Pattern of Prescription Opioid Use and Misuse among War-Injured Adults Receiving Treatments in Mekelle Trauma Centers, Northern Ethiopia

Pattern of Prescription Opioid Use and Misuse among War-Injured Adults Receiving Treatments in Mekelle Trauma Centers, Northern Ethiopia | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Pattern of Prescription Opioid Use and Misuse among War-Injured Adults Receiving Treatments in Mekelle Trauma Centers, Northern Ethiopia Gebrehiwot Teklay, Awet Hadush, Yirga Legesse Nirayo This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6527013/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Opioid analgesics are commonly used for managing moderate to severe pain. While opioids can be effective for pain management, prolonged and inappropriate prescribing can pose risks such as abuse, and overdose. This study aimed to investigate the patterns of opioid use and misuse among war-injured adults in Mekelle trauma centers. A cross-sectional study design was used. The study participants were adults with war related traumatic injuries. Data was collected through a review of the medical records, patients self-report and from health care providers. Opioid misuse behavior was assessed using the Current Opioid Misuse Measure tool combined with clinical judgment. Statistical analysis was conducted using binary logistic regression. Results were presented as odds ratios with 95% confidence intervals. A p value of less than 0.05 was considered statistically significant. The study included a total of 310 adults with war-related traumatic injuries, predominantly male. About half of the participants were young adults aged between 18–24 years, with major traumatic injuries (Injury Severity Score above 15) and using opioids chronically. Tramadol was the most commonly prescribed opioid, accounting for 77.4% of all opioid prescriptions. Only 25.2% of participants were on multimodal analgesia. The intravenous route was the most commonly used route of opioid administration regardless of the injury severity and duration of analgesic use. The mean opioid dose used expressed as Morphine Milligram Equivalent (MME) per day (SD), was 45.04 (± 37.04). The mean duration of opioid treatment (SD) was 231.45 (± 257.17) days. Opioid misuse was identified in about 48% of the participants. Comorbid substance use (AOR = 62.03, p = 0.00), intravenous opioid administration (AOR = 8.09, p = 0.00), and not using multimodal analgesia (AOR = 0.016, p = 0.00) were independent predictors of opioid misuse. This study highlights significant challenges in opioid use, including the reliance on tramadol as the primary analgesic, and high rates of opioid misuse among traumatic injured adults potentially hindering their recovery. Training and educational programs targeting both healthcare providers and patients should emphasize the risks of long-term opioid use, safe practices, and alternative pain management options. Health sciences/Health care/Diagnosis Health sciences/Health care/Drug regulation Health sciences/Health care/Fracture repair Health sciences/Health care/Therapeutics Health sciences/Diseases Health sciences/Health care Health sciences/Medical research Health sciences/Risk factors Long-term use Misuse Multimodal analgesia Prescription opioids Tramadol Trauma Figures Figure 1 Figure 2 Introduction Opioids are a class of drugs naturally found in the opium poppy plant and commonly used to treat moderate to severe pain. These drugs include hydrocodone, oxymorphone, morphine, fentanyl, pethidine, codeine and tramadol [ 1 ]. Unlike other opioids, tramadol has norepinephrine and serotonin reuptake inhibition properties in addition to its mu-opioid binding activity. It is commonly used in low- and middle-income countries (LMIC) [ 2 ] and its consumption is increasing globally [ 3 ]. The need for effective pain management remains high and prompt in low and middle-income African countries primarily due to limited access to opioid analgesics [ 4 ]. Guidelines recommend multimodal analgesia for the treatment of pain in both children and adults [ 5 – 7 ]. Nonopioid therapies like acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), antidepressants, antiepileptics, and local anesthetics can be used as alternative for many common types of acute pain. Clinicians should maximize the use of nonpharmacologic and nonopioid pharmacologic therapies when appropriate for the specific condition and patient and only consider opioid therapy for acute pain if the benefits outweigh the risks. Opioids are essential for treating moderate-to-severe acute pain when other therapies are contraindicated or insufficiently effective [ 5 – 7 ]. The daily dose of opioids is usually expressed as morphine milligram equivalents (MME). Increasing opioid dosages to ≥ 50 MME/day may not provide additional benefit in pain relief and can increase the risk of adverse effects and addiction [ 7 ]. Oral administration of opioids is preferable over intravenous for postoperative analgesia in patients who can use the oral route [ 5 , 8 ]. Proper administration and monitoring of pain management are crucial to prevent harmful effects and the risk of misuse and addiction associated with opioids [ 6 , 7 ]. Pain management is a significant issue in low-income countries like Ethiopia, where it is inadequately managed [ 9 – 12 ], and there are increased reports of opioid misuse, particularly tramadol [ 13 ]. The nonmedical use of tramadol has reached a public health crisis in African countries [ 14 ]. In Ethiopia, tramadol was not a controlled substance until recently and was easily accessible without a prescription [ 15 ], and it was classified as controlled substance due to reports of abuse. However, there is limited information on the pattern of opioid misuse and its health consequences in the country. This study aims to assess the patterns of prescription opioid use and misuse among adults with traumatic injuries to inform policy decisions and improve treatment outcomes while minimizing adverse effects of opioid use. Methods Study Area and Period This study was conducted in two trauma centers in Mekelle, the capital city of Tigray, the northern most region of Ethiopia, situated 783km away from Addis Ababa. Tigray was significantly impacted by a devastating war that began on November 4, 2020, and concluded on November 3, 2022. The war resulted in the loss of hundreds of thousands of lives and led to severe health consequences [ 16 – 19 ]. The study was carried out from March to September 2024. Study Design and Participants A cross-sectional study design was used. The study participants were adults who sustained war-related injuries from bullets and/or heavy artillery and received treatments in the trauma centers in 2023 and 2024. The study involved the review of medical records and the assessment of patients’ opioid-related aberrant behaviors. Opioid misuse behavior was assessed using the Current Opioid Misuse Measure (COMM) [ 20 ] combined with clinical judgment. All post trauma or postoperative analgesic prescriptions were reviewed. Adult injured patients who received treatment in the trauma centers during the study period were eligible for inclusion in the study, irrespective of their sex, severity of injury and duration of trauma. Sample Size Determination and Sampling Techniques The required sample size for this study was calculated using a single proportion sample size estimation formula: n 0 = z 2 p(1-p)/d 2 Where, n o is the desired sample size; z is the standard normal deviation (1.96); p is the probability of opioid misuse (20%) based on previous study [ 21 ], and d is the desired degree of accuracy (0.05). Therefore, n o was determined to be 246. Finally, a total of 310 participants were included in the study. Participants were selected using a simple random sampling method, with bed numbers serving as the sampling frame. Each room had an average of five to ten beds. The first participant was selected randomly by lottery, and participants in every other bed number were included. Data Collection Tools and Methods The study involved a review of medical records and the assessment of patients’ opioid-related aberrant behaviors. The medical record review was conducted by pharmacy students. A data abstraction format was developed to record patient demographics, clinical information, and medication related characteristics. Data regarding patients’ opioid misuse behaviors were assessed using the COMM opioid misuse assessment tool and clinical judgment by physicians and nurses caring for the injured patients. Health professionals providing care for the injured patients evaluated each patient’s opioid medication taking behavior based on past medical histories, physical examination findings and clinical data. To ensure consistency in assessing opioid misuse, an eleven-item checklist was developed and utilized by the health providers. All data collectors and health providers received training on the study’s aim and data collection methods. Prior to the actual study, a pretest was done on 10 participants to assess the applicability of the data collection tools, methods and the performance of the data collectors. Data Analysis The collected data was checked for completeness and consistency, then it was edited, coded, and cleaned. The data was initially entered into Microsoft Excel and later transferred to SPSS Statistics version 29 for analysis. Descriptive statistics were used to determine the frequencies and percentages. Binary logistic regression was employed to identify the relationship