Use Of Opioid Analgesics Research Articles

Safety and Efficacy of Bupivacaine HCl Collagen-Matrix Implant (INL-001) in Open Inguinal Hernia Repair: Results from Two Randomized Controlled Trials.

IntroductionSurgical site infiltration with bupivacaine results in short-lived analgesia. The MATRIX-1 and MATRIX-2 studies examined the efficacy and safety of the bioresorbable bupivacaine HCl collagen-matrix implant (INL-001) for postsurgical pain after open inguinal hernia repair. INL-001, designed to provide early and extended delivery of bupivacaine, provides prolonged duration of perioperative analgesia.MethodsIn two phase 3 double-blind studies [MATRIX-1 (ClinicalTrials.gov identifier, NCT02523599) and MATRIX-2 (ClinicalTrials.gov identifier, NCT02525133)], patients undergoing open tension-free mesh inguinal hernia repair were randomized to receive 300-mg bupivacaine (three INL-001 100-mg bupivacaine HCl collagen-matrix implants) (MATRIX-1 n = 204; MATRIX-2 n = 213) or three placebo collagen-matrix implants (MATRIX-1 n = 101; MATRIX-2 n = 106) during surgery. Postsurgical medication included scheduled acetaminophen and as-needed opioids.ResultsPatients who received INL-001 in both studies reported statistically significantly lower pain intensity (P ≤ 0.004; primary end point) and opioid analgesic use (P < 0.0001) through 24-h post-surgery versus those who received a placebo collagen-matrix. Patients who received INL-001 reported lower pain intensity through 72 h (P = 0.0441) for the two pooled studies. In both studies, more of the patients (28–42%) who received INL-001 used no opioid medication 0–24, 0–48, and 0–72 h post-surgery versus those who received a placebo collagen-matrix (12–22%). Among patients who needed opioid medication, patients receiving INL-001 used fewer opioids than those who received a placebo collagen-matrix through 24 h in both studies (P < 0.0001) and through 48 h in MATRIX-2 (P = 0.0003). Most adverse events were mild or moderate, without evidence of bupivacaine toxicity or deleterious effects on wound healing.ConclusionThese findings indicate that INL-001 results in post-inguinal hernia repair analgesia that is temporally aligned with the period of maximal postsurgical pain and may reduce the need for opioids while offering a favorable safety profile.Trial RegistrationClinicalTrials.gov identifiers, NCT02523599; NCT02525133.FundingInnocoll Pharmaceuticals.Plain Language SummaryPlain language summary available for this article.

Survey results from an international hip course: comparison between experts and non-experts on hip arthroscopy clinical practice and post-operative rehabilitation

The purpose of this study was to compare the clinical practices between expert and non-expert arthroscopy hip surgeons. Registered orthopedic surgeons completed anonymous surveys during a hip arthroscopy meeting. The survey included 60 questions on physician's level of expertise, surgical anesthesia, procedures performed, hospital stay, pain control, rehabilitation and socioeconomic parameters, and the results are presented. Comparisons were made between hip arthroscopy experts (> 500 cases performed) and non-experts (≤ 500 cases performed) on aspects of patient care. Forty-eight (74%) surgeons responded. Forty-four questionnaires were filled out completely. There were no significant differences in recommendations between 15 (34%) hip arthroscopy experts and 29 (66%) non-experts on hip capsular management and cartilage repair techniques, use of antithrombotic prophylaxis and opioid analgesics, time of rehabilitation initiation and patient compliance factors, use of hip brace and CPM, and patient evaluation to return to sports following surgery. Surgical expertise was significantly associated with the performance of hip labral reconstruction (p = 0.016), subspine decompression (p = 0.039) and recommendation of a longer period of restricted weight bearing following the performance of microfractures (p = 0.011). There were no significant differences in clinical practice between surgeons who performed hip arthroscopy exclusively versus those who did not. Hip arthroscopy is a relatively new field, and clinical practice may vary among physicians based on the surgical expertise. In this study, hip arthroscopy experts agree with non-experts on most aspects of patient care. Surgical expertise was associated with performance of advanced techniques and recommendation of longer period of restricted weight bearing following performance of microfractures. This study highlights different care patterns that need to be investigated to determine which treatment results in improved patient care. V.

