Supercritical fluid extraction coupled on-line with supercritical fluid chromatography creates a powerful multidimensional analysis platform, but its adoption is limited by the resource-heavy process of method development. This research presents a surrogate optimization approach as a better alternative to traditional design of experiments and response surface methodology. Unlike fixed experimental designs, the surrogate model iteratively updates the response surface after each run, facilitating effective global optimization through continuous exploration and exploitation. The study adjusts both SFE- and SFC-specific variables-such as back-pressure regulation and split flow-to reduce peak FWHM and enhance extraction efficiency. Analytes, specifically reserpine, vigabatrin, hydromorphone, and hydrocodone, covering diverse physicochemical profiles, were optimized sequentially, guided by a molecular similarity metric, to broaden the design space. The surrogate model identified critical factors, including modifier concentration, chromatography pressure, dynamic extraction time, and flow rate, with adjusted coefficient of determination (R[2]) values reaching 0.97 as more data was collected and the model was refined. Response surface and parallel coordinate analyses showed that hydrocodone, hydromorphone, and vigabatrin favored high modifier concentrations, while reserpine had a distinct optimum more sensitive to static extraction time. Sensitivity analysis over 62.5-1000 ng mL[-1] yielded detection limits/quantification limits of 6.9/23.0 and 2.4/8.1 ng mL[-1] for hydrocodone and reserpine, respectively. Sequential optimization enhanced sensitivity by 15%, demonstrating the scalability and transferability of the surrogate optimization framework for developing SFE-SFC methods.

Background: Emergency department (ED) use for cancer-related pain is common, particularly among patients with metastatic disease who frequently require opioid analgesia. In October 2014, the U.S. Drug Enforcement Administration rescheduled hydrocodone combination products from Schedule III to Schedule II, introducing stricter prescribing and dispensing requirements. We evaluated whether hydrocodone rescheduling was associated with pain-related ED visits and hospitalizations among older adults with metastatic lung cancer. Methods: We conducted a retrospective SEER-Medicare cohort study of beneficiaries aged 66 years or older diagnosed with metastatic lung cancer. Diagnoses from January 2011 through September 2014 were classified as pre-policy, October 2014 was excluded as a transition month, and November 2014 through December 2018 constituted the post-policy period. Monthly 365-day cumulative incidences were estimated using the Aalen-Johansen estimator with death treated as a competing event. Segmented interrupted time-series models estimated immediate level and slope changes. Adjusted cause-specific Cox models evaluated time to first event. Results: The cohort included 52,371 beneficiaries. For narrowly defined neoplasm-related pain ED visits, the policy was associated with an immediate increase of 0.834 percentage points (95% CI, 0.330-1.338) and a post-policy slope increase of 0.030 percentage points per month (95% CI, 0.011-0.049). Pain-related hospitalizations increased immediately by 0.946 percentage points (95% CI, 0.336-1.556), with a slope increase of 0.024 percentage points per month (95% CI, 0.005-0.042). At 12 months, fitted cumulative incidences exceeded no-policy projections by 1.193 percentage points for ED visits and 1.228 percentage points for hospitalizations. Adjusted cause-specific hazard ratios were 1.14 for pain-related ED visits (95% CI, 1.00-1.30; p = 0.054) and 1.14 for hospitalizations (95% CI, 1.00-1.29; p = 0.049). Conclusions: Hydrocodone rescheduling was temporally associated with modest increases in acute-care encounters explicitly coded for neoplasm-related pain. The findings underscore the importance of preserving timely analgesic access for patients with advanced cancer.

