Search Results (773)

Cytisine is a plant-derived quinolizidine alkaloid found, among other sources, in the seeds of the common laburnum (Laburnum anagyroides). It has properties that enable it to act as a partial agonist of brain nicotinic α4β2 receptors, which play a key role in the development and maintenance of nicotine addiction. Clinical studies have shown that cytisine is a more effective smoking cessation aid than nicotine replacement therapy and at least as effective as varenicline in treating tobacco cigarette addiction. It may also be an effective agent in treating addiction to electronic cigarettes. Cytisine is also significantly cheaper than other anti-nicotine medications. This is of great importance for the population of smokers in developing countries, who cannot afford anti-nicotine treatment. In recent years, the role of cytisine in the pharmacotherapy of nicotine addiction worldwide has increased significantly. This drug is becoming available in an increasing number of countries, and in 2025 the World Health Organization (WHO) added cytisine to the list of essential medicines. The need for further development of the drug poses additional challenges for scientists, including the creation of new pharmaceutical forms, optimization of dosing regimens, and expansion of indications to include the treatment of nicotine addiction supplied into the body in forms other than traditional tobacco products. This review describes the use of cytisine in the treatment of nicotine addiction, the drug’s mechanism of action, pharmacokinetics, efficacy, safety of use, and the available pharmaceutical preparations. It also presents research directions on cytisine related to the development of innovative pharmaceutical products, new dosing regimens, and new indications associated with the treatment of addiction to various nicotine-containing products. Conclusions indicate that cytisine has a difficult dosing regimen, which is why patients do not adhere to it, limiting the effectiveness of the therapy. This necessitates optimizing the dosage of existing capsules and tablets or introducing, for example, new extended-release forms of the drug containing cytisine. Full article

Background/Objectives: Medication errors remain a patient safety concern in neonatal intensive care units (NICU), mainly due to multiple dilution steps, a lack of standardized preparation instructions, and the frequent use of high-alert medications. While standard concentrations (SCs) for intravenous (iv) medication are recommended internationally, a national standard is missing for NICUs in Germany. The aim of this study was to evaluate a proposal for a national list of standardized iv medication concentrations to be used in German NICUs. Methods: In collaboration with the German Society for Neonatology and Pediatric Intensive Care (GNPI) and the Federal Association of German Hospital Pharmacists (ADKA), a multiprofessional expert team, including experts from the medication safety initiatives TELE-KASPER and Kinderformularium.DE and affiliated with seven German university hospitals, evaluated SCs for infusion medication administered to infants weighing 500 g to 5 kg. The evaluation process was based on international SCs lists, clinical practice, stability data, and handling aspects. Medication used in at least four of the seven hospitals was shortlisted. In the first round of the consensus process, an online survey submitted to the German Level-1 NICUs (n = 165) and their affiliated hospital pharmacies identified preferred SCs. In the second round of the consensus process, the expert team further evaluated the results of the survey. Results: The survey response rate was 52%. The consensus process resulted in a list encompassing 50 iv medications and 80 appropriate SCs. Ancillary information on preparation, stability, osmolarity, pH, and practical administration was added. Conclusions: The proposed SCs for infusion medication used in NICUs have the potential to reduce medication errors, simplify electronic prescribing, and improve workflow efficiency. Implementation aligns with international patient safety initiatives to improve medication safety in pediatric patients. Full article

Objectives: As widely used first-line antihypertensive drugs, dihydropyridine calcium channel blockers (DHP-CCBs) have relatively few studies comparing their adverse reactions based on real-world data. This study aims to identify and compare the potential adverse drug reaction (ADR) signals of four DHP-CCBs (amlodipine, felodipine, nicardipine, and nifedipine) through the US Food and Drug Administration Adverse Event Reporting System (FAERS), providing a reference for further drug safety assessment and clinical medication risk awareness. Methods: Adverse event reports from medical professionals (Q3 2014–Q4 2024) were analyzed using signal detection methods, including reporting odds ratio (ROR), proportional reporting ratio (PRR), information component (IC), and the Medicines and Healthcare Products Regulatory Agency (MHRA) methods. Risk signals for the four DHP-CCBs were compared with both the full database and the DHP-CCBs background. For high-risk signals in amlodipine, multivariate logistic regression was used for validation. The analysis reveals distinct ADR profiles for the four DHP-CCBs. Results: Amlodipine is strongly linked to suicide-related risks, confirmed by logistic regression. Nicardipine and nifedipine show significant risks for pregnancy-related events, such as premature delivery and exposure during pregnancy. Nicardipine is also associated with hyponatremia, hyperkalemia, and lactic acidosis. These adverse events are not yet included in the FDA labeling for any of the DHP-CCBs. Although palpitations and angioedema are listed for felodipine, their signal strength is much higher compared to the other DHP-CCBs. Conclusions: The ADR risk profiles of the four DHP-CCBs differ significantly. This study identified several high-risk adverse events not included in current labels. Clinical use should consider each drug’s risk profile and patient-specific factors, with particular attention to serious risk signals. For pregnant and postpartum women, the benefits and risks of using nicardipine and nifedipine should be carefully evaluated. Full article

