Cost-effectiveness of sustained-release morphine for refractory breathlessness in COPD: A randomized clinical trial.

BACKGROUND: Chronic breathlessness is a frequent symptom in advanced Chronic Obstructive Pulmonary Disease (COPD) and has major impact on quality of life, daily activities and healthcare utilization. Morphine is used as palliative treatment of chronic breathlessness. The aim is to analyze cost-effectiveness of regular, low-dose morphine in patients with advanced COPD from a healthcare and societal perspective. METHODS: In a randomized controlled trial, participants with advanced COPD were assigned to 10 mg regular, oral sustained-release morphine or placebo twice daily for four weeks. Quality of life (COPD Assessment Test; CAT), quality-adjusted life years (QALY's; EQ-5D-5L), healthcare costs, productivity, and patient and family costs were collected. Incremental cost-effectivity ratio's (ICERs) using healthcare costs and CAT scores, and incremental cost-utility ratio's (ICURs) using societal costs and QALY's were calculated. RESULTS: Data of 106 of 124 participants were analyzed, of which 50 were in the morphine group (mean [SD] age 65.4 [8.0] years; 58 [55%] male). Both ICER and ICUR indicated dominance for morphine treatment. Sensitivity analyses substantiated these results. From a healthcare perspective, the probability that morphine is cost-effective at a willingness to pay €8000 for an minimal clinically important difference of 2 points increase in CAT score is 63%. From a societal perspective, the probability that morphine is cost-effective at a willingness to pay €20,000 per QALY is 78%. CONCLUSION: Morphine for four weeks is cost-effective regarding the healthcare and the societal perspective. To estimate the long-term costs and effects of morphine treatment, a study of longer follow-up should be performed. TRIAL REGISTRATION: ClinicalTrials.gov (NCT02429050).

The role of opioidergic system in modulating cost/benefit decision-making in alcohol-preferring AA rats and Wistar rats.

Research has highlighted the association of a positive family history of alcoholism with a positive treatment response to opioid antagonists in those with a gambling disorder. However, the role of the opioidergic system in gambling behavior is not well understood, and preclinical studies are needed to clarify this. In this study, Alko Alcohol (AA) and Wistar rats went through operant lever pressing training where the task was to choose the more profitable of two options. Different sized sucrose rewards guided the lever choices, and the probability of gaining rewards changed slowly to a level where choosing the smaller reward was the most profitable option. After training, rats were administered subcutaneously with opioid agonist morphine or opioid antagonist naltrexone to study the impact of opioidergic mechanisms on cost/benefit decisions. No difference was found in the decision-making between AA rats or Wistar rats after the morphine administration, but control data revealed a minor decision enhancing effect in AA rats. Naltrexone had no impact on the decisions in AA rats but promoted unprofitable decisions in Wistar rats. Supporting behavioral data showed that in both rat strains morphine increased, and naltrexone decreased, sucrose consumption. Naltrexone also increased the time to accomplish the operant task. The results suggest that opioid agonists could improve decision-making in cost-benefit settings in rats that are naturally prone to high alcohol drinking. The naltrexone results are ambiguous but may partly explain why opioid antagonists lack a positive pharmacotherapeutic effect in some subgroups of gamblers.

A preliminary assessment of vital-signs-integrated patient-assisted intravenous opioid analgesia (VPIA) for postsurgical pain.

BACKGROUND: We developed a Vital-signs-integrated Patient-assisted Intravenous opioid Analgesia (VPIA) analgesic infusion pump, a closed-loop vital signs monitoring and drug delivery system which embodied in a novel algorithm that took into account patients' vital signs (oxygen saturation, heart rate). The system aimed to allow responsive titration of personalized pain relief to optimize pain relief and reduce the risk of respiratory depression. Moreover, the system would be important to enable continuous monitoring of patients during delivery of opioid analgesia. METHODS: Nineteen patients who underwent elective gynecological surgery with postoperative patient controlled analgesia (PCA) with morphine were recruited. The subjects were followed up from their admission to the recovery room/ ward for at least 24 h until assessment of patient satisfaction on the VPIA analgesic infusion pump. RESULTS: The primary outcome measure of incidence of oxygen desaturation showed all patients had at least one episode of oxygen desaturation (< 95%) during the study period. Only 6 (31.6%) patients had oxygen desaturation that persisted for more than 5 min. The median percentage time spent during treatment that oxygen saturation fell below 95% was 1.9%. Fourteen (73.7%) out of 19 patients encountered safety pause, due to transient oxygen desaturation or bradycardia. The patients' median [IQR] pain scores at rest and at movement after post-op 24 h were 0.0 [2.0] and 3.0 [2.0], respectively. The average morphine consumption in the first 24 h was 12.5 ± 7.1 mg. All patients were satisfied with their experience with the VPIA analgesic infusion pump. CONCLUSIONS: The use of VPIA analgesic infusion pump, when integrated with continuous vital signs monitor and variable lockout algorithm, was able to provide pain relief with good patient satisfaction. TRIAL REGISTRATION: This study was registered on clinicaltrials.gov registry (NCT02804022) on 28 Feb 2016.

