-
Journal of Pain and Symptom Management Jun 2024Opioid use prior to cancer diagnosis increases the likelihood of long-term use during survivorship, however, patterns of use before and after diagnosis are not...
BACKGROUND
Opioid use prior to cancer diagnosis increases the likelihood of long-term use during survivorship, however, patterns of use before and after diagnosis are not understood.
METHODS
We used population-based dispensing data linked with cancer and death notifications to identify two cohorts of adults residing in New South Wales initiating opioids within 24 months prior to a first cancer diagnosed between 2014 and 2016: 'survivors' (alive 24 months following diagnosis) and 'decedents' (died within 24 months). We used group-based trajectory modelling to identify trajectories of monthly opioid dispensings and dispensed oral morphine equivalent milligrams (OMEmg) during the 24 months before/after cancer diagnosis.
RESULTS
THERE WERE 21,843 SURVIVORS WITH FOUR PRE-DIAGNOSIS OPIOID DISPENSING TRAJECTORIES: : infrequent (58% of the cohort), late increasing (26%), moderate (10%), and sustained dispensing (6%). We observed an overall increase in dispensed OMEmg of 83 OMEmg (95%CI: 76-91) during the month of diagnosis, with strong opioid formulations comprising most treatment post-diagnosis. Within each pre-diagnosis opioid trajectory group, we observed five to six post-diagnosis trajectory groups, including no opioid dispensing. Moderate and sustained pre-diagnosis groups had large proportions of people continuing or increasing opioid dispensing after diagnosis, while small proportions discontinued opioid treatment. We observed similar trajectories in the decedent cohort.
CONCLUSIONS
There is considerable heterogeneity in opioid use before and after cancer diagnosis. Our findings suggest non-cancer factors drive a significant proportion of post-diagnosis opioid use, but use increased significantly from the month of cancer diagnosis and never returned to pre-diagnosis levels.
PubMed: 38878910
DOI: 10.1016/j.jpainsymman.2024.06.006 -
The Lancet. Global Health Jul 2024Opioid analgesics are essential for managing acute and chronic pain in diseases such as cancer. Inadequate opioid access remains a major public health concern in...
BACKGROUND
Opioid analgesics are essential for managing acute and chronic pain in diseases such as cancer. Inadequate opioid access remains a major public health concern in low-income regions including Africa. This study aimed to provide updated and comprehensive data on changes in opioid consumption, specifically in Africa.
METHODS
This longitudinal study has updated and expanded upon the International Narcotics Control Board data obtained from 1999 to 2021, assessing opioid consumption trends across all African countries. The defined daily doses for statistical purposes (SDDD) was used to determine the changes in opioid consumption in Africa. In addition, we used sub-analyses of the data to delve into individual substances, income levels, cancer incidence, cancer mortality, and sub-regional cluster analysis (based on the language spoken) to identify possible disparities and inform further research and tailored solutions.
FINDINGS
Our results indicate a persistently low and stagnant trend in opioid consumption between 2001-03 and 2019-21, from 73 SDDD (95% CI 69-77) to 55 SDDD (32-79). In-depth analysis revealed a morphine consumption increase from 735 SDDD in 1999 to 1115 SDDD in 2021. Moreover, opioid consumption was closely related to country-level income levels, with most of the low-income and lower-middle-income African countries reporting low opioid consumption. Notably, the escalating incidence and mortality rates associated with cancer in Africa indicated a misalignment with the trajectory of opioid use. Additionally, French-speaking African countries exhibited lower opioid usage than the rest of the continent, suggesting avenues for research into cultural, political, and social aspects.
INTERPRETATION
In the context of global doubling in opioid consumption, Africa has shown insufficient and stagnant opioid consumption during the last 20 years. These findings underscore the need for policy reform to facilitate safe and responsible opioid access in Africa, particularly for legitimate indications such as cancer pain and palliative care.
FUNDING
None.
TRANSLATION
For the French translation of the abstract see Supplementary Materials section.