Background: The introduction of targeted therapy in oncology has led to several challenges. These medicines are relatively new in clinical practice and are not well known to specialists with regard to adverse drug reactions (ADRs) and potential drug–drug interactions (pDDIs). In addition, cancer affects multiple body systems, including weight loss, anemia, liver and kidney function, depression, and pain. Patients frequently have comorbidities, leading to polypharmacy and the use of special foods, nutritional supplements, and herbal products for self-medication. Identification of pDDIs is essential, as concomitant use of multiple medicinal products increases the risk of ADRs and may compromise treatment. Objective: This study aims to retrospectively review and analyze data on ADRs and pDDIs in the treatment of non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) inhibitors and to evaluate the relationship between them. Method: EudraVigilance and UpToDate^® Lexidrug™ application were used to screen suspected ADRs and pDDIs, respectively. Descriptive statistical analysis was performed. Results: After reviewing Line Listing Reports (LLRs) from 2021 to 2023 in EudraVigilance, the number of suspected adverse drug reactions (ADRs) reported was higher when drug interactions classified as risk categories D and X were identified, compared with cases involving EGFR inhibitor monotherapy or other drug combinations. Of the 144 cases involving category D and/or X interactions, 63 demonstrated a possible association with the reported ADRs of EGFR inhibitors. The most common pDDIs detected were erlotinib–ranitidine (14 cases, category D) and osimertinib–amiodarone (13 cases, category D). Conclusions: Although EGFR inhibitors improve overall and progression-free survival in NSCLC, screening for pDDIs before treatment is essential to improve safety and quality of life. Full article

Purpose: Opioids are widely used for pain management but are associated with adverse events that may differ between women and men. However, post-marketing safety data are rarely examined at the individual level to characterize these sex differences. This study aimed to identify sex disparities in opioid-associated adverse events using the FDA Adverse Event Reporting System (FAERS) to inform safer opioid selection for women. Methods: Opioid drugs were identified using the FDA’s Opioid Analgesic Risk Evaluation and Mitigation Strategy (REMS) list and official drug labeling. Relevant FAERS reports were extracted, and adverse events were classified into 27 System Organ Classes (SOCs) based on the Medical Dictionary for Regulatory Activities (MedDRA). Sex-specific signals of disproportionate reporting were evaluated using proportional reporting ratios and reporting odds ratios for drug–SOC pairs. Results: Across most opioid drugs and SOCs, adverse events were reported more frequently in women than in men. The largest sex disparities were observed for codeine, fentanyl, tapentadol, hydrocodone, and sufentanil, with significantly higher disproportionate reporting rates among women. These findings indicate pronounced sex-specific differences in the post-marketing safety profiles of several commonly used opioids. Conclusions: Women demonstrate higher disproportionate reporting of adverse events for certain opioid medications, particularly codeine and fentanyl. These results suggest the need for increased awareness of sex-specific safety differences and support sex-informed prescribing and monitoring strategies to improve opioid safety in women. Since pharmacists are medication experts and play a key role in promoting rational and safe use, our findings may further support pharmacists counseling patients and monitoring for opioid-related adverse events. Full article