Slow release oral morphine versus methadone for opioid use disorder in the fentanyl era (pRESTO): Protocol for a non-inferiority randomized clinical trial.

BACKGROUND: North America is facing an unprecedented public health crisis of opioid-related morbidity and mortality, increasingly as a result of the introduction of illicitly manufactured fentanyl into the street drug market. Although the treatment of opioid use disorder (OUD) is a key element in the response to the opioid overdose epidemic, currently available pharmacotherapies (e.g., methadone, buprenorphine) may not be acceptable to or effective in all patients. Available evidence suggests that slow-release oral morphine (SROM) has similar efficacy rates as methadone with respect to promoting abstinence, and with improvements in a number of patient-reported outcomes among persons using heroin. However, little is known about the relative effectiveness and acceptability of SROM compared to methadone in the context of fentanyl use. This study aims to address this research gap. METHODS: pRESTO is a 24-week, open-label, two arm, non-inferiority, randomized controlled trial comparing SROM versus methadone for the treatment of OUD. Participants will be 298 clinically stable, non-pregnant adults with OUD, recruited from outpatient clinics in Vancouver, Canada, where the majority of the illicit opioids are contaminated with fentanyl. The primary outcome is suppression of illicit opioid use, measured by bi-weekly urine drug screens. Secondary outcomes include: treatment retention, medication safety, overdose events, treatment satisfaction, psychological functioning, changes in drug-related problems, changes in quality of life, opioid cravings, other substance use, and cost-effectiveness. DISCUSSION: pRESTO will be among the first studies to evaluate treatment options for individuals primarily using synthetic street opioids, providing important evidence to guide treatment strategies for this population.

Patient-Controlled Intravenous Morphine Analgesia Combined with Transcranial Direct Current Stimulation for Post-Thoracotomy Pain: A Cost-Effectiveness Study and A Feasibility For Its Future Implementation.

This prospective randomized study aims to evaluate the feasibility and cost-effectiveness of combining transcranial direct current stimulation (tDCS) with patient controlled intravenous morphine analgesia (PCA-IV) as part of multimodal analgesia after thoracotomy. Patients assigned to the active treatment group (a-tDCS, n = 27) received tDCS over the left primary motor cortex for five days, whereas patients assigned to the control group (sham-tDCS, n = 28) received sham tDCS stimulations. All patients received postoperative PCA-IV morphine. For cost-effectiveness analysis we used data about total amount of PCA-IV morphine and maximum visual analog pain scale with cough (VASP-Cmax). Direct costs of hospitalization were assumed as equal for both groups. Cost-effectiveness analysis was performed with the incremental cost-effectiveness ratio (ICER), expressed as the incremental cost (RSD or US$) per incremental gain in mm of VASP-Cmax reduction. Calculated ICER was 510.87 RSD per VASP-Cmax 1 mm reduction. Conversion on USA market (USA data 1.325 US$ for 1 mg of morphine) revealed ICER of 189.08 US$ or 18960.39 RSD/1 VASP-Cmax 1 mm reduction. Cost-effectiveness expressed through ICER showed significant reduction of PCA-IV morphine costs in the tDCS group. Further investigation of tDCS benefits with regards to reduction of postoperative pain treatment costs should also include the long-term benefits of reduced morphine use.

Postoperative outcomes following pediatric intracranial electrode monitoring: A case for stereoelectroencephalography (SEEG).