Laws limiting the prescribing or dispensing of opioids for acute pain in the United States: A national systematic legal review

BackgroundOpioid overdose is a continuing public health crisis. In response to an increasing recognition of the negative outcomes sometimes associated with the use of opioid analgesics, states have taken a number of steps attempting to reduce inappropriate prescribing of these medications. These include the imposition of strict legal limitations on the amount or duration that opioid analgesics may be prescribed or dispensed to patients with acute pain. MethodsWe conducted a systematic, multi-source legal review of state laws that impose mandatory limits on the ability of medical professionals to prescribe or dispense opioids for the treatment of acute pain. We also systematically searched for and examined publicly available documents on state legislative and regulatory bodies’ websites. All relevant laws were downloaded and systematically coded. ResultsBy the end of 2017, twenty-six states had passed laws that impose mandatory limits on the prescribing or dispensing of opioids for acute pain. The oldest of these laws became effective as early as 1989, but most are much newer: approximately 65% (17/26) were passed in 2017. There is wide variation in the characteristics of these laws. ConclusionJust over half of all states have enacted laws that restrict the prescribing or dispensing of opioids for acute pain. To date, there is no data on whether and to what extent these laws mediate opioid-related morbidity and mortality, as well as whether they are associated with negative unintended outcomes. Research into these questions is urgently needed.

A284 - Perioperative Transversus Abdominis Plane (TAP) Block for Bariatric Surgery to Reduce the Use of Opioid Analgesics

A284 - Perioperative Transversus Abdominis Plane (TAP) Block for Bariatric Surgery to Reduce the Use of Opioid Analgesics

Laparoscopic Ventral Hernia Repair in South Auckland, New Zealand—A Retrospective Review

BackgroundEthnic disparities in surgical care and outcomes have been previously reported in studies for other surgical procedures. In addition, it has been reported that ethnic differences in postoperative analgesia exist. We aimed to determine ethnic disparities in postoperative outcomes, total opioid analgesia use, and complication rates of all patients who underwent a laparoscopic ventral hernia repair (LVHR) at our institution over a 3-y period. MethodsA retrospective review of all patients who underwent an LVHR at Counties Manukau Health from January 1, 2013, to December 31, 2015, was performed in line with the Strengthening the Reporting of Observational Studies in Epidemiology statement. ResultsA total of 267 ventral hernias were repaired in 254 patients at Counties Manukau Health over the study period, of which most were primary umbilical ventral hernias. The majority of patients in our cohort were New Zealand European and male. Major complications, as per the Clavien-Dindo classification grade 3 and above, were observed in six patients with no deaths (2.4%). There were no statistically significant ethnic disparities in length of stay, receipt of opioid analgesia, and rates of complication observed after linear regression modeling after adjustment for confounding factors. ConclusionsOur study showed that the majority of patients who had a ventral hernia repaired at our institution were mostly New Zealand European and male. Although significant ethnic disparities in patient characteristics were observed, these were not associated with ethnic disparities in postoperative outcomes after an LVHR.

The Nature of Trauma Pain and Its Association with Catastrophizing and Sleep.

