Research

10 pages, 241 KiB

Open AccessArticle

The Complex Balance between Analgesic Efficacy, Change of Dose and Safety Profile Over Time, in Cancer Patients Treated with Opioids: Providing the Clinicians with an Evaluation Tool

by Oscar Corli, Luca Porcu, Claudia Santucci and Cristina Bosetti

J. Clin. Med. 2020, 9(2), 502; https://doi.org/10.3390/jcm9020502 - 12 Feb 2020

Cited by 2 | Viewed by 1794

Abstract

Background: Scanty data exist on the integration between the analgesic effect of opioids, dose changes, and adverse events in cancer patients. Methods: To provide further information on this issue, we analysed data on 498 advanced-stage cancer patients treated with strong opioids. At baseline [...] Read more.

Background: Scanty data exist on the integration between the analgesic effect of opioids, dose changes, and adverse events in cancer patients. Methods: To provide further information on this issue, we analysed data on 498 advanced-stage cancer patients treated with strong opioids. At baseline and three visits (at days 7, 14, and 21), pain intensity, oral morphine-equivalent daily dose, and the prevalence of major adverse events were measured. The proportion of responders (pain intensity decrease ≥30% from baseline) and non-responders, as well as of patients with low or high dose escalation, was calculated. Results: Pain intensity strongly decreased from baseline (pain intensity difference −4.0 at day 7 and −4.2 at day 21) in responders, while it was quite stable in non-responders (pain intensity difference −0.8 at day 7 and −0.9 at day 21). In low dose escalation patients (82.4% at final visit), daily dose changed from 52.3 to 65.3 mg; in high dose escalation patients (17.6%), it varied from 94.1 to 146.7 mg. Among responders, high dose escalation patients experienced significantly more frequent adverse events compared to low or high dose escalation patients, while no differences were observed in non-responders. Conclusions: The response to opioids results from the combination of three clinical aspects, which are strongly interrelated. These results provide some thoughts to help clinical evaluations and therapeutic decisions regarding opioid use. Full article

(This article belongs to the Special Issue Application of Opioids in Clinical Medicine)

13 pages, 242 KiB

Open AccessArticle

Genome-Wide Association Study of Opioid Cessation

by Jiayi W. Cox, Richard M. Sherva, Kathryn L. Lunetta, Emma C. Johnson, Nicholas G. Martin, Louisa Degenhardt, Arpana Agrawal, Elliot C. Nelson, Henry R. Kranzler, Joel Gelernter and Lindsay A. Farrer

J. Clin. Med. 2020, 9(1), 180; https://doi.org/10.3390/jcm9010180 - 09 Jan 2020

Cited by 14 | Viewed by 4514

Abstract

The United States is experiencing an epidemic of opioid use disorder (OUD) and overdose-related deaths. However, the genetic basis for the ability to discontinue opioid use has not been investigated. We performed a genome-wide association study (GWAS) of opioid cessation (defined as abstinence [...] Read more.

The United States is experiencing an epidemic of opioid use disorder (OUD) and overdose-related deaths. However, the genetic basis for the ability to discontinue opioid use has not been investigated. We performed a genome-wide association study (GWAS) of opioid cessation (defined as abstinence from illicit opioids for >1 year or <6 months before the interview date) in 1130 African American (AA) and 2919 European ancestry (EA) participants recruited for genetic studies of substance use disorders and who met lifetime Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria for OUD. Association tests performed separately within each ethnic group were combined by meta-analysis with results obtained from the Comorbidity and Trauma Study. Although there were no genome-wide significant associations, we found suggestive associations with nine independent loci, including three which are biologically relevant: rs4740988 in PTPRD (p_{AA + EA} = 2.24 × 10⁻⁶), rs36098404 in MYOM2 (p_EA = 2.24 × 10⁻⁶), and rs592026 in SNAP25-AS1 (p_EA = 6.53 × 10⁻⁶). Significant pathways identified in persons of European ancestry (EA) are related to vitamin D metabolism (p = 3.79 × 10⁻²) and fibroblast growth factor (FGF) signaling (p = 2.39 × 10⁻²). UK Biobank traits including smoking and drinking cessation and chronic back pain were significantly associated with opioid cessation using GWAS-derived polygenic risk scores. These results provide evidence for genetic influences on opioid cessation, suggest genetic overlap with other relevant traits, and may indicate potential novel therapeutic targets for OUD. Full article

(This article belongs to the Special Issue Application of Opioids in Clinical Medicine)