BACKGROUND: For patients with medically refractory epilepsy, intracranial electrode monitoring can help identify epileptogenic foci. Despite the increasing utilization of stereoelectroencephalography (SEEG), the relative risks or benefits associated with the technique when compared with the traditional subdural electrode monitoring (SDE) remain unclear, especially in the pediatric population. Our aim was to compare the outcomes of pediatric patients who received intracranial monitoring with SEEG or SDE (grids and strips). METHODS: We retrospectively studied 38 consecutive pediatric intracranial electrode monitoring cases performed at our institution from 2014 to 2017. Medical/surgical history and operative/postoperative records were reviewed. We also compared direct inpatient hospital costs associated with the two procedures. RESULTS: Stereoelectroencephalography and SDE cohorts both showed high likelihood of identifying epileptogenic zones (SEEG: 90.9%, SDE: 87.5%). Compared with SDE, SEEG patients had a significantly shorter operative time (118.7 versus 233.4 min, P < .001) and length of stay (6.2 versus 12.3 days, P < .001), including days spent in the intensive care unit (ICU; 1.4 versus 5.4 days, P < .001). Stereoelectroencephalography patients tended to report lower pain scores and used significantly less narcotic pain medications (54.2 versus 197.3 mg morphine equivalents, P = .005). No complications were observed. Stereoelectroencephalography and SDE cohorts had comparable inpatient hospital costs (P = .47). CONCLUSION: In comparison with subdural electrode placement, SEEG results in a similarly favorable clinical outcome, but with reduced operative time, decreased narcotic usage, and superior pain control without requiring significantly higher costs. The potential for an improved postoperative intracranial electrode monitoring experience makes SEEG especially suitable for pediatric patients.

The Impact of Morphine Equivalent Daily Dose Threshold Guidelines on Prescribed Dose in a Workers' Compensation Population.

BACKGROUND: Prescription opioid overdose has increased markedly and is of great concern among injured workers receiving workers' compensation insurance. Given the association between high daily dose of prescription opioids and negative health outcomes, state workers' compensation boards have disseminated Morphine Equivalent Daily Dose (MEDD) guidelines to discourage high-dose opioid prescribing. OBJECTIVE: To evaluate the impact of MEDD guidelines among workers' compensation claimants on prescribed opioid dose. METHODS: Workers' compensation claims data, 2010-2013 from 2 guideline states and 3 control states were utilized. The study design was an interrupted time series with comparison states and average monthly MEDD was the primary outcome. Policy variables were specified to allow for both instantaneous and gradual effects and additional stratified analyses examined evaluated the policies separately for individuals with and without acute pain, cancer, and high-dose baseline use to determine whether policies were being targeted as intended. RESULTS: After adjusting for covariates, state fixed-effects, and time trends, policy implementation was associated with a 9.26 mg decrease in MEDD (95% confidence interval, -13.96 to -4.56). Decreases in MEDD also became more pronounced over time and were larger in groups targeted by the policies. CONCLUSIONS: Passage of workers' compensation MEDD guidelines was associated with decreases in prescribed opioid dose among injured workers. Disseminating MEDD guidelines to doctors who treat workers' compensation cases may address an important risk factor for opioid-related mortality, while still allowing for autonomy in practice. Further research is needed to determine whether MEDD policies influence prescribing behavior and patient outcomes in other populations.

Naloxone-precipitated withdrawal ameliorates impairment of cost-benefit decision making in morphine-treated rats: Involvement of BDNF, p-GSK3-ß, and p-CREB in the amygdala.

Several studies indicated that morphine administration impairs cognitive brain functions. Therefore, in the current study, we investigated the effect of subchronic exposure to morphine and its withdrawal on effort- and/or delay-based forms of cost-benefit decision making and alterations in p-CREB/CREB ratio, p-GSK3ß/GSK3ß ratio, and BDNF level during decision making in the amygdala. Our data displayed an impairment of both forms of cost-benefit decision making following subchronic exposure to morphine. However, preference of high reward/high effort and/or high delay reward increased after naloxone injection. In molecular section, levels of BDNF and p-CREB/CREB ratio increased during cost-benefit decision making while p-GSK3ß/GSK3ß ratio decreased in both forms of decision making. In morphine-treated rats, level of BDNF and p-CREB/CREB ratio reduced during both forms of decision making while p-GSK3ß/GSK3ß ratio increased during delay-based and did not have a significant difference with the control group during effort-based decision making. On the withdrawal day, BDNF level raised while p-GSK3ß/GSK3ß ratio attenuated compared to morphine-treated group in both form of decision making. In addition, p-CREB/CREB ratio increased only during delay-based decision making on the withdrawal day. In conclusion, our data revealed that subchronic exposure to morphine interferes with the cost-benefit decision making may be via changes in level of BDNF, p-CREB/CREB and p-GSK3ß/GSK3ß ratio in the amygdala.

