduction and discontinuation among Medicaid patients using chronic opioid therapy following implementation of this policy. MethodsUsing Medicaid administrative claims data, this was a retrospective cohort of patients on chronic stable opioid therapy between July and December 2016. Outcomes assessed were 1) 30% reduction in opioid dose and 2) an absolute discontinuation between January to December 2017. Multivariable logistic regressions evaluated association between dose reduction outcomes and clinical and demographic factors. ResultsOf 4,643 Medicaid patients on chronic opioid therapy, 3853 (83%) had a dose reduction and 651 (14%) discontinued opioids; patients with back pain were more likely to have a dose reduction (adjusted odds ratio [aOR] 1.19; 95% 1.01 to 1.41). Factors associated with discontinuation included having a mental health diagnosis (aOR 1.30; 95% CI 1.08 to 1.56), substance use disorder (aOR 1.90; 95% CI 1.41 to 2.56), opioid use disorder (aOR 1.55; 95% CI 1.21 to 1.99), and receipt of buprenorphine (aOR 2.82; 95% CI 1.30 to 6.15). Discontinuation was less likely in Black patients (aOR 0.50; 95% CI 0.29 to 0.85), in older age groups, and in those with a higher opioid dose at baseline. ConclusionsMost Medicaid beneficiaries had a dose reduction following implementation of Oregon's back pain policy. Opioid discontinuation was associated with factors that suggest providers pursue this strategy for patients at higher overdose risk.

Variation in Opioid Agonist Dosing in Clinical Trials by Race and Ethnicity

Racial and ethnic disparities in access to treatment and quality of treatment for opioid use disorder (OUD) have been identified in usual care settings. In contrast, disparities in treatment quality within clinical trials are relatively unexamined. To estimate racial and ethnic differences in the dose of opioid agonist treatment for OUD in the first 4 weeks of treatment in clinical trials. This cohort study performed analysis of the methadone and buprenorphine treatment arms of 3 trials conducted by the National Institute on Drug Abuse Clinical Trials Network between May 2006, and January 31, 2017, at multiple Clinical Trials Network sites across the US. Trial participants who were randomized to and initiated buprenorphine or methadone treatment and who identified as Hispanic, non-Hispanic Black, or non-Hispanic White were included in the present study. Data were analyzed from November 1, 2023, to August 5, 2024. Combined race and ethnicity as self-classified by the patient at trial enrollment. The maximum daily dose of buprenorphine or methadone received in each week for the first 4 weeks of treatment. The mean dose and the percentage of patients receiving a higher dose (buprenorphine ≥16 mg and methadone ≥60 mg) were compared across race and ethnicity groups. A total of 1748 patients (1263 who initiated buprenorphine and 485 who initiated methadone treatment) were included in the analysis (1168 [66.8%] male; median age, 33 [IQR, 26-45] years). Of these, 138 patients (7.9%) identified as Black, 273 (15.6%) as Hispanic, and 1337 (76.5%) as White. In week 4, Black patients received buprenorphine doses 2.5 (95% CI -4.6 to -0.5) mg lower and methadone doses 16.7 (95% CI, -30.7 to -2.7) mg lower compared with White patients, after standardizing by age and sex. In week 4, the percentage of patients receiving a higher dose of medication (buprenorphine ≥16 mg; methadone ≥60 mg) was 16.9 (95% CI, -31.9 to -1.9) points lower for Black patients compared with White patients. Hispanic and White patients received similar buprenorphine doses; Hispanic patients received lower methadone doses than White patients. In this cohort study of data from 3 clinical trials, White patients generally received higher doses of medication than Black patients. Future research is needed to understand the mechanisms of and interventions to reduce disparities in OUD treatment quality and how such disparities impact generalizability of trial results.

Long-term opioid prescribing and the incidence of opioid-related hospitalizations or emergency department visits among patients with metastatic cancer.

200 Background: Many patients with metastatic cancer experience cancer-related pain which is commonly managed using opioids. Although opioids are an effective tool for cancer pain management, their use can result in adverse effects which may be related to long-term use and are understudied in this population. Therefore, we aimed to describe long-term opioid prescribing (LTOP) practices among patients with metastatic cancer and investigate the incidence of opioid-related hospitalizations and emergency department (ED) visits among recipients of long-term prescribing. Methods: This retrospective cohort study used population-based data from Alberta, Canada to identify patients diagnosed with stage IV cancers between 2004-2017 who had at least 1-year of follow-up and were opioid naïve at diagnosis. LTOP was defined as receipt of a ≥90-day supply of opioids with less than a 30-day gap in supply within a 180-day period. Prescribing practices were characterized according to timing (early vs. end-of-life [EoL] onset), morphine equivalent dose, duration, and concurrent medication use. The EoL phase of disease was defined as the year preceding death. The incidence rate of opioid-related encounters was compared between different characteristics of LTOP. Results: The study included a total of 10927 patients, 2521 (23%) of whom received long-term opioid prescribing after diagnosis. LTOP became more common as patients approached EoL, with most patients (53%) having LTOP initiated only within their last year of life. 85 patients (3.4%) experienced an opioid-related hospitalization or ED visit after initiation of LTOP, with an incidence rate of 2.36 (95% CI 1.92, 2.86) encounters per 100 person-years. Higher opioid dosage and concurrent prescribing of anxiolytics, benzodiazepines, antidepressants, and neuroleptic medications were significantly associated with a higher incidence of opioid-related encounters. Conclusions: Long-term opioid prescribing is commonly experienced by patients living with metastatic cancer as a chronic disease. The concurrent use of psychoactive drugs during LTOP was associated with experiencing opioid-related hospitalizations/ED visits.

