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Aim: Concerns exist regarding potential adverse neurodevelopmental outcomes associated with paracetamol exposure during pregnancy and early infancy. This review evaluates the evidence for the impact of paracetamol use for patent ductus arteriosus (PDA) treatment on neurodevelopmental outcomes in preterm infants., Methods: A literature search was performed via Medline, Ovid Embase and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases. The search details are below: ('Infant, Newborn' [MeSH] OR 'neonate*' [Title/Abstract]) AND ('Paracetamol' [MeSH] OR 'Acetaminophen' [Title/Abstract]) AND ('Ductus Arteriosus, Patent/drug therapy' [MeSH] OR 'patent ductus arteriosus' [Title/Abstract]) AND ('Neurodevelopmental Disorders' [MeSH] OR 'neurodevelopment*' [Title/Abstract] OR 'Child Development' [MeSH] OR 'Developmental Disabilities' [MeSH]). All studies were critically appraised and synthesised., Results: Seven studies reported neurodevelopmental outcomes after paracetamol use for PDA treatment in preterm infants <32 weeks gestation. The studies varied in dosage, route, and duration of paracetamol administration and in the methods used to assess neurodevelopmental outcomes. None of the studies revealed different outcomes between paracetamol-exposed preterm infants and controls., Conclusion: Current low-to-moderate quality evidence suggests no association between paracetamol used for PDA treatment and adverse neurodevelopmental outcomes in preterm infants. Future well-powered studies with standardised neurodevelopmental assessments are warranted to strengthen the current evidence base., (© 2024 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Introduction: Headaches are a common condition seen in the Emergency Department (ED), with numerous trials focused on improving care for these patients. However, there is limited recent large-scale, robust data available on the incidence, admission rates, evaluation, and treatment in the ED setting., Methods: This was a cross-sectional study of ED presentations for headache from 1/1/2016 to 12/31/2023 using the Epic Cosmos national database. All ED visits with headache-relevant ICD-10 coding were included. Outcomes included percentage of total ED visits, admission rates, computed tomography (CT) brain imaging, lumbar puncture (LP) performance, and medication administration. Medications were analyzed by class (NSAIDs, acetaminophen, dopamine antagonists, diphenhydramine, opioids, intravenous fluids, caffeine, and magnesium sulfate). Subgroup analyses were performed by specific types of dopamine antagonists., Results: Of 188,482,644 ED encounters, 6,007,090 (3.2%) were due to headache. Of these, 246,082 (4.1%) were admitted. Nearly half (46.6%) of patients received at least one CT. Rates of CT head without contrast increased from 38.2% to 47.9% over time, while rates of CT angiography rose from 2.8% to 10.2%. 1.4% of all patients received an LP, with rates decreasing from 1.8% to 1.1% over time. The most common medication was NSAIDs (45.3%), followed by dopamine antagonists (44.8%), diphenhydramine (38.1%), acetaminophen (24.8%), opioids (16.3%), magnesium sulfate (0.2%), and caffeine (0.1%). 50.8% of patients received intravenous fluids. Rates of opioids declined over time, while dopamine antagonists, acetaminophen, and intravenous fluid administration increased., Conclusion: Headaches represent a common reason for ED presentation, with approximately 4% of patients being admitted. Imaging is frequently performed, with rises in CT without contrast and CT angiography rates over time, while LP rates have been declining. NSAIDs remain the most common medication given, with opioids declining over time while non-opioid agents such as dopamine antagonists have increased. These findings can help inform health policy initiatives, such as those focused on radiologic imaging and evidence-based medication administration., Competing Interests: Declaration of competing interest We have no conflicts of interest to declare and this manuscript has not been submitted elsewhere., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Context: The safety of medication for pediatric patients has always been a concern, and non steroidal anti-inflammatory drugs (NSAIDs) are one of the essential and commonly used drugs in children. Therefore, it is necessary to conduct a study on the efficacy and safety of NSAIDs in pediatric patients., Objective: To study the use and safety of nonsteroidal anti-inflammatory drugs (NSAIDs) among 22 553 pediatric patients from 14 hospitals in Shanghai., Methods: We collected the clinical data of 22 553 