In September 2023, the Japan Society of Pain Clinicians (JSPC) issued this consensus statement on chronic pain treatment in cancer survivors. With recent advances in the early diagnosis and treatment of cancer, its prognosis has improved, so prolonged pain in cancer survivors is considered to represent chronic pain and should be addressed. In this statement, we emphasize that not all cancer survivor pain is cancer pain. Pain that is not cancer pain should be managed with analgesics other than opioids and nerve blocks, and pain that persists despite this approach should be treated as non-cancer chronic pain so as to prevent opioid overuse. In addition, cancer survivors at any stage of disease have a potentially life-threatening condition and constantly carry the fear of cancer recurrence. Therefore, even non-cancer pain should not be treated in the same way as general chronic pain, but should be managed with consideration of emotional distress. In the future, we plan to create educational tools for healthcare professionals and to conduct online seminars, both with the goal of providing cancer survivors with appropriate assessment and treatment of chronic pain.

Non-invasive ventilation (NIV) treatment is effective and potentially lifesaving in patients with respiratory acidosis and acute exacerbation of chronic obstructive pulmonary disease (AECOPD). However, feelings of anxiety during NIV treatment are common, potentially leading to premature patient-initiated termination of treatment.The primary aim of this study is to examine whether psychiatric disorders are a risk factor of premature patient-initiated termination of NIV treatment. The secondary aim is to examine the patterns in use of sedative drugs during NIV treatment.

This retrospective cohort study includes 195 patients with AECOPD receiving NIV between 1 January and 31 December 2018, in hospitals in the Northern Region of Denmark. Information was obtained from medical records. Psychiatric disorders were defined by the use of psycholeptics at home, right before admission.Primary outcome was premature patient-initiated termination of NIV treatment. Secondary outcome was the use of any sedative drug during NIV treatment.

Patient-initiated premature termination was seen in 41 (21%) of cases. This group had a significantly higher mortality (43.9% vs. 19.5% in the total population, p < 0.01). A higher risk of patient-initiated premature termination was seen in patients with psychiatric disorders (Odds ratio 2.18, p < 0.05) and older age (Odds ratio 1.06, p < 0.05). No significant difference in the use of sedative drugs was seen (34.1% vs. 38.1% in the total population, p 0.12).

A significantly higher risk of premature patient-initiated termination of NIV treatment was seen in patients with psychiatric disorders and older patients, but not in patients with active smoking or excessive use of alcohol. No significant difference in the pattern of sedative drug use during treatment was seen.

Prescription opioids for noncancer pain in the United Kingdom have increased over the past 2 decades, alongside associated harms. Policies addressing opioid prescribing must be tailored to individual patient needs with specific disease systems. The aim of this study was to evaluate clinical conditions associated with new opioid initiation in noncancer pain using nationally representative UK data. Primary care electronic health records from January 1, 2006, to September 31, 2021, were used from the Clinical Research Practice Datalink to identify incident opioid prescriptions. Patient histories were reviewed using code lists for opioid-related conditions with a 5-year look-back for chronic conditions and a 1-year look-back for surgical indications before opioid initiation. In total, 3,030,077 new opioid use episodes in 2,027,402 patients were identified, with 61% being women, 77% aged 45 years and older, and 48% from the highest deprivation quintile. Ten systems associated with opioid initiation were identified, which were not mutually exclusive, as patients could have opioids prescribed for multiple indications. The most common were musculoskeletal (80.8%), respiratory (57.6%), infections (30.4%), trauma/injury (20.4%), neurology (19.9%), and postsurgical indications (5.5%). Osteoarthritis (60.7%) and low back pain (41.0%) were the most frequent musculoskeletal conditions. Orthopedic surgeries accounted for 41.2% of all postsurgical indications. This is the first study in the United Kingdom evaluating large-scale national data to assess indications associated with opioid initiation. Nearly 3 quarters of new opioid prescriptions for noncancer pain were in patients with musculoskeletal conditions, often for conditions with limited evidence for opioid efficacy. These findings could inform targeted interventions and future policies to support nonpharmacological interventions in the most common conditions where opioid harms outweigh benefits.

Tramadol is a synthetic opioid with a central effect from the aminocyclohexanol group, which has two main mechanisms of action, including as a weak agonist of opioid receptors and as a norepinephrine and serotonin reuptake inhibitor. The present study presents a review based on clinical trials designed in 2023. In July 2023, six international databases, including Medline/PubMed, ProQuest, Scopus, EMBASE, Google Scholar, and ISI (Web of Science), were searched and 58 articles were included in the study. The results of most studies showed that tramadol can be used as an analgesic drug, although in some studies it was shown that tramadol is not therapeutically superior in reducing pain compared to other treatments. Also, complications related to this treatment have been reported in some studies. Physicians should consider these factors to prevent drug toxicity, poor pain relief, use disorder in patients, and unpredictable complications. It should be noted that there is not enough evidence to support the long-term effectiveness of tramadol, but this argument also extends to nonopioid and other types of opioid analgesics, and the lack of long-term trials is due to regulatory and ethical issues. Although opioids can cause addiction when used for a long time, tramadol has a reasonable safety profile. According to the patient's condition and the clinical judgment of the medical professional, tramadol can be prescribed for patients, but the consequences of its use must be considered and a personalized treatment algorithm should be selected if the benefits outweigh the risks of the drug.

» Although spine surgery is effective in reducing pain and improving functional status, it is associated with unacceptably high rates of complications, thus necessitating comprehensive preoperative patient optimization.» Numerous risk factors that can impact long-term surgical outcomes have been identified, including malnutrition, cardiovascular disease, osteoporosis, substance use, and more.» Preoperative screening and personalized, evidence-based interventions to manage medical comorbidities and optimize medications can enhance clinical outcomes and improve patient satisfaction following spine surgery.» Multidisciplinary team-based approaches, such as enhanced recovery after surgery protocols and multidisciplinary conferences, can further facilitate coordinated care from across specialties and reduce overall hospital length of stay.

The complexities surrounding the use of medications, substance abuse, and the recreational use of plants are multifaceted and warrant a comprehensive examination. This review highlights the complexities surrounding the consumption of chemical substances in excess or for non-medical purposes, obtained through legal prescriptions, over-the-counter purchases, or illicit means, with an emphasis on the predictive role of stressors and individual-level variables in the development of substance use disorders, as well as the influence of the regulatory environment on patterns of consumption. Additionally, the alarming escalation in the mortality rate associated with illicit drug and opioid overdoses is also underscored. The recreational use of prescription medications can lead to significant health risks, particularly when combined with other substances; therefore, the need for interventions and preventive measures to address substance abuse among various populations is imperative. Furthermore, novel insights on substance abuse addiction, exploring the neurobiological mechanisms underlying addiction, and discussing treatment approaches and interventions are elucidated. Advancements in technology for detecting substance abuse are also highlighted, displaying innovative tools for more effective identification and monitoring. In conclusion, the complexities of medications, substance abuse, and the recreational use of plants reveal a landscape marked by overlapping motivations and health implications. The distinction between medical and recreational use is critical for understanding user behavior and addressing public health concerns.

