Search Results (96)

Background/Objectives: Opiates comprise naturally occurring opium alkaloids and their semisynthetic derivatives. Routine urine drug screening relies on enzyme immunoassays (EIAs) to rapidly detect opiate exposure; however, EIAs provide limited insight into opiate-associated metabolic patterns. Methods: We retrospectively analyzed liquid chromatography–quadrupole time-of-flight mass spectrometry (LC-qToF-MS) datasets from comprehensive urine drug screening of 363 patients at the University of Pittsburgh Medical Center Clinical Toxicology Laboratory. Multiple statistical analyses were applied to identify the features associated with opiate (OPIA)-EIA-positive, oxycodone (OXY)-EIA-positive, and 6-monoacetylmorphine (6MAM)-EIA-positive specimens (42, 34, and seven specimens, respectively) designated as EIA-associated discovery feature sets. The feature sets selected by ≥2 statistical analyses were defined as EIA-associated consensus feature set and further evaluated using MS-FINDER for feature annotation. Results: Among 14,883 features, 138, 121, and 104 features were assigned to the OPIA-, OXY-, and 6MAM-EIA discovery feature sets, respectively. Consensus feature sets included oxycodone/opiate metabolites, acetaminophen metabolites, and norfentanyl for OPIA-EIA; oxycodone metabolites, α-phenylalanylaspartic acid, and 4-pyridoxic acid for OXY-EIA; and norfentanyl, 6-monoacetylmorphine, and 3-hydroxycotinine artifact for 6MAM-EIA. Conclusions: These metabolomic patterns indicate a dominant exposure gradient model, in which OXY-EIA-positive specimens primarily reflect prescribed oxycodone exposure, 6-MAM-EIA-positive specimens reflect illicit heroin/fentanyl exposure with polysubstance/recreational use signature, and OPIA-EIA-positive specimens occupy an intermediate, mixed profile shaped by immunoassay cross-reactivity and real-world co-exposures. Associations involving α-phenylalanylaspartic acid and 4-pyridoxic acid are hypothesis-generating and require further validation. These findings illustrate the value of archived clinical toxicology datasets for metabolomic discovery and as a foundation for sentinel laboratory-based surveillance of evolving drug and chemical exposures. Full article

Background/Objectives: Postoperative opioid requirements vary substantially after gastrointestinal surgery. Oxycodone-based patient-controlled intravenous analgesia (PCIA) is used for postoperative pain control, but perioperative factors associated with early postoperative oxycodone requirement remain insufficiently defined. This study investigated factors associated with 48 h oxycodone consumption after gastrointestinal surgery. Methods: This single-center retrospective cohort study included 493 adults who underwent elective gastrointestinal surgery and received oxycodone-based PCIA between January and December 2025. The primary outcome was cumulative oxycodone consumption within 48 h after surgery. Multivariable linear regression was used for the primary continuous-outcome analysis. An exploratory analgesia-adjusted model additionally included regional block, incisional local infiltration, and routine postoperative non-opioid analgesic use. High consumption, defined as a 48 h dose >38 mg, was evaluated using exploratory logistic regression models. Results: The median 48 h oxycodone consumption was 34 mg (interquartile range, 27–38 mg), and 105 patients (21.3%) had high consumption. In the prespecified clinical continuous-outcome model, gastric surgery, rectal surgery, open surgery, converted-to-open surgery, radical resection, and longer operation time were associated with higher 48 h oxycodone consumption, whereas older age was associated with lower consumption. After adjustment for available analgesia-related variables, the main associations remained broadly stable, although the association for converted-to-open surgery was attenuated. Regional block and incisional local infiltration were associated with lower 48 h oxycodone consumption in the analgesia-adjusted model. In the exploratory logistic models, younger age, rectal surgery, open or converted-to-open surgery, radical resection, and longer operation time were associated with high consumption. Body mass index (BMI) was not independently associated with oxycodone requirement. Conclusions: Age and procedure-related characteristics were associated with 48 h oxycodone requirement after gastrointestinal surgery. These routinely available perioperative factors may help identify patients who warrant earlier postoperative pain reassessment, closer acute pain service follow-up, and individualized multimodal analgesic planning. Prospective multicenter validation is required before formal risk-stratified analgesic protocols can be recommended. Full article

