Nonopioid Alternatives Research Articles

Development of Macrocyclic Neurotensin Receptor Type 2 (NTS2) Opioid-Free Analgesics.

The opioid crisis has highlighted the urgent need to develop non-opioid alternatives for managing pain, with an effective, safe, and non-addictive pharmacotherapeutic profile. Using an extensive structure-activity relationship approach, here we have identified a new series of highly selective neurotensin receptor type 2 (NTS2) macrocyclic compounds that exert potent, opioid-independent analgesia in various experimental pain models. To our knowledge, the constrained macrocycle in which the Ile12 residue of NT(7-12) was substituted by cyclopentylalanine, Pro7 and Pro10 were replaced by allyl-glycine followed by side-chain to side-chain cyclization is the most selective analog targeting NTS2 identified to date (Ki 2.9 nM), showing 30,000-fold selectivity over NTS1. Of particular importance, this macrocyclic analog is also able to potentiate the analgesic effects of morphine in a dose- and time-dependent manner. Exerting complementary analgesic actions via distinct mechanisms of nociceptive transmission, NTS2-selective macrocycles can therefore be exploited as opioid-free analgesics or as opioid-sparing therapeutics, offering superior pain relief with reduced adverse effects to pain patients.

Evidence for the Use of Opioid Medication for Pediatric Acute Pain in the Outpatient Setting: Technical Report.

This technical report summarizes the results of a systematic review designed to support the American Academy of Pediatrics' "Clinical Practice Guideline: Opioid Prescribing for Acute Pain Management in Children and Adolescents in Outpatient Settings." PubMed and Excerpta Medica Database were searched from 2010 to 2023 to identify randomized clinical trials and systematic reviews related to outpatient opioid prescribing to children. Overall, 11 randomized controlled trials were included. Although data were limited, no evidence was found that pain control by opioids is superior to nonopioid alternatives. Further, opioids are often associated with adverse events. The review also suggests that family and patient education and providing disposal methods may decrease risks associated with opioid prescription. Future studies can build on this foundation of evidence to support the appropriate use of opioids for acute pain in children treated in the outpatient setting.

Systemic administration of Resolvin D1 reduces cancer-induced bone pain in mice: Lack of sex dependency in pain development and analgesia.

Bone cancer produces severe pain that is treated with opioids, but serious side effects limit opioid utilization. There is therefore a need to develop effective and safe non-opioid alternatives. The lipid mediator, Resolvin D1 (RvD1), could be a prospective candidate for cancer pain treatment. To assess RvD1 and other potential candidates, appropriate animal models that recapitulate clinical features must be used. Although several preclinical models of cancer pain have been developed, the influence of sex on the development of cancer pain and the effectiveness of RvD1 have not been studied. Using a mouse model of fibrosarcoma growth in and around the calcaneus bone, we demonstrated that the mechanical hyperalgesia in the tumor-bearing hind paw develops independently of sex, except that it developed a little sooner in female mice. A single intravenous injection of RvD1 (0.001-10 μg/kg) decreased hyperalgesia in both sexes with similar potency (ED50 = 0.0015 μg/kg) and efficacy. Repeated daily administration of 10 μg/kg RvD1 prolonged the analgesic effect and completely abolished hyperalgesia. This was also independent of sex. In this preclinical mouse model of bone cancer pain, the development of pain and the analgesic effectiveness of RvD1 are not influenced by sex.

Nanotechnology-Enhanced Naloxone and Alternative Treatments for Opioid Addiction.

Opioids are commonly prescribed to address intense, ongoing pain associated with cancer, as well as long-lasting noncancer-related pain when alternative methods have proven ineffective. Individuals who exhibit both chronic pain and misuse of opioids face a significant danger of experiencing adverse health outcomes and the potential loss of life related to opioid use. Thus, there is a current movement to prescribe naloxone to those considered high-risk for opioid overdose. Naloxone has been explored as an antidote to reverse acute respiratory depression. Conversely, naloxone can give rise to other problems, including hypertension and cardiac arrhythmias. Thus, the importance of nanotechnology-enabled drug delivery strategies and their role in mitigating naloxone side-effects are significant. In this review, we explore the latest advancements in nanotechnology-enabled naloxone and alternative methods for addressing the opioid crisis through the utilization of non-opioid natural alternatives for chronic pain management.