between the dependent variable (opioid misuse) and independent variables (age, sex, severity of injury, type of analgesics, duration of opioid use, dose of opioid, comorbidities and co-medications). The results of the statistical analysis were presented as odds ratios (OR) with 95% confidence intervals (CI), and a p value of less than 0.05 was considered statistically significant. Operational Definitions Severity of Traumatic Injury According to the Injury Severity Score (ISS), the severity of traumatic injury is numerically scored from 0 to 75, with higher scores indicating greater injury severity. A score of 12 is considered moderate severity, while a score above 15 is classified as major trauma, often necessitating specialized care [ 22 ]. Chronic Opioid Use prolonged use of opioid medications prescribed by a healthcare provider or obtained from other sources. A cut-off point of above three months is typically used. Morphine Milligram Equivalent (MME) A measurement used to compare the potency of different opioids and routes to oral morphine. For instance, 10mg of intravenous morphine is equivalent to 30mg of oral morphine. The MME per day of intravenous tramadol was calculated as 0.3 X dose of tramadol X number of doses per day. The MME per day of oral tramadol was calculated as 0.2 X dose of tramadol X number of doses per day [ 7 ]. Multimodal Analgesia involves the use of non-opioid and opioid analgesics. Nonopioid therapies include acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), antidepressants and antiepileptics. Opioid Misuse Any use of a prescription opioid outside of the manner and intent for which it was prescribed. This includes opioid-related aberrant behaviors such as overuse, using to get high, diversion or sharing with others, having multiple prescribers or nonprescribed sources of the medication, and concurrent use of other illicit substances, or nonprescribed controlled medications. Misuse is a necessary but not sufficient criterion for opioid use disorder. Opioid misuse was assessed using the COMM tool [ 20 ] combined with clinical gestalt. The COMM is a 17-item patient self-assessment tool used to monitor patients on long-term opioid therapy and identify aberrant behaviors associated with opioid medication misuse. A score of 9 or higher is considered positive. Results In this study, a total of 310 adults with war related traumatic injuries were included. Half of the participants had moderate injuries, and received opioids for post-operative acute pain, while the remaining had major injuries (ISS above 15) and received opioids chronically for more than 3 months. Most of the study participants were male, with almost half of them being young adults aged between 18 and 24 years. The study also found that 25.2% of the participants received multimodal analgesia, while the majority (74.8%) relied solely on opioids. Multimodal analgesia was less commonly used among participants with major injuries who were taking opioids chronically. Tramadol was prescribed to the majority (77.4%) of the study participants, with the intravenous route being the most commonly used regardless of the severity of injury or duration of analgesic use (Fig. 1 and Fig. 2 ). The mean and standard deviations (SD) of opioid dose used expressed as MME per day was 45.04 (± 37.04), with about 18% of the participants receiving doses above 50 MME, where the risks are supposed to outweigh the benefits. The mean duration of opioid treatment was 231.45 (± 257.17) days. Opioid-related aberrant behaviors or misuse were assessed in half of the study participants, with concurrent substance use such as smoking, diazepam and marijuana identified in 8.7% of participants (Table 1 ). These substances likely increase the risk of opioid misuse and addiction, and were commonly reported among participants on chronic opioid use. Table 1 Demographic and clinical characteristics of adults with war-related traumatic injuries in selected trauma centers in Mekelle (N = 310), 2024. Variables N % Age 18–24 167 53.9 ≥ 25 143 46.1 Sex Male 274 88.4 Female 36 11.6 Severity of injury Major 154 49.7 Moderate 156 50.3 Comorbid Substance Use* Yes 27 8.7 No 283 91.3 Multimodal analgesia^ Yes 78 25.2 No 232 74.8 Type of Opioid used Tramadol 240 77.4 Morphine 16 5.2 Combination of Tramadol and Morphine 16 5.2 Morphine followed by Tramadol or vice versa 38 12.3 Rout of Opioid Administration IV 198 63.9 PO 60 19.4 Both IV and PO 52 16.8 Duration opioid treatment > 2 years 128 41.3 3–12 months 26 8.4 2–12 weeks 93 30.0 < 2 weeks 63 20.3 Opioid dose (MME per day) ≥ 50 57 18.4 < 50 253 81.6 Opioid misuse Yes 149 48.1 No 161 51.9 * Comorbid substance use includes smoking, diazepam and marijuana; ^ non-opioidal analgesics commonly used include Non-steroidal anti-inflammatory drugs, Acetaminophen, Amitriptyline, Pregabalin or combination of these. Mean duration of opioid treatment (SD) = 231.45 (± 257.17); Mean MME/d (SD) = 45.04 (± 37.04); IV, intravenous; PO, oral; MME: Morphine milligram equivalent; N: Number. The univariable binary logistic analysis of factors associated with opioid misuse revealed that young adults (COR = 1.75, p = 0.01), comorbid substance use (COR = 7.16, p = 0.00), tramadol use (COR = 6.43, p = 0.00), intravenous route of opioid administration (COR = 5.33, p = 0.00) and daily opioid doses above 50 MME (COR = 3.44, p = 0.00) were more likely to misuse opioids. On the other hand, participants taking multimodal analgesia (COR = 0.09, p = 0.00) were less likely to misuse opioids (Table 2 ). However, in the multivariable binary logistic regression comorbid substance use (AOR = 62.03, p = 0.00), intravenous route of opioid administration (AOR = 8.09, p = 0.00), and not using multimodal analgesia (AOR = 0.016, p = 0.00) were independent predictors for opioid misuse (Table 3 ). Table 2 Univariate binary logistic regression of opioid misuse among adults with war-related traumatic injuries in selected trauma centers in Mekelle (N = 310), 2024. Variables Opioid Misuse p value COR 95% CI Yes No Age 18–24 91 76 0.01 α 1.75 1.12–2.76 ≥ 25 58 85 1 Sex Male 127 147 0.10 0.55 0.27–1.12 Female 22 14 1 Comorbid substance use Yes 23 4 0.00 α 7.16 2.41–21.25 No 126 157 1 Multimodal analgesia Yes 9 69 0.00 α 0.09 0.04–0.18 No 140 92 1 Type of Opioid Tramadol 137 103 0.00 α 6.43 3.28–12.59 Morphine 12 58 1 Route Intravenous 138 113 0.00 α 5.33 2.64–10.74 Oral 11 48 1 Pattern of opioid use Chronic 80 74 0.17 1.36 0.87–2.13 Acute 69 87 1 Duration of opioid use > 2 years 70 58 0.13 1.93 0.81–4.58 3–12 months 10 16 0.08 1.52 0.95–2.43 < 3months 69 87 1 Dose in MME/day ≥ 50 41 16 0.00 α 3.44 1.83–6.45 < 50 108 145 1 α Statistically significant association; MME: Morphine milligram equivalent; COR: Crude odds ratio; CI: Confidence interval; N: Number Table 3 Multivariable binary logistic regression of opioid misuse among adults with war-related traumatic injuries in selected trauma centers in Mekelle (N = 310), 2024. Variables Opioid Misuse p value AOR 95% CI Yes No Age 18–24 91 76 0.13 1.57 0.88–2.79 ≥ 25 58 85 1 Comorbid substance use Yes 23 4 0.000 α 62.03 9.71–396.3 No 126 157 1 Multimodal analgesia Yes 9 69 0.000 α 0.016 0.003–0.08 No 140 92 1 Type of Opioid Tramadol 137 103 0.92 1.06 0.33–3.47 Morphine 12 58 1 Route Intravenous 138 113 0.000 α 8.09 3.54–18.48 Oral 11 48 1 Dose in MME/day ≥ 50 41 16 0.07 2.14 0.94–4.86 < 50 108 145 1 α Statistically significant association; MME: Morphine milligram equivalent; AOR: Adjusted odds ratio; CI: Confidence interval; N: Number Discussion The findings from this study provide important insights into opioid prescribing practices and factors associated with an increased risk of opioid misuse among traumatic injured patients in a resource-constrained setting. The study revealed that tramadol was the most commonly prescribed opioid in both acute and chronic post-traumatic pain management, highlighting the underutilization of multimodal analgesia. Only a quarter of the patients received co-analgesics such as NSAIDs, acetaminophen, antidepressants and antiepileptics, contrasting with guideline recommendations in high-income countries [ 5 – 7 ], where multimodal analgesia is widely adopted to reduce opioid consumption and mitigate risks. Studies have shown that multimodal analgesia in post-operative pain management reduces opioid use [ 23 , 24 ]. Similar to the current study, Rostom et al [ 25 ] also reported severe underutilization of multimodal analgesia in trauma patients. In the multivariable regression analysis, participants taking multimodal analgesia were 98.4% less likely to develop opioid related misuse compared to those not taking it (AOR = 0.016; p = 0.00). The absence of multimodal analgesia in the study setting represents a missed opportunity to reduce opioid-related misuse, harm and improve pain management outcomes. Opioid-related misuse was assessed in half of the study participants, a prevalence considerably higher than rates reported in other studies. [ 26 – 29 ]. Tramadol was the most commonly prescribed opioid, prescribed in 77.4% of the study participants. Similar to this finding, in a study in Brazil, tramadol was the most commonly prescribed opioid [ 2 ]. However, the current study finding is quite high compared to another study done in high-income countries [ 30 ], where stronger opioids such as morphine and oxycodone are more commonly prescribed than tramadol. Recent studies have reported a global increase in the consumption of tramadol [ 3 , 31 ]. The reliance on tramadol may reflect its wide accessibility, perceived