Objectives: To evaluate the clinical impact and treatment adaptations during the immediate-release oxycodone hydrochloride shortage. Methods: This retrospective, observational study was conducted during the oxycodone shortage period (May 2024–March 2025) in patients with cancer pain. Pain intensity was assessed using the Numerical Rating Scale (NRS) at baseline (prior to switching, while receiving oxycodone) and at follow-up (after switching to alternative analgesics). Changes in pain intensity were evaluated using within-patient differences (ΔNRS), with clinically meaningful worsening defined as an increase of ≥2 points. Descriptive and inferential statistics were used to summarize patient characteristics and outcomes. Results: Of 300 patients screened, 55 met inclusion criteria (mean age 65.2 ± 11.0 years; 63.6% male). Pain intensity increased significantly following treatment modification during the period of oxycodone unavailability, with mean NRS scores rising from 4.3 ± 1.7 to 5.9 ± 2.5 (p < 0.001). The mean ΔNRS was +1.56 (95% CI 0.79–2.34), with clinically meaningful worsening observed in 36 patients (65.5%). No statistically significant association was observed between substitute analgesic type and clinically meaningful worsening (p = 0.11). Conclusions: The oxycodone shortage was associated with worsened pain control and increased need for treatment modifications in cancer patients, highlighting the importance of uninterrupted access to essential opioids. Full article

Background: Oxycodone is a widely prescribed semi-synthetic opioid central to pain management. However, establishing its role in death when detected in postmortem toxicology is challenging. Quantitative evidence to support forensic interpretation remains limited. Methods: A systematic review and meta-analysis was conducted following PRISMA 2020 guidelines. PubMed and Scopus were searched through 3 March 2026, for studies reporting quantitative postmortem oxycodone concentrations in human biological matrices. Peripheral blood was predefined as the primary matrix for quantitative synthesis. Random-effects meta-analysis with restricted maximum likelihood estimation was performed on logarithmically transformed concentrations to compare fatal intoxications versus non-intoxication deaths and mono- versus mixed-intoxication cases. Pooled estimates were reported as geometric mean concentrations with 95% confidence and prediction intervals. Secondary analyses evaluated metabolite-to-parent ratios, alternative matrices, and postmortem interval (PMI). Results: Twenty-three studies comprising 4335 oxycodone-positive decedents were included in the qualitative synthesis, and 14 studies in the quantitative meta-analysis. Fatal intoxication cases (n = 1555) showed a pooled geometric mean peripheral blood oxycodone concentration of 0.37 mg/L (95% CI: 0.24–0.58; I² = 93.5%), compared with 0.08 mg/L (95% CI: 0.04–0.15; I² = 98.5%) in non-intoxication deaths (n = 1409). Mono-intoxication cases (n = 135) exhibited higher concentrations (0.52 mg/L; 95% CI: 0.22–1.21; I² = 82.3%) than mixed-drug fatalities (n = 511; 0.29 mg/L; 95% CI: 0.13–0.65; I² = 93.1%). Metabolite data indicated that noroxycodone and oxymorphone patterns may assist in distinguishing acute intake and metabolic variability. Alternative matrices, particularly vitreous humor and solid tissues provided complementary interpretative information, while PMI contributed concentration variability. Conclusions: The key quantitative findings of this meta-analysis indicate higher peripheral blood oxycodone levels in fatal intoxications than in non-intoxication deaths. However, substantial heterogeneity precludes the definition of absolute concentration cut-offs, emphasizing the need to approach postmortem oxycodone interpretation within a probabilistic forensic framework integrating circumstantial evidence, sampling time, metabolite ratios, and data from alternative biological matrices. Full article