This monograph evaluates the scientific and regulatory underpinnings for bioequivalence (BE) waiver of immediate-release (IR) solid oral meloxicam formulations, as a surrogate for in vivo pharmacokinetic trials. In compliance with ICH (The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use), FDA (Food and Drug Administration), and PMDA (Pharmaceuticals and Medical Devices Agency) bioequivalence guidelines, a systematic characterization was performed on meloxicam’s critical attributes, encompassing solubility, permeability, dissolution behavior, pharmacokinetic profiles, therapeutic index, and drug-excipient compatibility. Classified as BCS Class II (low solubility, high permeability), meloxicam nonetheless exhibits a broad therapeutic window and pharmacokinetic characteristics aligning with BE Category I, thus enabling generic product approval via BE waiver with negligible risks of systemic exposure inequivalence. It is noteworthy that current in vitro methodologies are not consistently capable of capturing C_max disparities of BCS Class II weak acids. BE waiver eligibility for meloxicam IR formulations necessitates three prerequisites: (a) excipient composition identical to the reference listed drug and validated by regulatory authorities; (b) ≥85% dissolution within 30 min at pH 1.2, 4.5, and 6.8; (c) comparable dissolution profiles across these pH conditions. Non-adherence mandates a mandatory in vivo BE assessment. Full article

Background: Fibromyalgia (FM) and eating disorders (ED) represent distinct clinical entities traditionally managed within separate medical specialties, yet emerging evidence suggests significant comorbidity and potential shared pathophysiological mechanisms. Both conditions disproportionately affect women, involve complex multifactorial etiologies and substantially impair quality of life. Despite documented clinical overlaps, the mechanistic connections linking these conditions remain poorly characterized, and integrated treatment approaches are lacking. Objective: This narrative review examines the role of oxidative stress and nuclear factor erythroid 2-related factor 2 (Nrf2) pathway dysfunction as a unifying molecular mechanism connecting fibromyalgia and eating disorders, with emphasis on implications for integrated rehabilitation strategies. Methods: We synthesized current evidence on oxidative stress pathophysiology in fibromyalgia and eating disorders, focusing on Nrf2-Keap1 pathway function, clinical comorbidity patterns and rehabilitation interventions targeting antioxidant defense mechanisms. In PubMed, representative search strings included “(fibromyalgia [MeSH] OR fibromyalgia [Title/Abstract]) AND (“eating disorders” [MeSH] OR “anorexia nervosa” [MeSH] OR “bulimia nervosa” [MeSH])” and “fibromyalgia AND (“oxidative stress” OR Nrf2 OR “redox”)”. Articles in English published through December 2025 were considered, with additional records identified by manually screening reference lists. Results: Fibromyalgia patients exhibit elevated oxidative stress markers, impaired antioxidant enzyme function and compromised Nrf2 activity correlating with disease severity, with studies reporting approximately 30–50% reductions in coenzyme Q10 levels compared with healthy controls. Similarly, eating disorders demonstrate mitochondrial dysfunction and oxidative stress dysregulation, though patterns differ across eating disorder phenotypes. Nrf2 serves as the master regulator of cellular antioxidant defense, coordinating expression of over 500 genes involved in detoxification, cytoprotection, inflammation modulation and metabolic regulation. Evidence suggests Nrf2 activity is regulated by energy balance, potentially linking nutritional status with cellular stress responses. Rehabilitation interventions, including graduated exercise and nutritional optimization with Nrf2-activating foods (cruciferous vegetables, polyphenols, omega-3 fatty acids), offer mechanism-based therapeutic approaches through hormetic Nrf2 activation and direct Keap1 modification. Conclusions: Multidisciplinary rehabilitation programs integrating physical therapy, exercise prescription and nutritional strategies targeting Nrf2 activation offer evidence-based, mechanism-driven approaches to address shared oxidative stress pathophysiology. Nrf2 pathway dysfunction represents a promising and biologically plausible molecular target that may help to unify our understanding of fibromyalgia and eating disorders pending confirmation from prospective clinical studies in comorbid populations. Future research should prioritize prospective clinical trials testing Nrf2-targeted interventions in comorbid populations and collaborative patient-centered care models. Full article

Background and Clinical Significance: Withdrawal symptoms from an abrupt discontinuation or rapid dose reduction in amantadine has been documented as early as 1987. Symptoms can align with several diagnoses, including but not limited to infection, fever, worsening of Parkinson’s disease, seizures, and an altered mental status. In the case described, the timely diagnosis of amantadine withdrawal was delayed due to its nonspecific presentation. Case Presentation: A man in his 60s presented with lethargy, confusion, and delayed responses. His past medical history included parkinsonism, a seizure, type 2 diabetes, and schizoaffective disorder. Outpatient medications included amantadine, benztropine, divalproex, levetiracetam, paliperidone, risperidone, and semaglutide. He was admitted for an altered mental status, and home medications were held when he became NPO. A nasogastric tube was placed, and amantadine was restarted. Following the amantadine reinitiation, the patient returned to baseline and, after ruling out other causes, was diagnosed with amantadine withdrawal. He ultimately completed a 20-day admission and was discharged to a nursing home. Conclusions: The timely diagnosis of amantadine withdrawal was delayed due to its nonspecific presentation. For patients taking amantadine, clinicians should include amantadine withdrawal in their list of differential diagnoses, and in cases of altered mentation, a careful review of the medication list is essential. Full article