Nearly 2.8 million people are hospitalized in the USA annually for traumatic injuries, which include orthopedic and internal organ injuries. Early post-injury pain is predictive of poor outcomes, including inability to eventually return to work, and long-term psychological distress. The goal of the present study was to improve our scientific understanding of trauma-related pain by examining (1) the nature and frequency of inpatient trauma pain and (2) the associations between inpatient trauma pain, education, opioid analgesic equivalent use, pain catastrophizing, and sleep quality. The study included 120 patients hospitalized at a major level I regional trauma center for the care of (1) closed long bone or calcaneus fractures and/or (2) an intraabdominal injury caused by blunt force trauma and requiring surgical repair (i.e., laparotomy). Medical records were reviewed to obtain demographic information and information about opioid use during hospitalization. In addition, participants were administered measures of average pain intensity, pain catastrophizing, and sleep quality. Education, opioid analgesic equivalents, catastrophizing, and poor sleep quality together accounted for 28% of the variance of average pain intensity over a 24-h period (p < .001), with each variable making a significant independent association. Two of the factors associated with pain intensity in the study sample-catastrophizing and sleep quality-are modifiable. It is therefore possible that interventions that target these variables in patients who are hospitalized for trauma could potentially result in better long-term outcomes, including a reduced risk for developing chronic pain. Research to evaluate this possibility is warranted.

Neonatal abstinence syndrome in countries with no to low medical opioid consumption: a scoping review

To describe the current state of evidence on the care of neonates with neonatal abstinence syndrome in countries with low to virtually no medical opioid analgesic consumption. While access to opioids for medical use improves globally, misuse grows as a health concern. One unintended consequence has been an increase in the incidence of neonatal abstinence syndrome. Because most evidence is generated in countries with adequate opioid analgesic consumption, a picture of evidence in lower opioid-consuming countries is not available. A scoping review methodology was employed and augmented with principles of international development literature review. Electronic database searches (PubMed and CINAHL) located 1106 articles. Google was employed to access an additional 17 non-indexed articles. From the total of 1123 articles located, 27 articles from 15 countries were included. Minimal evidence was produced in low to virtually no medical opioid-consuming countries. Sources were primarily review articles, descriptive, comparative or case reports. Seventy-one per cent of the articles identified at least one specific clinical practice related to the care of infants with neonatal abstinence syndrome. As opioid analgesic use increases globally, a subsequent increase in neonatal abstinence syndrome is likely. It will be beneficial for providers and policymakers to be proactive in considering implications for neonatal and maternal populations and collaborate with providers who have been gaining experience in this area. A number of these countries are heroin-growing regions and already experiencing issues. Policymakers may use these findings to support data collection and reporting, context and resource relevant guideline development, and advocacy for inclusion of the maternal-infant population in global opioid research priority setting. International collaboration for establishing gender and culturally appropriate practices globally is critical.

Enhanced recovery after surgery in gynecologic oncology.

Enhanced recovery protocols consist of a bundle of concepts including early feeding, opioid-sparing multimodal pain management, and euvolemia, with the overarching goal of hastening postoperative recovery. Enhanced recovery after surgery has been shown to reduce hospital length of stay, reduce costs, and decrease perioperative opioid requirements in benign and oncologic gynecologic surgery. Interventions without supporting evidence of benefit, such as the use of mechanical bowel preparation, routine use of nasogastric tubes and surgical drains, caloric restriction, routine use of intravenous opioid analgesics, and over-vigorous intravenous hydration should be discouraged to improve broader endpoints such as patient satisfaction and overall recovery. Successful implementation requires engagement from a multidisciplinary team including surgeons, anesthesiologists, nurses, and pharmacists.

Factors Associated with Prescription Opioid Analgesic Use in the US Population, 2011-2014.

This study examined factors associated with prescription opioid analgesic use in the US population using data from a nationally representative sample. It focused on factors previously shown to be associated with opioiduse disorder or overdose. Variations in the use of different strength opioid analgesics by demographic subgroup were also examined. Data came from respondents aged 16 years and older who participated in the National Health and Nutrition Examination Survey (2011-2014). Respondents were classified as opioid users if they reported using one or more prescription opioid analgesics in the past 30 days. Opioid users reported poorer self-perceived health than those not currently using opioids. Compared with those not using opioids, opioid users were more likely to rate their health as being "fair" or "poor" (40.4% [95% confidence interval {CI} = 34.9%-46.2%] compared with 15.6% [95% CI = 14.3%-17.1%]), experienced more days of pain during the past 30 days (mean = 14.3 [95% CI = 12.9-15.8] days compared with 2.3 [95% CI = 2.0-2.7] days), and had depression (22.5% [95% CI = 17.3%-28.7%] compared with 7.1% [95% CI = 6.2%-8.0%]). Among those who reported using opioids during the past 30 days, 18.8% (95% CI = 14.4%-24.1%) reported using benzodiazepine medication during the same period and 5.2% (95% CI = 3.5%-7.7%) reported using an illicit drug during the past six months. When opioid strength was examined, a smaller percentage of adults aged 60 years and older used stronger-than-morphine opioids compared with adults aged 20-39 and 40-59 years. Higher percentages of current opioid users than nonusers reported having many of the factors associated with opioid use disorder and overdose.