Guidance recommends that prescribed opioids for acute pain should not be continued beyond the expected period of healing and may lead to long-term use if a large supply is provided or repeat prescriptions are requested. This project investigated how opioids are used by opioid-naïve trauma patients in the first 6 months following discharge from hospital. The findings indicate that patients are frequently discharged from hospital with an opioid prescription and for some this will continue beyond the recommended maximum duration of 3 months and will include dose escalation. Clinicians should be aware of the potential risks associated with prolonged opioid use, including the increased risk of accidental overdose and potential death, and be able to identify which patients are at most risk. Screening for indicators for long-term use may prove more useful than formal risk stratification tools in an acute pain population.

The varicella-zoster virus (VZV) can cause herpes zoster (HZ), which may progress to postherpetic neuralgia (PHN), leading to severe inflammatory responses and pain.

This study investigates the relationship between pain duration characteristics and pain intensity in patients with herpes zoster-related pain, hypothesizing that persistent pain correlates with higher pain intensity compared to intermittent pain.

A retrospective study was conducted at the Second Affiliated Hospital of Guangxi Medical University, China. Data from patients treated for herpes zoster-related pain between January 2019 and February 2024 were analyzed. Pain intensity was measured using the Numerical Rating Scale (NRS-11), and pain duration was categorized as intermittent or persistent. Multivariate regression models were used to assess the association between pain duration and intensity, adjusting for potential confounders.

A total of 840 patients were included. Persistent pain was significantly associated with higher NRS-11 scores compared to intermittent pain (β = 0.71, 95% CI 0.50-0.91, p < 0.001). Subgroup analyses showed that persistent pain was associated with higher pain intensity in both acute HZ and PHN patients (HZ: β = 0.71, 95% CI 0.45-0.96, p < 0.001; PHN: β = 0.76, 95% CI 0.40-1.13, p < 0.001). Inflammatory markers, such as C-reactive protein (CRP) and white blood cell count, were positively correlated with pain intensity.

Pain duration significantly impacts pain intensity in HZ patients. Considering pain duration is crucial for effective pain management. Further research should explore the mechanisms underlying persistent pain to develop better treatment strategies.

Patients with chronic non-cancer pain are referred to pain centres to improve their pain treatment. The discontinuation of pain medications in case of poor efficacy can be difficult to accept for patients, particularly opioid analgesics. Previous research has described that from the patients' perspective, the psychological relief of a negative effect of chronic pain and withdrawal symptoms of prescription opioids represent drivers of persistent use and first stage of opioid use disorder, despite insufficient pain relief. There is no validated tool to investigate this psychological dependence. This study aimed to assess discordance between patients and pain specialists in their perception of dependence on pain medication and investigate associations with characteristics of patients, type of pain and iatrogenic pharmacodependence.

Self-administered questionnaires (patients and physicians) were administered in six pain centres in France. A question on perceived dependence on pain medications was addressed to the patient and the physician in a matched pair. Discordance between them was evaluated by the Cohen kappa coefficient. Demographics, pain, anxiety and depression, pain medication withdrawal symptoms, diverted use, and craving represented variables studied in a multivariate model as potentially associated with patient-physician discordance.

According to the 212 pairs of completed questionnaires, a perceived dependence was reported by the majority of patients (65.6%) and physicians (68.4%). However, the concordance was fair (kappa=0.38; CI [95%]: 0.25-0.51). Almost all patients (89.3%) were treated with an opioid analgesic. A higher likelihood of discordance was observed when patients suffered from nociplastic pain (odds ratio [OR]: 2.72, 95% [CI]: 1.29-5.84).

Medical shared-decision for changing pain treatment could be improved by taking into account the perception of patient dependence on medications for pain relief and or psychoactive effects, particularly in nociplastic pain for which the treatment is challenging.

Policy Points Opioid treatment agreements (OTAs) are controversial because of the lack of evidence that their use reduces opioid-related harms and the potential risks they pose of stigmatizing patients and undermining the clinician-patient relationship. Even so, their use is now required in most jurisdictions, and their use is influencing the outcomes of civil and criminal lawsuits. More research is needed to evaluate how OTAs are implemented given existing requirements. If additional research does not resolve the current level of uncertainty regarding OTA benefits, then policymakers in jurisdictions where they are required should consider eliminating OTA mandates or providing flexibility in the legal requirements to make room for clinicians and health care institutions to implement best practices.

Opioid treatment agreements (OTAs) are documents that clinicians present to patients when prescribing opioids that describe the risks of opioids and specify requirements that patients must meet to receive their medication. Notwithstanding a lack of evidence that OTAs effectively mitigate opioids' risks, professional organizations recommend that they be implemented, and jurisdictions increasingly require them. We sought to identify the jurisdictions that require OTAs, how OTAs might affect the outcomes of lawsuits that arise when things go wrong, and instances in which the law permits flexibility for clinicians and health care institutions to adopt best practices.

We surveyed the laws and regulations of all 50 states and the District of Columbia to identify which jurisdictions require the use of OTAs, the circumstances in which OTA use is mandatory, and the terms OTAs must include (if any). We also surveyed criminal and civil judicial decisions in which OTAs were discussed as evidence on which a court relied to make its decision to determine how OTA use influences litigation outcomes.

Results show that a slight majority (27) of jurisdictions now require OTAs. With one exception, the jurisdictions' requirements for OTA use are triggered at least in part by long-term prescribing. There is otherwise substantial variation and flexibility within OTA requirements. Results also show that even in jurisdictions where OTA use is not required by statute or regulation, OTA use can inform courts' reasoning in lawsuits involving patients or clinicians. Sometimes, but not always, OTA use legally protects clinicians from liability.

Our results show that OTA use is entwined with legal obligations in various ways. Clinicians and health care institutions should identify ways for OTAs to enhance clinician-patient relationships and patient care within the bounds of relevant legal requirements and risks.

Pain is a common complaint, and the consumption of analgesics is prevalent. Community pharmacists, as primary contact points for patients, can play a crucial role in guiding patients toward rational pharmacotherapy or alternative pain management strategies. However, there are no specific educational curricula or standard guidelines to support this role, and the perception of this potential role is not well known. We conducted an anonymous online questionnaire among community pharmacists in Norway to assess their knowledge, perspectives, and willingness to engage in pain care. The survey also explored potential facilitators and barriers, and the use of any current guidelines. Seventy-one community pharmacists participated from various regions in Norway. Findings revealed that community pharmacists felt knowledgeable and willing to engage in pain management but anticipated barriers such as time constraints and a lack of standard guidelines. Participants also highlighted the need for better collaboration with other healthcare professionals and continuous professional development to enhance their role. To optimize the role of community pharmacists in pain management, therefore, integrating them into multidisciplinary healthcare teams, minimizing barriers, and providing continuous education and standard guidelines seem essential. This approach can empower community pharmacists and improve pain management outcomes.

