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PloS One 2024Opioids administered in hospital during the immediate postoperative period are likely to influence post-surgical outcomes, but inpatient prescribing during the admission...
BACKGROUND
Opioids administered in hospital during the immediate postoperative period are likely to influence post-surgical outcomes, but inpatient prescribing during the admission is challenging to access. Modified-release(MR) preparations have been especially associated with harm, whilst certain populations such as the elderly or those with renal impairment may be vulnerable to complications. This study aimed to assess postoperative opioid utilisation patterns during hospital stay for people admitted for major/orthopaedic surgery.
METHODS
Patients admitted to a teaching hospital in the North-West of England between 2010-2021 for major/orthopaedic surgery with an admission for ≥1 day were included. We examined opioid administrations in the first seven days post-surgery in hospital, and "first 48 hours" were defined as the initial period. Proportions of MR opioids, initial immediate-release(IR) oxycodone and initial morphine milligram equivalents (MME)/day were calculated and summarised by calendar year. We also assessed the proportion of patients prescribed an opioid at discharge.
RESULTS
Among patients admitted for major/orthopaedic surgery, 71.1% of patients administered opioids during their hospitalisation. In total 50,496 patients with 60,167 hospital admissions were evaluated. Between 2010-2017 MR opioids increased from 8.7% to 16.1% and dropped to 11.6% in 2021. Initial use of oxycodone IR among younger patients (≤70 years) rose from 8.3% to 25.5% (2010-2017) and dropped to 17.2% in 2021. The proportion of patients on ≥50MME/day ranged from 13% (2021) to 22.9% (2010). Of the patients administered an opioid in hospital, 26,920 (53.3%) patients were discharged on an opioid.
CONCLUSIONS
In patients hospitalised with major/orthopaedic surgery, 4 in 6 patients were administered an opioid. We observed a high frequency of administered MR opioids in adult patients and initial oxycodone IR in the ≤70 age group. Patients prescribed with ≥50MME/day ranged between 13-22.9%. This is the first published study evaluating UK inpatient opioid use, which highlights opportunities for improving safer prescribing in line with latest recommendations.
Topics: Humans; Analgesics, Opioid; Male; Female; Middle Aged; Aged; Retrospective Studies; Pain, Postoperative; Orthopedic Procedures; Adult; Electronic Prescribing; Inpatients; England; Hospitalization; Aged, 80 and over; Oxycodone; Adolescent
PubMed: 38917135
DOI: 10.1371/journal.pone.0305531 -
Journal of Palliative Medicine Jun 2024Delirium management is crucial in palliative care. Morphine effectively relieves dyspnea due to heart failure. However, the effect of morphine, which is used to relieve...
Delirium management is crucial in palliative care. Morphine effectively relieves dyspnea due to heart failure. However, the effect of morphine, which is used to relieve dyspnea due to heart failure, on the incidence of delirium has not been examined to date. To evaluate the effect of morphine, which is used to relieve dyspnea due to heart failure, on delirium. Retrospective observational study. Subjects were identified from Osaka University Hospital records, located in Japan, from January 1, 2010, to September 30, 2021. The case group consisted of admissions for heart failure or cardiomyopathy registered in electronic medical records. Morphine was administered to relieve dyspnea due to heart failure, and no surgeries or procedures were performed. The control group consisted of admissions for heart failure or cardiomyopathy in the Diagnosis Procedure Combination (DPC) database, which did not include administration of morphine, oxycodone, or fentanyl during the hospitalization period and patients did not undergo surgery or any other procedure. The incidence of delirium was assessed. The odds ratios for morphine in the multivariate logistic regression analysis with propensity score and univariate logistic regression analysis after propensity score matching were 1.406 (95% confidence interval (CI) [0.249-7.957]) and 1.034 (95% CI [0.902-1.185]), respectively. Morphine, which is used to relieve dyspnea due to heart failure, had minimal effect on the incidence of delirium. This information is likely to be beneficial for the future use of morphine in the management of dyspnea in patients with heart failure.
PubMed: 38916066
DOI: 10.1089/jpm.2023.0704 -
International Journal of Molecular... May 2024The impact of age on mesenchymal stromal cell (MSC) characteristics has been well researched. However, increased age is concomitant with increased prevalence of...