11 pages, 1079 KiB

Open AccessArticle

Changes in Opioid Prescribing Behaviors among Family Physicians Who Participated in a Weekly Tele-Mentoring Program

by Santana Díaz, Jane Zhao, Shawna Cronin, Susan Jaglal, Claire Bombardier and Andrea D. Furlan

J. Clin. Med. 2020, 9(1), 14; https://doi.org/10.3390/jcm9010014 - 19 Dec 2019

Cited by 5 | Viewed by 3494

Abstract

A weekly tele-mentoring program was implemented in Ontario to help address the growing opioid crisis through teaching and mentoring family physicians on the management of chronic pain and opioid prescribing. This study assessed opioid prescribing behaviours among family physicians who attended the tele-mentoring [...] Read more.

A weekly tele-mentoring program was implemented in Ontario to help address the growing opioid crisis through teaching and mentoring family physicians on the management of chronic pain and opioid prescribing. This study assessed opioid prescribing behaviours among family physicians who attended the tele-mentoring program compared to two groups of Ontario family physicians who did not attend the program. We conducted a retrospective cohort study with two control groups: a matched cohort, and a random sample of 3000 family physicians in Ontario. Each physician was followed from one year before the program, which is the index date, and one year after. We examined the number and proportion of patients on any opioid, on high dose opioids, and the average daily morphine equivalent doses prescribed to each patient. We included 24 physicians who participated in the program (2760 patients), 96 matched physicians (11,117 patients) and 3000 random family doctors (374,174 patients). We found that, at baseline, the tele-mentoring group had similar number of patients on any opioid, but more patients on high dose opioids than both control groups. There was no change in the number of patients on any opioid before and after the index date, but there was a significant reduction in high-dose opioid prescriptions in the extension for community healthcare outcomes (ECHO) group, compared to a non-significant increase in the matched cohort, and a non-significant reduction in the Ontario group during the same comparable periods. Participation in the program was associated with a greater reduction in high-dose opioid prescribing. Full article

(This article belongs to the Special Issue Application of Opioids in Clinical Medicine)

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9 pages, 948 KiB

Open AccessArticle

Comparison of Postoperative Opioid Consumption and Pain Scores in Primary Versus Repeat Cesarean Delivery in Opioid Naïve Patients

by Amanda Chao, Ioana Pasca, Matthew Alschuler, Jay Lee, Michelle Woodfin, Justin Pugh, Briahnna Austin, Mark Ringer and Davinder Ramsingh

J. Clin. Med. 2019, 8(12), 2221; https://doi.org/10.3390/jcm8122221 - 16 Dec 2019

Cited by 5 | Viewed by 2943

Abstract

Background: Cesarean deliveries represent a large percentage of deliveries worldwide. Patients undergoing repeat cesarean deliveries are known to have increased risks for surgical complications. However, little is known regarding potential differences in pain. We sought to compare postoperative opioid consumption and pain scores [...] Read more.

Background: Cesarean deliveries represent a large percentage of deliveries worldwide. Patients undergoing repeat cesarean deliveries are known to have increased risks for surgical complications. However, little is known regarding potential differences in pain. We sought to compare postoperative opioid consumption and pain scores in opioid naïve patients undergoing primary versus repeat non-emergent cesarean delivery. Methods: This was a retrospective cohort study. Patient inclusion criteria included: having a non-emergent cesarean delivery, receiving a spinal procedure for surgical anesthesia without general anesthesia, and following the same postoperative pain management protocols. Exclusion criteria included: history of opioid tolerance, illicit drug use, or prior, non-obstetric, major abdominal surgery. The primary outcome marker was total morphine equivalents consumed 0–72 h post-procedure compared between the primary versus repeat cesarean delivery groups. Secondary outcome markers were opioid consumption and pain scores in 24-h period increments for the first 72 h postoperatively. Results: 1617 patients were screened. 217 primary and 377 repeat cesarean deliveries met criteria for comparison. Reduced opioid consumption was demonstrated for the total opioid consumption 0–72 h for the repeat cesarean delivery group (median = 35) compared to the primary cesarean delivery group (median = 58), p = 0.0005. When divided into 24-h periods, differences were demonstrated for the 24–48 and 48–72 h periods but not the 0–24 h period. Pain scores did not differ statistically. Conclusion: Opioid naïve obstetric patients who undergo non-emergent repeat cesarean delivery demonstrate lower opioid consumption in the postoperative period. Providers should be aware of this potential difference in order to better educate patients and provide adequate pain management. Highlights: The study reviewed differences in opioid consumption between primary and repeat cesarean deliveries. All patients received the same protocol for spinal dosage and pain management. Repeat cesarean deliveries were associated with lower opioid consumption. Full article