Community Pharmacists' Knowledge and Attitude Towards Opioid Pain Medication Use in Bahir Dar City, North-West Ethiopia.

Opioid use is a major global public health problem, affecting 16 million individuals worldwide. According to a 2023 WHO report, out of the 600,000 substance-related deaths worldwide, 80% were attributed to opioid use. Pharmacists play a vital role in reducing unnecessary opioid exposure while facilitating access to non-opioid alternatives. To do so, pharmacists should have sufficient knowledge regarding opioid-containing medications and a positive attitude about opioid use problems. This study aimed to evaluate community pharmacists' knowledge of opioid-containing medications and their attitude toward opioid use problems. A cross-sectional study was conducted using a self-administered, structured questionnaire distributed to 105 community pharmacists from July 1-30, 2023 in Bahir Dar City, Ethiopia. The tool included demographic information and questions designed to assess participants' knowledge and attitudes. Out of the 105 pharmacists included in this study, majority were males (54.3%), nearly half held a bachelor's degree (49.5%), and slightly above one-third had over a decade experience (39%). Regarding knowledge and attitude towards opioids, 62 individuals (59%) exhibited good knowledge, and 64 (61%) demonstrated less stigma toward opioid usage. Factors affecting knowledge include: education level (AOR (95% CI): 8.43 (1.76-40.35) and 9.93 (1.04-85.33) for bachelors and postgraduates respectively and age 1.45 (1.20-1.77)]. Meanwhile, experience [AOR (95% CI): 4.64(1.20-17.90) and 4.29 (1.23-15.05)] for 5-9 years and ≥10 years respectively and education level [AOR (95% CI): 4.08 (1.40-11.93) for bachelors and 6.40 (1.42-28.96)] for postgraduates were linked to attitude. A gap in knowledge and more stigmatizing behavior was observed among community pharmacists. These findings imply the importance of tailored educational interventions to address knowledge gaps and promote positive attitudes toward opioid usage among community pharmacists. Therefore, it is imperative to deliver up-to-date information on opioids, emphasizing their high addiction potential, to ensure pharmacists are well-equipped with the latest information.

Non-opioid psychiatric medications for chronic pain: systematic review and meta-analysis.