Opioid use prior to elective surgery is strongly associated with persistent use following surgery: an analysis of 14 354 Medicare patients.

BACKGROUND: Persistent opioid use following total joint replacement (TJR) surgery is common; however, the association between pre-surgical opioid use and surgery type has not been established. The objective of this study was to determine the association between pre-surgery opioid use and persistent post-surgery opioid use in TJR patients compared to other elective surgical patients. METHODS: This is a retrospective cohort study, of univariate and multinomial logistic regression of linked, de-identified Medicare Benefits Schedule and Pharmaceutical Benefits Schedule data, adjusted for perioperative opioid use, age and sex. Oral morphine equivalents daily doses (OMEDD) were calculated and opioid use was categorized into three mutually exclusive categories for each observation window: low (0-5 OMEDD), moderate (5-10 OMEDD), high (10+ OMEDD). Persistent opioid use was defined as opioid use between 180 and 270 days after the date of surgery. RESULTS: Persistent opioid use was associated with older age, female gender and pre-surgery opioid use. There was no increased risk for persistent opioid use for TJR patients compared to other surgical patients. The intensity of pre-surgery opioid usage is strongly associated with persistent opioid use in all observed surgical patients. CONCLUSIONS: Our results suggest that many patients who use opioids prior to surgery will persist in their opioid use following surgery. No association was found between persistent opioid use and TJR surgery, but rather a risk reduction compared to other elective surgeries when associations with opioid use are controlled for. Primary care clinicians and surgeons should monitor the duration and dosage of perioperative opioid use.

Comparative Assessment of the Effectiveness of Noncompetitive NMDA Receptor Antagonists Amantadine and Hemantane in Morphine Withdrawal Syndrome Model.

Activities of noncompetitive NMDA receptor antagonists (aminoadamantane derivatives) were assessed in random-bred rats with modeled morphine withdrawal syndrome. A single intraperitoneal injection of hemantane (10 or 20 mg/kg) significantly and dose-dependently moderated some behavioral symptoms (teeth-chattering, ptosis, and vocalization) and reduced total score of morphine withdrawal syndrome. In morphine-abstinent rats, hemantane partially prevented the decrease in the thresholds of tactile sensitivity, but had no effect on locomotor activity and body weight loss. Under conditions of morphine withdrawal, intraperitoneal injection of amantadine (10 or 20 mg/kg) decreased motor activity and promoted body weight loss in parallel with the development of mechanical allodynia, but had no effect on the total withdrawal score. Comparison of aminoadamantane derivatives by behavioral and physiological parameters demonstrated the advantage of hemantane during morphine abstinence indicating the need of its study as a promising anti-addiction remedy.

Dynamic assessment of the pupillary reflex in patients on high-dose opioids.

Background and aims Pupil size and reaction are influenced by opioids, an effect that is not considered to be affected by opioid tolerance. As clinicians have observed patients on high-dose opioids who exhibited seemingly normal pupil sizes, we wanted to dynamically assess the pupillary reflex in cancer patients on high-dose opioids. Methods We performed a dynamic assessment of the pupillary reflex in cancer patients on high-dose opioids and a control group of healthy volunteers using a portable, monocular, infrared pupillometer. We also performed a clinical examination and measured blood concentrations of opioids and their active metabolites. Results Sixty three patients who were on opioids for 2 months (median time) and on an oral morphine equivalent dose of 250 mg (median dose) were investigated. Most patients used more than one opioid. When correcting for age, pupil size in the group that had received no increase of opioid dose over the last 14 days was not significantly different from pupil size in the healthy volunteer group (p = 0.76), while the group that had increased the dose of opioids differed significantly from healthy volunteers (p = 0.006). We found no statistically significant correlation between total oral morphine equivalents and pupillary reactions or between blood opioid or opioid metabolite concentrations and baseline pupillary changes. Conclusion Pupillary changes do take place in patients on opioids. However, tolerance to these changes occurs when medication is not increased over time. Dynamic pupillometry can give additional information about the degree of tolerance to opioids. Implications These findings elucidate previous misconceptions regarding pupillary effects and tolerance to opioids.

Real-world misuse, abuse, and dependence of abuse-deterrent versus non-abuse-deterrent extended-release morphine in Medicaid non-cancer patients.