Tramadol is frequently co-prescribed with oxycodone or hydrocodone after surgery under the assumption that its dual mechanism of action provides an opioid-sparing benefit. However, evidence supporting this practice is limited and inconsistent. We conducted a secondary analysis of the multicenter IGNITE ADOPT-PGx pragmatic trial of patients undergoing elective surgery who were prescribed oxycodone alone (n = 317) versus tramadol + oxycodone (n = 96), or hydrocodone alone (n = 563) versus tramadol + hydrocodone (n = 42). Co-primary outcomes of this study were cumulative morphine milligram equivalents (MME) consumed during the 10 days following surgery and composite pain scores at day 10 defined as the sum of current pain and average and worst pain in the past 7 days (score ranges from 3 to 15). Inverse probability of treatment weighting (IPTW) was used to adjust for demographic characteristics, comorbidities, and concomitant analgesics. Sensitivity analyses restricted to CYP2D6 normal metabolizers and sites prescribing both monotherapy and combination therapy and subgroup analysis including total knee arthroplasty patients were conducted. Compared to oxycodone alone, the combination of oxycodone and tramadol was associated with higher MME (adjusted mean 205.2 vs 122.5; P < 0.0001) and lower mobility, without meaningful differences in pain scores (adjusted mean 9.6 vs 9.4; P = 0.41). Similar findings were observed for hydrocodone-only vs hydrocodone + tramadol groups. Results were consistent in sensitivity and subgroup analyses. Co-administration of tramadol with oxycodone or hydrocodone was associated with substantially higher total MME and reduced mobility without any demonstrable improvement in pain control.

Suzetrigine (Journavx), from a new class of non-opioid analgesics, is the first approved agent indicated for adults with moderate to severe pain in almost 3 decades. Reviewed are the drug's unique pharmacology, history of development, clinical evidence of safety and effectiveness, with an emphasis on implications for nursing practice. Literature describing the basic pharmacology as well as the results from extant clinical trials are integrated in this narrative educational review.

Opioid use disorder (OUD) remains a global public health concern, exerting a significant economic burden on societies worldwide. To combat the rise of substance use disorder, a complementary vaccine-based intervention was developed to support and strengthen the existing treatment modalities. Hapten-protein conjugate vaccines are employed as a promising novel strategy for neutralizing nonimmunogenic small-molecule drugs such as opioids by eliciting drug-specific antibodies that sequester opioids in circulation before reaching the brain. In this study, multiple parameters to optimize the efficacy of the TT-6-AmHap heroin conjugate vaccine were investigated in mice and rats, focusing on dose optimization, hapten density, booster timing, and cross-reactivity with other prescription opioids. Binding antibody responses were quantified, and vaccine efficacy was assessed using nociceptive assays following a drug challenge. Immunization with TT-6-AmHap vaccine in combination with adjuvants ALF43 and Alhydrogel[®] (ALFA), demonstrated a robust in-vivo efficacy across multiple opioid challenges including heroin, hydrocodone, and hydromorphone. Both antibody titers to 6-AmHap and protective efficacy were maintained following repeated heroin challenges up to 54 weeks. Notably, these repeat heroin challenges did not induce any measurable decline in antibody titers. Further characterization of the vaccine responses indicated a strong correlation between hapten density on the carrier protein and both binding antibody titers and overall vaccine efficacy. These findings support the continued development of hapten-based conjugate vaccines for OUD and demonstrate that an optimized vaccine can provide long-lasting protection against the antinociceptive effects of opioids in animals, laying the groundwork for future translational studies.

Chronic low back pain (LBP) is a major cause of disability around the world, and pharmaceutical treatments like opioids are often used to treat it. However, the efficacy and safety of opioids in LBP continue to be controversial due to inconsistent results and associated side effects. This systematic review assesses the effectiveness and safety of opioid medication in the treatment of LBP. A systematic search was performed utilising various electronic databases, including PubMed, Scopus, Google Scholar, MEDLINE, the Cochrane Library, and Web of Science, following a structured methodology in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) principles. Randomised controlled trials that were published in English within the past two decades and evaluated the use of opioids in adults with LBP were included. The Cochrane Risk of Bias tool and the Critical Appraisal Skills Programme (CASP) checklist were used to screen for bias, and a narrative synthesis was done because the studies were not all the same. There were six randomised, double-blind, placebo-controlled trials involving between 83 and 905 people. Opioid formulations, including buprenorphine, hydrocodone, oxycodone/naloxone, and oxymorphone, exhibited overall efficacy in diminishing pain intensity relative to placebo, especially in opioid-naïve individuals. But the magnitude and consistency of the advantage varied across studies, and some treatments showed only a small statistical difference. There were only a few reports of functional improvement, and they were not always constant. Nausea, constipation, and drowsiness were common side effects, although long-term safety outcomes were not fully evaluated. In general, opioids may help with short-term pain relief in people with LBP, but they aren't very useful in the long term because they aren't very effective and very safe and there isn't much evidence for their long-term use. It is advisable to select patients and use them with caution. More high-quality research is needed to understand their role in long-term management better.