Using trajectory models to assess the effect of hydrocodone upscheduling among chronic hydrocodone users.

In October 2014, the US Drug Enforcement Agency moved hydrocodone combination products (HCPs) from schedule III to II of the Controlled Substances Act, further restricting their access. The aim of the study is to quantify the effect of hydrocodone's "upscheduling" on the use of opioid and nonopioid analgesics among chronic users. Using IQVIA LRx LifeLink anonymized pharmacy data 2013 to 2015, we performed interrupted time series analysis and group-based trajectory modeling to characterize the effect of rescheduling on 316731 long-term hydrocodone users. Main measures were the number of prescriptions, patients, tablets, and morphine milligram equivalents of opioids and nonopioid analgesics pre and post the policy change. We used logistic regression to assess the relationship between sociodemographic characteristics and these measures. The schedule change was associated with significant declines in opioid prescriptions (20.9%, from 421798 to 333627) and the number of patients using opioids (11.4%, from 307974 to 272804). Majority of hydrocodone users filled prescriptions for nonopioid analgesics with some declines in the number of users after the schedule change (5.2%, from 181085 to 171758). Based on group-based trajectory models, majority of patients continued to fill HCP prescriptions consistently after the policy change, while 15.4% showed large declines in HCP use, accounting for two-thirds of the decrease in opioid volume. There was no evidence that the policy change was associated with significant increases in the use of alternative analgesics. The upscheduling of hydrocodone led to reductions in opioid use, which were concentrated among a small subset of chronic hydrocodone users, without evidence of commensurate increases in the use of alternative pharmacologic pain treatments.

Relationship Between Opioid Analgesic Prescription and Unemployment in Patients Seeking Acupuncture for Chronic Pain in Urban Primary Care.

The widespread use of opioid analgesics to treat chronic nonmalignant pain has contributed to the ongoing epidemic of opioid-related morbidity and mortality. Previous studies have also demonstrated a relationship between opioid analgesic use and unemployment due to disability. These studies have been limited to mainly white European and North American populations. The objective of this study is to explore the relationship between opioid analgesic use for chronic nonmalignant pain in an urban, mainly black and Hispanic, low-income population. This is a cross-sectional observational study. Subjects were recruited from six urban primary care health centers. Adults with chronic neck, back, or osteoarthritis pain participating in an acupuncture trial were included. Survey data were collected as a part of the Acupuncture Approaches to Decrease Disparities in Pain Treatment two-arm (AADDOPT-2) comparative effectiveness trial. Participants completed a baseline survey including employment status, opioid analgesic use, the Brief Pain Inventory, the global Patient Reported Outcomes Measurement Information Systems quality of life measure, the Patient Health Questionnaire-9 (PHQ-9), and demographic information. A multivariable logistic regression model was built to examine the association between opioid analgesic use and unemployment. Opioid analgesic use was associated with three times the odds of unemployment due to disability while controlling for potential confounders, including depression, pain severity, pain interference, global physical and mental functioning, and demographic characteristics. This study adds to the growing body of evidence that opioid analgesics should be used with caution in chronic nonmalignant pain.

Effect of Bupivacaine on Postoperative Pain after Laparoscopic Cholecystectomy.