Subcutaneous thrombotic vasculopathy (STV) is a rare, non-inflammatory occlusive disorder of the cutaneous microvasculature that predominantly involves the subcutaneous tissue and may closely mimic inflammatory vasculitis. We describe a case of STV with overlapping features of leukocytoclastic vasculitis (LCV) in a 23-year-old woman presenting with rapidly progressive, painful purpuric skin lesions. The patient had a history of polysubstance use disorder and reported intravenous injection of crushed oral oxycodone and methylphenidate tablets. Histopathological examination of a deep skin biopsy revealed fibrin-rich thrombi occluding small vessels of the dermis and subcutaneous tissue. Fine granular IgA deposits in the walls of numerous superficial dermal blood vessels shown using direct immunofluorescence suggested LCV. Overall, the findings supported a mixed thrombotic-inflammatory vasculopathy with predominant features of STV. This case highlights the diagnostic complexity of STV and may suggest intravenous injection of crushed oral medications as a potential trigger through particle-induced microvascular obstruction and secondary thrombosis. In addition, we conducted a literature review indicating that STV remains a rare and likely underrecognized entity, with only a limited number of reported cases. Full article

Background: The aim of the study is (1) to assess safety of opioids in nursing mothers after cesarean delivery and in breastfed infants and (2) to evaluate the role of CYP2D6 genetics in maternal and infant clinical outcomes after cesarean delivery. Methods: A total of 210 mother–infant dyads were enrolled after cesarean delivery. Oxycodone 5 mg orally was administered every 4–6 h as needed as part of a standardized opioid-sparing ERAS protocol. Primary outcomes were opioid-related adverse effects, including maternal respiratory depression (RD) and postoperative nausea and vomiting (PONV) and neonatal composite side effects (i.e., RD monitoring, sedation, and limpness). Results: In total, 77% of mothers received opioids during postpartum hospital stay, none experienced respiratory depression, 13% reported PONV, and composite opioid-related side effects were observed in 13% of neonates. Compared to mothers without opioid consumption, higher in-hospital opioid consumption was borderline significantly associated with a higher risk of neonatal composite side effects (adjusted relative risk, aRR = 3.79; 95%CI: 1.01–14.28; p = 0.07), with a similar trend toward higher risk in maternal PONV (aRR = 2.56; 95%CI: 0.70–9.29; p = 0.36). Mothers with a CYP2D6 ultra-rapid metabolizer phenotype also showed higher rates of PONV and neonatal composite side effects compared with normal or intermediate phenotypes, although these associations were not statistically significant. Conclusions: Higher maternal in-hospital opioid consumption is associated with a higher risk of neonatal composite side effects. Using the lowest effective doses of opioids as needed could reduce the risk of opioid-related side effects in neonates. Preoperative genotyping may help identify mothers and breastfed neonates at increased risk for opioid-related adverse outcomes. Additional studies are needed to evaluate preoperative genotyping and to evaluate the causality of increased neonatal adverse outcomes. Full article

Background: Robotic hysterectomy and Enhanced Recovery After Surgery (ERAS) are two significant improvements in gynecologic surgery, both associated with decreased postoperative pain and faster recovery. Spinal analgesia guarantees excellent pain coverage; however, its appropriateness in robotic procedures is still controversial. The aim of the study was to compare postoperative pain control after robotic hysterectomy in patients receiving spinal analgesia versus intravenous low-dose oxycodone. Methods: Consecutive patients undergoing robotic hysterectomy from January 2022 to July 2023 were included in the analysis. Until August 2022, patients received spinal analgesia, while from September 2022, low-dose oxycodone was administered intraoperatively. All patients were managed following the ERAS protocol. Primary outcomes were the VAS pain score and opioid rescue use, while secondary outcomes included postoperative nausea and vomiting (PONV), mobilization, oral intake, and length of hospital stay (LOS). Results: Of 114 patients, 67 (58.8%) received spinal analgesia and 47 (41.2%) received intravenous low-dose oxycodone. No differences were reported in the VAS pain score at day 0 (1.5 ± 1.6 vs. 1.6 ± 2.2, p = 0.78) and day 1 (2.0 ± 2.1 vs. 1.3 ± 1.8, p = 0.07). At day 2, the VAS pain score was 1.4 ± 1.6 in the spinal analgesia group and 0.7 ± 1.0 in the oxycodone group (p = 0.01). No differences were reported in the need for opioid rescue at days 1 and 2 (p = 1.00). At day 0, 26 patients (38.8%) experienced PONV in the spinal analgesia group versus 8 (17.0%) in the oxycodone group (p = 0.01). Conclusions: Patients receiving intraoperative low-dose oxycodone experienced comparable satisfactory postoperative pain control with a lower incidence of PONV when compared to the spinal analgesia group. Full article