Topics: Humans; Longitudinal Studies; Analgesics, Opioid; Africa; Neoplasms
PubMed: 38876759
DOI: 10.1016/S2214-109X(24)00146-3 -
Cancer Radiotherapie : Journal de La... Jun 2024Many cancer patients develop bone metastases, however the prognosis of overall survival differs. To provide an optimal treatment for these patients, especially towards...
PURPOSE
Many cancer patients develop bone metastases, however the prognosis of overall survival differs. To provide an optimal treatment for these patients, especially towards the end of life, a reliable prediction of survival is needed. The goal of this study was to find new clinical factors in relation to overall survival.
MATERIALS AND METHODS
Prospectively 22 clinical factors were collected from 734 patients. The Kaplan-Meier and Cox regression models were used.
RESULTS
Most patients were diagnosed with lung cancer (29%), followed by prostate (19.8%) and breast cancer (14.7%). Median overall survival was 6.4months. Fourteen clinical factors showed significance in the univariate analyses. In the multivariate analyses 6 factors were found to be significant for the overall survival: Karnofsky performance status, primary tumor, gender, total organs affected, morphine use and systemic treatment options after radiotherapy.
CONCLUSION
Morphine use and systemic treatment options after radiotherapy, Karnofsky performance status, primary tumor, gender and total organs affected are strong prediction factors on overall survival after palliative radiotherapy in patients with bone metastasis. These factors are easily applicable in the clinic.
PubMed: 38871605
DOI: 10.1016/j.canrad.2023.09.003 -
Saudi Pharmaceutical Journal : SPJ :... Jul 2024Chronic exposure to opioids can lead to downregulation of astrocytic glutamate transporter 1 (GLT-1), which regulates the majority of glutamate uptake. Studies from our...
Effects of novel beta-lactam, MC-100093, and ceftriaxone on astrocytic glutamate transporters and neuroinflammatory factors in nucleus accumbens of C57BL/6 mice exposed to escalated doses of morphine.
Chronic exposure to opioids can lead to downregulation of astrocytic glutamate transporter 1 (GLT-1), which regulates the majority of glutamate uptake. Studies from our lab revealed that beta-lactam antibiotic, ceftriaxone, attenuated hydrocodone-induced downregulation of GLT-1 as well as cystine/glutamate antiporter (xCT) expression in central reward brain regions. In this study, we investigated the effects of escalating doses of morphine and tested the efficacy of novel synthetic non-antibiotic drug, MC-100093, and ceftriaxone in attenuating the effects of morphine exposure in the expression of GLT-1, xCT, and neuroinflammatory factors (IL-6 and TGF-β) in the nucleus accumbens (NAc). This study also investigated the effects of morphine and beta-lactams in locomotor activity, spontaneous alternation percentage (SAP) and number of entries in Y maze since opioids have effects in locomotor sensitization. Mice were exposed to moderate dose of morphine (20 mg/kg, i.p.) on days 1, 3, 5, 7, and a higher dose of morphine (150 mg/kg, i.p.) on day 9, and these mice were then behaviorally tested and euthanized on Day 10. Western blot analysis showed that exposure to morphine downregulated GLT-1 and xCT expression in the NAc, and both MC-100093 and ceftriaxone attenuated these effects. In addition, morphine exposure increased IL-6 mRNA and TGF-β mRNA expression, and MC-100093 and ceftriaxone attenuated only the effect on IL-6 mRNA expression in the NAc. Furthermore, morphine exposure induced an increase in distance travelled, and MC-100093 and ceftriaxone attenuated this effect. In addition, morphine exposure decreased the SAP and increased the number of arm entries in Y maze, however, neither MC-100093 nor ceftriaxone showed any attenuating effect. Our findings demonstrated for the first time that MC-100093 and ceftriaxone attenuated morphine-induced downregulation of GLT-1 and xCT expression, and morphine-induced increase in neuroinflammatory factor, IL-6, as well as hyperactivity. These findings revealed the beneficial therapeutic effects of MC-100093 and ceftriaxone against the effects of exposure to escalated doses of morphine.
PubMed: 38868175
DOI: 10.1016/j.jsps.2024.102108 -
Trials Jun 2024Critically ill patients are exposed to several physical and emotional stressors, needing analgesic and sedative drugs to tolerate invasive procedures and the harsh...