The escalating number of deaths related to opioid usage has intensified the pursuit of non-opioid alternatives for managing chronic pain. It's often observed that psychiatric comorbidities coexist in patients suffering from chronic pain. There are a variety of psychotropic medications that have demonstrated effectiveness in treating both psychiatric symptoms and pain. This systematic review and meta-analysis aim to assess the effectiveness of various psychiatric drugs in managing specific types of chronic pain, including fibromyalgia, neuropathic pain, and chronic low back pain. A comprehensive search of five major databases was conducted through February 2023 to identify randomized controlled trials (RCTs) that met our inclusion criteria, focusing on outpatients Over 18 years of age with chronic pain. The study assessed the effectiveness of duloxetine, mirogabalin, pregabalin, gabapentin, and tricyclic antidepressants (TCAs), including serotonin-norepinephrine reuptake inhibitors (SNRIs), across various chronic pain conditions such as fibromyalgia, neuropathic pain, and chronic low back pain. The primary outcome measures included pain reduction, improvement in function, and quality of life. Of the 29 RCTs in the systematic review, 20 studies qualified for the meta-analysis. The analysis was stratified by pain type and treatment duration (short-term ≤14 weeks vs. long-term >14 weeks), using Hedge's g standardized mean differences and a random-effects model, along with sensitivity and subgroup analyses. The overall short-term intervention effect across all studies was significant (SMD -1.45, 95% CI -2.15 to -0.75, p < 0.001), with considerable heterogeneity (I2 = 99%). For fibromyalgia, both duloxetine and mirogabalin demonstrated substantial efficacy with SMDs of -2.42 (95% CI -3.67 to -1.18, p < 0.0001) and -2.10 (95% CI -3.28 to -0.92, p = 0.0005), respectively. Conversely, treatments for neuropathic pain and chronic low back pain, including those with amitriptyline and desipramine, did not show significant benefits. The effectiveness of gabapentin could not be conclusively determined due to limited representation in the data. Additionally, no consistent long-term benefits were observed for any of the medications. While the results of this study underscore the importance of exploring non-opioid alternatives for chronic pain management, particularly in light of the opioid crisis, it is crucial to interpret the findings carefully. Our analysis suggests that certain psychiatric medications, such Duloxetine and mirogabalin demonstrated significant short-term efficacy in fibromyalgia patients. However, their effectiveness in treating neuropathic pain and chronic low back pain was not statistically significant. Additionally, the effectiveness of gabapentin and other medications, such as pregabalin for neuropathic pain, could not be conclusively determined due to limited data and high study heterogeneity. No consistent long-term benefits were observed for any of the drugs studied, raising questions about their sustained efficacy in chronic pain management. These findings highlight the need for further research to understand better the role of psychiatric medications in managing specific chronic pain conditions without prematurely concluding that they are ineffective or unsuitable for these purposes.

Opioid Prescribing Patterns After Colorectal Resections in the United States of America.

Background The opioid epidemic is a significant source of morbidity and mortality in the United States of America. Minimizing opioid prescribing after operations has become an important component of post-operative care pathways. We hypothesized that opioid prescribing has decreased over time after colorectal resections. Methods This is a retrospective study from 2012 to 2019 using the Optum Clinformatics database (Eden Prairie, MN). We included patients aged 18 years or older who had an elective colorectal resection. Our primary outcome was the rate of opioid prescription at post-operative discharge. Secondary outcomes included the rates of gabapentinoid (GABA) prescribing post-operatively. Results Of 17,900 patients, the most common procedure was sigmoid colectomy (35%). Most procedures were open (N=10,626, 59.4%). The most common indication was benign disease (N=12,439, 69.5%). Post-operative opioid prescribing decreased from 64.4% in 2012 to 46.7% in 2019. In the adjusted model, the odds of post-operative opioid prescription were 37% lower in 2019 than in 2012 (OR, 0.63; 95% CI, 0.56-0.72; p<0.0001). At 60 days and one year post surgery, opioid prescribing decreased from 11.6% and 5.9% in 2012 to 7.2% and 5.2% in 2019 (p<0.0001).At 60 days, gabapentinoid prescribing increased from 2.3% in 2012 to 4.0% in 2019 (p=0.0016). Conclusions Our data show that opioid prescribing is common after colorectal surgery with an overall post-operative prescription rate of 55.8%. The modification of post-operative pathways to include guidance on opioid prescribing and non-opioid alternatives may curb opioid prescribing, decrease the number of new persistent opioid users, and decrease the number of opioids available for diversion.

Non-opioid versus Opioid Peri-operative Analgesia In Neurosurgery (NOPAIN): Study protocol for a multi-centric randomised controlled trial.