OBJECTIVE: Opioids with abuse-deterrent properties may reduce widespread abuse, misuse, and diversion of these products. This study aimed to quantify misuse, abuse, dependence, and health resource use of extended-release morphine sulfate with sequestered naltrexone hydrochloride (ER-MSN; EMBEDA®), compared with non-abuse-deterrent extended-release morphine (ERM) products in Medicaid non-cancer patients. METHODS: Administrative medical and pharmacy claims data were analyzed for 10 Medicaid states from 1 January 2015, to 30 June 2016. Patients were included if they received a prescription for ER-MSN or any oral, non-abuse-deterrent ERM. Index date was the date of first prescription for an ER-MSN or ERM. Abuse/dependence, non-fatal overdose, emergency department (ED) visits, and ED/inpatient readmissions were determined for each participant. An overall measure of misuse and abuse was also calculated. To account for differences in follow-up, all counts are expressed per 100 patient-years. RESULTS: There were 4,857 patients who received ER-MSN and 10,357 who received an ERM. The average age in the two cohorts was approximately 45 years old. From pre-index to follow-up, the number of patients per 100 patient-years with a diagnosis code indicating abuse or dependence increased by 0.91 (95% confidence interval [CI]: 0.85, 0.97) in the ER-MSN cohort and 2.23 (95% CI: 2.14, 2.32) in the ERM cohort. The number of patients per 100 patient-years with an opioid-related non-fatal overdose increased by 0.05 (95% CI: 0.04, 0.06) in the ER-MSN cohort compared with 0.11 (95% CI: 0.09, 0.13) in the ERM cohort. The opioid abuse overall composite score increased by 1.36 (95% CI: 1.24, 1.48) in the post-index period in the ER-MSN cohort compared to 3.21 (95% CI: 3.10, 3.32) in the ERM cohort. CONCLUSION: Misuse, abuse, and dependence events were numerically lower in patients receiving ER-MSN compared with those receiving ERM products.

Evaluations of Morphine and Fentanyl for Mechanically Ventilated Patients With Respiratory Disorders in Intensive Care: A Systematic Review of Methodological Trends and Reporting Quality.

BACKGROUND: Mechanically ventilated patients with respiratory disorders may require sedatives, such as opioids. OBJECTIVES: To define methodological trends, gaps, and the reporting quality of the comparative clinical and economic evaluations of fentanyl and morphine in ventilated patients in the intensive care unit. METHODS: We conducted a literature review of the MEDLINE, Embase, OVID, ScienceDirect, Springer Link, and EconLit databases, comparing studies in the management of ventilated patients with respiratory disorders in the intensive care unit using either fentanyl or morphine, or both. We assessed the methodological aspects of the literature characteristics and trends of, for example, modeling, data sources, cost calculation, and data analysis, appraising the quality of reporting via the CONsolidated Standards Of Reporting Trials, STrengthening the Reporting of OBservational studies in Epidemiology, and the Consolidated Health Economic Evaluation Reporting Standards checklists. RESULTS: Among 1327 articles, 33 (comprising 22 in adults, 8 in neonates, and 3 in pediatrics) met the inclusion criteria. No head-to-head morphine versus fentanyl evaluations explicitly confined to subjects with respiratory conditions were undertaken. Studies relied on various scales to measure the sedation level as a primary study outcome, limiting the comparability of study conclusions. Seven articles of adults were identified to be economic studies from the hospital perspective. On the basis of different endpoints, the same sedation regimen performed differently in various studies. None of the randomized controlled trials, observational cohorts, or pharmacoeconomics studies met most of the assessed reporting quality criteria. CONCLUSIONS: Our review identified poor reporting quality and high heterogeneity of methods used, potentially limiting the degree to which studies could be interpreted, decisions could be influenced, and findings could be generalized.

Intra-operative low-dose ketamine does not reduce the cost of post-operative pain management after surgery: a randomized controlled trial in a low-income country.

BACKGROUND: In developing countries, post-operative pain remains underestimated and undertreated due to economic constraints, lack of awareness and limited resources. In contrast, ketamine is an effective, readily available, easy to use and inexpensive drug frequently used in poor settings. OBJECTIVES: The aim of this study was to explore the overall reduction in the medication treatment cost of acute post-operative pain by adding intra-operative low-dose ketamine to traditional intravenous morphine for surgery in a low-income country. METHODS: A double blind randomized controlled trial with placebo-controlled parallel group was performed in Mulago National Hospital (Uganda). Consenting adults scheduled for elective surgery were randomized into two study arms: Group K received ketamine 0.15mg/kg bolus at induction and a continuous infusion of 0.12 mg/kg/hour till start of skin closure; Group C (control) received normal saline. Both groups received Morphine 0.1 mg/kg IV at debulking. The total medication cost was registered. NRS pain scores and other measurements such vital signs and incidence of major and minor side effects were also recorded. RESULTS: A total of 46 patients were included. Patients' baseline characteristics were comparable in both groups. No statistically significant difference was found between the groups concerning the overall medication cost of post-operative pain management. Pain scores, patients' satisfaction in the first 24 hours after surgery and hospital length of stay were similar in both groups. CONCLUSION: Our results do not support the utilization of intra-operative low dose ketamine as a cost-saving post-operative pain treatment strategy for all types of surgery in low-resource settings.

