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Pharmacy (Basel, Switzerland) Apr 2024Opioids remain commonly prescribed in older adults, despite the known association with falls and fall-related injuries. This retrospective cohort study sought to...
Opioids remain commonly prescribed in older adults, despite the known association with falls and fall-related injuries. This retrospective cohort study sought to determine the association of opioid use and falls in older adult opioid users. Using a one-year lookback period in electronic health records, daily morphine milligram equivalents (MMEs) were calculated using prescription orders. Fall history was based on patient self-reporting. A receiver operating characteristic (ROC) curve was used to identify the threshold of average daily MMEs at which the likelihood of falls was increased. Older opioid users were most often women and White, with 30% having fallen in the prior year. In ROC analyses (n = 590), the threshold where fall risk increased was 37 MMEs ( = 0.07). Older adults prescribed more than 37 MMEs daily may be at increased fall risk and should be targeted for deprescribing interventions. Additionally, analysis on patient characteristics and covariates suggest that sex, age, COPD, sleep apnea, cancer, and psychiatric conditions may indicate an increased risk of falls in older adults taking chronic opioids ( < 0.05). Multifactorial interventions may be needed to modify fall risk beyond medication use alone.
PubMed: 38668088
DOI: 10.3390/pharmacy12020062 -
The Journal of Pain Apr 2024Both endocannabinoid (EC) and endogenous opioid systems are involved in nociceptive processing and may work together synergistically based on preclinical models. This...
Both endocannabinoid (EC) and endogenous opioid systems are involved in nociceptive processing and may work together synergistically based on preclinical models. This study evaluated the interactive effects of preoperative beta-endorphin (BE) concentrations (a key analgesic endogenous opioid) in cerebrospinal fluid (CSF) and ECs (CSF and plasma 2-arachidonoylglycerol and plasma anandamide) on postoperative opioid use and pain intensity in a prospective cohort of n = 112 pregnant patients undergoing scheduled cesarean delivery. Maternal blood and CSF samples were collected preoperatively for BE and EC assays. Patients completed measures of outpatient opioid use (number of tablets used and days of use) and average pain intensity at 2 weeks postoperatively. Results of general linear model analyses controlling for maternal age, body mass index at time of delivery, and race revealed significant multiplicative interactions between EC and BE concentrations on number of opioid tablets used (based on pill count), days of opioid use, and total milligram morphine equivalents used in the 2-week follow-up period. Elevated preoperative plasma and CSF 2-arachidonoylglycerol predicted reduced outpatient opioid analgesic use, particularly for patients low in CSF BE. Similar analyses for pain intensity at 2-week follow-up indicated a significant interaction (P < .02) characterized by higher preoperative BE concentrations being associated with lower subsequent pain only for individuals with low preoperative plasma anandamide concentrations. Further exploration of interactions between EC and endogenous opioid inhibitory systems as they influence responses to opioid analgesics in other clinical pain populations may help guide the development of precision pain management approaches. PERSPECTIVE: In the postoperative setting of patients undergoing cesarean delivery, elevated ECs were linked to reduced outpatient opioid analgesic use in individuals who had low endogenous opioid concentrations in CSF. Further exploration of interactions between these 2 inhibitory systems as they impact responses to pain management interventions appears warranted.
PubMed: 38663651
DOI: 10.1016/j.jpain.2024.104548 -
Green Chemistry : An International... Apr 2024Asymmetric organocatalysis has been recognized as one of the "top 10 emerging technologies" in chemistry by IUPAC in 2019. Its potential to make chemical processes more...
Asymmetric organocatalysis has been recognized as one of the "top 10 emerging technologies" in chemistry by IUPAC in 2019. Its potential to make chemical processes more sustainable is promising, but there are still challenges that need to be addressed. Developing new and reliable enantioselective processes for reproducing batch reactions on a large scale requires a combination of chemical and technical solutions. In this manuscript, we combine a robust immobilized chiral phosphoric acid with a new packed-bed reactor design. This combination allows scaling up of the enantioselective addition of thiols to imines from a few milligrams to a multi-decagram scale in a continuous flow process without physical or chemical degradation of the catalyst.