Many patients suffer from post-operative pain after neurosurgery despite using intra-operative opioids. Opioid side effects are problematic in neurosurgical patients. Hence, non-opioid alternatives for the management of nociception and pain are needed. Previous studies comparing opioids with non-opioids in the neurosurgical population were few, from single centres, of small sample sizes and were equivocal in findings, which prevented change in clinical practice. To overcome these limitations, we are conducting a multi-centre trial with objectives to compare intra-operative rescue opioid requirements and post-operative pain scores (primary objectives), adverse events, quality of recovery from anaesthesia, quality of sleep and patient satisfaction during hospital stay, and persistent post-surgical pain and quality of life at 3 and 6 months (secondary objectives) in patients receiving opioid and non-opioid analgesia for brain tumour surgeries. This study protocol describes the methodology of a multi-centre randomised controlled trial. Ethics committee approval has been obtained from all five centres, the trial has been registered with the Clinical Trial Registry- India, and insurance has been obtained for this investigator-initiated funded study. In patients undergoing supra-tentorial brain tumour surgery (population), we will compare fentanyl (intervention) 1 µg/kg/h with dexmedetomidine (comparator) 0.5 µg/kg/h administered during surgery with regards to intra-operative rescue opioid requirement and post-operative pain (primary outcomes). We describe the study protocol of the multi-centre trial (protocol version 2, dated 29/01/2022). The first patient was recruited on 19/10/2022, and we will complete recruitment before March 2024. We expect our study to establish dexmedetomidine as an effective non-opioid analgesic vis-à-vis opioids in the neurosurgical population.

Opioid versus non-opioid postoperative pain management in otolaryngology.

The opioid epidemic in the United States has had devastating consequences, with many opioid-related deaths and a significant economic toll. Opioids have a significant role in postoperative pain management. Here we aim to analyze differences in postoperative opioid and non-opioid pain medications regimens following common otolaryngological surgeries between two large tertiary care medical centers: the Milton S. Hershey Medical Center, USA (HMC) and The Chaim Sheba Medical center, Israel (SMC). A retrospective chart review of patients undergoing common otolaryngological procedures during the years 2017-2019 was conducted at two tertiary care centers, one in the U.S. and the other in Israel. Types and doses of postoperative pain medications ordered and administered during admission were analyzed. Average doses ordered and administered in 24h were calculated. Opioid medications were converted to a standardized unit of morphine milliequivalents (MME). Chi-square test and Wilcoxon rank-sum test were used to compare the groups. The study included 204 patients (103 U.S., 101 Israel). Patient demographics were similar except for a longer length of stay in Israel (p < 0.01). In the U.S., 95% of patients were ordered opioids compared to 70% in Israel (P < 0.01). In the U.S., 68.9% of patients ordered opioids received the medications compared to 29.7% in Israel. The median opioid dose ordered in the U.S. was 45MME/24h compared to 30MME/24h in Israel (P < 0.01), while median dose received in the U.S. was 15MME/24h compared to 3.8MME/24h in Israel (P < 0.01). Opioid prescriptions at discharge were given to 92% of patients in the U.S. compared to 4% of patients in Israel (p < 0.01). A significantly higher number of patients in the U.S. were prescribed acetaminophen and ibuprofen (p < 0.0001). Dipyrone was prescribed to 78% of patients in Israel. HMC demonstrated a significantly more permissive approach to both prescribing and consuming opioid medications for postoperative pain management than SMC for similar, common otolaryngological surgeries. Non-opioid alternatives and examining the cultural and medical practice-based differences contributing to the opioid epidemic should be discussed and reevaluated.

Perioperative Use of Ketamine.

Postoperative pain continues to be one of the most common challenges following surgeries. Multimodal analgesia has been of particular focus as non-opioid alternatives have been encouraged due to concerns of the opioid epidemic. Ketamine has been an especially useful adjunct in multimodal pain regimens within the past few decades. This article highlights the current use and advances surrounding the perioperative use of ketamine. Ketamine has antidepressive effects at subanesthetic doses. Intraoperative ketamine may be beneficial in reducing postoperative depression. Additionally, newer studies are exploring whether ketamine can be useful in reducing postoperative sleep disturbances. Ketamine continues to be a great tool in perioperative pain control, especially during an opioid epidemic. As its use continues to expand and gain more popularity in the perioperative period, more research could shed light on the additional nonanalgesic benefits of ketamine use.

A Systematic Review of Non-Opioid Pain Management in Chiari Malformation (Type 1) Patients: Current Evidence and Novel Therapeutic Opportunities.