Postoperative pain (POP) is a challenging clinical phenomenon that affects the majority of surgical patients and demands effective management to mitigate adverse outcomes such as persistent pain. The primary goal of POP management is to alleviate suffering and facilitate a seamless return to normal function for the patient. Despite compelling evidence of its drawbacks, opioid analgesia remains the basis of POP treatment. Novel therapeutic approaches rely on multimodal analgesia, integrating different pharmacological strategies to optimize efficacy while minimizing adverse effects. The recognition of the imperative role of the endocannabinoid system in pain regulation has prompted the investigation of cannabinoid compounds as a new therapeutic avenue. Cannabinoids may serve as adjuvants, enhancing the analgesic effects of other drugs and potentially replacing or at least reducing the dependence on other long-term analgesics in pain management. This narrative review succinctly summarizes pertinent information on the molecular mechanisms, clinical therapeutic benefits, and considerations associated with the plausible use of various cannabinoid compounds in treating POP. According to the available evidence, cannabinoid compounds modulate specific molecular mechanisms intimately involved in POP. However, only two of the eleven clinical trials that evaluated the efficacy of different cannabinoid interventions showed positive results.

To determine whether chronic pain persists after complete spinal cord injury (SCI).

Prospective observational study regarding the outcome of pre-existent chronic pain of inpatients admitted with new clinically diagnosed complete cervical SCI. For patients who acknowledged chronic pain of ≥3 years duration before the SCI, further questions explored whether they still experienced that pain, whether they were experiencing current posttraumatic pain, and whether they had any past exposure to opioids. The included patients were identified during the initial consultation in the trauma center for treatment of the SCI.

Level I trauma center.

From a total of 49 participants with acute cervical SCI with clinically diagnosed complete motor and sensory tetraplegia admitted between 2018 and 2020, 7 were selected on the basis of a history of chronic pain.

Collected complete history and performed physical examination with serial follow-ups during the acute hospital stay until death or discharge.

The primary outcome was a finding of chronic pain experienced before new clinical diagnosis of complete SCI, compared with whether or not that pain continued after the SCI injury. The secondary outcome was the relation of persistent pain with opioid use; it was formulated after data collection.

Among 49 patients with clinically diagnosed complete cervical SCIs, 7 had experienced prior chronic pain. Four participants experienced a continuation of the prior pain after their complete tetraplegia (4/7), whereas 3 participants did not (3/7). All the participants with continued pain had been previously treated with opioids, whereas those whose pain ceased had not received chronic opioid therapy.

There may be a unique form of chronic pain that is based in the brain, irrespective of peripheral pain or spinal mechanisms. Otherwise healthy people with longstanding antecedent chronic pain whose pain persists after acute clinically complete SCI with tetraplegia may provide a new model for evaluation of brain-based pain. Opioids may be requisite for this type of pain.

Short-acting opioids have been utilized for pain management with little known about their use in patients on Workers' Compensation (WC) insurance. Our goal was to investigate this association in the ambulatory care setting.

Using the National Ambulatory Medical Care Survey, visits from patients aged 18-64 during the years 2010 until 2018 were evaluated (excluding 2017 due to data availability). Demographic and co-morbidity data from each visit was obtained along with the visit year. The first short-acting opioid medication prescribed in the database was considered. Survey-weighted frequencies were evaluated. Logistic regression estimated the crude and adjusted odds ratios (OR) with 95% confidence intervals for the use of short-acting opioid prescription.

There were 155,947 included visits with 62.5% for female patients. Most patients were White with 11.7% identifying as Black, and 6% identifying as another race. Over 13% of the sample was of Hispanic descent. WC was the identified insurance type in 1.6% of the sample population. Of these patients, 25.6% were prescribed a short-acting opioid, compared with 10.1% of those with another identified insurance. On multivariable regression, Black patients had increased odds of being prescribed a short-acting opioid compared to white patients (OR: 1.22, 95% CI: 1.11-1.34). Those on WC had 1.7-fold higher odds of being prescribed short-acting opioids (95% CI: 1.46-2.06).

Certain patient characteristics, including having WC insurance, increased the odds of a short-acting opioid prescription. Further work is needed to identify prescribing patterns in specific high-risk occupational groups, as well as to elicit potential associated health outcomes.

To examine the association between prescription opioid use trajectories and risk of opioid use disorder (OUD) or overdose among nonmetastatic breast cancer survivors by treatment type.

This retrospective cohort study included female nonmetastatic breast cancer survivors with at least 1 opioid prescription fill in 2010-2019 Surveillance, Epidemiology and End Results linked Medicare data. Opioid mean daily morphine milligram equivalents (MME) calculated within 1.5 years after initiating active breast cancer therapy. Group-based trajectory models identified distinct opioid use trajectory patterns. Risk of time to first OUD/overdose event within 1 year after the trajectory period was calculated for distinct trajectory groups using Cox proportional hazards models. Analyses were stratified by treatment type.

Four opioid use trajectories were identified for each treatment group. For 38,030 survivors with systemic endocrine therapy, 3 trajectories were associated with increased OUD/overdose risk compared with early discontinuation: minimal dose (< 5 MME; adjusted hazard ratio [aHR] = 1.73 [95% CI  1.43-2.09]), very low dose (5-25 MME; 2.67 [2.05-3.48]), and moderate dose (51-90 MME; 6.20 [4.69-8.19]). For 9477 survivors with adjuvant chemotherapy, low-dose opioid use was associated with higher OUD/overdose risk (aHR = 7.33 [95% CI 2.52-21.31]) compared with early discontinuation. For 3513 survivors with neoadjuvant chemotherapy, the differences in OUD/OD risks across the 4 trajectories were not significant.

Among Medicare nonmetastatic breast cancer survivors receiving systemic endocrine therapy or adjuvant chemotherapy, compared with early discontinuation, low-dose or moderate-dose opioid use were associated with six- to sevenfold higher OUD/overdose risk. Breast cancer survivors at high-risk of OUD/overdose may benefit from targeted interventions (e.g., pain clinic referral).

Despite the existence of internationally consistent guidelines for the management of pain, efficient regional anesthesia techniques, safe pain medications, and organizational structures, e.g., acute pain services, various studies have shown that pain is still common among both surgical and non-surgical in-patients.

The primary objective of this study was to evaluate, on a multi-center basis, the point pain prevalence of surgical and non-surgical in-patients. We further analyzed pain intensities, in-hospital pain triggers, pain-related impairments, pain assessments, patient information about pain, and patient satisfaction with pain therapy. This benchmark information should lead to better implementation of pain management strategies and thus improve health care quality.

We surveyed all adult in-patients in three general hospitals in Austria (general hospital Klagenfurt am Wörthersee, general hospital Villach, general hospital Wolfsberg) on the index day with two standardized questionnaires for both surgical and non-surgical patients.