pediatric patients who received NSAIDs during their stay in 14 hospitals in Shanghai from January 2005 to May 2011, which were then retrospectively analyzed. The use of nimesulide, paracetamol, and ibuprofen was observed among these children. The age and gender distribution, discharge status, length of hospital stay, and types of diseases treated with NSAIDs were analyzed. The relationship between death and length of hospital stay was assessed. The safety of NSAIDs in these children was discussed., Results: The response rate of nimesulide and ibuprofen was 71.23% and 73.12%, respectively. There was no significant difference in response rate between the two drugs (P > .05). The response rate of paracetamol was the lowest among the three drugs (59.67%, P < .05). The average length of hospital stay was significantly longer in children receiving paracetamol than in those receiving nimesulide. The average length of hospital stay was significantly longer in children receiving nimesulide than in those receiving ibuprofen (P < .05). The diseases treated with nimesulide were less diverse than those treated with ibuprofen and paracetamol. To be specific, bronchopneumonia was predominant among all the diseases treated with nimesulide. Although bronchopneumonia was also the most common among all the diseases treated with ibuprofen and paracetamol, the diseases treated with these two drugs were more diverse. The incidence of abnormal liver function among children receiving nimesulide was significantly lower than in those receiving ibuprofen and paracetamol (P < .05). There was no significant difference in the incidence of abnormal liver function caused by paracetamol and ibuprofen (P > .05)., Conclusion: Nimesulide and ibuprofen achieved a generally higher response rate than paracetamol among the surveyed children from Shanghai. Although bronchopneumonia was the most common diagnosis among all children treated with NSAIDs, the diagnoses were less diverse in those treated with nimesulide. The length of hospital stay was the shortest among children receiving ibuprofen, while the response rate of paracetamol was the lowest. The incidence of abnormal liver function was the lowest in children receiving nimesulide. All of the three NSAIDs might induce liver function impairment, but the risk was not significantly different between them. This study also has some limitations, such as limited drug types and regional limitations. In summary, Nimesulide is a highly effective and safe non steroidal anti-inflammatory drug that can meet the clinical medication needs of pediatric patients. Future research is contemplating the clinical benefits of Nimesulide in treating more diagnostic types besides pediatric bronchopneumonia, in order to investigate its greater medicinal value.

Objectives: The opioid crisis has prompted consideration of analgesic prescriptions. This study explored the value of preoperative acetaminophen for pain control following microsuspension laryngoscopy (MSL) and compared the results with a previous study of pain and opioid use following MSL (Tsang et al.)., Methods: A prospective open-label clinical trial was conducted in patients undergoing MSL. All patients were administered preoperative acetaminophen. Short-form McGill Pain Questionnaire (SF-MPQ), pain visual analogue scale (VAS), and present pain intensity (PPI) scores were collected preoperatively and on postoperative days (PODs) 1, 3, 7, and 14. Statistical analysis identified variables associated with opioid use or increased pain scores, and compared outcomes with Tsang et al. RESULTS: Eighty-nine patients were included (mean age 52.8 ± 17.3 years, 40 males). All patients received preoperative 1 g acetaminophen (77 (86.5%) orally) with no adverse effects. On POD1, opioid usage was 10%. Median [IQR] pain scores were 5 [2-11], 21 [12.3-56.8], and 3 [2-3.3] on SF-MPQ, VAS, and PPI, respectively. Post-Anesthesia Care Unit (PACU) opioid requirements significantly correlated with POD1 opioid consumption (τb = 0.214; p ≤ 0.05), and significant associations with PACU opioid administration were found for total anesthesia time (OR (95%CI) = 1.271 (1.043-1.548), p = 0.017) and total laryngoscope suspension time (OR (95%CI) = 0.791 (0.651-0.962, p = 0.019)). This cohort demonstrated reduced opioid usage on POD1 compared with Tsang et al (23%)., Conclusions: Preoperative acetaminophen is a safe intervention, resulting in decreased postoperative opioid use following MSL. Anesthesia time correlated with need for postoperative opioids., Level of Evidence: 4 Laryngoscope, 134:4625-4635, 2024., (© 2024 The American Laryngological, Rhinological and Otological Society, Inc.)