Chiari Malformation Type I (CM) includes a range of cranial abnormalities at the junction of the skull with the spine, with common symptoms including pain and headaches. Currently, CM pain is managed medically through anti-inflammatory drugs, muscle relaxants, and opioids, while surgical management includes posterior fossa decompression. Given the adverse effects of opioid use, and an ongoing opioid epidemic, there is a need for safe, non-opioid alternatives for clinical pain management. This systematic review was performed to provide an update on the current literature pertaining to the treatment of CM pain with non-opioid alternatives. A literature search was performed in June 2022 utilizing the PubMed and Google Scholar databases, and articles were identified that included information regarding non-opioid pain management in CM patients. A total of 90 articles were obtained from this search, including 10 relevant, drug-specific studies. Two independent reviewers selected and included all relevant articles based on the chosen search criteria to minimize bias risk. Currently available treatments for neurosurgical pain management include anticonvulsants, corticosteroids, NSAIDs, anti-inflammatory drugs, NMDA receptor antagonists, local anesthetics, nerve blocks, scalp blocks, and neuromuscular blocks. While more information is needed on the use of non-opioid pain management, the present literature provides potential evidence of its efficacy amongst the CM patient population, on account of the success that non-opioid pain management has demonstrated within other neurological pain syndromes. Further research into non-pharmacological pain management would also benefit the CM population and could be generalized to related conditions.

Implementation and Assessment of No Opioid Prescription Strategy at Discharge After Major Urologic Cancer Surgery

Postoperative opioid prescriptions are associated with delayed recovery, perioperative complications, opioid use disorder, and diversion of overprescribed opioids, which places the community at risk of opioid misuse or addiction. To assess a protocol for eliminating postdischarge opioid prescriptions after major urologic cancer surgery. This cohort study of the no opioid prescriptions at discharge after surgery (NOPIOIDS) protocol was conducted between May 2017 and June 2021 at a tertiary referral center. Patients undergoing open or minimally invasive radical cystectomy, radical or partial nephrectomy, and radical prostatectomy were sorted into the control group (usual opioids), the lead-in group (reduced opioids), and the NOPIOIDS group (no opioid prescriptions). The NOPIOIDS group received a preadmission educational handout, postdischarge instructions for using nonopioid analgesics, and no routine opioid prescriptions. The lead-in group received a postdischarge instruction sheet and reduced opioid prescriptions at prescribers' discretion. The control group received opioid prescriptions at prescribers' discretion. Primary outcome measures included rate and dose of opioid prescriptions at discharge and for 30 days postdischarge. Additional outcome measures included patient-reported pain and satisfaction level, unplanned health care utilization, and postoperative complications. Of 647 opioid-naive patients (mean [SD] age, 63.6 [10.0] years; 478 [73.9%] male; 586 [90.6%] White), the rate of opioid prescriptions at discharge for the control, the lead-in, and the NOPIOIDS groups was 80.9% (157 of 194), 57.9% (55 of 95), and 2.2% (8 of 358) (Kruskal-Wallis test of medians: P < .001), and the overall median (IQR) tablets prescribed was 14 (10-20), 4 (0-5.3), and 0 (0-0) per patient in the control, lead-in, and NOPIOIDS groups, respectively (Kruskal-Wallis test of medians: P < .001). In the NOPIOIDS group, median and mean opioid dose was 0 tablets for all procedure types, with the exception of kidney procedures (mean [SD], 0.5 [1.7] tablets). Patient-reported pain surveys were received from 358 patients (72.6%) in the NOPIOIDS group, demonstrating low pain scores (mean [SD], 2.5 [0.86]) and high satisfaction scores (mean [SD], 86.6 [3.8]). There was no increase in postoperative complications in the group with no opioid prescriptions. This perioperative protocol, with emphasis on nonopioid alternatives and patient instructions, may be safe and effective in nearly eliminating the need for opioid prescriptions after major abdominopelvic cancer surgery without adversely affecting pain control, complications, or recovery.