Introduction: Chronic low-back pain (CLBP) is a leading cause of disability, often requiring opioid therapy when conservative treatments fail. Transdermal buprenorphine and oral oxycodone/naloxone are commonly used, but their comparative effectiveness and safety remain underexplored. Materials and Methods: In this retrospective cohort study, 173 patients with CLBP treated at our center between June 2022 and May 2024 were analyzed. Group A (n = 88) received transdermal buprenorphine (5–15 μg/h), while Group B (n = 85) was treated with oral oxycodone/naloxone (10/5–20/10 mg/day). Treatment lasted four weeks, with dose titration after one week if pain was uncontrolled. Pain intensity (VAS), functional status (ODI), rescue medication use, and adverse effects were assessed at baseline and during follow-up. Results: Both groups showed significant reductions in VAS and ODI scores. Buprenorphine led to a greater functional improvement (ODI reduction p = 0.04) and a trend toward greater pain reduction (VAS p = 0.08). Rescue drug use was significantly lower in Group A (53.4%) compared to Group B (78.8%, p = 0.003). Adverse events were more frequent in the oxycodone group, particularly nausea and constipation. Conclusions: Transdermal buprenorphine provided comparable or superior analgesia with better tolerability and reduced reliance on rescue medication. It represents a safer, effective alternative for CLBP management in routine clinical practice. Full article

Background and Objectives: This systematic review and network meta-analysis evaluated the effects of postoperative opioid use on nausea and vomiting in women undergoing laparoscopic hysterectomy. Materials and Methods: A systematic search of PubMed, EMBASE, the Cochrane Library, and RISS was conducted to identify randomized controlled trials that met the eligibility criteria. The Cochrane Risk of Bias 2 tool was used to assess the quality of the included studies. A frequentist network meta-analysis was performed to compare the risks of opioid-associated postoperative nausea and vomiting (O-PONV). Quantitative statistics were presented in forest plots, and the ranking of treatments was determined using the P-score. Results: Seventeen studies involving 1315 participants and 18 postoperative analgesic interventions were included. No significant differences were found among the opioid monotherapies—buprenorphine, butorphanol, fentanyl, oxycodone, sufentanil, and tapentadol. However, among the combination therapies, oxycodone/ketorolac therapy was associated with a significantly higher risk of O-PONV than other ketorolac-containing regimens, including dexmedetomidine, remifentanil, and fentanyl. Conclusions: No significant differences in O-PONV risk were observed among the six opioid monotherapy groups. An opioid-sparing regimen, such as dexmedetomidine/ketorolac, showed a lower risk of O-PONV than an oxycodone-based regimen, underscoring the importance of incorporating patient-centered considerations, such as patient preference and route of administration, into postoperative pain management. Full article