BACKGROUND
Critically ill patients are exposed to several physical and emotional stressors, needing analgesic and sedative drugs to tolerate invasive procedures and the harsh intensive care unit (ICU) environment. However, this pharmacological therapy presents several side effects: guidelines suggest using a light sedation target, keeping critically ill patients calm, conscious, and cooperative. Personalized music therapy (MT) can reduce stress and anxiety, decreasing the need for drugs. The aim of the current investigation is to compare different approaches for MT in the ICU: a personalized approach, with music selected by patients/families and listened through headphones, or a generalized approach, with ambient music chosen by a music therapist and transmitted through speakers.
PRIMARY OUTCOME
number of days "free from neuroactive drugs" in the first 28 days after ICU admission.
SECONDARY OUTCOMES
total amount of neuroactive drugs (midazolam, propofol, morphine, fentanyl, haloperidol), stress during ICU stay (sleep at night, anxiety and agitation, use of physical restraints, stressors evaluated at discharge), the feasibility of generalized MT (interruptions requested by staff members and patients/families).
METHODS
Randomized, controlled trial with three groups of critically ill adults: a control group, without MT; a personalized MT group, with music for at least 2 h per day; a generalized MT group, with music for 12.5 h/day, subdivided into fifteen 50-min periods.
DISCUSSION
One hundred fifty-three patients are expected to be enrolled. This publication presents the rationale and the study methods, particularly the strategies used to build the generalized MT playlist. From a preliminary analysis, generalized MT seems feasible in the ICU and is positively received by staff members, critically ill patients, and families.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT03280329. September 12, 2017.
Topics: Humans; Music Therapy; Critical Illness; Randomized Controlled Trials as Topic; Time Factors; Hypnotics and Sedatives; Treatment Outcome; Intensive Care Units; Stress, Psychological; Critical Care; Analgesics
PubMed: 38867317
DOI: 10.1186/s13063-024-08220-8 -
Drug Metabolism and Disposition: the... Jun 2024The role of the kidney as an excretory organ for exogenous and endogenous compounds is well recognized, but there is a wealth of data demonstrating that the kidney has...
The role of the kidney as an excretory organ for exogenous and endogenous compounds is well recognized, but there is a wealth of data demonstrating that the kidney has significant metabolizing capacity for a variety of exogenous and endogenous compounds that in some cases surpass the liver. The induction of drug-metabolizing enzymes by some chemicals can cause drug-drug interactions and intraindividual variability in drug clearance. In this study, we evaluated the expression and induction of cytochrome P450 (P450) and UDP-glucuronosyltransferase (UGT) isoforms in 3D-cultured primary human renal proximal tubule epithelial cells (RPTEC) to elucidate their utility as models of renal drug metabolism. CYP2B6, CYP2E1, CYP3A4, CYP3A5, and all detected UGTs (UGT1A1, UGT1A4, UGT1A6, UGT1A9, and UGT2B7) mRNA levels in 3D-RPTEC were significantly higher than those in 2D-RPTEC and HK-2 cells and were close to the levels in the human kidney cortex. CYP1B1 and CYP2J2 mRNA levels in 3D-RPTEC were comparable to those in 2D-RPTEC, HK-2 cells, and the human kidney cortex. Midazolam 1'-hydroxylation, trifluoperazine N-glucuronidation, serotonin O-glucuronidation, propofol O-glucuronidation, and morphine 3-glucuronidation in the 3D-RPTEC were significantly higher than the 2D-RPTEC and comparable to those in the HepaRG cells, although bupropion, ebastine, and calcitriol hydroxylations were not different between the 2D- and 3D-RPTEC. Treatment with ligands of the aryl hydrocarbon receptor and farnesoid X receptor induced CYP1A1 and UGT2B4 expression, respectively, in 3D-RPTEC compared to 2D-RPTEC. We provided information on the expression, activity, and induction abilities of P450s and UGTs in 3D-RPTEC as an in vitro human renal metabolism model. This study demonstrated that the expression of P450s and UGTs in 3D-RPTEC was higher than those in 2D-RPTEC and HK-2 cells. The results were comparable to that in the human kidney cortex. 3D-RPTEC are useful for evaluating the induction of kidney P450s, UGTs, and human renal drug metabolism .