To determine whether intraoperative local injection of 0.5% bupivacaine around port sites would decrease early postoperative pain after laparoscopic cholecystectomy, and the use of intravenous opioid analgesics postoperatively. Randomised controlled trial. Department of Surgery, Khyber Teaching Hospital, Peshawar, from July 2016 to June 2017. Patients who underwent laparoscopic cholecystectomy were divided into two groups. Group A had instillation of 20 ml of 0.5% Inj. bupivacaine at the end of procedure into port sites and group B had no bupivacaine injection at trocar sites. Both groups had postoperative intravenous ketorolac 30 mg three times daily and intravenous opioid analgesics on demand. Pain was assessed 2 hours after recovery from general anesthesia, and at 6, 12 and 24 hours through visual analog scale 0-10. One hundred and twenty patients completed this study with 60 patients in each group. A significant difference in mean postoperative pain scores was observed at 2 and 6 hours after surgery between the groups. Pain scores at 2 and 6 hours after surgery were 3.97 +1.327 and 3.02 ±1.08 in group A, while it was 4.65 +1.448 and 4.72 ±1.277 in group B with p-values of 0.008 and 0.005, respectively. There was no significant difference in mean postoperative pain scores at 12 and 24 hours between the groups, with pain scores of 3.72 ±0.78 and 3.75 ±0.95 (p=0.488 and 0.744, respectively). However, there was a significant difference in opioid analgesics use in first 24 hours with less analgesics use in bupivacaine injected group. Injecting 0.5% bupivacaine at trocar sites during laparoscopic cholecystectomy offers significant reduction in early postoperative pain.

Predictors of the Predominance of NonIndex Pain After Palliative Radiation Therapy for Painful Tumors

PurposeEven when index pain (pain caused by the irradiated tumor) is palliated after radiation therapy (RT), patients may not derive the full benefits of RT in the presence of another, more intense pain. In this case-control study with prospectively collected data, we sought to identify predictors of the predominance of nonindex pain after palliative RT. Methods and MaterialsBrief Pain Inventory data were collected from patients who received RT for painful tumors. The treating radiation oncologists prospectively evaluated the intensity and origin of nonindex pain. Patients were diagnosed with predominance of other pain (POP) if nonindex pain of malignant or unknown origin was present and had a greater worst pain score than the index pain at the 1- or 2-month follow-up. Changes in pain interference from baseline to follow-up were compared between the 2 groups using Mann-Whitney U tests. Using variables that were identified as significant in a multivariable logistic regression analysis, we developed a prediction model for POP. ResultsOf the 170 patients who were evaluable at the 2-month follow-up, 24 (14%) were diagnosed with POP. At the 2-month follow-up examination of the patients with POP, none of the items of the pain interference scores were reduced from baseline; in contrast, patients without POP experienced significant reductions in all items. Multivariable analysis using the backward elimination method indicated that age ≤65 years, the presence of nonindex pain of malignant or unknown origin at baseline, and no opioid analgesic use at baseline were significant independent predictors of POP. As the number of the risk factors increased, the proportion of patients with POP increased. ConclusionsWe identified three predictors of POP. For patients likely to have POP, careful follow-up is important, and new palliative RT or analgesics should be used when needed.

Prescription opioid analgesic use in France: Trends and impact on morbidity–mortality