Effect of cultural background and healthcare environment on postoperative opioid requirement.

PURPOSE: The objective of this prospective observational study was to investigate the interactions between cultural background, healthcare environment, and postoperative pain experience. METHODS: We enrolled 128 Chinese patients living in rural mainland China and 134 patients in Hong Kong with a higher level of Western cultural influences (defined by educational attainment, place of residence, and ability to understand English). All patients had major abdominal surgery and received patient-controlled analgesia with intravenous morphine for postoperative pain relief. The primary endpoint was total opioid requirement up to 48 hr after surgery. Other measures included pain intensity, opioid-related side effects, and genetic markers for opioid responsiveness. RESULTS: The mean (95% confidence interval) cumulative opioid requirement, expressed as morphine equivalent, during the first 48 hr after surgery was significantly less in patients from mainland China (18.8 [15.7 to 22] mg) compared with patients from Hong Kong (42.0 [38.3 to 45.6] mg, P < 0.0001). In a multivariable analysis, opioid requirement was influenced by ethnicity, duration of surgery, and severity of pain upon admission to the postanesthetic care unit. CONCLUSIONS: These results suggest that postoperative pain behaviours and opioid requirement may be influenced by cultural background and healthcare environment in two populations of Chinese descent. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry (ACTRN12614000601639); registered 6 May, 2014.

RéSUMé: OBJECTIF: L'objectif de cette étude observationnelle prospective était d'étudier les interactions entre le contexte culturel, l'environnement de soins de santé et l'expérience de la douleur postopératoire. MéTHODES: Nous avons recruté 128 patients chinois vivant en zones rurales en Chine continentale et 134 patients vivant à Hong-Kong avec un haut niveau d'influences culturelles occidentales (définies par le niveau d'éducation atteint, le lieu de résidence et la capacité à comprendre l'anglais). Tous les patients avaient subi une chirurgie abdominale majeure et reçu une analgésie contrôlée par le patient par morphine intraveineuse pour le soulagement de la douleur postopératoire. Le critère d'évaluation principal était la demande totale en opioïdes pendant les 48 premières heures suivant la chirurgie. D'autres mesures ont inclus l'intensité de la douleur, les effets indésirables liés aux opioïdes et des marqueurs génétiques de sensibilité aux opioïdes. RéSULTATS: Le besoin cumulé moyen (intervalle de confiance à 95 %) cumulé en opioïdes, exprimé sous forme d'équivalent-morphine, au cours des 48 premières heures suivant la chirurgie était significativement inférieur pour les patients de Chine continentale (18,8 [15,7 à 22] mg) comparativement aux patients de Hong-Kong (42,0 [38,3 à 45,6] mg, P < 0,0001). Une analyse multifactorielle a montré que la demande en opioïdes était influencée par l'origine ethnique, la durée de l'intervention chirurgicale et l'intensité de la douleur au moment de l'arrivée dans l'unité de soins postanesthésiques. CONCLUSIONS: Ces résultats suggèrent que les comportements postopératoires envers la douleur et le besoin d'opioïdes peuvent être influencés par l'arrière-plan culturel et l'environnement des soins de santé dans deux populations différentes d'origine chinoise. ENREGISTREMENT DE L'ESSAI CLINIQUE: Registre des essais cliniques d'Australie et de Nouvelle-Zélande (ACTRN12614000601639); enregistré le 6 mai 2014.

Ensuring and Restoring Balance on Access to Controlled Substances for Medical and Scientific Purposes: Joint Statement from Palliative Care Organizations.