Pramipexole inhibits formalin-induce acute and long-lasting mechanical hypersensitivity via NF-kB pathway in rats.

Pain is one of the most frequent causes for patients to seek medical care. It interferes with daily functioning and affects the quality of life of the patient. There is a clear need to investigate nonopioid or non-nonsteroidal anti-inflammatory drug alternatives for the treatment of pain. In this study, we determined the effect of acute pre- and posttreatment with pramipexole (PPX), a dopamine D2/D3 selective agonist, on formalin 1%-induced acute and long-lasting nociceptive behavior sensitivity in rats. Moreover, we sought to investigate whether the antiallodynic and antihyperalgesic effect induced by PPX was mediated through the nuclear factor-κB(NF-kB) signaling pathway. Moreover, acute systemic pretreatment with PPX (1 and 3 mg/kg, ip) suppressed the formalin-induced nociceptive behavior during both phases of the formalin test and the development of formalin-induced secondary mechanical allodynia and hyperalgesia in both paws. Acute systemic posttreatment with PPX (3 mg/kg, ip) reverted the formalin-induced long-lasting secondary mechanical allodynia and hyperalgesia. Furthermore, PPX inhibits the protein expression of NF-κB-p65 and the levels of tumor necrosis factor-α and interleukin-1β in the spinal cord of animals with secondary mechanical allodynia and hyperalgesia induced by formalin. These data suggest that PPX has a potential role in producing anti-inflammatory activity. Moreover, the antiallodynic and antihyperalgesic effects induced by PPX can be mediated through the NF-kB signaling pathway.

Barriers to Adequate Pain Control and Opioid Use Among Cancer Survivors: Implications for Nursing Practice.

Cancer survivors can experience long-term negative effects from cancer and its treatment. Pain is one of the most common and distressing symptoms that cancer survivors experience. Opioids are often prescribed for pain; however, cancer survivors who have completed active treatment may have unique challenges with regard to pain management. The aim of this study was to explore barriers to pain management and perceptions of opioid use among cancer survivors. This research was an exploratory pilot study using in-depth qualitative interviews with adult cancer survivors who were recruited from community-based survivorship organizations. Data were analyzed using applied thematic analysis techniques. Participants (n = 25) were mostly women (96%), diagnosed with breast cancer (88%) and stages I to III disease (84%), with a mean age of 56.2 years. Three themes on barriers to adequate pain control emerged: (1) taking just enough to take the edge off: self-medicating behaviors and nonadherence to prescribed regimen; (2) lack of insurance coverage and costly alternative pain treatment options; and (3) chronicity of cancer-related pain not adequately addressed and often mismanaged. Discussions with cancer survivors unveiled personal accounts of unmanaged pain resulting from limited pain management/opioid education, fear of opioid addiction, negative perceptions/experiences with opioids, lack of insurance coverage for alternative pain therapies, and regulatory policies limiting access to opioids. There is a clear need for improved access to multimodal pain management options and nonopioid alternatives for cancer survivors. Oncology nurses should endeavor to support policies and procedures aimed at opioid education, training, and legislation.

Alternatives to opioids for managing chronic pain: a patient education programme in the US

As the US is experiencing an opioid epidemic, patients with non-malignant chronic pain must understand the risks of opioids and identify safe and effective treatment alternatives. Multidisciplinary pain management programmes have been shown to be effective in reducing non-malignant chronic pain. A pilot project was conducted in a primary care clinic in the US with the aim of educating patients on the neurophysiology of pain, biopsychosocial responses to pain, risks and benefits of opioids and non-opioid alternatives, and pain management techniques. The programme was shown to be associated with use of reduced amounts of opioids, reduced catastrophising and reduced pain among the 13 participants. After the programme, participants reported having a better understanding of pain and pain management and being willing to work with primary care clinicians to decrease their use of opioids. Programmes that teach patients how to manage chronic pain and reduce opioid use are crucial to addressing the opioid epidemic in the US.