PubMed: 38654978
DOI: 10.1039/d4gc00019f -
Saudi Journal of Anaesthesia 2024Optimal pain control with limited muscle weakness is paramount for a swift initiation of physical therapy and early discharge. Fascia iliaca compartment block (FICB) has...
Pericapsular nerve group block and lateral femoral cutaneous nerve block versus fascia iliaca block for multimodal analgesia after total hip replacement surgery: A retrospective analysis.
BACKGROUND
Optimal pain control with limited muscle weakness is paramount for a swift initiation of physical therapy and early discharge. Fascia iliaca compartment block (FICB) has been recommended since it offers good pain control with a low risk of motor block. Pericapsular nerve group (PENG) block with lateral femoral cutaneous block (LFCN) has been proposed as an effective alternative to FICB that offers better pain control with a considerably lower risk of motor block. We aimed to compare the aforementioned blocks and determine which one yielded the lowest numeric rating scale (NRS) score.
METHODS
We designed a retrospective analysis of patients undergoing elective total hip arthroplasty. The primary outcome was the NRS score at 6, 12, and 24 hours. The secondary outcomes were total opioid consumption, time to first PRN opioid, and time to first postoperative ambulation.
RESULTS
52 patients were recruited, (13 PENG plus LFCN, 39 FICB). PENG plus LCFN resulted in a lower NRS at all three-time points (mean difference and 95%CI at 6 h 0.378 [-0.483; 1.240], at 12 h 0.336 [-0.378; 1.050], and at 24 h 0.464 [0.013; 0.914] = 0.02). Moreover, less PRN opioids were requested in the PENG plus LCFN vs. FICB group (0 [0;7.5] vs 60 [15;80] milligrams of morphine equivalents, = 0.001). No delay in the first ambulation or initiation of physical rehabilitation was reported in either group.
CONCLUSIONS
PENG plus LCFN seems to offer better pain control and lead to less PRN opioids. Neither block hindered physical therapy nor ambulation. These results need to be confirmed with a larger prospective and randomized study.
PubMed: 38654885
DOI: 10.4103/sja.sja_881_23 -
Journal of the American Academy of... Apr 2024Opioid use after revision total hip arthroplasty (rTHA) has not been well characterized. The purpose of this study was to characterize preoperative, perioperative, and...
BACKGROUND
Opioid use after revision total hip arthroplasty (rTHA) has not been well characterized. The purpose of this study was to characterize preoperative, perioperative, and postoperative opioid use during rTHA.
METHODS
Patients undergoing revision THA from 2010 to 2018 were screened for opioid use 3 months before revision surgery and tracked 24 months postoperatively. Patients were categorized as naïve or tolerant. Opioid prescriptions and average morphine milligram equivalents (MME) were compared between the two groups.
RESULTS
One hundred twenty-four of 247 patients (50%) in the tolerant group averaged a preoperative MME of 23.7 mg/day. Postoperatively, tolerant patients received significantly higher daily MME at all time points, including at 3 months 31.4 versus 18.1 mg/day (P < 0.001), 6 months 19.9 versus 2.95 mg/day (P < 0.001), 12 months 14.3 versus 3.5 mg/day (P < 0.001), and 24 months 10.7 versus 2.17 mg/day (P < 0.001). Tolerant patients were more likely to have a prescription at 6 months (44% versus 22%), 12 months (41.4% versus 24%), and 24 months (38% versus 19.3%) (P < 0.001, P = 0.002, P < 0.001, respectively).
DISCUSSION
Opioid-tolerant patients had higher postoperative MME requirements for longer recovery duration. Both groups reduced opioid use at 3 months and plateaued at 6 months. These findings can help the revision surgeon counsel patients and expectations.