COVID-19 has been a growing global concern in the past four years. Several syndromes associated with this multi-organ viral infection have been observed since the outbreak. According to estimates, 10-15% of people with SARS-CoV- infection may have post-COVID-19 syndrome. Even months after infection, common residual signs and symptoms include myalgia, exhaustion, shortness of breath, rapid heartbeat, stroke, and memory and cognitive impairment which can negatively affect survivors' quality of life and may consequently lead to their death. Therefore, it is necessary to think about potential therapy options for dealing with both short and long-term impacts. Paracetamol (a common analgesic and antipyretic) and Dexketoprofen Trometamol (a non-steroidal anti-inflammatory drug) are used together to relieve post-COVID symptoms like myalgia (muscle pain) and headache. Additionally, to prevent thrombotic events, Rivaroxaban is recommended for 35 days following discharge. Thus an eco-friendly HPLC-DAD technique was developed for simultaneous quantification of Paracetamol, Dexketoprofen Trometamol, and Rivaroxaban which are co-administered for treatment of post-COVID-19 syndrome. The suggested method was found to be linear in the concentration ranges of 3.00-45.00 µg/mL, 0.5-50.00 µg/mL, and 0.15-20.00 µg/mL, and a limit of detection down to 0.531 µg/mL, 0.095 µg/mL and 0.047 µg/mL for Paracetamol, Dexketoprofen Trometamol and Rivaroxaban, respectively. This method was effectively used to quantify the studied drugs in their bulk powder and spiked human plasma with high percentage recoveries (96.55-99.46%). The suggested approach was validated per International Conference on Harmonization (ICH) requirements and found to be within the acceptable ranges. The method was developed using Green Analytical Chemistry (GAC) principles, with the solvents used and run time having a significant effect on the method's greenness. "Non-toxic" ethanol served as the organic modifier in the mobile phase, moreover, the total run time was 12 min making it suitable for the routine analysis of the mentioned drugs in plasma samples. To get a full image of the method's greenness profile; two most recent greenness assessment tools, the Green Analytical Procedure Index (GAPI), and the Analytical GREEnness metric (AGREE), were employed, with White Analytical Chemistry (WAC) principles proving its environmental safety., (© 2024. The Author(s).)

Background: Paracetamol and ibuprofen are the most commonly used drugs for pain treatment in children and their combination has shown improved analgesic effect compared to treatment with either drug alone. Current literature lacks specific guidelines regarding the settings in which this combination should be adopted., Methods: The survey, conducted with Delphi methodology, involved 75 hospital and outpatient pediatricians with clinical experience in the management of pain in children. Pediatricians involved were asked to validate or not the results of the previous NominalGroup Tecnique (NGT) consensus and thus specify the optimal clinical settings in which the paracetamol/ibuprofen fixed-dose combination could be adopted., Results: The results confirm the importance of the fixed-dose paracetamol and ibuprofen combination for the control of mild-to-moderate acute pain in children. Particularly, this association seems to be appropriate in case of headache, earache, odontalgia and musculoskeletal pain, and in specific settings such as post-operative and post-procedural pain. The broadening of the panel brought to slight variations in clinical management practices between hospital and outpatient specialists. Nonetheless, overall consensus supports the notion that the fixed dose combination is more efficacious than monotherapies and it is well tolerated. Moreover, experts unanimously agree on the usefulness of the combination for caregivers, leading to improved adherence and effectiveness., Conclusions: Both the NGT consensus and the broader Delphi consensus confirm the usefulness of the paracetamol-ibuprofen fixed-dose combination in pediatric pain. This is attributed to its superior effectiveness compared to monotherapies, a good tolerability profile, and improved compliance and ease of use. Some pain settings related to chronic, inflammatory and rheumatological pathologies remain to be investigated to evaluate the use of this combination., (© 2024. The Author(s).)

Brief rationale: Zoledronic acid treatment against osteoporosis is limited by APR. Main result: Combination therapy (hydrocortisone plus non-steroidal anti-inflammatory drugs, acetaminophen, and prednisolone) reduced intolerable APR levels and provided complete symptom relief in most patients. Significance of the paper: Combination therapy can enhance patient outcomes in osteoporosis management., Purpose: Osteoporosis is a common condition associated with high morbidity rates, often requiring treatment with bisphosphonates such as zoledronic acid. However, the persistence to zoledronic acid infusion is commonly limited by acute phase response (APR). This retrospective study aimed to evaluate the efficacy of a novel combination therapy in preventing APR symptoms., Methods: A retrospective case-control study was conducted on 931 patients who received their first zoledronic acid infusion between 2011 and 2021. We evaluated the efficacy of combination therapy comprising a single dose of hydrocortisone prior to the infusion and a 3-d oral regimen of non-steroidal anti-inflammatory drugs, acetaminophen, and prednisolone following the infusion. Patients were divided into protocol (receiving combination therapy) and control groups (without treatment). Baseline characteristics, APR incidence, and the efficacy of symptom control were compared between groups using Fisher's exact test and Student's t-test., Results: There was no difference in APR incidence between the protocol (n = 507) and control group (n = 407; p = 0.1442). However, the protocol group exhibited lower intolerable APR levels (3.72% vs. 16.71%; p < 0.0001) and complete symptom relief in 96.28% of cases., Conclusion: The combination therapy protocol effectively reduced intolerable APR and relieved symptoms in most patients following zoledronic acid infusion. This study highlights the importance of proactive management strategies for APR and emphasizes the potential of combination therapy in alleviating APR symptoms and reducing the occurrence of severe APR in patients undergoing osteoporosis management., (© 2024. The Author(s).)