efficacy, safety and lower abuse potential compared to other opioids [ 32 ]. Additionally, patient pressure to receive tramadol for its euphoric effect might contribute to the increased rate of tramadol use. The safety, efficacy and relatively lower abuse potential of tramadol have also been also observed in other studies [ 33 – 35 ]. In contrast, tramadol was more commonly misused than morphine, hydromorphone and oxymorphone [ 36 ]. The prevalence of opioid misuse particularly tramadol misuse was a significant concern in the current study. The pattern of analgesic prescribing observed in this study such as using tramadol alone as the mainstay of analgesia, at relatively high dose, administered mainly through the IV route and being used for prolonged duration may contribute to the high prevalence of misuse. Further investigations are needed to explore pharmacogenomic factors contributing to tramadol misuse and abuse in the study setting, as a significant number of Ethiopians were identified to be cytochrome P450 (CYP2D6) ultra-rapid metabolizers [ 37 – 38 ]. CYP2D6 is an isoenzyme that converts tramadol to an active metabolite, O-desmethyltramadol (M1), which has about 200 times the affinity for the mu-opioid receptor than tramadol itself [ 39 ]. The oral route is preferable over intravenous administration of opioids for postoperative analgesia in patients who can take orally [ 5 , 8 ]. However, in this study, intravenous administration was the most common route of administration in both acute and chronic post traumatic conditions. In the binary logistic regression, intravenous route of opioid administration was found to be an independent predictor of opioid misuse. Participants administering opioids intravenously were 8 times more likely to develop opioid misuse compared to the oral route. The reliance on IV routes in the current study may reflect the potential preference and pressure from abusers, as this route has an immediate effect. Concurrent substance use was observed in 8.7% of participants, with comorbid substance use identified as the strongest predictor of opioid misuse. This is consistent with findings in other studies, where tramadol misuse was linked with other substance use such as alcohol, marijuana, ecstasy, and methamphetamine [ 40 ]. Similarly, the use of alcohol and marijuana was common among adolescents misusing prescription opioids [ 41 ]. This study has limitations, including recall biases when assessing opioid misuse by health care providers due to the large number of patients they have been treating. The COMM is a self-assessment tool filled out by patients, posing a potential for underreporting of substance use and self-selection bias. As a cross-sectional design, we were unable to definitively conclude the opioid misuse as opioid use disorder based on the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria, as it requires observation of aberrant behaviors over a 12-month period. Further studies are needed to understand magnitude of opioid use disorder and related harm among patients with chronic pain. Nationwide studies are needed to assess the impact of policy changes related to tramadol and its impact on misuse prevalence. Future research should investigate the impact of pharmacogenomic factors, specifically CYP2D6 genetic polymorphism, on tramadol safety and dosing changes among Ethiopians. Conclusion This study highlights challenges in opioid use, including the of multimodal analgesia, reliance on tramadol as the primary analgesia, and a high prevalence of opioid misuse among traumatic injured adults. Clinicians must monitor patients prescribed opioids responsibly, weigh the benefits against the risk for long-term use, and integrate routine screening for comorbid substance use into pain management practices. Educational programs should focus on the risks of opioid use, safe practices, and alternative pain management options for both patients and healthcare providers. Abbreviations AOR Adjusted odds ratio COR Crude odds ratio CI Confidence Interval COMM Current Opioid Misuse Measure CYP2D6 cytochrome P450 DSM-5 Diagnostic and Statistical Manual of Mental Disorders ISS Injury Severity Score IV intravenous LMICs Low- and Middle-Income Countries MME Morphine milligram equivalent NSAID Nonsteroidal anti-inflammatory drugs N Number PO oral,SPSS,Statistical Package for Social Science SD Standard Deviation Declarations Ethical approval and consent to participate This study was conducted after obtaining official approval from Mekelle University, College of Health Science, School of Pharmacy, and Ethical Committee (Approval Number: MU-IRB 2236/2024). The study was done after obtaining written informed consent to participate. The aims of the study were discussed with participants and health professionals working in the trauma centers. The privacy and confidentiality of participants' information was kept confidential. Identification code was used instead of patients’ name and health facility name. All methods used in this study were done in accordance with the ethical standards of the institutional and/or national research committee. All methods used in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the Declaration of Helsinki. Consent for Publication Not applicable Data Availability The data supporting the conclusions of this study are presented in the main manuscript. Any additional data can be obtained by contacting the corresponding author. Competing Interests The author reports no conflicts of interest in this work. Funding We received no funding for the study. Authors' Contributions G.T. and A.H. both contributed to the study design, and data collection. All authors contributed to the data analysis and report writing. G.T. developed the draft manuscript which was finalized with input from A.H. and Y.L.N. 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Epub 2020 Sep 21. PMID: 33010713. Porter, E. D., Sacks, O. A., Ramkumar, N. & Barth, R. J. Jr. Surgery Prescription Opioid Misuse and Diversion in US Adults and Associated Risk Factors. J. Surg. Res. 275 , 208–217. 10.1016/j.jss.2022.01.030 (2022). Epub 2022 Mar 17. PMID: 35306256. Richards, G. C., Aronson, J. K., Mahtani, K. R. & Heneghan, C. Global, regional, and national consumption of controlled opioids: a cross-sectional study of 214 countries and non-metropolitan territories. Br. J. Pain . 16 (1), 34–40 (2022). Epub 2021 May 4. PMID: 35111312; PMCID: PMC8801686. Jayawardana, S. et al. Global consumption of prescription opioid analgesics between 2009–2019: a country-level observational study. EClinicalMedicine 42 , 101198. 10.1016/j.eclinm.2021.101198 (2021). PMID: 34820610; PMCID: PMC8599097. Iqbal, M. J., Ali, M., Ghafoor, R., khan, A. M. & Raza, M. M. Study the different incidences of Tramadol in different cities of Punjab. Pakistan Clin. Invest. (Lond) . 11 (1), 26–30 (2021). Acharya, M. et al. Development of a potential opioid misuse measure from administrative dispensing data and contrasting opioid misuse among individuals on long-term tramadol, long-term short-acting hydrocodone or long-term short-acting oxycodone therapy in Arkansas. Curr. Med. Res. Opin. 38 (11), 1947–1957 (2022). Epub 2022 Aug 28. PMID: 36000252; PMCID: PMC10507676. Dunn, K. E., Bergeria, C. L., Huhn, A. S. & Strain, E. C. A Systematic Review of Laboratory Evidence for the Abuse Potential of Tramadol in Humans. Front. Psychiatry . 10 , 704. 10.3389/fpsyt.2019.00704 (2019). PMID: 31616329; PMCID: PMC6775208. Wilder-Smith, C. H., Schimke, J., Osterwalder, B. & Senn, H. J. Oral tramadol, a [x-opioid agonist and monoamine reuptake-blocker, and morphine for strong cancer-related pain. Ann. Oncol. 5 , 141–146 (1994). Dart, R. C., Iwanicki, J. L., Black, J. C., Olsen, H. A. & Severtson, S. G. Measuring prescription opioid misuse and its consequences. Br. J. Clin. Pharmacol. 87 (4), 1647–1653. 10.1111/bcp.14791 (2021). Epub 2021 Mar 8. PMID: 33606888. Aklillu, E. et al. Frequent distribution of ultrarapid metabolizers of debrisoquine in an ethiopian population carrying duplicated and multiduplicated functional CYP2D6 alleles. J. Pharmacol. Exp. Ther. 278 (1), 441–446 (1996). Ahmed, J. H. et al. CYP2D6 Genotype Predicts Plasma Concentrations of Tamoxifen Metabolites in Ethiopian Breast Cancer Patients. Cancers (Basel) . 11 (9), 1353. 10.3390/cancers11091353 (2019). Allegaert, K. et al. Tramadol and o-desmethyl tramadol clearance maturation and disposition in humans: a pooled pharmacokinetic study. Clin Pharmacokinet. ;54(2):167 – 78. (2015). 10.1007/s40262-014-0191-9 . PMID: 25258277. Nazarzadeh, M., Bidel, Z. & Carson, K. V. The association between tramadol hydrochloride misuse and other substances use in an adolescent population: Phase I of a prospective survey. Addict. Behav. 39 (1), 333–337. 10.1016/j.addbeh.2013.09.013 (2014). Epub 2013 Sep 14. PMID: 24090628. Jones, C. M. et al. Prescription Opioid Misuse and Use of Alcohol and Other Substances Among High School Students - Youth Risk Behavior Survey, United States, 2019. MMWR Suppl. ; 69 (1):38–46. doi: 10.15585/mmwr.su6901a5 . (2020). PMID: 32817608; PMCID: PMC7440199. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6527013","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":495667364,"identity":"1dc57ae7-878a-4406-b63a-abafe846fee0","order_by":0,"name":"Gebrehiwot Teklay","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA7UlEQVRIiWNgGAWjYHACNiA+wAMkGB8ACR4+Qup5EFqYmQ1AAmzEagFiZjYJmKV4gT3/4mOPKyruyBgc7z9W+TXHToaNgfnhoxv4bJF4lm545swzHoMzh9luy25LBjqMzdg4B6+WM2aSjW2HecxuJLPdltzGDNTCwyaNX8v5b5KN/4Ba7j9mK5bcVk+EFv4eNsnGBpAtzGyMH7cdJkLLDTZzw4Zjh3nszyQbSzNuO87DxkzAL+z9h589bKg5bC/ZfvDhx5/bqu352ZsfPsanhUEiAcFm5gGT+JSDAP8BBJvxByHVo2AUjIJRMCIBAPl/RkPqF4ciAAAAAElFTkSuQmCC","orcid":"","institution":"Mekelle University","correspondingAuthor":true,"prefix":"","firstName":"Gebrehiwot","middleName":"","lastName":"Teklay","suffix":""},{"id":495667365,"identity":"633d5d00-44f0-42b1-8507-74be2d086997","order_by":1,"name":"Awet Hadush","email":"","orcid":"","institution":"Axum University referral Hospital Axum University","correspondingAuthor":false,"prefix":"","firstName":"Awet","middleName":"","lastName":"Hadush","suffix":""},{"id":495667366,"identity":"a5b12238-6173-4166-b336-8fd75b0d0ba1","order_by":2,"name":"Yirga Legesse Nirayo","email":"","orcid":"","institution":"Mekelle University","correspondingAuthor":false,"prefix":"","firstName":"Yirga","middleName":"Legesse","lastName":"Nirayo","suffix":""}],"badges":[],"createdAt":"2025-04-25 08:38:19","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6527013/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6527013/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":88472730,"identity":"ebb3c395-9df5-4f29-9da6-d2eb5f51cfbc","added_by":"auto","created_at":"2025-08-06 19:41:11","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":72934,"visible":true,"origin":"","legend":"\u003cp\u003eTypes of opioids commonly prescribed for acute and chronic pain management among adults with war-related traumatic injuries in selected trauma centers in Mekelle, 2024.\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-6527013/v1/e9d9e681f811d74782ddcfc7.png"},{"id":88472732,"identity":"6146c822-7941-430a-9b3f-b6afd259ba52","added_by":"auto","created_at":"2025-08-06 19:41:11","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":69987,"visible":true,"origin":"","legend":"\u003cp\u003eRoutes of opioid administration in acute and chronic pain management among adults with war-related traumatic injuries in selected trauma centers in Mekelle, 2024.\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-6527013/v1/f68fb08d6c2a29e968b2cd81.png"},{"id":106481743,"identity":"9d5273e2-d71d-4c4d-8cc5-528bde967dbd","added_by":"auto","created_at":"2026-04-09 04:56:02","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":884415,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6527013/v1/6daf66a2-d590-48c0-9d49-f652bda12f2d.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Pattern of Prescription Opioid Use and Misuse among War-Injured Adults Receiving Treatments in Mekelle Trauma Centers, Northern Ethiopia","fulltext":[{"header":"Introduction","content":"\u003cp\u003eOpioids are a class of drugs naturally found in the opium poppy plant and commonly used to treat moderate to severe pain. These drugs include hydrocodone, oxymorphone, morphine, fentanyl, pethidine, codeine and tramadol [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Unlike other opioids, tramadol has norepinephrine and serotonin reuptake inhibition properties in addition to its mu-opioid binding activity. It is commonly used in low- and middle-income countries (LMIC) [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e] and its consumption is increasing globally [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. The need for effective pain management remains high and prompt in low and middle-income African countries primarily due to limited access to opioid analgesics [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eGuidelines recommend multimodal analgesia for the treatment of pain in both children and adults [\u003cspan additionalcitationids=\"CR6\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Nonopioid therapies like acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), antidepressants, antiepileptics, and local anesthetics can be used as alternative for many common types of acute pain. Clinicians should maximize the use of nonpharmacologic and nonopioid pharmacologic therapies when appropriate for the specific condition and patient and only consider opioid therapy for acute pain if the benefits outweigh the risks. Opioids are essential for treating moderate-to-severe acute pain when other therapies are contraindicated or insufficiently effective [\u003cspan additionalcitationids=\"CR6\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe daily dose of opioids is usually expressed as morphine milligram equivalents (MME). Increasing opioid dosages to \u0026ge;\u0026thinsp;50 MME/day may not provide additional benefit in pain relief and can increase the risk of adverse effects and addiction [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Oral administration of opioids is preferable over intravenous for postoperative analgesia in patients who can use the oral route [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Proper administration and monitoring of pain management are crucial to prevent harmful effects and the risk of misuse and addiction associated with opioids [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e\u003cp\u003ePain management is a significant issue in low-income countries like Ethiopia, where it is inadequately managed [\u003cspan additionalcitationids=\"CR10 CR11\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e], and there are increased reports of opioid misuse, particularly tramadol [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. The nonmedical use of tramadol has reached a public health crisis in African countries [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. In Ethiopia, tramadol was not a controlled substance until recently and was easily accessible without a prescription [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e], and it was classified as controlled substance due to reports of abuse. However, there is limited information on the pattern of opioid misuse and its health consequences in the country. This study aims to assess the patterns of prescription opioid use and misuse among adults with traumatic injuries to inform policy decisions and improve treatment outcomes while minimizing adverse effects of opioid use.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eStudy Area and Period\u003c/h2\u003e\u003cp\u003eThis study was conducted in two trauma centers in Mekelle, the capital city of Tigray, the northern most region of Ethiopia, situated 783km away from Addis Ababa. Tigray was significantly impacted by a devastating war that began on November 4, 2020, and concluded on November 3, 2022. The war resulted in the loss of hundreds of thousands of lives and led to severe health consequences [\u003cspan additionalcitationids=\"CR17 CR18\" citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. The study was carried out from March to September 2024.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eStudy Design and Participants\u003c/h3\u003e\n\u003cp\u003eA cross-sectional study design was used. The study participants were adults who sustained war-related injuries from bullets and/or heavy artillery and received treatments in the trauma centers in 2023 and 2024. The study involved the review of medical records and the assessment of patients\u0026rsquo; opioid-related aberrant behaviors. Opioid misuse behavior was assessed using the Current Opioid Misuse Measure (COMM) [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e] combined with clinical judgment. All post trauma or postoperative analgesic prescriptions were reviewed. Adult injured patients who received treatment in the trauma centers during the study period were eligible for inclusion in the study, irrespective of their sex, severity of injury and duration of trauma.\u003c/p\u003e\n\u003ch3\u003eSample Size Determination and Sampling Techniques\u003c/h3\u003e\n\u003cp\u003eThe required sample size for this study was calculated using a single proportion sample size estimation formula: n\u003csub\u003e0\u003c/sub\u003e\u0026thinsp;=\u0026thinsp;z\u003csup\u003e2\u003c/sup\u003ep(1-p)/d\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eWhere, n\u003csub\u003eo\u003c/sub\u003e is the desired sample size; z is the standard normal deviation (1.96); p is the probability of opioid misuse (20%) based on previous study [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e], and d is the desired degree of accuracy (0.05). Therefore, n\u003csub\u003eo\u003c/sub\u003e was determined to be 246. Finally, a total of 310 participants were included in the study. Participants were selected using a simple random sampling method, with bed numbers serving as the sampling frame. Each room had an average of five to ten beds. The first participant was selected randomly by lottery, and participants in every other bed number were included.\u003c/p\u003e\n\u003ch3\u003eData Collection Tools and Methods\u003c/h3\u003e\n\u003cp\u003eThe study involved a review of medical records and the assessment of patients\u0026rsquo; opioid-related aberrant behaviors. The medical record review was conducted by pharmacy students. A data abstraction format was developed to record patient demographics, clinical information, and medication related characteristics. Data regarding patients\u0026rsquo; opioid misuse behaviors were assessed using the COMM opioid misuse assessment tool and clinical judgment by physicians and nurses caring for the injured patients. Health professionals providing care for the injured patients evaluated each patient\u0026rsquo;s opioid medication taking behavior based on past medical histories, physical examination findings and clinical data. To ensure consistency in assessing opioid misuse, an eleven-item checklist was developed and utilized by the health providers. All data collectors and health providers received training on the study\u0026rsquo;s aim and data collection methods. Prior to the actual study, a pretest was done on 10 participants to assess the applicability of the data collection tools, methods and the performance of the data collectors.