Overall, a pain prevalence of 40.0%, with no statistically significant difference between surgical and non-surgical patients, was shown. Higher pain prevalence in female patients, high pain prevalence in the age group 18-30 years, and highest pain prevalence in the age group over 90 years old was found. Overall pain intensity was relatively low, but unacceptable maximum pain within the preceding 24 h was shown. Different in-hospital pain triggers like patient's care and mobilization were found. Our survey has shown that pain has an impact on personal hygiene, mobilization, mood, sleep, and appetite. However, patients were very satisfied with their pain therapy.

Medical staff and nurses have to be sensitized to the urgent need to improve pain management strategies.

Background: Opioid misuse and substance use disorders (SUDs) including opioid use disorder (OUD) are common and negatively impact quality of life. Hospice clinicians' experiences with these conditions have not been well described. Objectives: We sought to explore hospice clinicians' knowledge, practices, and comfort caring for patients with opioid misuse (e.g., a pattern of unsanctioned opioid use escalation, or concurrent illicit substance use) and SUDs. Design: We recruited hospice clinicians in the United States via national hospice and palliative care organizations to complete an online survey designed by the study authors and pilot tested with an interdisciplinary group of current/former hospice clinicians. Results: One hundred seventy-five clinicians (40% nurses, 40% physicians, 16% nurse practitioners) responded to the survey; most had cared for two or more hospice patients with opioid misuse or SUD in the past month. The majority felt confident identifying opioid misuse (94%) and taking SUD histories (79%). Most (62%) felt it is their role to treat hospice patients for SUD, though 56% lacked comfort in using buprenorphine for OUD treatment. While the majority felt it is their role to treat pain in hospice patients with SUDs (94%) and that hospice can help patients with SUDs (94%), many were not comfortable managing pain in patients taking buprenorphine (45%) or naltrexone (49%) for SUDs. Most felt comfortable managing pain in patients taking methadone for SUD (73%). Conclusions: Opioid misuse and SUD are common in hospice. Though clinicians are comfortable taking relevant histories, they feel less comfortable managing patients' opioid misuse or SUD, or these patients' pain.

In response to the opioid epidemic, the Centers for Disease Control and Prevention released best practice recommendations for prescribing, yet adoption of these guidelines has been fragmented and frequently met with uncertainty by both patients and providers. This study aims to describe the development and implementation of a comprehensive approach to improving opioid stewardship in a large network of primary care providers. The authors developed a 3-tier approach to opioid management: (1) establishment and implementation of best practices for prescribing opioids, (2) development of a weaning process to decrease opioid doses when the risk outweighs benefits, and (3) support for patients when opioid use disorders were identified. Across 44 primary care practices caring for >223,000 patients, the total number of patients prescribed a chronic opioid decreased from 4848 patients in 2018 to 3106 patients in 2021, a decrease of 36% (P < 0.001). The percent of patients with a controlled substance agreement increased from 13% to 83% (P < 0.001) and the percent of patients completing an annual urine drug screen increased from 17% to 53% (P < 0.001). The number of patients coprescribed benzodiazepines decreased from 1261 patients at baseline to 834 at completion. A total of 6.5% of patients were referred for additional support from a certified alcohol and substance abuse counselor embedded within the program. Overall, the comprehensive opioid management program provided the necessary structure to support opioid prescribing and resulted in improved adherence to best practices, facilitated weaning of opioids when medically appropriate, and enhanced support for patients with opioid use disorders.

Urine drug screen (UDS) is a useful test conducted in patients receiving opioids for chronic pain to aid in validating patient adherence to opioid treatment and to detect any nonmedical opioid use (NMOU). One controversial topic regarding its use in palliative care is whether to conduct the test universally and randomly in all patients who are receiving opioids for chronic pain irrespective of their level of risk for NMOU, or to conduct the test selectively in only those with a high risk for engaging in NMOU behaviors. In this "Controversies in Palliative Care" article, 3 expert clinicians independently answer this question. Specifically, each expert provides a synopsis of the key studies that inform their thought processes, share practical advice on their clinical approach, and highlight the opportunities for future research. They all agreed that UDS has some utility in routine palliative care practice but acknowledged the insufficient existing evidence supporting its efficacy. They also underscored the need to improve clinician proficiency in UDS interpretation to enhance its utility. Two experts endorsed random UDS in all patients receiving opioids regardless of their risk profile while the other expert recommended targeted UDS until there is more clinical evidence to support universal, random testing. Use of more methodologically robust study designs in UDS research, examination of the cost-effectiveness of UDS tests, development of innovative programs to manage NMOU behaviors, and investigation of the impact of improved clinician proficiency in UDS interpretation on clinical outcomes, were important areas of future research that the experts identified.

Chronic opioid use disturbs circadian rhythm and sleep, encouraging opioid use and relapse. The orexin (OX) system is recruited by opioids and regulates physiological processes including sleep. Dual OX receptor antagonists (DORAs), developed for insomnia treatment, may relieve withdrawal-associated sleep disturbances. This study investigated whether DORA-12, a recently developed DORA, reduces physiological activity disturbances during oxycodone abstinence and consequently prevents oxycodone-seeking behavior. Male and female Wistar rats were trained to intravenously self-administer oxycodone (0.15 mg/kg, 21 sessions; 8 h/session) in the presence of a contextual/discriminative stimulus (SD). The rats were subsequently housed individually (22 h/day) to monitor activity, food and water intake. They received DORA-12 (0-30 mg/kg, p.o.) after undergoing daily 1-h extinction training (14 days). After extinction, the rats were tested for oxycodone-seeking behavior elicited by the SD. Hypothalamus sections were processed to assess oxycodone- or DORA-12-associated changes to the OX cell number. In males, oxycodone-associated increases in activity during the light-phase, reinstatement, and decreases in the number of OX cells observed in the vehicle-treated group were not observed with DORA-12-treatment. Oxycodone-associated increases in light-phase food and water intake were not observed by day 14 of 3 mg/kg DORA-12-treatment and dark-phase water intake was increased across treatment days. In females, OX cell number was unaffected by oxycodone or DORA-12. Three and 30 mg/kg DORA-12 increased females' day 7 dark-phase activity and decreased reinstatement. Thirty mg/kg DORA-12 reduced oxycodone-associated increases in light-phase food and water intake. The results suggest that DORA-12 improves oxycodone-induced disruptions to physiological activities and reduces relapse.

Opioids are used for the treatment of refractory pain, but their inappropriate use has detrimental consequences for health. Understanding the current experiences and perceptions of patients in a spontaneous and colloquial environment regarding the key drugs involved in the opioid crisis is of utmost significance.

The study aims to analyze Twitter content related to opioids, with objectives including characterizing users participating in these conversations, identifying prevalent topics and gauging public perception, assessing opinions on drug efficacy and tolerability, and detecting discussions related to drug dispensing, prescription, or acquisition.