PubMed: 38866474
DOI: 10.1124/dmd.124.001685 -
Frontiers in Pharmacology 2024As a class of analgesics, opioids are frequently used to treat both acute and chronic moderate to severe pain. Patients frequently receive opioid painkillers after...
BACKGROUND
As a class of analgesics, opioids are frequently used to treat both acute and chronic moderate to severe pain. Patients frequently receive opioid painkillers after orthopedic accidents or surgeries. Evidence suggests that opioid drug users have a 55.1% higher risk of fracture and poor bone repair than non-users of opioid drugs. The key pathogenic alterations in the incidence and progression of poor bone repair are over apoptosis and aging of osteoblasts due to the stress caused by oxidation. Dexmedetomidine (Dex) has been proven to protect against a variety of degenerative illnesses by reducing oxidative stress. However, nothing is known about how it affects bone repair.
METHODS
PI3K/Akt/Nrf2 pathway was detected by immunofluorescence and Western blot. SOD, CAT, JC-1, dihydroethidium and mitosox were used in the Oxidative Stress. Micro-CT, H&E and Masson's staining, immunohistochemically were performed to evaluate the therapeutic effects of DEX on calvarial defects in the morphine-induced rat model.
RESULTS
We found that morphine-induced an imbalance in the metabolism and catabolism of primary rat Osteoblasts. However, these conditions could be inhibited by DEX treatment. In the meantime, DEX induced the expression of Nrf2-regulated antioxidant enzymes such as NQO1, HO-1, GCLm, GCLc, and TrxR1. DEX-mediated Nrf2 activation is linked to the PI3K/Akt signaling system. Furthermore, it has been established that intravenous DEX enhanced the growth of bone healing in a model of a surgically produced rat cranial lesion.
CONCLUSION
This is the first description of the unique DEX mechanism acting as a Nrf2 activator against morphine-mediated oxidative harm, raising the possibility that the substance may be used to prevent bone defects.
PubMed: 38863982
DOI: 10.3389/fphar.2024.1396713 -
The Journal of Pediatric Pharmacology... Jun 2024The choice of optimal analgesia following an adenotonsillectomy is a clinical issue because of the risk of respiratory depression and bleeding. The objective of this...
OBJECTIVE
The choice of optimal analgesia following an adenotonsillectomy is a clinical issue because of the risk of respiratory depression and bleeding. The objective of this study was to assess the effect of celecoxib on opioid use and pain scores in children hospitalized after adenotonsillectomy and to document its adverse effects.
METHODS
This retrospective study was conducted in a tertiary care pediatric hospital. We compared a group of subjects aged 1 to 17 years who were prescribed celecoxib and opioids between January 2017 and June 2020 following an adenotonsillectomy during a 3-day or less hospitalization to a group of matched controls for sex, age, and length of stay who were prescribed opioids.
RESULTS
A total of 228 patients were identified (76 in the celecoxib + opioids group, 152 in the control group). Opioid use, in oral morphine equivalent daily dose, was lower in the celecoxib + opioids group at 0 to 24 hours of hospitalization (0.15 vs 0.20 mg/kg/day, p = 0.05). Initiating celecoxib within 24 hours of surgery (n = 60) significantly reduced opioid requirement for up to 48 hours compared with controls (0-24 hours: 0.12 vs 0.20 mg/kg/day, p = 0.002; 25-48 hours: 0.02 vs 0.09 mg/kg/day, p = 0.001). A shorter length of stay was observed for patients receiving celecoxib + opioids during the first 24-hour post--operative period (27 vs 32 hours, p = 0.01). With celecoxib use, no significant change in pain scores and occurrence of adverse effects including bleeding was found.
CONCLUSIONS
Using celecoxib early after an adenotonsillectomy has reduced both opioid use and duration of hospital stay without increasing adverse effects or bleeding.