The impact of age on mesenchymal stromal cell (MSC) characteristics has been well researched. However, increased age is concomitant with increased prevalence of polypharmacy. This adjustable factor may have further implications for the functionality of MSCs and the effectiveness of autologous MSC procedures. We applied hyperspectral microscopy of cell autofluorescence-a non-invasive imaging technique used to characterise cytometabolic heterogeneity-to identify changes in the autofluorescence signals of MSCs from (1) young mice, (2) old mice, (3) young mice randomised to receive polypharmacy (9-10 weeks of oral therapeutic doses of simvastatin, metoprolol, oxycodone, oxybutynin and citalopram), and (4) old mice randomised to receive polypharmacy. Principal Component Analysis and Logistic Regression Analysis were used to assess alterations in spectral and associated metabolic characteristics. Modelling demonstrated that cells from young mice receiving polypharmacy had less NAD(P)H and increased porphyrin relative to cells from old control mice, allowing for effective separation of the two groups (AUC of ROC curve > 0.94). Similarly, cells from old polypharmacy mice were accurately separated from those from young controls due to lower levels of NAD(P)H ( < 0.001) and higher porphyrin ( < 0.001), allowing for an extremely accurate logistic regression (AUC of ROC curve = 0.99). This polypharmacy regimen may have a more profound impact on MSCs than ageing, and can simultaneously reduce optical redox ratio (ORR) and increase porphyrin levels. This has implications for the use of autologous MSCs for older patients with chronic disease.
Topics: Animals; Mesenchymal Stem Cells; Mice; Polypharmacy; Aging; Male; Optical Imaging; NADP
PubMed: 38892017
DOI: 10.3390/ijms25115830 -
Journal of Psychopharmacology (Oxford,... Jun 2024The orexin (OX) system has received increasing interest as a potential target for treating substance use disorder. OX transmission in the posterior paraventricular...
BACKGROUND
The orexin (OX) system has received increasing interest as a potential target for treating substance use disorder. OX transmission in the posterior paraventricular nucleus of the thalamus (pPVT), an area activated by highly salient stimuli that are both reinforcing and aversive, mediates cue- and stress-induced reinstatement of reward-seeking behavior. Oral administration of suvorexant (SUV), a dual OX receptor (OXR) antagonist (DORA), selectively reduced conditioned reinstatement of oxycodone-seeking behavior and stress-induced reinstatement of alcohol-seeking behavior in dependent rats.
AIMS
This study tested whether OXR blockade in the pPVT with SUV reduces oxycodone or sweetened condensed milk (SCM) seeking elicited by conditioned cues or stress.
METHODS
Male Wistar rats were trained to self-administer oxycodone (0.15 mg/kg, i.v., 8 h/day) or SCM (0.1 ml, 2:1 dilution [v/v], 30 min/day). After extinction, we tested the ability of intra-pPVT SUV (15 µg/0.5 µl) to prevent reinstatement of oxycodone or SCM seeking elicited by conditioned cues or footshock stress.
RESULTS
The rats acquired oxycodone and SCM self-administration, and oxycodone intake correlated with signs of physical opioid withdrawal, confirming dependence. Following extinction, the presentation of conditioned cues or footshock elicited reinstatement of oxycodone- and SCM-seeking behavior. Intra-pPVT SUV blocked stress-induced reinstatement of oxycodone seeking but not conditioned reinstatement of oxycodone or SCM seeking or stress-induced reinstatement of SCM seeking.
CONCLUSIONS
The results indicate that OXR signaling in the pPVT is critical for stress-induced reinstatement of oxycodone seeking, further corroborating OXRs as treatment targets for opioid use disorder.
PubMed: 38888086
DOI: 10.1177/02698811241260989 -
Biomedicine & Pharmacotherapy =... Jul 2024Several opioids have pharmacogenetic and drug-drug interactions which may compromise their analgesic effectiveness, but are not routinely implemented into supportive... (Observational Study)
Observational Study
BACKGROUND
Several opioids have pharmacogenetic and drug-drug interactions which may compromise their analgesic effectiveness, but are not routinely implemented into supportive pain management. We hypothesized that CYP2D6 phenotypes and concomitant use of CYP2D6 substrates or inhibitors would correlate with opioid analgesic outcomes.
MATERIALS AND METHODS
An observational cross-sectional study was conducted with 263 adult chronic non cancer pain (CNCP) patients from a real-world pain unit under long-term CYP2D6-related opioid treatment (tramadol, hydromorphone, tapentadol or oxycodone). Metabolizer phenotype (ultrarapid [UM], normal [NM], intermediate [IM] or poor [PM]) was determined by the CYP2D6 genotype. The socio-demographic (sex, age, employment status), clinical (pain intensity and relief, neuropathic component, quality of life, disability, anxiety and depression), pharmacological (opioid doses and concomitant pharmacotherapy) and safety (adverse events) variables were recorded.