In this cross-sectional study, we gathered public tweets concerning major opioids posted in English or Spanish between January 1, 2019, and December 31, 2020. A total of 256,218 tweets were collected. Approximately 27% (69,222/256,218) were excluded. Subsequently, 7000 tweets were subjected to manual analysis based on a codebook developed by the researchers. The remaining databases underwent analysis using machine learning classifiers. In the codebook, the type of user was the initial classification domain. We differentiated between patients, family members and friends, health care professionals, and institutions. Next, a distinction was made between medical and nonmedical content. If it was medical in nature, we classified it according to whether it referred to the drug's efficacy or adverse effects. In nonmedical content tweets, we analyzed whether the content referred to management issues (eg, pharmacy dispensation, medical appointment prescriptions, commercial advertisements, or legal aspects) or the trivialization of the drug.

Among the entire array of scrutinized pharmaceuticals, fentanyl emerged as the predominant subject, featuring in 27% (39,997/148,335 posts) of the tweets. Concerning user categorization, roughly 70% (101,259/148,335) were classified as patients. Nevertheless, tweets posted by health care professionals obtained the highest number of retweets (37/16,956, 0.2% of their posts received over 100 retweets). We found statistically significant differences in the distribution concerning efficacy and side effects among distinct drug categories (P<.001). Nearly 60% (84,401/148,335) of the posts were devoted to nonmedical subjects. Within this category, legal facets and recreational use surfaced as the most prevalent themes, while in the medical discourse, efficacy constituted the most frequent topic, with over 90% (45,621/48,777) of instances characterizing it as poor or null. The opioid with the greatest proportion of tweets concerning legal considerations was fentanyl. Furthermore, fentanyl was the drug most frequently offered for sale on Twitter, while methadone generated the most tweets about pharmacy delivery.

The opioid crisis is present on social media, where tweets discuss legal and recreational use. Opioid users are the most active participants, prioritizing medication efficacy over side effects. Surprisingly, health care professionals generate the most engagement, indicating their positive reception. Authorities must monitor web-based opioid discussions to detect illicit acquisitions and recreational use.

This is a retrospective, observational study.

Spinal cord stimulation (SCS) has found its application in chronic pain treatment, with failed back surgery syndrome (FBSS) as one of the most important indications. However, to date, little is known about the long-term effectiveness of the treatment. The aim of this study is to analyze retrospectively the long-term outcomes of SCS treatment in a single multidisciplinary pain center on predominant radicular pain, using devices of a single manufacturer.

Patient data on overall patient satisfaction, pain intensity, and adverse events were retrospectively collected in our clinical practice between January 1998 and January 2018, for 191 patients who received a permanent SCS implant. Secondary health measures included the influence of opioid and nicotine use on pain reduction after therapy.

The trial-to-implant ratio was 93.6%. At a mean follow-up of 10.6 years, 78.5% of the patients were satisfied with the treatment outcome, with a significant pain reduction of an average three points on a Numeric Rating Scale. Opioid and nicotine usage did not have a significant link with the pain reduction one year after the treatment. Furthermore, devices had an average battery lifespan of 8.4 years. A total of 248 revisions were recorded. A total of 24 patients (11.7%) acquired an infection; 7 of 204 patients had an infection during the trial period, 2 of 191 patients had an infection in the first postoperative year, and 15 of 191 patients had an infection after the first year. The average time to infection, if not in the first year, was 10.1 years.

A successful long-term outcome regarding pain relief in patients with predominant radicular pain due to FBSS is established with SCS therapy.

To determine risk factors for nonelective emergency department visits (NEDVs) and whether primary care visits incorporating risk mitigation tools prevented NEDVs among patients using long-term opioid therapy (LOT).

We retrospectively searched the electronic health records at Mayo Clinic primary care outpatient practices in Arizona and Florida in all of 2018 and 2019 for the records of individual adult patients using LOT. Patient and clinician demographic characteristics and patient risk factors were compared between patients with and without risk mitigation visits. Univariate and multivariable logistic regression was used to determine risk factors for NEDVs.

Among 457 patients using LOT identified during the study period, most were women (n=266, 58.2%), and the median age was 69 years. Long-term opioid therapy risk mitigation visits were performed equally by family medicine and internal medicine clinicians and by a significantly higher proportion of Florida clinicians than Arizona clinicians (87.0% vs 70.5%; P<.001). Older age, falls, and mental health care utilization all increased the risk of NEDVs. Risk mitigation visits were protective against NEDVs (odds ratio, 0.56; 95% CI, 0.35-0.89; P=.01) after adjustment for older age, falls, and mental health care utilization.

Risk mitigation visits are effective in preventing NEDVs, and all patients using LOT should have such visits when possible.

Abdominal pain is one of the most common and impactful symptoms associated with inflammatory bowel disease (IBD), including both Crohn's disease and ulcerative colitis. A great deal of research has been undertaken over the past several years to improve our understanding and to optimize management of this issue. Unfortunately, there is still significant confusion about the underlying pathophysiology of abdominal pain in these conditions and the evidence underlying treatment options in this context. There is also a relative paucity of comprehensive reviews on this topic, including those that simultaneously evaluate pharmacological and nonpharmacological therapeutic options. In this review, our multidisciplinary team examines evidence for various currently available medical, surgical, and other analgesic options to manage abdominal pain in IBD.

People with mental health disorders (MHD) like depression and anxiety are more likely to experience substance use disorders (SUDs) than those without MHD. This study assesses opioid prescription patterns for acute or chronic pain management in patients receiving medication for depression and/or anxiety.

Cross-sectional data trend analysis of 24.5 million adult medical claims was conducted using medical and pharmacy data (2012-2019) for adults aged 21-64 from the IBM Watson MarketScan Medicaid Multi-State Database. Information on sex, age, race, provider type, acute or chronic pain, and prescriptions for opioids and antidepressant and/or antianxiety medication from outpatient encounters were analyzed. For those receiving opioid prescriptions within 14 days of a pain diagnosis, ICD-10-CM codes were used to categorize diagnoses as chronic pain (back pain, neck pain, joint pain, and headache); or acute pain (dental-, ENT-, and orthopedic-related pain). Nearly 8 million adults had at least one prescription for antidepressant or antianxiety medications (MHD), with 2.5 million of those (32%) also diagnosed with an acute or chronic pain condition (pain + MHD). Among the pain + MHD group, 34% (0.85 million) received an opioid prescription within 14 days of diagnosis. Individuals with chronic pain diagnoses received a higher proportion of opioid prescriptions than those with acute pain. Among individuals with pain + MHD, the majority were aged 50-64 (35%), female (72%), and non-Hispanic white (65.1%). Nearly half (48.2%) of the opioid prescriptions given to adults with an MHD were provided by physicians. Compared to other physician types, Health Care Providers (HCPs) in emergency departments were 50% more likely to prescribe an opioid for dental pain to those with an MHD, whereas dentists were only half as likely to prescribe an opioid for dental pain management. Although overall opioid prescriptions for pain management declined from 2012 to 2019, adults with an MHD received opioids for pain management at nearly twice the level as adults without an MHD.