Background: Fixed-dose combination drugs (FDCs) are combinations of two or more active ingredients in a single dosage form. These formulations have proven effective in combating the development of resistance in diseases such as tuberculosis and malaria. Despite the benefits observed in the aforementioned cases, fixed-dose antibiotics combinations (FDACs) are increasingly raising questions about their rationality. This is the case for several FDACs listed in the AWaRe classification as not recommended, which unfortunately remain available on the pharmaceutical market, particularly in low- and middle-income countries like the Democratic Republic of Congo (DRC). Objectives: To identify the essential medicines available in pharmacies open to the public in the city of Kinshasa and to assess their inclusion in the DRC’s National List of Essential Medicines (NLEM) and in the World Health Organization’s (WHO) List of Essential Medicines (LEM). The rationality of the FDACs circulating in the city of Kinshasa were also evaluated based on the 2023 AWaRe classification. Methods: A cross-sectional and descriptive study was conducted between February and October 2025 in Kinshasa. For this purpose, fifty registered pharmacies open to the public were selected by systematic random sampling as the research sample. Data collection consisted of completing a data collection form after we had provided the pharmacies’ owners with the necessary explanations regarding the importance of the study and guaranteed their anonymity. Results: The controlled FDACs encountered comprised 27 specialties across 15 different formulations. Out of 15 formulations, 12 (80%) were included on the WHO list of non-recommended antibiotics and were not included in the DRC’s NLEM nor in the WHO’s LEM. Some had been withdrawn from the market in their countries of manufacture. Of the 15 FDACs evaluated for their rationality and compliance, the injectable FDACs presented problems related to the relevance and completeness of information contained on their packaging. On their primary packaging, there was a significant difference in the expiration dates of the powder and sterile water for injection contained in the combination pack, ranging from 6 to 36 months. Furthermore, the secondary packaging lacked data related to the sterile water for injection contained in the combination pack. In addition, several medications contained the same therapeutic combination. For injectable FDAC, for example, the combination Ceftriaxone-Sulbactam was represented by eight medications. For oral FDACs, the combination Sulfamethoxazole-Trimethoprim was represented by seven medications. Globally, 100% of these drug combinations originated from India. Conclusions: Fifteen varieties of FDACs were available in Kinshasa, most of which (80%) were unsuitable. It is important that public health authorities address this situation and develop stricter guidelines for granting marketing authorizations, particularly for FDACs. Full article

Background: Medication-related osteonecrosis of the jaw (MRONJ) remains a challenging complication associated with antiresorptive and antiangiogenic therapies, characterized by impaired bone healing, infection, and compromised vascularization. Advanced biomaterials capable of promoting bone regeneration and modulating the local microenvironment are being investigated as potential therapeutic strategies. Graphene-based biomaterials have recently emerged as promising candidates due to their unique physicochemical properties and multifunctional biological effects. Objective: This systematic review aimed to analyze and synthesize current evidence on graphene-based 3D scaffolds and related graphene-based biomaterials for bone regeneration, with particular attention to their potential relevance in MRONJ treatment and prevention. Data Sources: A systematic literature search was conducted in PubMed and Scopus databases, complemented by manual screening of reference lists from relevant publications. Eligibility Criteria: Studies investigating graphene-based scaffolds, composites, or graphene-derived biomaterials for bone regeneration were considered. Experimental in vitro and in vivo studies, as well as translational studies addressing osteogenesis, angiogenesis, antimicrobial activity, immunomodulation, or drug-delivery properties relevant to bone healing and MRONJ, were included. Editorials, conference abstracts, and non-English publications were excluded. Methods: Titles and abstracts were independently screened by the authors, followed by full-text assessment for eligibility. Data regarding scaffold composition, graphene derivatives, biological mechanisms, and regenerative outcomes were qualitatively synthesized due to heterogeneity in study designs and outcome measures. Results: The identified literature highlights the multifaceted role of graphene-based biomaterials in bone regeneration. Graphene and its derivatives enhance osteogenic differentiation, promote angiogenesis, modulate immune responses, and exhibit intrinsic antimicrobial properties. In addition, graphene-based scaffolds provide versatile platforms for drug delivery and photothermal or photodynamic therapeutic strategies. These multifunctional properties may address key pathophysiological mechanisms involved in MRONJ, including impaired bone remodeling, infection control, and tissue regeneration. Limitations: The available evidence is predominantly derived from preclinical studies, with limited direct investigation in MRONJ-specific models and considerable heterogeneity in scaffold design and experimental methodologies. Conclusions: Graphene-based 3D scaffolds represent a promising and versatile platform for bone regenerative strategies potentially applicable to MRONJ management. Further translational research and well-designed preclinical and clinical studies are required to clarify their safety, efficacy, and therapeutic applicability. Registration: This review was conducted according to PRISMA 2020 guidelines. The review protocol was not registered. Full article