(This article belongs to the Special Issue Application of Opioids in Clinical Medicine)

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11 pages, 1551 KiB

Open AccessArticle

The Trends in Opioid Use in Castile and Leon, Spain: A Population-Based Registry Analysis of Dispensations in 2015 to 2018

by Francisco Herrera-Gómez, Eduardo Gutierrez-Abejón, Ignacio Ayestarán, Paloma Criado-Espegel and F. Javier Álvarez

J. Clin. Med. 2019, 8(12), 2148; https://doi.org/10.3390/jcm8122148 - 05 Dec 2019

Cited by 10 | Viewed by 2213

Abstract

Opioids are driving-impairing medicines (DIM). To assess the evolution and trends of opioid analgesics use between 2015 and 2018 in Castile and Leon (Spain), a population-based registry study was conceived. The length of opioid use and its concomitant use with other DIMs were [...] Read more.

Opioids are driving-impairing medicines (DIM). To assess the evolution and trends of opioid analgesics use between 2015 and 2018 in Castile and Leon (Spain), a population-based registry study was conceived. The length of opioid use and its concomitant use with other DIMs were studied. Analyses were done considering age and gender distributions. Adjusted consumption for licensed drivers is also presented. Of the 5 million dispensations recorded between 2015 and 2018, opioid analgesics were dispensed to 11.44% of the general population and 8.72% of vehicle drivers. Increases among daily users (2.6 times higher) and chronic users (1.5% higher) were noted, supporting the overall increase in opioid use (1.5%). The use of multiple drugs including other DIMs was a common finding (mean ± SD, 2.54 ± 0.01). Acute use (5.26%) and chronic use (3.20%) were also frequent. Formulations combining opioid analgesics with nonopioid analgesics were preferred. The use of opioids increased in Spain between 2015 and 2018. Concomitant use with other DIMS especially affects women and the elderly. Frequent use of opioid analgesics with other DIMs is a serious problem for drivers and increases the risk of accidents. Promoting safe driving should be a main objective of health authorities, to be achieved by developing and implementing educational activities for healthcare professionals and patients. Full article

(This article belongs to the Special Issue Application of Opioids in Clinical Medicine)

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9 pages, 1303 KiB

Open AccessArticle

Remifentanil Alleviates Propofol-Induced Burst Suppression without Affecting Bispectral Index in Female Patients: A Randomized Controlled Trial

by Dahye Jung, Sungwon Yang, Min Soo Lee and Yoonki Lee

J. Clin. Med. 2019, 8(8), 1186; https://doi.org/10.3390/jcm8081186 - 08 Aug 2019

Cited by 2 | Viewed by 3393

Abstract

The bispectral index is affected by various factors, such as noxious stimuli and other drugs, such as muscle relaxants. The burst suppression ratio from bispectral index monitoring is correlated with electroencephalographic burst suppression, which is associated with deep anesthesia, metabolic disorders, and brain [...] Read more.

The bispectral index is affected by various factors, such as noxious stimuli and other drugs, such as muscle relaxants. The burst suppression ratio from bispectral index monitoring is correlated with electroencephalographic burst suppression, which is associated with deep anesthesia, metabolic disorders, and brain injury. We assessed patients undergoing total intravenous anesthesia and examined the effects of remifentanil on the bispectral index, burst suppression ratio, and hemodynamic changes immediately after loss of consciousness with propofol. Seventy American Society of Anesthesiologists physical status class I and II Korean female patients scheduled for general anesthesia were administered propofol with an effect-site concentration of 5 μg/mL, using a target-controlled infusion (TCI). After losing consciousness, patients received either saline or remifentanil at an effect-site concentration of 5 ng/mL for 10 min. During this period, we recorded the bispectral index values, including burst suppression ratio, blood pressure, and heart rate. With remifentanil infusion, burst suppression ratios were lower (p < 0.01) but bispectral values were not different. The burst suppression ratio was significantly different at 6, 7, 8, and 10 min after remifentanil infusion (p < 0.05). In female patients with propofol-induced unconsciousness, remifentanil alleviated the burst suppression ratio without affecting the bispectral value. Full article