Exceeding the guideline-recommended maximum daily dose of opioids for long-term treatment of non-cancer pain in Germany – a large retrospective observational study

BackgroundHigh-dose long-term opioid therapy (LTOT) has been associated with increased mortality and hospitalizations. Therefore, the evidence-based German guideline on LTOT for chronic non-cancer pain (CNCP) recommends to only exceed the maximum daily dose (MDD) of opioids in exceptional cases. This study aimed to determine the portion of LTOT patients who exceeded the guideline-recommended MDD and identify predictors of exceeding in administrative claims data.MethodsThe retrospective observational analysis of opioid prescriptions in patients receiving LTOT for CNCP was based on administrative claims by a large German statutory health insurance company. Patients with at least two quarters of opioid prescriptions between January 2018 and June 2019 were included and followed up for two years. Predictors were identified by logistic regression. In addition, the number of patients still in opioid therapy and the extent of exceeded MDDs were analyzed over time.ResultsThe sample consisted of 113,475 patients. Overall, 10.5% of the patients exceeded the guideline-recommended MDD averaged over the observation period. Strong predictors for exceeding the MDD were receiving opioid prescriptions from > 7 physicians (OR = 7.66, p < .001), receiving predominantly strong opioids (OR = 6.79, p < .001) and receiving opioids for at least one year prior to inclusion (OR = 5.35, p < .001). Within the non-exceeding group, 28.1% discontinued opioid therapy. In contrast, 9.9% of patients in the exceeding group discontinued opioid therapy, whereas the vast majority remained on treatment until the end of the observation period. Furthermore, a slight increase in prescribed doses was observed over time.ConclusionsThe results indicate that a moderate proportion of patients exceeded the guideline-recommended MDD. However, certain patient groups were more likely to receive high doses. This applied in particular to those who were already on treatment at the time of inclusion and continued to receive opioids until the end of the observation period. Further research should examine whether the continuous opioid therapy among the patients with exceeding the guideline-recommended MDD might be related to specific indications, a lack of therapeutic options or avoidance of withdrawal.Trial registrationGerman Clinical Trials Register (drks.de/search/en). Identifier: DRKS00024854. Registered 28 April 2021.

Frailty and Medication Appropriateness in Rural Adults: Proposing Interventions through Pharmacist-Physician Collaborative Efforts.

Background: Frailty and polymedication are closely interrelated. Addressing these concurrent conditions in primary care settings relies on the utilization of potentially inappropriate medication (PIM) lists and medication reviews (MRs), particularly in rural areas, where healthcare professionals serve as the sole point of access to the medical system. The aim of this study was to examine the relationship between medication appropriateness and variables related to frailty in a rural municipality in order to propose potential strategies for therapy optimization. Methods: This cross-sectional study included all adult community dwellers aged 50 and above officially registered in the municipality of Tiriez (Albacete, Spain) in 2023 (n = 241). The primary outcome variable was frailty (assessed using the fatigue, resistance, ambulation, illness, and loss of weight (FRAIL) scale). The independent variables were age, gender, medication regimen, history of falls, comorbidities, PIMs (evaluated using the screening tool of older persons' prescriptions (STOPP) 2023 criteria), fall-risk-increasing drugs (FRID), and anticholinergic burden (ACB). Results: The prevalence of frailty was approximately 20%. FRID and ACB scores were statistically associated (p-value < 0.001) with frailty, 1.1 ± 1.3 vs. 2.5 ± 1.7, and 1.0 ± 1.3 vs. 2.8 ± 2.5, respectively. Regardless of age, frailty was observed to be more prevalent among females (odds ratio (OR) [95% confidence interval (CI)]: 3.5 [1.5, 9.0]). On average, 2.1 ± 1.6 STOPP criteria were fulfilled, with the prolonged use of anxiolytics and anti-peptic-ulcer agents being the most frequent. Priority interventions (PIs) included opioid dose reduction, benzodiazepine withdrawal, and the assessment of antidepressant and antiplatelet treatment plans. Conclusions: The optimization of medication in primary care is of paramount importance for frail patients. Interventional measures should focus on ensuring the correct dosage and combination of drugs for each therapeutic regimen.