The central principle of "balance" represents the dual obligation of governments to establish a system of control that ensures the adequate availability of controlled substances for medical and scientific purposes while simultaneously preventing their nonmedical use, diversion, and trafficking, two primary goals of the international control system. On the one hand, although strong opioids, including morphine, are absolutely necessary for the relief of severe pain, legitimate access to opioids for pain treatment and palliative care is lacking in the majority of the world's countries. On the other hand, in a few high-income countries with higher consumption of prescription opioids, diversion and nonmedical use are increasingly prevalent. This report presents examples of unbalanced systems and a joint statement from global and regional palliative care organizations to promote development of balanced systems for optimal public health outcomes. Although nonmedical use of controlled substances poses a risk to society, the system of control is not intended to be a barrier to their availability for medical and scientific purposes, nor to interfere in their legitimate medical use for patient care. As representatives of palliative care organizations, we urge heads of state to act and to take measures to ensure and restore balanced systems in their countries and call on public health leaders and regulators to work together.

Evaluating the early impacts of delisting high-strength opioids on patterns of prescribing in Ontario. / Évaluation des premiers effets du retrait des opioïdes à forte concentration sur les schémas de prescription en Ontario.

INTRODUCTION: Ontario delisted high-strength fentanyl, hydromorphone and morphine from the public drug formulary for non-palliative care prescribers on 31 January, 2017. Our aim is to assess the early impact of this policy on prescribing patterns and to examine whether this impact varied by prescriber type, opioid type and opioid strength. METHODS: We conducted a population-based, cross-sectional study on palliative and non-palliative care patients dispensed fentanyl, hydromorphone or morphine through the Ontario public drug program between 1 January, 2014, and 31 July, 2017. For each month during the study period, we reported the total number of high-strength opioid recipients stratified by prescriber type, and the total volume of each drug dispensed, stratified by strength. We used interventional autoregressive integrated moving average (ARIMA) models to assess the policy's impact on prescribing patterns. RESULTS: We observed a 98% decrease in the total number of publicly funded recipients of high-strength opioids between December 2016 and July 2017 (5930 to 133 recipients) for all prescribers. The policy led to a significant decline in the total volume of all three opioids dispensed: hydromorphone from 20 374 621 to 16 952 097 mg (p < .01); morphine from 40 644 190 to 33 555 480 mg (p < .03); and fentanyl from 9 604 913 to 5 842 405 mcg/h (p < .01). For both fentanyl and hydromorphone, this reduction generally corresponded to an increase in the number of low-strength opioids dispensed. CONCLUSION: Delisting high-strength opioids substantially reduced the number of highstrength opioid recipients and reduced the overall volume of long-acting opioids dispensed in Ontario through the public drug program. Future studies should examine its impact on patient outcomes.

INTRODUCTION: Le 31 janvier 2017, l'Ontario a retiré le fentanyl, l'hydromorphone et la morphine à forte concentration des médicaments remboursables par les programmes publics de médicaments s'ils sont prescrits par des médecins en soins non palliatifs. Nous avons voulu évaluer les premiers effets de cette politique sur les schémas de prescription et déterminer si ces effets variaient en fonction du type de prescripteur ainsi que du type d'opioïdes et de leur concentration. MÉTHODOLOGIE: Nous avons mené une étude transversale représentative de la population auprès de patients nécessitant des soins palliatifs et des soins non palliatifs à qui du fentanyl, de l'hydromorphone ou de la morphine couverts par les programmes publics de médicaments de l'Ontario avaient été prescrits entre le 1er janvier 2014 et le 31 juillet 2017. Pour chacun des mois de la période à l'étude, nous avons calculé le nombre total de patients ayant reçu des opioïdes à forte concentration (réparti par type de prescripteurs) ainsi que le volume total de chaque médicament délivré (réparti par concentration). Nous avons utilisé des modèles autorégressifs à moyennes mobiles intégrés (ARMMI) interventionnels pour évaluer les effets des changements apportés par la politique sur les habitudes de prescription. RÉSULTATS: Entre décembre 2016 et juillet 2017, le nombre total de patients ayant reçu des opioïdes à forte concentration remboursés par le régime public a diminué de 98 % pour l'ensemble des prescripteurs, passant de 5 930 à 133. La nouvelle politique a entraîné une baisse substantielle du volume total des trois opioïdes délivrés, soit de 20 374 621 à 16 952 097 mg (p < 0,01) pour l'hydromorphone, de 40 644 190 à 33 555 480 mg (p < 0,03) pour la morphine et de 9 604 913 à 5 842 405 mcg/h (p < 0,01) pour le fentanyl. Dans le cas du fentanyl et de l'hydromorphone, cette diminution a dans l'ensemble coïncidé avec une augmentation du nombre d'opioïdes à faible concentration délivrés. CONCLUSION: Le retrait des opioïdes à forte concentration a sensiblement réduit le nombre de patients à qui ces médicaments ont été prescrits, ainsi que le volume total d'opioïdes à action prolongée délivrés en Ontario dans le cadre du régime public de médicaments. D'autres études devraient être menées pour en examiner les effets sur les patients.