(This article belongs to the Special Issue Application of Opioids in Clinical Medicine)

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8 pages, 689 KiB

Open AccessArticle

Remifentanil-Sparing Effect of Pectoral Nerve Block Type II in Breast Surgery under Surgical Pleth Index-Guided Analgesia during Total Intravenous Anesthesia

by Jung Ju Choi, Youn Yi Jo, Seung Hwan Kim, Wol Seon Jung, Dongchul Lee, Kwan Yeong Kim and Hyun Jeong Kwak

J. Clin. Med. 2019, 8(8), 1181; https://doi.org/10.3390/jcm8081181 - 07 Aug 2019

Cited by 18 | Viewed by 3322

Abstract

The pectoral nerve block type II (Pecs II block) can provide adequate perioperative analgesia in breast surgery. The surgical pleth index (SPI) is used to monitor the nociception balance using pulse oximetry. We investigated the remifentanil-sparing effect of Pecs II block under SPI [...] Read more.

The pectoral nerve block type II (Pecs II block) can provide adequate perioperative analgesia in breast surgery. The surgical pleth index (SPI) is used to monitor the nociception balance using pulse oximetry. We investigated the remifentanil-sparing effect of Pecs II block under SPI guided analgesia during total intravenous anesthesia (TIVA). Thirty-nine patients undergoing breast surgery under remifentanil-propofol anesthesia were randomly assigned to the intervention (Pecs group, n = 20) or control group (n = 19). Remifentanil and propofol concentrations were adjusted to maintain an SPI of 20–50 and a bispectral index of 40–60, respectively. The Pecs group received an ultrasound-guided Pecs II block preoperatively using 30 mL of 0.5% ropivacaine. Total infused remifentanil during the surgery was significantly less in the Pecs group than in the control group (6.8 ± 2.2 μg/kg/h vs. 10.1 ± 3.7 μg/kg/h, p = 0.001). Pain scores on arrival at the postanesthetic care unit (PACU) (3 (2–5) vs. 5 (4–7)) and the rescue analgesic requirement in the PACU (9 vs. 2) was significantly lower in the Pecs group than in the control group. In conclusion, Pecs II block was able to reduce the intraoperative remifentanil consumption by approximately 30% and improve the postoperative pain in PACU in patients undergoing breast surgery under SPI-guided analgesia during TIVA. Full article

(This article belongs to the Special Issue Application of Opioids in Clinical Medicine)

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18 pages, 2620 KiB

Open AccessArticle

Geospatial-Temporal and Demand Models for Opioid Admissions, Implications for Policy

by Lawrence Fulton, Zhijie Dong, F. Benjamin Zhan, Clemens Scott Kruse and Paula Stigler Granados

J. Clin. Med. 2019, 8(7), 993; https://doi.org/10.3390/jcm8070993 - 08 Jul 2019

Cited by 2 | Viewed by 3346

Abstract

Background: As the opioid epidemic continues, understanding the geospatial, temporal, and demand patterns is important for policymakers to assign resources and interdict individual, organization, and country-level bad actors. Methods: GIS geospatial-temporal analysis and extreme-gradient boosted random forests evaluate ICD-10 F11 opioid-related admissions and [...] Read more.

Background: As the opioid epidemic continues, understanding the geospatial, temporal, and demand patterns is important for policymakers to assign resources and interdict individual, organization, and country-level bad actors. Methods: GIS geospatial-temporal analysis and extreme-gradient boosted random forests evaluate ICD-10 F11 opioid-related admissions and admission rates using geospatial analysis, demand analysis, and explanatory models, respectively. The period of analysis was January 2016 through September 2018. Results: The analysis shows existing high opioid admissions in Chicago and New Jersey with emerging areas in Atlanta, Salt Lake City, Phoenix, and Las Vegas. High rates of admission (claims per 10,000 population) exist in the Appalachian area and on the Northeastern seaboard. Explanatory models suggest that hospital overall workload and financial variables might be used for allocating opioid-related treatment funds effectively. Gradient-boosted random forest models accounted for 87.8% of the variability of claims on blinded 20% test data. Conclusions: Based on the GIS analysis, opioid admissions appear to have spread geographically, while higher frequency rates are still found in some regions. Interdiction efforts require demand-analysis such as that provided in this study to allocate scarce resources for supply-side and demand-side interdiction: Prevention, treatment, and enforcement. Full article

(This article belongs to the Special Issue Application of Opioids in Clinical Medicine)

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