Topics: Humans; Arthroplasty, Replacement, Hip; Analgesics, Opioid; Male; Female; Reoperation; Pain, Postoperative; Middle Aged; Aged; Drug Tolerance; Retrospective Studies
PubMed: 38648392
DOI: 10.5435/JAAOSGlobal-D-23-00165 -
Chemical & Pharmaceutical Bulletin 2024Preparation of drug metabolites at the milligram scale is essential for determining the structure and toxicity of drug metabolites. However, their preparation using...
Preparation of drug metabolites at the milligram scale is essential for determining the structure and toxicity of drug metabolites. However, their preparation using recombinant proteins and human liver microsomes (HLM) is often difficult because of technical and ethical issues. Reproducing human drug metabolism in food-derived microorganisms may be useful for overcoming these challenges. In this study, we identified an unknown metabolite of the anaesthetic drug lidocaine, which is metabolised by HLM. By screening for lidocaine metabolic activity in five types of foods (blue cheese, shiitake mushroom, natto, yoghurt, and dry yeast), we found that bacteria isolated from natto reproduced the lidocaine metabolic reaction that occurs in HLM. A fraction containing the unknown lidocaine metabolite was prepared through mass cultivation of a Bacillus subtilis standard strain, ethyl acetate extraction, open column chromatography, and HPLC purification. We identified the unknown metabolite as 3-(2,6-dimethylphenyl)-1-ethyl-2-methyl-4-imidazolidinone using NMR. Our results showed that food-derived microorganisms can produce large amounts of human drug metabolites via large-scale cultivation. Additionally, food microorganisms that can reproduce drug metabolism in humans can be used to examine drug metabolites at a low cost and without ethical issues.
Topics: Humans; Microsomes, Liver; Lidocaine; Bacillus subtilis; Molecular Structure; Chromatography, High Pressure Liquid
PubMed: 38644165
DOI: 10.1248/cpb.c24-00050 -
Journal of Pharmaceutical and... Aug 2024The misuse of pharmaceuticals has significantly increased in recent decades, becoming a major public health concern. The risks associated with medication misuse are...
Milligram scale enantioresolution of promethazine and its main metabolites, determination of their absolute configuration and assessment of enantioselective effects on human SY-SY5Y cells.
The misuse of pharmaceuticals has significantly increased in recent decades, becoming a major public health concern. The risks associated with medication misuse are particularly high in cases of overdose, especially when the active substances are chiral, as enantioselectivity plays an important role in toxicity. Promethazine (PMZ) is a chiral antihistamine marketed as a racemate and it is misused in "Purple Drank", a recreational drug beverage, that combines codeine and/or PMZ, with soda or alcohol leading to serious health consequences and fatalities in consumers around the world, particularly among teenagers. Information regarding the enantioselectivity in the toxicity of (R,S)-PMZ and its main metabolites, namely promethazine sulfoxide (PMZSO) and desmonomethyl promethazine (DMPMZ), is unknown. This work reported, for the first time, the enantioseparation, in milligram scale, of (R,S)-PMZ, (R,S)-DMPMZ, (R,S)- PMZSO and the determination of their absolute configurations by electronic circular dichroism (ECD). The enantioseparation of all the six enantiomers was accomplished in a homemade semi-preparative column with amylose tris-3,5-dimethylphenylcarbamate (AD) coated with aminopropyl Nucleosil silica. The enantiomeric purity was evaluated using the analytical Lux® 3 µm i-Amylose-3 column, yielding enantiomeric purity values ranging between 94.4% and 99.7%. The elution order of all the enantiomers was accomplished combining the ECD results with an optical rotation detector. The elution order of the enantiomers was influenced only by the chiral selector, rather than the mobile phase. The cytotoxicity of the racemates and the isolated enantiomers towards differentiated SH-SY5Y cells was evaluated. (R,S)-DMPMZ exhibited a significantly higher cytotoxicity than (R,S)-PMZ, suggesting the metabolic bioactivation of (R,S)-PMZ. Conversely, no significant cytotoxicity was found for (R,S)-PMZSO, underscoring a metabolic detoxification pathway. Remarkably, enantioselectivity was observed for the cytotoxicity of PMZ; (R)-PMZ was significantly more cytotoxic than (S)-PMZ. The results underscore the importance to isolate the enantiomers in their enantiomerically form and their correct identification for toxicity enantioselectivity studies, which are vital to understand the drug's behaviour and safety, especially in case of overdoses.