While data from USA and Canada demonstrate an opioid overdose epidemic, very little nation-wide European studies have been published on this topical subject. Using a nationally representative sample of the French Claims database (>700,000 patients), the exhaustive nationwide hospital discharge database, and national mortality registry, all patients dispensed at least one prescription opioid (PO) in 2004-2017 were identified, to describe trends in PO analgesic use, shopping behaviour, opioid-related hospitalizations and deaths. Annual prevalence of PO use and shopping behaviour (≥1day of overlapping prescriptions from ≥2 prescribers, dispensed by ≥3 pharmacies) was estimated. In 2004-2017, the annual prevalence of weak opioid use codeine, tramadol and opium rose by 150%, 123%, and 244%, respectively (p<0.05). Strong opioid use increased from 0.54% to 1.1% (+104%, p<0.05), significantly for oxycodone (+1950%). Strong opioid use in chronic noncancer pain rose by 88% (p<0.05) and 1180% for oxycodone. Opioid shopping increased from 0.50% to 0.67% (+34%, p<0.05), associated with higher mortality risk HR=2.8 [95% confidence interval (CI): 1.2-6.4]. Opioid-related hospitalizations increased from 15 to 40 per 1,000,000 population (+167%, 2000-2017), and opioid-related deaths from 1.3 to 3.2 per 1,000,000 population (+146%, 2000-2015). This study provided a first European approach to a nationwide estimation with complete access to several national registries. In 2004-2017 in France, PO use excluding dextropropoxyphene more than doubled. The increase in oxycodone and fentanyl use, and nontrivial increasing trend in opioid-related morbidity-mortality should prompt authorities to closely monitor PO consumption in order to prevent alarming increases in opioid-related morbidity-mortality. In 2004-2017, prescription opioid use in France at least doubled and oxycodone use increased particularly, associated with a nontrivial increase in opioid-related morbidity-mortality. Although giving no indication for an 'opioid epidemic,' these findings call for proper monitoring of opioid use.

EUS-guided celiac ganglion radiofrequency ablation versus celiac plexus neurolysis for palliation of pain in pancreatic cancer: a randomized controlled trial (with videos)

Although EUS-guided celiac plexus neurolysis (EUS-CPN) is frequently performed, its efficacy for palliation of pain in pancreatic cancer is suboptimal. Recently, EUS-guided radiofrequency ablation (EUS-RFA) has been proposed as a palliative treatment option for pancreatic neoplasms. We performed a single-blind, randomized trial to compare the effectiveness of EUS-CPN and EUS-RFA for palliation of pain in pancreatic cancer. Patients with abdominal pain because of locally advanced or metastatic pancreatic cancer underwent EUS-CPN (n= 14) or EUS-RFA (n= 12). EUS-RFA was performed using a 1F monopolar probe passed via a 19-gauge FNA needle, by targeting the area of celiac plexus or visualized ganglia. Primary outcome was pain severity as measured by the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire pancreatic cancer module (PAN26) administered pretreatment and at 2 and 4 weeks post-treatment. Secondary outcome measures were comparison of quality of life as determined by the PAN26 and EORTC Quality of Life Questionnaire core questionnaire (C30) and opioid analgesia use between the 2 groups. Both the PAN26 (49.0 vs 57.0, P< .001) and C30 (51.9 vs 64.4, P= .032) revealed less pain for EUS-RFA than for EUS-CPN. Also, the EUS-RFA cohort experienced significantly less-severe GI symptoms, were able to plan more for the future, and had better emotional functioning compared with the EUS-CPN group. Compared with EUS-CPN, EUS-RFA provided more pain relief and improved the quality of life for patients with pancreatic cancer. (Clinical trials registration number: NCT03152487.).

Risk of Pain and Gastrointestinal Complaints at 6Months After Elective Abdominal Surgery