\u003c/p\u003e\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\u003ch2\u003eData Analysis\u003c/h2\u003e\u003cp\u003eThe collected data was checked for completeness and consistency, then it was edited, coded, and cleaned. The data was initially entered into Microsoft Excel and later transferred to SPSS Statistics version 29 for analysis. Descriptive statistics were used to determine the frequencies and percentages. Binary logistic regression was employed to identify the relationship between the dependent variable (opioid misuse) and independent variables (age, sex, severity of injury, type of analgesics, duration of opioid use, dose of opioid, comorbidities and co-medications). The results of the statistical analysis were presented as odds ratios (OR) with 95% confidence intervals (CI), and a p value of less than 0.05 was considered statistically significant.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003eOperational Definitions\u003c/h2\u003e\u003cp\u003e\u003cstrong\u003eSeverity of Traumatic Injury\u003c/strong\u003e\u003cp\u003eAccording to the Injury Severity Score (ISS), the severity of traumatic injury is numerically scored from 0 to 75, with higher scores indicating greater injury severity. A score of 12 is considered moderate severity, while a score above 15 is classified as major trauma, often necessitating specialized care [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e].\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eChronic Opioid Use\u003c/strong\u003e\u003cp\u003eprolonged use of opioid medications prescribed by a healthcare provider or obtained from other sources. A cut-off point of above three months is typically used.\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eMorphine Milligram Equivalent (MME)\u003c/strong\u003e\u003cp\u003eA measurement used to compare the potency of different opioids and routes to oral morphine. For instance, 10mg of intravenous morphine is equivalent to 30mg of oral morphine. The MME per day of intravenous tramadol was calculated as 0.3 X dose of tramadol X number of doses per day. The MME per day of oral tramadol was calculated as 0.2 X dose of tramadol X number of doses per day [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eMultimodal Analgesia\u003c/strong\u003e\u003cp\u003einvolves the use of non-opioid and opioid analgesics. Nonopioid therapies include acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), antidepressants and antiepileptics.\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eOpioid Misuse\u003c/strong\u003e\u003cp\u003eAny use of a prescription opioid outside of the manner and intent for which it was prescribed. This includes opioid-related aberrant behaviors such as overuse, using to get high, diversion or sharing with others, having multiple prescribers or nonprescribed sources of the medication, and concurrent use of other illicit substances, or nonprescribed controlled medications. Misuse is a necessary but not sufficient criterion for opioid use disorder. Opioid misuse was assessed using the COMM tool [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e] combined with clinical gestalt. The COMM is a 17-item patient self-assessment tool used to monitor patients on long-term opioid therapy and identify aberrant behaviors associated with opioid medication misuse. A score of 9 or higher is considered positive.\u003c/p\u003e\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eIn this study, a total of 310 adults with war related traumatic injuries were included. Half of the participants had moderate injuries, and received opioids for post-operative acute pain, while the remaining had major injuries (ISS above 15) and received opioids chronically for more than 3 months. Most of the study participants were male, with almost half of them being young adults aged between 18 and 24 years. The study also found that 25.2% of the participants received multimodal analgesia, while the majority (74.8%) relied solely on opioids. Multimodal analgesia was less commonly used among participants with major injuries who were taking opioids chronically.\u003c/p\u003e\u003cp\u003eTramadol was prescribed to the majority (77.4%) of the study participants, with the intravenous route being the most commonly used regardless of the severity of injury or duration of analgesic use (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The mean and standard deviations (SD) of opioid dose used expressed as MME per day was 45.04 (\u0026plusmn;\u0026thinsp;37.04), with about 18% of the participants receiving doses above 50 MME, where the risks are supposed to outweigh the benefits. The mean duration of opioid treatment was 231.45 (\u0026plusmn;\u0026thinsp;257.17) days. Opioid-related aberrant behaviors or misuse were assessed in half of the study participants, with concurrent substance use such as smoking, diazepam and marijuana identified in 8.7% of participants (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). These substances likely increase the risk of opioid misuse and addiction, and were commonly reported among participants on chronic opioid use.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eDemographic and clinical characteristics of adults with war-related traumatic injuries in selected trauma centers in Mekelle (N\u0026thinsp;\u003cb\u003e=\u003c/b\u003e\u0026thinsp;310), 2024.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eVariables\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eN\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003e%\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eAge\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e18\u0026ndash;24\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e167\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e53.9\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026ge;\u0026thinsp;25\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e143\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e46.1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eSex\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e274\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e88.4\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eFemale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e36\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e11.6\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eSeverity of injury\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMajor\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e154\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e49.7\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eModerate\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e156\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e50.3\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eComorbid Substance Use*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e27\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e8.7\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e283\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e91.3\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eMultimodal analgesia^\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e78\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e25.2\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e232\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e74.8\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e\u003cp\u003eType of Opioid used\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eTramadol\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e240\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e77.4\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMorphine\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e5.2\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCombination of Tramadol and Morphine\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e5.2\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMorphine followed by Tramadol or vice versa\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e38\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e12.3\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003eRout of Opioid Administration\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eIV\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e198\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e63.9\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePO\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e60\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e19.4\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBoth IV and PO\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e52\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e16.8\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e\u003cp\u003eDuration opioid treatment\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026gt;\u0026thinsp;2 years\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e128\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e41.3\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3\u0026ndash;12 months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e26\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e8.4\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2\u0026ndash;12 