Normalization of the H3K9me2/H3K14ac-ΔFosB pathway in the nucleus accumbens underlying the reversal of morphine-induced behavioural and synaptic plasticity by Compound 511

BackgroundAlthough opioid agonist-based treatments are considered the first-line treatment for opioid use disorders, nonopioid alternatives are urgently needed to combat the inevitable high relapse rates. Compound 511 is a formula derived from ancient traditional Chinese medical literature on opiate rehabilitation. Previously, we observed that Compound 511 could effectively prevent the acquisition of conditioned place preference (CPP) during early morphine exposure. However, its effects on drug-induced reinstatement remain unclear. PurposeThis study aims to estimate the potential of Compound 511 for the therapeutic intervention of opioid relapse in rodent models and explore the potential mechanisms underlying the observed actions. Study design/MethodsThe CPP and locomotor sensitization paradigm were established to evaluate the therapeutic effect of Compound 511 treatment on morphine-induced neuroadaptations, followed by immunofluorescence and western blot (WB) analysis of the synaptic markers PSD-95 and Syn-1. Furthermore, several addiction-associated transcription factors and epigenetic marks were examined by qPCR and WB, respectively. Furthermore, the key active ingredients and targets of Compound 511 were further excavated by network pharmacology approach and experimental validation. ResultsThe results proved that Compound 511 treatment during abstinence blunted both the reinstatement of morphine-evoked CPP and locomotor sensitization, accompanied by the normalization of morphine-induced postsynaptic plasticity in the nucleus accumbens (NAc). Additionally, Compound 511 was shown to exert a selectively repressive influence on morphine-induced hyperacetylation at H3K14 and a reduction in H3K9 dimethylation as well as ΔFosB activation and accumulation in the NAc. Finally, two herbal ingredients of Compound 511 and six putative targets involved in the regulation of histone modification were identified. ConclusionOur findings indicated that Compound 511 could block CPP reinstatement and locomotor sensitization predominantly via the reversal of morphine-induced postsynaptic plasticity through epigenetic mechanisms. Additionally, 1-methoxy-2,3-methylenedioxyxanthone and 1,7-dimethoxyxanthone may serve as key ingredients of Compound 511 by targeting specific epigenetic enzymes. This study provided an efficient nonopioid treatment against opioid addiction.

High quality interventions that reduced the overall number of frequent emergency department visitors for pain-related complaints

Background: Pain is one of the most common complaints that patients present to the emergency department for; emergency medicine providers are tasked with providing appropriate pain relief while simultaneously limiting the risk of personal and societal harm that may result from opioid misuse. The Lakeland Regional Medical Center developed a medical management program that identified frequent emergency department visitors with a chief complaint of pain. Individualized care plans were developed for these patients. Summary: Generation and dissemination of care plans led to a decrease in emergency room visits and hospital admissions. The authors describe their experience with a quality improvement initiative that identifies frequent emergency department visitors with a chief complaint of pain and provides individualized care plans to these patients. The goals of the program are to improve patient's quality and consistency of care, through interventions that eliminate the prescribing of opioids while providing non-opioid alternatives.

Evaluation of the use of individualized patient care plans in frequent emergency department visitors with pain complaints

BackgroundPain is one of the most common complaints that patients present to the emergency department for; emergency medicine providers are tasked with providing appropriate pain relief while simultaneously limiting the risk of personal and societal harm that may result from opioid misuse. The Lakeland Regional Medical Center developed a medical management program that identified frequent emergency department visitors with a chief complaint of pain. Individualized care plans were developed for these patients. A retrospective review was then conducted to assess the efficacy of these care plans in reducing the number of emergency department visits for pain-related complaints by the patients entered into the medical management program.ResultsThere were 294 patients; 65% were male, and the median age was 41 (interquartile range: 33 to 51). A total of 80% percent of the patients were white, and the payors were as follows: 53% were self-pay, 42% were government programs, and 5% had private insurance. The three most common chronic pain complaints were 39% abdominal pain, 24% back/neck pain, and 23% headache/migraine (patients could have more than one area of pain). A total of 60% of the patients had a primary care provider, and another 18% had a pain management provider in addition to primary care.Post plan admissions were significantly reduced to a median of 1 (IQR 0 to 3) with the Wilcoxon signed-rank test’s p-value of less than 0.001.ConclusionThe authors describe their experience with a quality improvement initiative that identifies frequent emergency department visitors with a chief complaint of pain and provides individualized care plans to these patients. The goals of the program are to improve patient’s quality and consistency of care, through interventions that eliminate the prescribing of opioids while providing non-opioid alternatives.