Substance use disorders (SUDs) remain a major global health challenge with limited treatment options and high relapse rates. Vaccines that induce drug-sequestering antibodies have shown promise, but their efficacy is hindered by the poor immunogenicity of small-molecule haptens. Adjuvants, substances that enhance immune responses, are critical for overcoming this limitation and improving vaccine efficacy. This review synthesizes over two decades of preclinical and clinical research to guide rational adjuvant design for SUD vaccines. Five major adjuvant classes are examined: aluminum-salt adjuvants, emulsion adjuvants, toll-like receptor (TLR) agonists, protein immunopotentiators, and cytokine modulators. Their physicochemical properties, innate immune activation profiles, and applications in nicotine, stimulant, and opioid vaccines are discussed. Comparative analyses reveal pronounced drug-specific and carrier-specific variability. Case studies illustrate the superior performance of a complementary TLR-agonist pair in a nicotine nanovaccine versus its limited effect in oxycodone vaccines. They also reveal the differential efficacy of an oil-in-water emulsion adjuvant across antigen types. Four principles emerge: (i) no adjuvant is universally optimal; (ii) drug pharmacology influences immune signaling; (iii) adjuvant-carrier compatibility is important; (iv) complementary adjuvant pairings often outperform single agents. These insights support a precision-vaccinology paradigm that tailors adjuvant strategies to each drug class and the delivery vehicle, advancing the development of next-generation SUD vaccines. Full article

Opioids are known to constrict pupils, and mobile phone-based self-administered eye scanning (MPSES) offers a potential method for monitoring opioid use in real-world settings. A clinical trial with 12 volunteers measured pupil size using MPSES under different light conditions (approx. 50 or approx. 500 lux) in the lab and over a week at home. Each participant made approximately 21 home tests, 12 in the lab without oxycodone and 16 in the lab after oxycodone intake. At the second visit the participants received a single dose of 20 mg oxycodone, and their pupil size was monitored hourly for 5 h. The pupil size after oxycodone intake was compared to drug-naïve tests performed at the lab and at home. Logistic regression models were built using measured pupil size and light conditions measured by the phone during each test, and a dichotomous variable indicating tests before or after oxycodone dosing as the outcome. The model demonstrated high classification accuracy (AUC = 0.94), with 82% true positives, 9% false positives, 91% true negatives and 18% false negatives. Misclassifications were largely due to difficulties measuring pupil size in individuals with corneal arcus, causing most of the false positive findings, and other interindividual differences. This shows that MPSES, including monitoring of ambient light conditions, can effectively detect opioid use within the 50–500 lux range. Our study paves the way for using MPSES to detect opioid use. Full article

Introduction: The management of peri-operative pain significantly impacts the post-operative recovery following kidney transplant. For decades, regional blocks have been utilized for post-operative pain management following abdominal surgery. The data on the routine use of regional blocks peri-operatively during kidney transplants are limited. We aim to review our current clinical practice of peri-operative use of regional blocks during kidney transplants and management of peri-operative pain up to 24 h. Methods: A consecutive series of 100 patients who underwent kidney transplant was reviewed. All demographic data including patient’s age, gender, race, and body mass index were collected. Pre-transplant co-morbidities were summarized for all patients and included the American Society of Anesthesiologists (ASA) score. Patients were divided into two groups based on whether they received a transversus abdominis plane (TAP) block. Group A consisted of patients who received an ultrasound-guided TAP block, while Group B included patients who did not receive any form of TAP block. The intra-operative and post-operative use of analgesia was recorded for up to 24 h post kidney transplant. All peri-operative complications were reviewed. The chi-square test and Fisher’s exact test was used to compare symptoms (nausea, vomiting, and pruritus) between the two groups. Similarly, the use of analgesia was also compared. Results: A total of 100 patients were identified and equally distributed between the two groups [Group A = 50 (TAP block), Group B = 50 (non-TAP block)]. There was a statistically significant reduction in the use of intraoperative fentanyl (p = 0.04) in Group A. There was no difference in the post-operative use of hydromorphone (p = 0.665), oxycodone (p = 0.75), and acetaminophen (p = 0.64) up to 24 h after the kidney transplant procedure. There was no difference between post-operative nausea (p = 0.766), vomiting (p = 0.436), and pruritus. There were no complications recorded secondary to the use of regional blocks in Group A. Conclusions: The use of regional anesthesia in kidney transplant recipients is a safe approach without complications. The study concluded that regional blocks decrease the use of intra-operative opioids. However, there was no difference in the use of post-operative requirements for analgesia or side effects up to 24 h after kidney transplant. Full article