weeks\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e93\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e30.0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;2 weeks\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e63\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e20.3\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eOpioid dose (MME per day)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026ge;\u0026thinsp;50\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e57\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e18.4\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;50\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e253\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e81.6\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eOpioid misuse\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e149\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e48.1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e161\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e51.9\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e* Comorbid substance use includes smoking, diazepam and marijuana; ^ non-opioidal analgesics commonly used include Non-steroidal anti-inflammatory drugs, Acetaminophen, Amitriptyline, Pregabalin or combination of these. Mean duration of opioid treatment (SD)\u0026thinsp;=\u0026thinsp;231.45 (\u0026plusmn;\u0026thinsp;257.17); Mean MME/d (SD)\u0026thinsp;=\u0026thinsp;45.04 (\u0026plusmn;\u0026thinsp;37.04); IV, intravenous; PO, oral; MME: Morphine milligram equivalent; N: Number.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eThe univariable binary logistic analysis of factors associated with opioid misuse revealed that young adults (COR\u0026thinsp;=\u0026thinsp;1.75, p\u0026thinsp;=\u0026thinsp;0.01), comorbid substance use (COR\u0026thinsp;=\u0026thinsp;7.16, p\u0026thinsp;=\u0026thinsp;0.00), tramadol use (COR\u0026thinsp;=\u0026thinsp;6.43, p\u0026thinsp;=\u0026thinsp;0.00), intravenous route of opioid administration (COR\u0026thinsp;=\u0026thinsp;5.33, p\u0026thinsp;=\u0026thinsp;0.00) and daily opioid doses above 50 MME (COR\u0026thinsp;=\u0026thinsp;3.44, p\u0026thinsp;=\u0026thinsp;0.00) were more likely to misuse opioids. On the other hand, participants taking multimodal analgesia (COR\u0026thinsp;=\u0026thinsp;0.09, p\u0026thinsp;=\u0026thinsp;0.00) were less likely to misuse opioids (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). However, in the multivariable binary logistic regression comorbid substance use (AOR\u0026thinsp;=\u0026thinsp;62.03, p\u0026thinsp;=\u0026thinsp;0.00), intravenous route of opioid administration (AOR\u0026thinsp;=\u0026thinsp;8.09, p\u0026thinsp;=\u0026thinsp;0.00), and not using multimodal analgesia (AOR\u0026thinsp;=\u0026thinsp;0.016, p\u0026thinsp;=\u0026thinsp;0.00) were independent predictors for opioid misuse (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eUnivariate binary logistic regression of opioid misuse among adults with war-related traumatic injuries in selected trauma centers in Mekelle (N\u0026thinsp;=\u0026thinsp;310), 2024.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"7\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" morerows=\"1\" nameend=\"c2\" namest=\"c1\" rowspan=\"2\"\u003e\u003cp\u003eVariables\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003eOpioid Misuse\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003ep value\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eCOR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e95% CI\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eAge\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e18\u0026ndash;24\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e91\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e76\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.01\u003csup\u003eα\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1.75\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e1.12\u0026ndash;2.76\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026ge;\u0026thinsp;25\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e58\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e85\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eSex\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e127\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e147\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.55\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.27\u0026ndash;1.12\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eFemale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e22\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eComorbid substance use\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e23\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.00\u003csup\u003eα\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e7.16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e2.41\u0026ndash;21.25\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e126\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e157\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eMultimodal analgesia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e69\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.00\u003csup\u003eα\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.09\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.04\u0026ndash;0.18\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e140\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e92\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eType of Opioid\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eTramadol\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e137\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e103\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.00\u003csup\u003eα\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e6.43\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e3.28\u0026ndash;12.59\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMorphine\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e58\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eRoute\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eIntravenous\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e138\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e113\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.00\u003csup\u003eα\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e5.33\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e2.64\u0026ndash;10.74\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eOral\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e48\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003ePattern of opioid use\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eChronic\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e80\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e74\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.17\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1.36\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.87\u0026ndash;2.13\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAcute\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e69\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e87\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"2\" rowspan=\"3\"\u003e\u003cp\u003eDuration of opioid use\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026gt;\u0026thinsp;2 years\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e70\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e58\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1.93\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.81\u0026ndash;4.58\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3\u0026ndash;12 months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.08\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1.52\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.95\u0026ndash;2.43\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;3months\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e69\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e87\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eDose in MME/day\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026ge;\u0026thinsp;50\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e41\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.00\u003csup\u003eα\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e3.44\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e1.83\u0026ndash;6.45\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;50\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e108\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e145\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"7\"\u003e\u003csup\u003eα\u003c/sup\u003eStatistically significant association; MME: Morphine milligram equivalent; COR: Crude odds ratio; CI: Confidence interval; N: Number\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eMultivariable binary logistic regression of opioid misuse among adults with war-related traumatic injuries in selected trauma centers in Mekelle (N\u0026thinsp;=\u0026thinsp;310), 2024.