RESULTS
The whole population (66 % female, 65 (14) years old, 70 % retired and 63 % attended for low back pain) were classified as PM (5 %), IM (32 %), NM (56 %) and UM (6 %). Multiple linear and logistic regressions showed higher pain intensity and neuropathic component at younger ages when using any CYP2D6 substrate (p = 0.022) or inhibitor (p = 0.030) drug, respectively, with poorer pain relief when CYP2D6 inhibitors (p=0.030) were present.
CONCLUSION
The concomitant use of CYP2D6 substrates or inhibitors during opioid therapy for CNCP may result in lack of analgesic effectiveness. This aspect could be relevant for pharmacological decision making during CNCP management.
Topics: Humans; Male; Female; Cytochrome P-450 CYP2D6; Analgesics, Opioid; Drug Interactions; Cross-Sectional Studies; Cytochrome P-450 CYP2D6 Inhibitors; Middle Aged; Aged; Pain Management; Chronic Pain; Treatment Outcome; Adult; Pain Measurement
PubMed: 38876046
DOI: 10.1016/j.biopha.2024.116882 -
Journal of Neuroimmune Pharmacology :... Jun 2024The opioid epidemic has received considerable attention, but the impact on perinatal opioid-exposed (POE) offspring remains underexplored. This study addresses the...
The opioid epidemic has received considerable attention, but the impact on perinatal opioid-exposed (POE) offspring remains underexplored. This study addresses the emerging public health challenge of understanding and treating POE children. We examined two scenarios using preclinical models: offspring exposed to oxycodone (OXY) in utero (IUO) and acute postnatal OXY (PNO). We hypothesized exposure to OXY during pregnancy primes offspring for neurodevelopmental deficits and severity of deficits is dependent on timing of exposure. Notable findings include reduced head size and brain weight in offspring. Molecular analyses revealed significantly lower levels of inflammasome-specific genes in the prefrontal cortex (PFC). Gene Set Enrichment Analysis (GSEA) and Ingenuity Pathway Analysis (IPA) highlighted the enrichment of genes associated with mitochondrial and synapse dysfunction in POE offspring. Western blot analysis validated IPA predictions of mitochondrial dysfunction in PFC-derived synaptosomes. Behavioral studies identified significant social deficits in POE offspring. This study presents the first comparative analysis of acute PNO- and IUO-offspring during early adolescence finding acute PNO-offspring have considerably greater deficits. The striking difference in deficit severity in acute PNO-offspring suggests that exposure to opioids in late pregnancy pose the greatest risk for offspring well-being.
Topics: Animals; Oxycodone; Pregnancy; Female; Prenatal Exposure Delayed Effects; Male; Analgesics, Opioid; Behavior, Animal; Rats; Rats, Sprague-Dawley; Neurodevelopmental Disorders; Prefrontal Cortex
PubMed: 38874861
DOI: 10.1007/s11481-024-10129-7 -
Biomedicine & Pharmacotherapy =... Jul 2024The lysine-specific demethylase 1 (KDM1A) is reported to be a regulator in learning and memory. However, the effect of KDM1A in oxycodone rewarding memory has yet to be...
The lysine-specific demethylase 1 (KDM1A) is reported to be a regulator in learning and memory. However, the effect of KDM1A in oxycodone rewarding memory has yet to be studied. In our study, rewarding memory was assessed by using conditioned place preference (CPP) in male mice. Next generation sequencing and chromatin immunoprecipitation-PCR were used to explore the molecular mechanisms. Oxycodone significantly decreased PP1α mRNA and protein levels in hippocampal neurons. Oxycodone significantly increased KDM1A and H3K4me1 levels, while significantly decreased H3K4me2 levels in a time- and dose-dependent manner. Behavioral data demonstrated that intraperitoneal injection of ORY-1001 (KDM1A inhibitor) or intra-hippocampal injection of KDM1A siRNA/shRNA blocked the acquisition and expression of oxycodone CPP and facilitated the extinction of oxycodone CPP. The decrease of PP1α was markedly blocked by the injection of ORY-1001 or KDM1A siRNA/shRNA. Oxycodone-induced enhanced binding of CoRest with KDM1A and binding of CoRest with the PP1α promoter was blocked by ORY-1001. The level of H3K4me2 demethylation was also decreased by the treatment. The results suggest that oxycodone-induced upregulation of KDM1A via demethylation of H3K4me2 promotes the binding of CoRest with the PP1α promoter, and the subsequent decrease in PP1α expression in hippocampal neurons may contribute to oxycodone reward.