PubMed: 38863864
DOI: 10.5863/1551-6776-29.3.255 -
Upsala Journal of Medical Sciences 2024Standard dosages of analgesic and sedative drugs are given to intensive care patients. The resulting range of blood concentrations and corresponding clinical responses...
BACKGROUND
Standard dosages of analgesic and sedative drugs are given to intensive care patients. The resulting range of blood concentrations and corresponding clinical responses need to be better examined. The purpose of this study was to describe daily dosages, measured blood concentrations, and clinical responses in critically ill patients. The purpose was also to contribute to establishing whole blood concentration reference values of the drugs investigated.
METHODS
A descriptive study of prospectively collected data from 302 admissions to a general intensive care unit (ICU) at a university hospital. Ten drugs (clonidine, fentanyl, morphine, dexmedetomidine, ketamine, ketobemidone, midazolam, paracetamol, propofol, and thiopental) were investigated, and daily dosages recorded. Blood samples were collected twice daily, and drug concentrations were measured. Clinical responses were registered using Richmond agitation-sedation scale (RASS) and Numeric rating scale (NRS).
RESULTS
Drug dosages were within recommended dose ranges. Blood concentrations for all 10 drugs showed a wide variation within the cohort, but only 3% were above therapeutic interval where clonidine (57 of 122) and midazolam (38 of 122) dominated. RASS and NRS were not correlated to drug concentrations.
CONCLUSION
Using recommended dose intervals for analgesic and sedative drugs in the ICU setting combined with regular monitoring of clinical responses such as RASS and NRS leads to 97% of concentrations being below the upper limit in the therapeutic interval. This study contributes to whole blood drug concentration reference values regarding these 10 drugs.
Topics: Humans; Hypnotics and Sedatives; Analgesics; Male; Female; Middle Aged; Aged; Intensive Care Units; Prospective Studies; Adult; Midazolam; Critical Care; Dexmedetomidine; Fentanyl; Critical Illness; Propofol; Clonidine; Ketamine; Morphine; Aged, 80 and over; Dose-Response Relationship, Drug; Thiopental; Acetaminophen
PubMed: 38863729
DOI: 10.48101/ujms.v129.10560 -
Paediatric & Neonatal Pain Jun 2024Postoperative care pathways for adolescent idiopathic scoliosis patients undergoing posterior spinal fusion have demonstrated decreases in postoperative opioid...
Postoperative care pathways for adolescent idiopathic scoliosis patients undergoing posterior spinal fusion have demonstrated decreases in postoperative opioid consumption, improved pain control, and lead to decreased lengths of stay. Our objective was to implement postoperative steroids to reduce acute postoperative opioid consumption, pain scores, and length of stay. Dosing consisted of intravenous dexamethasone 0.1 mg/kg up to 4 mg per dose for a total of three doses at 8, 16, and 24 h postoperatively. As part of a quality initiative, we compared three cohorts of patients. The initial retrospective epidural cohort (EPI) ( = 59) had surgeon placed epidural catheters with infusion of ropivacaine 0.1% postoperatively for 18-24 h. Following an institutional change in postoperative care, epidural use was discontinued. A second cohort ( = 149), with prospectively collected data, received a surgeon placed erector spinae plane block and wound infiltration with a combination of liposomal and plain bupivacaine (LB). A third cohort ( = 168) was evaluated prospectively. This cohort received a surgeon placed erector spinae plane block and wound infiltration with liposomal and plain bupivacaine and additionally received postoperative dexamethasone for three doses (LB + D). Compared to the LB cohort, the LB + D cohort demonstrated statistically significant decreases in oral milligram morphine equivalents per kilogram at 0-24, 24-48, and 48-72 h. There was a statistically significant difference in median pain scores at 24-48 and 48-72 h in LB + D versus LB. The LB + D cohort's median length of stay in hours was significantly less compared to the LB cohort (52 h vs. 70 h, < 0.0001). Postoperative intravenous dexamethasone was added to an established postoperative care pathway for patients undergoing posterior spinal fusion for idiopathic scoliosis resulting in decreased VAS pain scores, opioid consumption, and shorter length of stay.
PubMed: 38863457
DOI: 10.1002/pne2.12117