Topics: Promethazine; Stereoisomerism; Humans; Cell Line, Tumor; Circular Dichroism; Cell Survival; Chromatography, High Pressure Liquid
PubMed: 38643704
DOI: 10.1016/j.jpba.2024.116152 -
BMC Musculoskeletal Disorders Apr 2024Clinicians and public health professionals have allocated resources to curb opioid over-prescription and address psychological needs among patients with musculoskeletal...
BACKGROUND
Clinicians and public health professionals have allocated resources to curb opioid over-prescription and address psychological needs among patients with musculoskeletal pain. However, associations between psychological distress, risk of surgery, and opioid prescribing among those with hip pathologies remain unclear.
METHODS
Using a retrospective cohort study design, we identified patients that were evaluated for hip pain from January 13, 2020 to October 27, 2021. Patients' surgical histories and postoperative opioid prescriptions were extracted via chart review. Risk of hip surgery within one year of evaluation was analyzed using multivariable logistic regression. Multivariable linear regression was employed to predict average morphine milligram equivalents (MME) per day of opioid prescriptions within the first 30 days after surgery. Candidate predictors included age, gender, race, ethnicity, employment, insurance type, hip function and quality of life on the International Hip Outcome Tool (iHOT-12), and psychological distress phenotype using the OSPRO Yellow Flag (OSPRO-YF) Assessment Tool.
RESULTS
Of the 672 patients, n = 350 (52.1%) underwent orthopaedic surgery for hip pain. In multivariable analysis, younger patients, those with TRICARE/other government insurance, and those with a high psychological distress phenotype had higher odds of surgery. After adding iHOT-12 scores, younger patients and lower iHOT-12 scores were associated with higher odds of surgery, while Black/African American patients had lower odds of surgery. In multivariable analysis of average MME, patients with periacetabular osteotomy (PAO) received opioid prescriptions with significantly higher average MME than those with other procedures, and surgery type was the only significant predictor. Post-hoc analysis excluding PAO found higher average MME for patients undergoing hip arthroscopy (compared to arthroplasty or other non-PAO procedures) and significantly lower average MME for patients with public insurance (Medicare/Medicaid) compared to those with private insurance. Among those only undergoing arthroscopy, older age and having public insurance were associated with opioid prescriptions with lower average MME. Neither iHOT-12 scores nor OSPRO-YF phenotype assignment were significant predictors of postoperative mean MME.
CONCLUSIONS
Psychological distress characteristics are modifiable targets for rehabilitation programs, but their use as prognostic factors for risk of orthopaedic surgery and opioid prescribing in patients with hip pain appears limited when considered alongside other commonly collected clinical information such as age, insurance, type of surgery pursued, and iHOT-12 scores.
Topics: Humans; Aged; United States; Analgesics, Opioid; Retrospective Studies; Quality of Life; Pain, Postoperative; Practice Patterns, Physicians'; Medicare; Arthroplasty; Arthralgia; Endrin
PubMed: 38643071
DOI: 10.1186/s12891-024-07418-w -
Cureus Mar 2024Introduction Understanding the different opioid pain relief requirements between patients with upper limb fractures can be useful in forming specific evidence-based...