Objectives: To examine the prescribing of non-vitamin K-dependent oral anticoagulants (DOACs) among multidose drug dispensing (MDD) users aged ≥65 years, and to describe associated drug–drug interactions (DDIs), concomitant use of fall-risk increasing drugs (FRIDs) and anticholinergic drugs (AC). Methods: Cross-sectional analysis of anonymized MDD medication lists from 87,519 patients in 2018. DDIs were identified using The Norwegian Medical Products Agency interaction tool, FRIDs were defined using the Swedish National Board of Health and Welfare list, and the CRIDECO Anticholinergic Load Scale assessed anticholinergic burden. Results: Among the 13,215 patients aged 65 and older the mean number of prescribed medications was 10.3. At least one DDI involving the prescribed DOACs was present in 26.8% of patients, whereas severe DDIs were rare (0.2%). Almost all (96.7%) used at least one FRID, and nearly half (46.8%) had an anticholinergic score ≥ 3. Conclusions: DOACs are frequently prescribed together with medications that increase the risk of falls and bleeding. These findings highlight the need for individualized risk–benefit evaluations and deprescribing or substituting high impact FRIDS and ACs when clinically appropriate. Full article

Background/Objectives: Hand, foot and mouth disease (HFMD) caused by enterovirus 71 (EV71) may cause severe complications and death in children. It is also a common cause of outbreaks in the Asia-Pacific Region. Incidence among children 1 to <2 years was over 3000/100,000 population in China. A systematic review and meta-analysis was performed to review evidence on vaccine efficacy (VE), immunogenicity, and safety of two doses of EV71 vaccine in children. Methods: Randomized controlled trials (RCTs) comparing EV71 vaccine with placebo or with another EV71 vaccine in children and adolescents aged ≤18 years were searched on PubMed, Medline, Embase, CENTRAL, and CNKI (Chinese) in week 5 November 2024. The reference list of each study and the websites of vaccine manufacturers were also searched. The Cochrane Risk of Bias 2 tool (RoB2) was used to assess the risk of bias. VE, immunogenicity (including seropositive rate, seroconversion rate, geometric mean titer (GMT), Geometric Mean Fold Increase (GMFI)), and rate of adverse events were analyzed. Results: A total of 4199 articles were identified, and 25 studies were finally included. VE (%) against EV71 HFMD in children aged ≤5 years at 12 months was 94.8% (95%CI 87.2–97.9) for Sinovac and 90.9% (95%CI 70.4–97.2) for Wuhan Institute of Biological Products (WIBP), while the Chinese Academy of Medical Sciences (CAMS) reported 97.4% (95%CI 92.9–99.0) at 11 months. At 1 month after the second dose, 99.19% (95%CI 98.15–99.65) of children aged ≤5 years in the vaccine group were seropositive, and 96.30% (95%CI 92.71–98.17) achieved seroconversion. GMT at 1 month after the second dose in the vaccine group was 46.78 (95%CI 26.18–83.61) times that in the placebo group. GMFI at 1 month after the second dose in the vaccine group was 28.41 (95%CI 22.18–36.39) times that of the placebo group. The rate of serious adverse events (AEs) was lower in the vaccine group than the placebo group (1.23% (95%CI 0.58–2.69) vs. 1.34% (95%CI 0.58–3.07)) at 1 month after the second dose. There was no significant difference in other adverse events between the vaccine and placebo groups. Conclusions: EV71 vaccines were effective, immunogenic and safe. Areas with a high incidence of EV71 may consider introducing EV71 vaccines. Full article