The incidence of chronic postoperative abdominal pain (CPAP) after abdominal surgery is substantial and decreases overall quality of life. One in 3 patients report pain-related interference with mood, sleep, and enjoyment of life and 12% visit the emergency department for pain-related symptoms. Previous studies lack data on preoperative health and pain status or are limited by small patient samples. The aim of this study was to assess risk factors for CPAP and gastrointestinal complaints 6 months after surgery. A prospective cohort study was performed including patients undergoing an elective laparotomy or laparoscopy at a tertiary referral center. Relevant patient, pain, surgical, and medical data as well as the Gastrointestinal Symptom Rating Scale (GSRS) were assessed before, during, and after hospital stay and at the outpatient clinic until 6 months after discharge. Linear and logistic regression analysis were used to assess risk factors. Of 518 included patients, 184 (36%) had CPAP. The median GSRS score was 5 (interquartile range = 3–10). The presence of preoperative pain for <3 months (odds ratio [OR] = 2.69, P = .016) or >3 months (OR = 3.99, P = .000), use of opioid analgesia preoperatively (OR = 3.54, P = .001), severe adhesions underneath the incision (OR = 1.63, P = .040), and the numeric rating scale pain score on postoperative day 2 (OR = 1.23, P = .004) independently increased the risk for chronic abdominal pain. Chronic pancreatitis as indication for surgery (B = 4.20, P = .03), ≥3 previous abdominal operations (B = 1.03, P = .03), presence of pain >3 months before surgery (B = 1.61, P < .01), upper gastrointestinal tract as the anatomic location of surgery (B = 1.43, P = .03), and a higher preoperative GSRS score (B = .36, P < .01) independently increased the GSRS score 6 months after surgery. The duration and severity of preoperative pain and more severe acute postoperative pain were the most relevant risk factors for CPAP. The number of operations and the anatomic location of the operation showed to be important risk factors for increasing the number of gastrointestinal complaints.Perspective: This prospective observational study shows the incidence and risk factors for CPAP after major abdominal surgery. Preoperative pain-related factors were associated with the occurrence of CPAP.

Prophylactic Effect of Polaprezinc, a Zinc-L-carnosine, Against Chemotherapy-induced Oral Mucositis in Pediatric Patients Undergoing Autologous Stem Cell Transplantation.

Polaprezinc suspension in sodium alginate (PZ-AG) reduces the incidence and severity of oral mucositis in adult patients receiving radiotherapy or high-dose chemotherapy. In the present study, the prophylactic effect of PZ-AG against oral mucositis was assessed in pediatric patients with hematological malignancies receiving high-dose chemotherapy followed by hematopoietic stem cell transplantation (HSCT). Data of 16 children who underwent HSCT during a period between January 2010 and December 2017 were obtained from medical records and they were retrospectively analyzed. Oral mucositis was evaluated by the WHO scale. Six (37.5%) of 16 children refused to take PZ-AG in a preliminary assessment and they were pretreated with azulene gargle. The remaining 10 (62.5%) patients were pretreated with PZ-AG for prevention of oral mucositis. Grade≥ 3 oral mucositis occurred in 5 (83.3%) of 6 patients receiving azulene gargle, but in 2 (20%) patients who took PZ-AG (p=0.035). The prevalence for the use of opioid analgesics was also significantly lower (30% vs. 100%, p=0.011), while the average duration of total parenteral nutrition use was significantly shorter (11.1 days vs. 24.3 days, p=0.016), in PZ-AG group than in azulene group. On the other hand, PZ-AG had no significant influence on the incidence of other adverse events, mean time to engraftment, or overall survival. PZ-AG was found to be highly effective in preventing oral mucositis in pediatric patients with hematological malignancies receiving high-dose chemotherapy followed by HSCT, as in adult patients.

Impaired chronic pain-like behaviour and altered opioidergic system in the TASTPM mouse model of Alzheimer's disease.

BackgroundChronic pain conditions, especially osteoarthritis (OA), are as common in individuals with Alzheimer's disease (AD) as in the general elderly population, which results in detrimental impact on patient's quality of life. However, alteration in perception of pain in AD coupled with deteriorating ability to communicate pain sensations often result in under‐diagnosis and inappropriate management of pain. Therefore, a better understanding of mechanisms in chronic pain processing in AD is needed. Here, we explored the development and progression of OA pain and the effect of analgesics in a transgenic mouse model of AD.MethodsUnilateral OA pain was induced chemically, via an intra‐articular injection of monosodium iodoacetate (MIA) in the left knee joint of AD‐mice (TASTPM) and age‐ and gender‐matched C57BL/6J (WT). Pharmacological and biochemical assessments were conducted in plasma and spinal cord tissue.Results MIA resulted in hind paw mechanical hypersensitivity (allodynia), initiating on day 3, in TASTPM and WT controls. However, from 14 to 28 days, TASTPM displayed partial attenuation of allodynia and diminished spinal microglial response compared to WT controls. Naloxone, an opioid antagonist, re‐established allodynia levels as observed in the WT group. Morphine, an opioid agonist, induced heightened analgesia in AD‐mice whilst gabapentin was devoid of efficacy. TASTPM exhibited elevated plasma level of β‐endorphin post‐MIA which correlated with impaired allodynia.ConclusionsThese results indicate an alteration of the opioidergic system in TASTPM as possible mechanisms underlying impaired persistent pain sensitivity in AD. This work provides basis for re‐evaluation of opioid analgesic use for management of pain in AD.SignificanceThis study shows attenuated pain‐like behaviour in a transgenic mouse model of Alzheimer's disease due to alterations in the opioidergic system and central plasticity mechanisms of persistent pain.