Although HCPs have reduced opioids for acute or chronic pain to patients at high-risk for SUD, for example, those with MHD, the use of opioids for pain management has remained at consistently higher levels for this SUD high-risk group, suggesting the need to revisit pain management guidelines for those receiving antidepressant or antianxiety drugs.

The optimal use of opioids after knee replacement (KR) remains to be determined, given the growing evidence that opioids are no more effective than other analgesics and that their adverse effects can impair quality of life. Therefore, the objective is to examine opioid prescriptions after KR.

In this retrospective study, we used descriptive statistics and estimated the association of prognostic factors using generalised negative binomial models.

The study is based on anonymised claims data of patients with mandatory health insurance at Helsana, a leading Swiss health insurance.

Overall, 9122 patients undergoing KR between 2015 and 2018 were identified.

Based on reimbursed bills, we calculated the dosage (morphine equivalent dose, MED) and the episode length (acute: <90 days; subacute: ≥90 to <120 days or <10 claims; chronic: ≥90 days and ≥10 claims or ≥120 days). The incidence rate ratios (IRRs) for postoperative opioids were calculated.

Of all patients, 3445 (37.8%) received opioids in the postoperative year. A large majority had acute episodes (3067, 89.0%), 2211 (65.0%) had peak MED levels above 100 mg/day and most patients received opioids in the first 10 postoperative weeks (2881, 31.6%). Increasing age (66-75 and >75 vs 18-65) was associated with decreased IRR (0.776 (95% CI 0.7 to 0.859); 0.723 (95% CI 0.649 to 0.805)), whereas preoperative non-opioid analgesics and opioids were associated with higher IRR (1.271 (95% CI 1.155 to 1.399); 3.977 (95% CI 4.409 to 3.591)).

The high opioid demand is unexpected given that current recommendations advise using opioids only when other pain therapies are ineffective. To ensure medication safety, it is important to consider alternative treatment options and ensure that benefits outweigh potential risks.

Chronic pancreatitis (CP) is a fibroinflammatory disorder that results in irreversible scarring to pancreatic parenchyma and presents with a myriad of symptoms including abdominal pain, nausea, weight loss, steatorrhea, and diabetes. Furthermore, patients with CP often have comorbid chemical dependencies to alcohol and tobacco, which can further complicate the management of CP. Recent literature proposes guidelines on how best to care for patients with CP and establishes requirements for centers of excellence. Here, we review the available data on endoscopic therapies, pain management, chemical dependency, and nutrition for patients with CP and propose quality metrics that may be used to establish a quality practice.

In response to the overuse of prescription opioid analgesics, clinical practice guidelines encourage opioid deprescribing (ie, dose reduction or cessation) in patients with chronic noncancer pain. Therefore, this study evaluated and compared international clinical guideline recommendations on opioid deprescribing in patients with chronic noncancer pain. We searched PubMed, EMBASE, PEDro, National Institute for Health and Care Excellence (United Kingdom), and MAGICapp databases from inception to June 4, 2021, with no language or publication restrictions. In addition, we searched the National Guideline Clearinghouse and International Guideline Network databases from inception to December 2018. Two independent reviewers conducted the initial title and abstract screening. After discrepancies were resolved through discussion, 2 independent reviewers conducted the full-text screening of each potentially eligible reference. Four independent reviewers completed the prepiloted, standardized data extraction forms of each included guideline. Extracted information included bibliographical details; strength of recommendations; and the outcomes, such as when and how to deprescribe, managing withdrawal symptoms, additional support, outcome monitoring, and deprescribing with coprescription of sedatives. A narrative synthesis was used to present the results. This study found that clinical practice guidelines agree on when and how to deprescribe opioid analgesics but lack advice on managing a patient's withdrawal symptoms, outcome monitoring, and deprescribing with coprescription of sedatives. Quality assessment of the guidelines suggests that greater discussion on implementation and dissemination is needed.

Neuromodulation, specifically spinal cord stimulation (SCS), has become a staple of chronic pain management for various conditions including failed back syndrome, chronic regional pain syndrome, refractory radiculopathy, and chronic post operative pain. Since its conceptualization, it has undergone several advances to increase safety and convenience for patients and implanting physicians. Current research and efforts are aimed towards novel programming modalities and modifications of existing hardware. Here we review the recent advances and future directions in spinal cord stimulation including a brief review of the history of SCS, SCS waveforms, new materials for SCS electrodes (including artificial skins, new materials, and injectable electrodes), closed loop systems, and neurorestorative devices.

Medical practitioners play an essential role in preventing pain, conducting comprehensive pain assessments, as well as promoting evidence-based practices. There is a need for the development of innovative, interprofessional and integrated pain medicine curricula for medical students. The Pain Medicine Curriculum Framework (PMCF) was developed to conceptualise a purposeful approach to the complex process of curriculum change and to prioritise the actions needed to address the gaps in pain medicine education. The PMCF comprises four dimensions: (1) future healthcare practice needs; (2) competencies and capabilities required of graduates; (3) teaching, learning and assessment methods; and (4) institutional parameters. Curricula need to meet the requirements of registration and accreditation bodies, but also equip graduates to serve in their particular local health system while maintaining the fundamental standards and values of these institutions. The curriculum needs to connect knowledge with experience and practice to be responsive to the changing needs of the increasingly complex health system yet adaptable to patients with pain in the local context. Appropriate learning, teaching and assessment strategies are necessary to ensure that medical practitioners of the future develop the required knowledge, skills and attitudes to treat the diverse needs of patients' experiencing pain. The historical, political, social and organisational values of the educational institution will have a significant impact on curriculum design. A more formalised approach to the development and delivery of a comprehensive pain medicine curriculum is necessary to ensure that medical students are adequately prepared for their future workplace responsibilities.

Opioid-induced respiratory depression (RD) is a potentially life-threatening adverse drug event. This study used the Japanese Adverse Drug Event Report (JADER) database to investigate the profile of opioid-related RD in non-cancer patients.

We analyzed data recorded in the JADER database between April 2004 and February 2020, which were downloaded from the Pharmaceutical and Medical Devices Agency website. Reporting odds ratios for RD were calculated for the 20 opioids approved in Japan, and daily dose and onset time were further analyzed for opioids used in chronic non-cancer pain (CNCP).

Among the opioids, RD adverse event signals were detected for 22 combinations of opioids and administration routes in non-cancer patients. Of these combinations, transdermal buprenorphine and oral tramadol/acetaminophen were approved for CNCP and tended to be reported more frequently in elderly patients. The median daily doses of transdermal buprenorphine and oral tramadol/acetaminophen were 10.0 and 22.5 mg of daily oral morphine equivalent doses, respectively, which are within the standard range for starting dosage. The median time-to-onset of transdermal buprenorphine and oral tramadol/acetaminophen was 6.5 and 4.0 days, respectively, and 75% of cases were reported within 20 to 40 days after the start of treatment. The hazard type for both opioids was classified as early failure.