Body dissatisfaction and eating disorder (ED) risk indicators can persist into later life but are less frequently assessed in routine care for older women. Among women aged 50 years and older, attendance on dietary care pathways in clinical settings may offer a pragmatic opportunity for early identification (screening) of ED risk indicators and related psychological distress, particularly during the menopausal transition. Thus, the aim of this study was to compare body dissatisfaction and ED risk indicators in older women attending dietary treatment versus those not following a dietary regimen. This cross-sectional study compared women aged ≥50 years without a prior ED diagnosis who were receiving medically supervised dietary treatment (DTG; n = 42) with peers not following any dietary regimen (NDG; n = 40) in Cádiz (Spain). Participants completed the Eating Disorder Inventory-3 Referral Form (EDI-3RF), AF-5 Self-Concept Questionnaire, List of Brief Symptoms (LBS-50), and the International Physical Activity Questionnaire (IPAQ) and underwent anthropometric assessment. Compared with those women in the NDG, those in the DTG had a higher body mass index (p = 0.002), higher drive for thinness (p < 0.001) and body dissatisfaction (p < 0.001), lower physical self-concept (p = 0.001), and higher total EDI-3RF scores (p < 0.001). Based on the EDI-3RF, 11.9% of the DTG met clinical referral criteria versus none in the NDG (p = 0.031). These findings indicate that, in this sample of women aged ≥ 50 years, women attending dietary care pathways exhibited a higher ED risk profile, higher psychopathological symptom levels, and lower physical self-concept than women not following a dietary regimen. Given the cross-sectional design, results should be interpreted as associations and may reflect pre-existing differences among women who enter dietary care; nonetheless, dietary care pathways may represent a practical opportunity to incorporate brief screening for body image concerns and ED risk indicators in older women. Full article

In 2022, the World Health Organization (WHO) released a list of four fungi identified as the most medically important global pathogens, resulting in Cryptococcus neoformans, Candidozyma auris (formerly Candida auris), Aspergillus fumigatus and Candida albicans being classified as the critical priority fungi. The purpose of this list is to encourage the prioritization of fungal research and public policies to strengthen its control and combat fungal diseases. Among the criteria used in the analysis by the WHO to determine these critical threat pathogens were numbers of deaths; annual incidence; current global distribution; trends in the last 10 years; hospitalization; complications and sequelae; preventability; access to diagnostic tests; evidence-based treatments; and antifungal resistance. Difficulties in treatment, including due to antifungal resistance, are a major factor in the morbidity and mortality of these fungi. The fungal cell wall plays a fundamental role in maintaining cellular architecture and contributing to fungal survival. Thus, new approaches targeting the cell wall have been and are being developed. This review article aims to bring together studies from the last ten years focusing on the development of new treatment alternatives targeting the cell walls of the four critical priority fungi and discussing their potential for combating these deadly fungi of worldwide clinical importance. Full article

Traumatic injuries represent a significant public health challenge, affecting millions worldwide annually and necessitating acute pain management that frequently involves the use of opioid analgesics to mitigate discomfort and facilitate recovery. Although opioids remain an integral part of post-traumatic injury pain management, their use exposes trauma survivors to the risk of developing persistent use, misuse, or opioid use disorder (OUD). Pre-injury health determinants, such as age, gender, psychiatric conditions, medical conditions, and substance use history, may interact with injury-related factors to acutely escalate the risk for misuse and addiction. Despite the growing recognition of these potential vulnerabilities, there remains a lack of evidence-based clinical decision support on modifiable and non-modifiable risk factors specific to post-traumatic injury opioid risk trajectories. This review summarizes the literature related to the multifactorial contributors to opioid misuse and addiction following traumatic injury such as patient-level (e.g., demographics, behavioral health), injury-related (e.g., severity, type), and system-level (e.g., prescribing patterns) characteristics. A comprehensive literature search, inclusive of the literature from 1995 to November 2025, was performed in PubMed/MEDLINE, Scopus, and Google Scholar using combinations of terms related to “opioids,” “misuse,” “addiction,” “trauma,” and “injury.” Search keywords and operators were developed in collaboration with a university librarian. Reference lists of articles were searched and synthesized. Case reports, case series, editorials, mini-reviews, letters to editor without original data, and qualitative studies were excluded. The findings of the review are expected to provide insight into clinical-decision making as it relates to the management of pain, pain-related distress and functional impact, and co-occurring conditions that may impact injury-related outcomes and the potential likelihood of substance misuse and addiction. Full article