Objectives: To evaluate pain perception and analgesic use between patients who underwent endometriosis-specific laparoscopic surgery compared to laparoscopic hysterectomy., Material and Methods: This retrospective cohort study included women diagnosed with endometriosis who underwent laparoscopic surgery from 1/2019 to 11/2022. The control group consisted of premenopausal women who underwent laparoscopic hysterectomy, which was considered a similarly extensive surgery. Demographics, preoperative and post-operative data were compared between groups. Post-operative pain scores on a visual analogue scale (VAS) between 0 (no pain) and 10 (worst pain) were compared between groups for each post-operative day (POD). Standard pain relief analgesia on POD 0-1 included fixed intravenous treatment with paracetamol and intramuscular diclofenac. The need for additional analgesics (morphine or dipyrone) beyond the standard pain relief protocol was compared between groups., Results: Among 200 patients who underwent laparoscopic surgery, 100 (50%) were in the endometriosis group and 100 (50%) in the hysterectomy group. The endometriosis group was characterized by younger age and lower parity (both, p<0.001). There was no significant difference between the groups in mean VAS scores for each post-operative day. However, among patients who needed additional analgesics beyond the standard protocol on POD 1, a higher percentage of women in the endometriosis group used opioids rather than milder analgesics, as compared to controls (1% vs. 0.2%, respectively, p = 0.03)., Conclusion: Increased post-operative morphine use was observed in patients with endometriosis following laparoscopic surgery, despite no significant difference in mean VAS scores during the post-operative days. These findings suggest that personalized pain relief protocols should be adjusted for women with endometriosis., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Yagur et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Context: There is uncertainty whether acetaminophen and ibuprofen are similar in their effects and safety when used as single or dual (alternating or combined) therapies., Objective: To assess the comparative efficacy of acetaminophen, ibuprofen alone, alternating, or combined through a systematic review and network meta-analysis., Data Sources: Medline, Embase, and CENTRAL from inception to September 20, 2023., Study Selection: Randomized trials comparing acetaminophen, ibuprofen, both alternating, and both combined, for treating children with fever., Data Extraction: Two reviewers independently screened abstracts and full texts, extracted the data, and assessed the risk of bias. We performed pairwise and network meta-analysis using the random-effects model., Results: We included 31 trials (5009 children). We found that combined (odds ratio [OR], 0.19; confidence interval [CI], 0.09-0.42) and alternating therapies (OR, 0.20; CI, 0.06-0.63) may be superior to acetaminophen, whereas ibuprofen at a high dose may be comparable (OR, 0.98; CI, 0.63-1.59) in terms of proportion of afebrile children at the fourth hour. These results were similar at the sixth hour. There were no differences between ibuprofen (low or high dose), or alternating, or combined with acetaminophen in terms of adverse events., Limitations: We only evaluated the efficacy and safety during the first 6 hours., Conclusions: Dual may be superior to single therapies for treating fever in children. Acetaminophen may be inferior to combined or alternating therapies to get children afebrile at 4 and 6 hours. Compared with ibuprofen, acetaminophen was also inferior to ibuprofen alone at 4 hours, but similar at 6 hours. PROSPERO registration: CRD42016035236., Competing Interests: CONFLICT OF INTEREST DISCLOSURES: The authors have indicated they have no conflicts of interest relevant to this article to disclose., (Copyright © 2024 by the American Academy of Pediatrics.)