Introduction Understanding the different opioid pain relief requirements between patients with upper limb fractures can be useful in forming specific evidence-based guidelines and balancing patient-clinician prescribing discussions with opioid stewardship. We investigated the predictors for opioid requirements in upper limb fractures. Methods We retrospectively investigated all upper limb fractures from the shoulder to the wrist treated at a major trauma center from January 2015 to January 2022. The data collected consisted of fracture location, demographics, comorbidities, and management options. Post-injury opioid prescriptions in the first post-injury year were calculated every month up to six months and then grouped from the seventh to the 12th month and converted to morphine milligram equivalents (MMEs). We then calculated days requiring at least one medication (representing the "coverage") and relative "strength" in each time period. Results Six thousand four hundred thirteen patients sustaining a combined 9125 fractures were included in the study, with an MME mean of 436. Fracture locations of the scapula, proximal humerus, humeral shaft, distal humerus, and proximal ulna all had significantly higher MME requirements (p<0.05) at the one-year level. The radius shaft and distal radius had significantly lower MME requirements (p<0.05). The patients with depression, diabetes, drug abuse history, obesity, pulmonary circulatory disorder, and rheumatological conditions required higher strength of opioids at the one-year level (p<0.05). The patients with chronic kidney disease, depression, pulmonary circulation disorder, and rheumatological conditions required higher coverage of opioids at the one-year level (p<0.05). Conclusion Our study presents a high-resolution breakdown of the post-injury opioid requirements for patients with upper limb injuries. Fractures of the scapula, proximal humerus, and shaft of the humerus were associated with increases in both opioid strength and coverage. Depression, pulmonary disease, and rheumatological conditions were all associated with increased opioid strength and coverage. This provides a framework for which clinicians and patients can more accurately anticipate the course of the rehabilitation journey and risk stratify appropriately at the outset of injury.
PubMed: 38638745
DOI: 10.7759/cureus.56499 -
Critical Care Explorations Apr 2024Pain management is essential for postoperative surgery. Given the association of opioids with adverse outcomes, interest in the use of nonopioid analgesics, such as...
BACKGROUND
Pain management is essential for postoperative surgery. Given the association of opioids with adverse outcomes, interest in the use of nonopioid analgesics, such as ketorolac, has increased. Published data on use in neonates are limited.
OBJECTIVES
To describe ketorolac dosing and safety and efficacy outcomes in the first 48 hours postcardiac surgery in neonates.
DESIGN
We performed a single-center retrospective cohort study of neonates (ages < 28 d) who received ketorolac following cardiac surgery from November 2020 to July 2023 (inclusive). The primary safety outcome was a clinically significant decline in renal function, as defined by the composite of an increase in serum creatinine by greater than or equal to 0.3 mg/dL from baseline within 96 hours of ketorolac initiation and urine output less than or equal to 0.5 mL/kg/hr for 6 hours. The secondary safety outcome was clinically significant bleeding, defined as the composite of major bleeding by the International Society on Thrombosis and Hemostasis pediatric criteria and severe/fatal bleeding by the criteria of Nellis et al (2019). Efficacy was measured by opioid utilization based on a standardized pain score-driven analgesia protocol.
INTERVENTIONS
Ketorolac was administered at 0.5 mg/kg every 6 hours as per an institutional clinical management algorithm.
MEASUREMENTS AND MAIN RESULTS
Thirty-nine patients met the eligibility criteria. The median ketorolac dose was 0.5 mg/kg/dose, and median (interquartile range [IQR]) duration of therapy was 48 hours (6-48 hr). No patients experienced a significant decline in renal function, and there were no clinically significant bleeding events. The median (IQR) IV morphine milligram equivalents (MMEs)/kg/d of opioid administration was 0.2 MME/kg/d (0.1-0.25 MME/kg/d) at the time of ketorolac initiation and 0.1 MME/kg/d (0.1-0.2 MME/kg/d) at 48 hours post-ketorolac initiation.
CONCLUSIONS
If validated prospectively, these findings suggest that a ketorolac regimen of 0.5 mg/kg/dose every 6 hours in neonates postcardiac surgery may be safe with regard to renal function and bleeding risk. Additional randomized studies would be needed to determine efficacy with regard to opioid-sparing capacity.
PubMed: 38633134
DOI: 10.1097/CCE.0000000000001078