Topics: Animals; Male; Epigenesis, Genetic; Mice; Oxycodone; Histone Demethylases; Hippocampus; Reward; Conditioning, Psychological; Mice, Inbred C57BL; Histones; Neurons; Memory
PubMed: 38870630
DOI: 10.1016/j.biopha.2024.116931 -
Obstetrics and Gynecology Jun 2024To test whether an individualized opioid-prescription protocol (IOPP) with a shared decision-making component can be used without compromising postcesarean pain...
OBJECTIVE
To test whether an individualized opioid-prescription protocol (IOPP) with a shared decision-making component can be used without compromising postcesarean pain management.
METHODS
In this multicenter randomized controlled noninferiority trial, we compared IOPP with shared decision making with a fixed quantity of opioid tablets at hospital discharge. We recruited at 31 centers participating in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Study participants had uncomplicated cesarean births. Follow-up occurred through 12 weeks postdischarge. Individuals with complicated cesarean births or history of opioid use in the pregnancy were excluded. Participants were randomized 1:1 to IOPP with shared decision making or fixed quantity (20 tablets of 5 mg oxycodone). In the IOPP group, we calculated recommended tablet quantity based on opioid use in the 24 hours before discharge. After an educational module and shared decision making, participants selected a quantity of discharge tablets (up to 20). The primary outcome was moderate to severe pain (score 4 or higher [possible range 0-10]) on the BPI (Brief Pain Inventory) at 1 week after discharge. A total sample size of 5,500 participants was planned to assess whether IOPP with shared decision making was not inferior to the fixed quantity of 20 tablets.
RESULTS
From September 2020 to March 2022, 18,990 individuals were screened and 5,521 were enrolled (n=2,748 IOPP group, n=2,773 fixed-quantity group). For the primary outcome, IOPP with shared decision making was not inferior to fixed quantity (59.5% vs 60.1%, risk difference 0.67%; 95% CI, -2.03% to 3.37%, noninferiority margin -5.0) and resulted in significantly fewer tablets received (median 14 [interquartile range 4-20] vs 20, P<.001) through 90 days postpartum.
CONCLUSION
Compared with fixed quantity, IOPP with shared decision making was noninferior for outpatient postcesarean analgesia at 1 week postdischarge and resulted in fewer prescribed opioid tablets at discharge.
CLINICAL TRIAL REGISTRATION
ClinicalTrials.gov, NCT04296396.
PubMed: 38857509
DOI: 10.1097/AOG.0000000000005649 -
Calcified Tissue International Jun 2024Patients with chronic kidney disease (CKD) report high pain levels, but reduced renal clearance eliminates many analgesic options; therefore, 30-50% of CKD patients have...
Patients with chronic kidney disease (CKD) report high pain levels, but reduced renal clearance eliminates many analgesic options; therefore, 30-50% of CKD patients have chronic opioid prescriptions. Opioid use in CKD is associated with higher fracture rates. Opioids may directly alter bone turnover directly through effects on bone cells and indirectly via increasing inflammation. We hypothesized that continuous opioid exposure would exacerbate the high bone turnover state of CKD and be associated with elevated measures of inflammation. Male C57Bl/6J mice after 8 weeks of adenine-induced CKD (AD) and non-AD controls (CON) had 14-day osmotic pumps (0.25-µL/hr release) containing either saline or 50-mg/mL oxycodone (OXY) surgically implanted in the subscapular region. After 2 weeks, all AD mice had elevated blood urea nitrogen, parathyroid hormone, and serum markers of bone turnover compared to controls with no effect of OXY. Immunohistochemical staining of the distal femur showed increased numbers of osteocytes positive for the mu opioid and for toll-like receptor 4 (TLR4) due to OXY. Osteocyte protein expression of tumor necrosis factor-α (TNF-α) and RANKL were higher due to both AD and OXY so that AD + OXY mice had the highest values. Trabecular osteoclast-covered surfaces were also significantly higher due to both AD and OXY, resulting in AD + OXY mice having 4.5-fold higher osteoclast-covered surfaces than untreated CON. These data demonstrate that opioids are associated with a pro-inflammatory state in osteocytes which increases the pro-resorptive state of CKD.
PubMed: 38856730
DOI: 10.1007/s00223-024-01239-8