Chronic Pain Opioid-Maintained Patients Receive Less Analgesic Opioid Prescriptions.

Treating pain and opioid use disorder represents a clinical challenge. While most studies that have assessed opioid analgesic use in opioid substitution treatment (OST) patients primarily address opioid analgesic misuse (1, 2), only few studies focused on OST patients assessed the prescription of analgesic opioids for chronic pain. We sought to compare the prevalence of analgesic opioid prescription (AOP) in two groups of chronic non-cancer pain (CNCP) patients: OST patients vs. the general population. This was a population-based cross-sectional study based on the French national healthcare claims database SNIIRAM (Système National d'Informations Inter-Régimes de l'Assurance Maladie) covering over 66 million people (98.8% of the French population). Overall, 67,173 participants ≥15 years old undergoing continuous OST in 2015 (“OST patients” group) were included and age- and gender-matched by means of a 1:1 ratio with 67,173 patients without OST (“control” group). In each group, patients with cancer conditions were excluded and those having received opioid and non-opioid analgesics for at least 3 months were identified (CNCP patients). Compared to control patients, CNCP OST patients received less AOP (47.8 vs. 68.0%, p < 0.0001) and more often non-opioid prescription (52.2 vs. 32.0%, p < 0.0001). In multivariate analysis, CNCP OST patients were 2.7 times less likely to be prescribed analgesic opioids (adjusted odds ratio [OR] = 2.7 [2.42–3.01], p < 0.0001) than control patients. AOP correlated in CNCP OST patients with: age ≤ 40 years old, female gender, low-income status, methadone-maintained treatment, mental health disorder, hepatitis C virus (HCV) infection, and alcohol abuse disorder. Opioid analgesics were less often prescribed in CNCP OST patients. AOP prevalence was 2.7-fold lower than in the general population. Chronic pain management in OST patients needs to be reinforced through additional physician training and a multidisciplinary approach.

Use of Opioid Analgesics Before and After Gastric Bypass Surgery in Sweden: a Population-Based Study

BackgroundLittle is known regarding the use of opioid analgesics among patients who have undergone bariatric surgery.The Roux-en-Y gastric bypass (RYGB) procedure has been shown to significantly increase the rate of absorption of and exposure to morphine, raising concerns regarding the potentially increased risk of side-effects and the development of substance-use disorder.ObjectivesThe aim of this study was to describe the pattern of opioid use over time following RYGB and to see if the pattern differs between patients with a high opioid consumption (HOC) prior to surgery and those with a low consumption (LOC).SettingUniversity Hospital of Örebro, Sweden.MethodsThe study was a descriptive retrospective population-based cohort study where two registers with complete coverage were cross-matched.ResultsThe study population comprised 35,612 persons (1628 HOC, and 33,984 LOC). After surgery, the number of HOC patients increased to 2218.Mean daily opioid consumption in the total population and the LOC group increased after surgery (p < .0005). In the HOC group, there was no difference between mean daily consumption before and after surgery.ConclusionIn this nationwide study, we have showed that there is an increase in consumption of opioid analgesics after gastric bypass surgery in Sweden. The increase in the number of individuals with high opioid consumption in the total population was mainly due to an increase in the group of patients with a low consumption prior to surgery.