Trends in opioid and non-opioid treatment for chronic non-cancer pain and cancer pain among privately insured adults in the United States, 2012-2019.

Recent clinical guidelines have emphasized non-opioid treatments in lieu of prescription opioids for chronic non-cancer pain, exempting cancer patients from these recommendations. In this study, we determine trends in opioid and non-opioid treatment among privately insured adults with chronic non-cancer pain (CNCP) or cancer. Using administrative claims data from IBM MarketScan Research Databases, we identified privately-insured adults who were continuously enrolled in insurance for at least one calendar year from 2012 to 2019. We identified individuals with CNCP diagnosis, defined as a diagnosis of arthritis, headache, low back pain, and/or neuropathic pain, and a individuals with cancer diagnosis in a calendar year. Outcomes included receipt of any opioid, non-opioid medication, or non-pharmacologic CNCP therapy and opioid prescribing volume, MME-per-day, and days’ supply. Estimates were regression-adjusted for age, sex, and region. Between 2012 and 2019, the proportion of patients who received any opioid decreased across both groups (CNCP: 49.7 to 30.5%, p<0.01; cancer: 86.0 to 78.7%, p<0.01). Non-opioid pain medication receipt remained steady for individuals with CNCP (66.7 to 66.4%, p<0.01) and increased for individuals with cancer (74.4 to 78.8%, p<0.01), while non-pharmacologic therapy use rose among individuals with CNCP (62.4 to 66.1%, p<0.01). Among those prescribed opioids, there was a decrease in the receipt of at least one prescription with >90 MME/day (CNCP: 13.9% in 2012 to 4.9% in 2019, p<0.01; Cancer: 26.2% to 7.6%, p<0.01); >7 days of supply (CNCP: 56.3% to 30.7%, p <0.01; Cancer: 47.5% to 22.7%, p<0.01), the mean number of opioid prescriptions (CNCP: 5.2 to 3.9, p<0.01; Cancer: 4.0 to 2.7, p<0.01) and mean MME/day (CNCP: 49.9 to 38.0, p<0.01; Cancer: 62.4 to 44.7, p<0.01). Overall, from 2012–2019, opioid prescribing declined for CNCP and cancer, with larger reductions for patients with CNCP. For both groups, reductions in prescribed opioids outpaced increases in non-opioid alternatives.

Policy changes are needed to further reduce perioperative opioid use.

Opioid prescriptions in the perioperative setting are a known risk factor for long-term opioid use and misuse. Recent initiatives in the United States to address the issue have focused on judicious prescribing patterns and quality measurement to minimize opioid dispensing. However, policy gaps have limited the effectiveness of current interventions. Expanded policy considerations are warranted, including patient-focused opioid risk screening and preferences for nonopioid pain management, with broader plan coverage for multimodal opioid-sparing pain management (OSPM). Additionally, formalized clinician education regarding specific nonopioid pain management alternatives may increase utilization, as will incorporation into perioperative OSPM clinical pathways. It is also important for patients to have access to the option for multimodal OSPM in the perioperative setting without financial disincentives, which may arise in surgery-specific bundled payment models. Finally, expansion of research activities regarding clinical and cost-efficacy outcomes may help to advance use of these options, laying the groundwork for development of a broader set of quality measures reflecting utilization and outcomes of multimodal OSPM in the perioperative setting.