Our findings suggest that elderly CNCP patients should be closely monitored after the start of opioid treatment, especially during the first week and, if possible, for 1 month, even if starting doses are within ranges recommended by the manufacturer and guidelines.

Chronic opioid use is a significant public health burden. Orthopaedic trauma is one of the main indications for opioid prescription. We aimed to assess the risk for long-term opioid use in a healthy patient cohort.

In this matched cohort study, bicycle trauma patients from a Swedish Level-I-Trauma Centre in 2006-2015 were matched with comparators on age, sex, and municipality. Information about dispensed opioids 6 months prior until 18 months following the trauma, data on injuries, comorbidity, and socioeconomic factors were received from national registers. Among bicycle trauma patients, the associations between two exposures (educational level and injury to the lower extremities) and the risk of long-term opioid use (> 3 months after the trauma) were assessed in multivariable logistic regression models.

Of 907 bicycle trauma patients, 419 (46%) received opioid prescriptions, whereof 74 (8%) became long-term users. In the first quarter after trauma, the mean opioid use was significantly higher in the trauma patients than in the comparators (253.2 mg vs 35.1 mg, p < 0.001) and fell thereafter to the same level as in the comparators. Severe injury to the lower extremities was associated with an increased risk of long-term opioid use [OR 4.88 (95% CI 2.34-10.15)], whereas high educational level had a protecting effect [OR 0.42 (95% CI 0.20-0.88)].

The risk of long-term opioid use after a bicycle trauma was low. However, opioids should be prescribed with caution, especially in those with injury to lower extremities or low educational level.

Due to its opioid and non-opioid mechanism of action, tapentadol is considered an atypical opioid with improved gastrointestinal tolerability versus traditional opioids. As for all opioid analgesics it is important to understand how to discontinue a treatment when it is not needed anymore. The aim of this article was to provide an overview of opioid therapy in non-cancer pain, with a specific focus on tapering of tapentadol in patients with chronic non-cancer pain, and suggestions on how to achieve tapering.

Studies for this narrative review were identified via PubMed using a structured search strategy, focusing on management of chronic non-cancer pain with opioids, and the efficacy, tolerability, and pharmacology of tapentadol prolonged release. Publications were limited to English-language articles published within the last ∼10 years.

The review discusses the use and discontinuation of opioids in general, as well clinical data on discontinuation of tapentadol specifically. We provide a flow chart, which can be used by clinicians in the context of their own clinical experience to appropriately taper tapentadol in patients with chronic non-cancer pain. The flow chart can be easily tailored to individual patient characteristics, duration of tapentadol treatment, response to progressive dosage reduction, and likelihood of withdrawal symptom occurrence.

While tapentadol is associated with a low frequency of opioid withdrawal symptoms after abrupt discontinuation, use of a tapering strategy is prudent. Tapering strategies developed for opioids in general can potentially be safely individualized in tapentadol-treated patients, although research on tapering strategies for tapentadol is required.

Background: Multiple studies have investigated the epidemic of persistent opioid use as a common postsurgical complication. However, there exists a knowledge gap in the association between the level of opioid exposure in the peri-surgical setting and post-discharge adverse outcomes to patients and healthcare settings. We analyzed the association between peri-surgical opioid exposure use and post-discharge outcomes, including persistent postsurgical opioid prescription, opioid-related symptoms (ORS), and healthcare resource utilization (HCRU). Methods: A retrospective cohort study included patients undergoing cesarean delivery, hysterectomy, spine surgery, total hip arthroplasty, or total knee arthroplasty in an academic healthcare system between January 2015 and June 2018. Peri-surgical opioid exposure was converted into morphine milligram equivalents (MME), then grouped into two categories: high (>median MME of each surgery cohort) or low (≤median MME of each surgery cohort) MME groups. The rates of persistent opioid use 30 and 90 days after discharge were compared using logistic regression. Secondary outcomes, including ORS and HCRU during the 180-day follow-up, were descriptively compared between the high and low MME groups. Results: The odds ratios (95% CI) of high vs. low MME for persistent opioid use after 30 and 90 days of discharge were 1.38 (1.24−1.54) and 1.41 (1.24−1.61), respectively. The proportion of patients with one or more ORS diagnoses was greater among the high-MME group than the low-MME group (27.2% vs. 21.2%, p < 0.01). High vs. low MME was positively associated with the rate of inpatient admission, emergency department admissions, and outpatient visits. Conclusions: Greater peri-surgical opioid exposure correlates with a statistically and clinically significant increase in post-discharge adverse opioid-related outcomes. The study findings warrant intensive monitoring for patients receiving greater peri-surgical opioid exposure.

To examine acceptability of study participation and feasibility of (1) recruitment, (2) data collection and (3) outcome measures for the prospective U-PAIN cohort.

Internal feasibility study of a prospective cohort.

64 patients, >18 years, with chronic pain at a multidisciplinary pain centre at a university hospital in Sweden.

Acceptability of study participation was measured with a study-specific 10-item Likert scale. A score <3 was considered feasible, for the two items that assessed respondent burden a higher score indicated lesser participant burden and a score >3 was feasible. Recruitment was assessed by participation rates at baseline and retention at the 1-year follow-up, with threshold values for feasibility at 75% and 80%, respectively. Data collection and outcome measures were examined by completions rates of study procedures (90% was considered feasible), sample scores, internal consistency (α>0.70 was considered feasible), and agreement between self-reported data and data retrieved from medical records on opioid use (ICC or κ>0.60 was considered feasible).

Acceptability for study procedures was feasible, but participation rates were low: 25%. The retention rate at 1-year follow-up was 81% for those included in the feasibility study, that is, filling out computerised patient-reported outcome measures, and 65% for those using paper and pencil format. The completion rates for the different data collection methods ranged from 83% to 95%. Agreement between self-reported opioid use and prescribed dose and between opioid use disorder according to Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), and clinical International Classification of Diseases-10 (ICD-10) diagnoses for opioid dependence were almost perfect (κ=0.91 and κ=0.90, respectively).

This feasibility study has helped to explore and improve methods for recruitment, data collection and use of outcome measures for the U-PAIN cohort. Low participation rate and high refusal rate at baseline is a challenge that needs to be further addressed.

Prescribing benzodiazepines to patients taking chronic opioid analgesic therapy increases risks of adverse events. In 2016, the Centers for Disease Control and Prevention recommended avoidance of benzodiazepine prescribing concurrently with opioids, and various organizations have instituted similar guidelines. We aimed to determine the frequency and patterns of benzodiazepine prescribing at Mayo Clinic primary care (Community Internal Medicine, Family Medicine) clinics for patients taking chronic opioid analgesic therapy and the characteristics of patients receiving the prescriptions and providers administering them.