Opioid equipotency conversions for hospitalized infants: a systematic review

AbstractHospitalized infants commonly receive opioids to reduce pain and minimize distress during invasive procedures. However, infant neurodevelopment is significantly impacted by cumulative and prolonged opioid exposures. While opioid conversion has been studied extensively in adults, no standardized equipotency opioid conversions exist for hospitalized infants and opioid stewardship efforts are inconsistent. We performed a systematic review to identify opioid dosing conversions commonly used in hospitalized infants &lt;1 year of age, finding fourteen articles which documented or cited a calculation of cumulative opioid exposure. Morphine milligram equivalents (MME) conversion factors varied widely, with nine studies citing conversion equivalent equations commonly used in adults. Efforts to expand safe opioid stewardship to hospitalized infants will require evidence-based consensus for opioid equipotency dose conversions which acknowledge the unique physiology of infants.

Is general practitioner involvement in the initiation of opioids for chronic non-cancer pain associated with opioid dose and concurrent drug use?

Objective Is the involvement of the regular general practitioner (GP) in the decision to initiate opioid treatment for chronic non-cancer pain (CNCP) associated with two main risk factors for serious adverse events: increased opioid dose and the concomitant use of prescribed benzodiazepines or benzodiazepine-related medications? Design and setting An anonymous web-based survey was conducted in the county of Rogaland, Norway, during the spring of 2021. Subjects GPs who self-reported applying at least once for reimbursement of opioids prescribed to treat CNCP. They were asked to answer the survey based on the last patient for whom they recalled submitting a reimbursement application. Main outcome measures 1) Total opioid dose in daily oral morphine equivalents (OMEQ). 2) Concurrent use of benzodiazepines and/or benzodiazepine-related drugs. Results The daily opioid dose was lower when the surveyed GPs initiated the opioid treatment (36 OMEQ, n = 25), than when others had initiated the treatment (108 OMEQ, n = 31, p = 0.001). For concurrent use of benzodiazepine or benzodiazepine-related drugs, no significant difference was found (33%, n = 9 with GP involvement vs. 47%, n = 16, p = 0.279 with no GP involvement). Conclusions GP involvement in the initiation of opioid medication for CNCP was associated with a lower opioid dose being prescribed. Implications GP involvement in the initiation of opioid prescriptions may facilitate safer prescribing.

Buprenorphine: Opioid Agonist-Antagonist for Refractory Pain of Sickle Cell Disease Patients During Hematopoietic Stem Cell Transplant, Uncontrolled By Full-Agonist Opioids.

Bone marrow transplant (BMT) offers potential cure for cancer and a spectrum of otherwise incur- able diseases. The BMT process can cause multi-systemic pain in patients with sickle cell disease (SCD) refractory to high-dose opioid analgesics during BMT because of their pre-existing opioid-tolerance. Because of frequent pain resulting in hyperalgesia and chronic opioid use, SCD patients undergoing BMT often experience excruciating pain uncontrolled by exceedingly high-dose opioids with severe and intolerable adverse effects. There is a small but growing body of literature about the successful buprenorphine effect for SCD's chronic pain management that had failed sufficient pain relief by the traditional full-agonist opioids in the outpatient setting. However, the buprenorphine use for acute inpatient pain management has not been previously researched. Pilot prospective clinical trial with buprenorphine-based pain management for acute BMT-related pain was initiated for SCD patients' pain uncontrolled by full-agonist opioids. Procedures/data/observations: Buprenorphine was started as scheduled and as-needed analgesics, supplemented by full-agonist opioids upon consultation for uncontrolled BMT-related pain of SCD patients. Patients' 24-hour opioid requirement by morphine equivalent daily doses (MEDD) were assessed at 3 time points: 1)immediately before pain escalation; 2)consultation; 3)discharge. MEDDs were compared to those of patients treated with full-agonist opioids only. Cases treated by full-agonist opioids (morphine/hydromorphone/fentanyl/methadone/oxycodone) had MEDD escalation by 1230-16300% by discharge compared to immediately before BMT-related pain escalation. Buprenorphine-supported cases had significantly smaller MEDD increase by 220-317%. Our case series suggests superior pain control by adding Buprenorphine prior to opioid dose escalation during BMT for SCD. Buprenorphine may provide the advantageous effect for other patients with complex pain background and experiencing difficult pain management during BMT due to pre-existing hyperalgesia and high opioid-tolerance. The evidence for buprenorphine's analgesic effect is moderate but growing, and more randomized controlled trials comparing the buprenorphine and other standard opioids are needed.