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"7\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" morerows=\"1\" nameend=\"c2\" namest=\"c1\" rowspan=\"2\"\u003e\u003cp\u003eVariables\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003eOpioid Misuse\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003ep value\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eAOR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003e95% CI\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eAge\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e18\u0026ndash;24\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e91\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e76\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1.57\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.88\u0026ndash;2.79\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026ge;\u0026thinsp;25\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e58\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e85\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eComorbid substance use\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e23\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.000\u003csup\u003eα\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e62.03\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e9.71\u0026ndash;396.3\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e126\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e157\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eMultimodal analgesia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eYes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e69\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.000\u003csup\u003eα\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.016\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.003\u0026ndash;0.08\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNo\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e140\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e92\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eType of Opioid\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eTramadol\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e137\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e103\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.92\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1.06\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.33\u0026ndash;3.47\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMorphine\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e58\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eRoute\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eIntravenous\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e138\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e113\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.000\u003csup\u003eα\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e8.09\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e3.54\u0026ndash;18.48\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eOral\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e48\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eDose in MME/day\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026ge;\u0026thinsp;50\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e41\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.07\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e2.14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.94\u0026ndash;4.86\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;50\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e108\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e145\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e\u003cp\u003e1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"7\"\u003e\u003csup\u003eα\u003c/sup\u003eStatistically significant association; MME: Morphine milligram equivalent; AOR: Adjusted odds ratio; CI: Confidence interval; N: Number\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe findings from this study provide important insights into opioid prescribing practices and factors associated with an increased risk of opioid misuse among traumatic injured patients in a resource-constrained setting. The study revealed that tramadol was the most commonly prescribed opioid in both acute and chronic post-traumatic pain management, highlighting the underutilization of multimodal analgesia. Only a quarter of the patients received co-analgesics such as NSAIDs, acetaminophen, antidepressants and antiepileptics, contrasting with guideline recommendations in high-income countries [\u003cspan additionalcitationids=\"CR6\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e], where multimodal analgesia is widely adopted to reduce opioid consumption and mitigate risks. Studies have shown that multimodal analgesia in post-operative pain management reduces opioid use [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Similar to the current study, Rostom et al [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e] also reported severe underutilization of multimodal analgesia in trauma patients.\u003c/p\u003e\u003cp\u003eIn the multivariable regression analysis, participants taking multimodal analgesia were 98.4% less likely to develop opioid related misuse compared to those not taking it (AOR\u0026thinsp;=\u0026thinsp;0.016; p\u0026thinsp;=\u0026thinsp;0.00). The absence of multimodal analgesia in the study setting represents a missed opportunity to reduce opioid-related misuse, harm and improve pain management outcomes. Opioid-related misuse was assessed in half of the study participants, a prevalence considerably higher than rates reported in other studies. [\u003cspan additionalcitationids=\"CR27 CR28\" citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. Tramadol was the most commonly prescribed opioid, prescribed in 77.4% of the study participants. Similar to this finding, in a study in Brazil, tramadol was the most commonly prescribed opioid [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. However, the current study finding is quite high compared to another study done in high-income countries [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e], where stronger opioids such as morphine and oxycodone are more commonly prescribed than tramadol. Recent studies have reported a global increase in the consumption of tramadol [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. The reliance on tramadol may reflect its wide accessibility, perceived efficacy, safety and lower abuse potential compared to other opioids [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. Additionally, patient pressure to receive tramadol for its euphoric effect might contribute to the increased rate of tramadol use. The safety, efficacy and relatively lower abuse potential of tramadol have also been also observed in other studies [\u003cspan additionalcitationids=\"CR34\" citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. In contrast, tramadol was more commonly misused than morphine, hydromorphone and oxymorphone [\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e]. The prevalence of opioid misuse particularly tramadol misuse was a significant concern in the current study. The pattern of analgesic prescribing observed in this study such as using tramadol alone as the mainstay of analgesia, at relatively high dose, administered mainly through the IV route and being used for prolonged duration may contribute to the high prevalence of misuse. Further investigations are needed to explore pharmacogenomic factors contributing to tramadol misuse and abuse in the study setting, as a significant number of Ethiopians were identified to be cytochrome P450 (CYP2D6) ultra-rapid metabolizers [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]. CYP2D6 is an isoenzyme that converts tramadol to an active metabolite, O-desmethyltramadol (M1), which has about 200 times the affinity for the mu-opioid receptor than tramadol itself [\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe oral route is preferable over intravenous administration of opioids for postoperative analgesia in patients who can take orally [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. However, in this study, intravenous administration was the most common route of administration in both acute and chronic post traumatic conditions. In the binary logistic regression, intravenous route of opioid administration was found to be an independent predictor of opioid misuse. Participants administering opioids intravenously were 8 times more likely to develop opioid misuse compared to the oral route. The reliance on IV routes in the current study may reflect the potential preference and pressure from abusers, as this route has an immediate effect.\u003c/p\u003e\u003cp\u003eConcurrent substance use was observed in 8.7% of participants, with comorbid substance use identified as the strongest predictor of opioid misuse. This is consistent with findings in other studies, where tramadol misuse was linked with other substance use such as alcohol, marijuana, ecstasy, and methamphetamine [\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]. Similarly, the use of alcohol and marijuana was common among adolescents misusing prescription opioids [\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThis study has limitations, including recall biases when assessing opioid misuse by health care providers due to the large number of patients they have been treating. The COMM is a self-assessment tool filled out by patients, posing a potential for underreporting of substance use and self-selection bias. As a cross-sectional design, we were unable to definitively conclude the opioid misuse as opioid use disorder based on the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria, as it requires observation of aberrant behaviors over a 12-month period. Further studies are needed to understand magnitude of opioid use disorder and related harm among patients with chronic pain. Nationwide studies are needed to assess the impact of policy changes related to tramadol and its impact on misuse prevalence. Future research should investigate the impact of pharmacogenomic factors, specifically CYP2D6 genetic polymorphism, on tramadol safety and dosing changes among Ethiopians.