Implementation of a Proactive Pilot Health Plan-Driven Opioid Tapering Program to Decrease Chronic Opioid Use for Conditions of the Back and Spine in a Medicaid Population.

BACKGROUND: In 2016, the Oregon Health Authority and the Health Evidence Review Commission implemented guidance for Oregon Medicaid members who were taking opioids for chronic pain related to conditions of the back and spine. This guidance required that an individualized taper plan be developed and initiated by January 1, 2017, and a discontinuation date for all chronic opioid therapy of January 1, 2018. PROGRAM DESCRIPTION: This program evaluated the effect of a proactive and voluntary health plan-driven opioid tapering program on morphine equivalent daily dose (MEDD) before the implementation of governmental guidance. Two mailings were sent to the providers of the targeted members with a variety of resources to facilitate an opioid taper. Pharmacy claims were analyzed to measure member opioid use, in the form of MEDD, after the provider outreach to be compared with their MEDDs before the outreach. OBSERVATIONS: A total of 113 members met the study inclusion criteria for the second provider outreach. Of the 19 members' providers who submitted responses via fax to the health plan in response to this outreach, 6 indicated they would initiate taper plans. Of the 6 members with taper plans, 5 had decreases in MEDD (3.6%, 4.5%, 42.9%, 45.5%, and 46.1%) after the 3-month data collection period, while the sixth member had no change in MEDD. Of the 113 members, 16 members (14.2%) had a decrease in MEDD; 23 members (20.4%) had no change in MEDD; and 72 members (63.7%) had an increase in MEDD. IMPLICATIONS: This study demonstrated that when a physician agrees to enroll patients in a health-plan driven clinical program it may result in decreased opioid use as referenced by MEDD. However, the results also showed the progressive nature of opioid use in this population. While these initial taper results were promising, a larger sample size and longer follow-up duration are needed to validate long-term adherence to an opioid tapering program and confirm that these results are attributable to the program and not other factors. DISCLOSURES: This study was sponsored by Moda Health. Patel is employed by Moda Health; Page and Saliba were employed by Moda Health during this project; and Traver was employed by Moda Health during part of this project. Page is now employed by Oregon State University (during the writing of this manuscript) to support the College of Pharmacy's contract with the Oregon Health Authority to provide professional pharmacist support for the Oregon Medicaid program. All other authors have nothing to disclose. Study concept and design were contributed by Page and Traver, who also collected the data. Data interpretation was performed by Page and Patel. The manuscript was written by Page and revised by Page, Patel, and Saliba.

Treating Neonatal Abstinence Syndrome in a Rural Hospital: Lessons Learned.

OBJECTIVE: Our level 1 nursery and pediatric unit in a rural hospital adopted a family-centered, symptom-based oral morphine weaning protocol for neonatal abstinence syndrome (NAS) in 2009. Length of stay (LOS), treatment duration (TD), and hospital charges for infants treated for NAS were then compared to published data in neonatal intensive care units (NICUs) nationwide. METHODS: The electronic medical records of infants born January 1, 2011, to April 1, 2017, whose discharge diagnosis included an ICD-9 or ICD-10 code for NAS or prenatal drug exposure were paired with maternal electronic medical record and reviewed. TD was calculated by subtracting the last day morphine was provided from the day it was started, and LOS was calculated by subtracting the discharge date from the date of birth. Infant characteristics, maximum Finnegan score, breastfeeding, discharge disposition, maternal demographics, prenatal use of drugs or medications, and toxicology results were abstracted. Predictors of TD and LOS were analyzed, and hospital charges were enumerated. RESULTS: Chart review identified 167 infants with prenatal drug exposure, 33 of whom were treated for NAS. Median TD for infants with NAS was 18 days (range, 9-37 days) compared to 15 days (range, 9-25 days) in NICUs. Median LOS for infants treated for NAS was 22 days (range, 12-41 days) compared to 20 days (range, 12-32 days) in NICUs, but hospital charges were less. Maternal prenatal use of cocaine (P = .016) predicted LOS. CONCLUSIONS: Family-centered NAS treatment in a rural hospital lasted 2 to 3 days longer than in NICUs, largely as a result of social issues; however, hospital charges were less.