Background/Objectives: Intramuscular immunization elicits systemic IgG and is the primary route of vaccine administration in humans. However, there is growing interest in utilizing other routes of administration to tailor antibody profiles, increase immunity at primary sites of infection, simplify administration, and eliminate needle waste. Here, we investigated the antibody profiles elicited by immunization with bacteriophage virus-like particle vaccine platforms at various routes of administration. Methods: We chose two model bacteriophage vaccines for investigation: bacteriophage MS2 virus-like particles (VLPs) recombinantly displaying a short, conserved peptide from Chlamydia trachomatis major outer membrane protein (MS2) and bacteriophage Qβ VLPs displaying oxycodone through chemical conjugation (Qβ). We comprehensively characterized the antibodies elicited systemically and at various mucosal sites when the vaccines were administered intramuscularly, intranasally or periocularly with or without an intramuscular prime using various prime/boost schemes. Results: Intranasal and periocular immunization elicited robust mucosal and systemic IgA responses for both MS2 and Qβ. The intramuscular prime followed by intranasal or periocular boosts elicited broad antibody responses, and increased antibodies titers at certain anatomical sites. Conclusions: These findings demonstrate the tractability of bacteriophage VLP-based vaccines in generating specific antibody profiles based on the prime–boost regimen and route of administration. Full article

The diagnosis of opioid use disorder (OUD) is prevalent due to increased prescribing of opioids. Long-term oxycodone self-administration can lead to addiction-like behavioral responses in rats. Herein, we sought to identify molecular pathways consequent to long-term exposure to oxycodone self-administration. Towards that end, we used male Sprague Dawley rats that self-administered oxycodone for 20 days according to short-(ShA, 3 h) and long-access (LgA, 9 h) paradigms. LgA rats escalated their oxycodone intake and developed into 2 phenotypes, labeled Long-access High (LgA-H) and Long-access Low (LgA-L) rats, based on their escalation. RNA sequencing analysis revealed the LgA-H has significantly different DEGs in comparison to other groups. DAVID analysis revealed the participation of LgA-H DEGs in potassium transport. RT-PCR analysis of striatal samples validated the increased levels of potassium channels. Since these increases correlated with oxycodone intake, we believe potassium channels are potential targets for the treatment of oxycodone use disorder Full article

Much attention has been paid to the public health crisis that has resulted from the opioid epidemic. Given the high number of opioid users that are of childbearing age, the impact of utero exposure is a serious concern. Unfortunately, there is little knowledge regarding the consequences of opioid exposure during early development. While neurobehavioral effects of opioid exposure are well-documented, effects of exposure on embryogenesis remain largely unexplored. To address this gap in knowledge, we investigated the effects of oxycodone and fentanyl exposure on gene expression in zebrafish (Danio rerio) embryos using whole embryo RNA sequencing. Embryos were exposed to environmentally relevant (oxycodone HCl 10.6 ng/L and fentanyl citrate 0.629 ng/L) and therapeutically relevant doses (oxycodone HCl 35.14 μg/L and fentanyl citrate 3.14 μg/L) from 2 to 24 h post-fertilization (hpf), followed by another 24 h of opioid-free development. mRNA profiling at 48 hpf revealed dose- and drug-specific gene expression changes. Lower doses of oxycodone and fentanyl both induced more differentially expressed transcripts (DETs) than higher doses, potentially indicative of opioid receptor desensitization occurring at higher concentrations. In total, 892 DETs (corresponding to 866 genes) were identified across all conditions suggesting continued differential gene expression well after cessation of opioid exposure. Gene ontology analysis revealed changes in gene expression relating to extracellular matrix (ECM) organization, cell adhesion, and visual and nervous system formation. Key pathways include those involved in axon guidance, synapse formation, and ECM biosynthesis/remodeling, all of which have potential implications on neural connectivity and sensory development. These findings demonstrate that very early developmental exposure to opioids induces persistent transcriptomic changes which may have lasting implications for vertebrate cellular functions. Overall, these data provide insights into the molecular mechanisms of opioid-induced alterations during development. Full article