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis study highlights challenges in opioid use, including the of multimodal analgesia, reliance on tramadol as the primary analgesia, and a high prevalence of opioid misuse among traumatic injured adults. Clinicians must monitor patients prescribed opioids responsibly, weigh the benefits against the risk for long-term use, and integrate routine screening for comorbid substance use into pain management practices. Educational programs should focus on the risks of opioid use, safe practices, and alternative pain management options for both patients and healthcare providers.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eAOR\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eAdjusted odds ratio\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eCOR\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eCrude odds ratio\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eCI\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eConfidence Interval\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eCOMM\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eCurrent Opioid Misuse Measure\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eCYP2D6\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003ecytochrome P450\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eDSM-5\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eDiagnostic and Statistical Manual of Mental Disorders\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eISS\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eInjury Severity Score\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eIV\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eintravenous\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eLMICs\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eLow- and Middle-Income Countries\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eMME\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eMorphine milligram equivalent\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eNSAID\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eNonsteroidal anti-inflammatory drugs\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eN\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eNumber\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003ePO\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eoral,SPSS,Statistical Package for Social Science\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv class=\"DefinitionListEntry\"\u003e\u003cdiv class=\"Term\"\u003eSD\u003c/div\u003e\u003cdiv class=\"Description\"\u003e\u003cp\u003eStandard Deviation\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthical approval and consent to participate\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was conducted after obtaining official approval from Mekelle University, College of Health Science, School of Pharmacy, and Ethical Committee (Approval Number: MU-IRB 2236/2024). The study was done after obtaining written informed consent to participate. The aims of the study were discussed with participants and health professionals working in the trauma centers.\u0026nbsp;The privacy and confidentiality of participants\u0026apos; information was kept confidential. Identification\u0026nbsp;code was used instead of patients\u0026rsquo; name and health facility name. All methods used in this study were done in accordance with the ethical standards of the institutional and/or national research committee. All methods used in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the Declaration of Helsinki.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for Publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data supporting the conclusions of this study are\u0026nbsp;presented in the main manuscript.\u0026nbsp;Any additional data can be obtained by contacting the corresponding author.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe author reports no conflicts of interest in this work.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe received no funding for the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eG.T. and A.H. both contributed to the study design, and data collection. All authors contributed to the data analysis and report writing. G.T. developed the draft manuscript which was finalized with input from A.H. and Y.L.N. All authors contributed to the interpretation of the findings and the revision of the manuscript, and all have read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors would like to thank the study participants, health care providers working in the trauma centers for their cooperation during the study. We would also like to thank the data collectors and friends who assist us during the study.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eNIDA. Prescription Opioids Drug Facts. June 12021. (2025). 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PMID: 32817608; PMCID: PMC7440199.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Long-term use, Misuse, Multimodal analgesia Prescription opioids, Tramadol, Trauma","lastPublishedDoi":"10.21203/rs.3.rs-6527013/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6527013/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eOpioid analgesics are commonly used for managing moderate to severe pain. While opioids can be effective for pain management, prolonged and inappropriate prescribing can pose risks such as abuse, and overdose. This study aimed to investigate the patterns of opioid use and misuse among war-injured adults in Mekelle trauma centers.\u003c/p\u003e\u003cp\u003eA cross-sectional study design was used. The study participants were adults with war related traumatic injuries. Data was collected through a review of the medical records, patients self-report and from health care providers. Opioid misuse behavior was assessed using the Current Opioid Misuse Measure tool combined with clinical judgment. Statistical analysis was conducted using binary logistic regression. Results were presented as odds ratios with 95% confidence intervals. A p value of less than 0.05 was considered statistically significant.\u003c/p\u003e\u003cp\u003eThe study included a total of 310 adults with war-related traumatic injuries, predominantly male. About half of the participants were young adults aged between 18\u0026ndash;24 years, with major traumatic injuries (Injury Severity Score above 15) and using opioids chronically. Tramadol was the most commonly prescribed opioid, accounting for 77.4% of all opioid prescriptions. Only 25.2% of participants were on multimodal analgesia. The intravenous route was the most commonly used route of opioid administration regardless of the injury severity and duration of analgesic use. The mean opioid dose used expressed as Morphine Milligram Equivalent (MME) per day (SD), was 45.04 (\u0026plusmn;\u0026thinsp;37.04). The mean duration of opioid treatment (SD) was 231.45 (\u0026plusmn;\u0026thinsp;257.17) days. Opioid misuse was identified in about 48% of the participants. Comorbid substance use (AOR\u0026thinsp;=\u0026thinsp;62.03, p\u0026thinsp;=\u0026thinsp;0.00), intravenous opioid administration (AOR\u0026thinsp;=\u0026thinsp;8.09, p\u0026thinsp;=\u0026thinsp;0.00), and not using multimodal analgesia (AOR\u0026thinsp;=\u0026thinsp;0.016, p\u0026thinsp;=\u0026thinsp;0.00) were independent predictors of opioid misuse.\u003c/p\u003e\u003cp\u003eThis study highlights significant challenges in opioid use, including the reliance on tramadol as the primary analgesic, and high rates of opioid misuse among traumatic injured adults potentially hindering their recovery. Training and educational programs targeting both healthcare providers and patients should emphasize the risks of long-term opioid use, safe practices, and alternative pain management options.\u003c/p\u003e","manuscriptTitle":"Pattern of Prescription Opioid Use and Misuse among War-Injured Adults Receiving Treatments in Mekelle Trauma Centers, Northern Ethiopia","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-08-06 19:41:07","doi":"10.21203/rs.3.rs-6527013/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"b9c6fc52-cae1-455e-8b9b-9b822707358b","owner":[],"postedDate":"August 6th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":52639882,"name":"Health sciences/Health care/Diagnosis"},{"id":52639883,"name":"Health sciences/Health care/Drug regulation"},{"id":52639884,"name":"Health sciences/Health care/Fracture repair"},{"id":52639885,"name":"Health sciences/Health care/Therapeutics"},{"id":52639886,"name":"Health sciences/Diseases"},{"id":52639887,"name":"Health sciences/Health care"},{"id":52639888,"name":"Health sciences/Medical research"},{"id":52639889,"name":"Health sciences/Risk factors"}],"tags":[],"updatedAt":"2026-04-09T04:55:32+00:00","versionOfRecord":[],"versionCreatedAt":"2025-08-06 19:41:07","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6527013","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6527013","identity":"rs-6527013","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}