This retrospective observational study included adult patients taking chronic opioid analgesic therapy for 2 full years in 2018 and 2019 at Mayo Clinic primary care practices in Arizona and Florida. We assessed electronic health records for these individual patients to determine whether they received a benzodiazepine prescription during the study period and how frequently they received a prescription. Variations in prescriptions by provider specialty, location, and sex were studied. Documented data included receipt of a benzodiazepine prescription by patients with at-risk alcohol use or alcohol use disorder, depression, anxiety, chronic obstructive pulmonary disease, falls, and psychiatric referral. Data were compared between patients who received benzodiazepines and those who did not with the Kruskal-Wallis test or χ² test, and the Wilcoxon signed rank test was used to assess whether the change in number of benzodiazepine prescriptions (2018 vs. 2019) was different from zero.

Study participants (N = 457) were predominantly women (n = 266, 58.2%); median age was 69 years. In total, 148 patients (32.4%) received benzodiazepine prescription. These patients were more likely to be women (P = .046) and younger (P = .02). Mean percentage change was 176.9% (P < .001) in number of benzodiazepine prescriptions provided from 2018 to 2019. Frequency of referral to mental health providers was low, as was presence of an established mental health provider despite a greater prevalence of anxiety (P < .001) and depression (P = .001) among patients receiving benzodiazepines.

Benzodiazepine prescription to individual patients taking chronic opioid analgesic therapy significantly increased from 2018 to 2019 despite the documented risks and harms associated with such practice. No statistically significant difference was observed in frequency of benzodiazepine prescriptions between practice location, sex of provider, or specialty.

Objective: Postherpetic neuralgia (PHN) is a clinical puzzle, especially in patients who still suffered from moderate and severe pain after standard treatment. This single-center, double-blinded, randomized controlled, prospective, and non-inferiority study observed the safety and effectiveness of the epidural application of morphine or hydromorphone, trying to provide an alternative method for those patients with refractory PHN. Methods: Eighty PHN patients with a visual analogue scale (VAS) still greater than 50 mm after routine management were randomly divided into two groups according to 1:1, respectively. One group received epidural morphine (EMO group), and the other group received epidural hydromorphone (EHM group). VAS, the number of breakthrough pain, quality of life (QOL), and anxiety/depression assessment (GAD-7 and PHQ-9 scores) were also observed before treatment, at 1, 3, 7, 14, 21, 28, 60, and 90 days after treatment, as well as side effects. Opioid withdrawal symptoms (OWSs) were also measured from 3 to 28 days after treatment. Results: The EHM group was non-inferior to the EMO group in terms of the VAS decrease relative to baseline (VDRB) after 1-week treatment. The VAS of the two groups on all days after treatment was significantly lower than the corresponding baseline findings (p < 0.05). The breakthrough pain (BTP) decreased significantly after treatment and lasted until 14 days after treatment (p < 0.05). There was no significant difference in BTP between the two groups at each time point (p > 0.05). In terms of the QOL, GAD-7, and PHQ-9 outcomes, those were significantly improved after treatment (p < 0.05), and there was no difference between the two groups (p > 0.05). No significant AE difference across the two groups was observed in this study. Few reports of OWS were found in this trial, and there were no significant differences between the two groups (p > 0.05). Conclusion: EHM was non-inferior to EMO in terms of the VDRB after 1-week treatment. For patients with VAS still greater than 50 mm after standard treatment, short-term application of EMO or EHM can ameliorate intractable pain, improve the quality of life, and have no obvious side effects. Short-term epidural opioid application will not lead to the appearance of OWS.

A good therapeutic alliance is relevant for healthcare providers exposed to patients' suffering, especially since patients and physicians may understand the painful experience differently. Our aim was to explore the impact of therapeutic alliance on analgesic outcomes in a real-world interdisciplinary pain unit (PU). A cross-sectional observational study was conducted on outpatients (n = 69) using opioids on a long-term basis for the treatment of chronic non-cancer pain, where clinical pharmacologists and pharmacists advised patients about their opioid treatment. Responses to the patient-doctor relationship questionnaire (PDRQ), sociodemographic and clinical information (pain level, quality of life and hospital use) were collected, whereas pharmacology data (analgesic prescription, adverse events, and compliance) were obtained from electronic health records. Patients were predominantly middle-aged (75 % women, 72 % retired), experiencing moderate pain (VAS 40-70 mm) on average, and under a high morphine equianalgesic dosage (95 ± 88 mg per day, mainly tapentadol or fentanyl). Patients with better PDRQ outcomes, and therefore better therapeutic alliance, showed lower pain intensity than patients with worse PDRQ outcomes (pain intensity: high scores 60 ± 47 mm and medium scores 60 ± 45 mm vs. low scores 80 ± 75 mm, p < 0.01). Along with this, pain intensity was lower when patients affirmed that, thanks to the health-care providers, they "gained new insight", "felt better", or "felt content with their doctor's treatment". What´s more, patients who affirmed "I benefit from the treatment" experienced increased pain relief (benefit 40 ± 30 vs. non-benefit 19 ± 26 mm, p = 0.010) and improved quality of life (benefit 33 ± 25 vs. non-benefit 18 ± 16 mm, p = 0.031). However, there was a percentage of patients who did not fully understand the provided information, which is something to be taken into account to improve in clinical routine. Therapeutic alliance supported by pharmacist experts on pain management can be an effective strategy to improve analgesic outcomes. Further efforts are needed to improve communication strategies for pain management. Future directions of research should include the analysis of the role of the pharmacist in poly-professional consultations as related to the advice of patients about their medication, and the mutual trust with the patients.

Chronic pain is a global public health problem that negatively impacts individuals' quality of life and imposes a substantial economic burden on societies. The use of medicinal cannabis (MC) is often considered by patients to help manage chronic pain as an alternative or supplement to more conventional treatments, given enabling legalization in a number of countries. However, healthcare professionals involved in providing guidance for patients related to MC are often doing so in the absence of strong evidence and clinical guidelines. Therefore, it is crucial to understand their perspectives regarding the clinical use and relevance of MC for chronic pain. As little is known about attitudes of HCPs with regard to MC use for chronic pain specifically, the aim of this review was to identify and synthesize the published evidence on this topic.

A systematic search was conducted across six databases: MEDLINE, EMBASE, CINAHL, Scopus, Web of Science, and PubMed from 2001 to March 26, 2021. Three authors independently performed the study selection and data extraction. Thematic analysis was undertaken to identify key themes.

A total of 26 studies were included, involving the United States, Israel, Canada, Australia, Ireland, and Norway, and the perspectives of physicians, nurses, and pharmacists. Seven key themes were identified: MC as a treatment option for chronic pain, and perceived indicated uses; willingness to prescribe MC; legal issues; low perceived knowledge and the need for education; comparative safety of MC versus opioids; addiction and abuse; and perceived adverse effects; CONCLUSION: To support best practice in the use of MC for chronic pain, healthcare professionals require education and training, as well as clinical guidelines that provide evidence-based information about efficacy, safety, and appropriate dosage of products for this indication. Until these gaps are addressed, healthcare professionals will be limited in their capacity to make treatment recommendations about MC for people/patients with chronic pain.