Background: Codeine was rescheduled in Australia to prescription only in February 2018. Initial studies reported an increase in population level paracetamol and ibuprofen sales following codeine upscheduling. However, to date no study has been able to investigate changes in non-opioid analgesic use at the individual patient level to determine if sales data reflect actual consumption patterns., Aim: To address this gap, we aimed to determine the impact of codeine rescheduling on non-opioid analgesic use in people who regularly used over-the-counter codeine, primarily for pain, prior to the rescheduling change., Method: We conducted a prospective cohort study with 260 participants who reported regular over-the-counter codeine consumption at cohort entry. Surveys were completed at baseline (November 2017, 3 months before rescheduling) and at 1 month (February 2018), 4 months (June 2018), and 12 months (February 2019), following rescheduling. The primary outcomes were mean daily doses of non-opioid analgesics, captured through a 7 day medication diary., Results: The mean daily paracetamol dose decreased from 1754.4 mg (95% CI 1300.5-2208.3) at baseline to 1023.8 mg (95% CI 808.5-1239.1) at the final time-point (+ 12 months) (p = .009). The mean daily ibuprofen dose decreased from 305.1mg (95% CI 217.9-392.4) at baseline to 161.2 mg (95% CI 98.5-224.0) 12 months after rescheduling (p = .03). No significant change in doses of other medications remained was found., Conclusion: In people who regularly consumed over-the-counter codeine, doses of non-opioid analgesics either reduced or remained stable following codeine rescheduling, suggesting concerns of medication substitution or overuse following the change were not realised., (© 2024. The Author(s).)

Background: Few studies report outcomes for enhanced recovery pathways in ambulatory anorectal surgery. We hypothesize that an ambulatory anorectal enhanced recovery pathway with multimodal analgesia can reduce postoperative opioid use., Objective: To compare postoperative opioid use in patients undergoing ambulatory anorectal surgery who receive multimodal analgesia versus standard of care without multimodal analgesia., Design: A prospective randomized trial of patients undergoing elective anal fistula or hemorrhoid surgery from September 2018 to May 2022., Setting: Urban teaching hospital., Patients: Adults aged 18 to 70 years undergoing elective anal fistula or hemorrhoid surgery from September 2018 to May 2022., Intervention: Multimodal enhanced recovery pathway including preoperative and postoperative nonopioid analgesia with oral acetaminophen, gabapentin, and ketolorac., Main Outcome Measures: Primary end point was oral opioid use during the first postoperative week. Secondary end points included maximum pain and nausea scores, adverse events, and emergency room or hospital admissions during the first 30 days postoperatively., Results: Of the 109 enrolled patients, 20 were lost to follow-up. The remaining 89 patients had a median age of 38 years (range, 20-67) and included 41 women (46%). There were no significant differences between the enhanced recovery protocol arm and non-enhanced recovery protocol arm in terms of preoperative and surgical characteristics. The primary end point of this study, that is, oral morphine milligram equivalents use during the first week, was significantly higher among patients in the non-enhanced recovery protocol arm (79 mg; range, 0-600) than patients in the enhanced recovery protocol arm (8 mg; range, 0-390; p = 0.002). On subgroup analysis, both fistula and hemorrhoid surgery patients assigned to the non-enhanced recovery protocol arm took significantly higher oral morphine milligram equivalents in the first week than patients in the enhanced recovery protocol arm. There was no significant difference in secondary end points., Limitations: Patients and providers were not blinded. Our findings are limited to hemorrhoid and fistula surgery and may not be applicable to other anorectal procedures., Conclusions: Enhanced recovery protocols including multimodal analgesia should be used in elective anal fistula and hemorrhoid surgery to decrease postoperative opioid use. See the Video Abstract ., Clinical Trial Registration: ClinicalTrials.gov ID NCT03738904., Implementacin De Protocolo De Recuperacin Acelerada Multimodal En Ciruga Anorrectal Ambulatoria Un Estudio Aleatorizado: ANTECEDENTES:Pocos estudios reportan resultados de programas de recuperación acelerada en la cirugía anorrectal ambulatoria. Presumimos que un programa anorrectal ambulatorio de recuperación acelerada con analgesia multimodal puede reducir el uso posoperatorio de opioides.OBJETIVO:Comparar el uso posoperatorio de opioides en pacientes sometidos a cirugía anorrectal ambulatoria que reciben analgesia multimodal versus atención estándar sin analgesia multimodal.DISEÑO:Un estudio prospectivo aleatorizado de pacientes sometidos a cirugía electiva de fístula anal o hemorroides desde septiembre de 2018 hasta mayo de 2022.LUGAR: Hospital universitario urbano.PACIENTES:Adultos de 18 a 70 años sometidos a cirugía electiva de fístula anal o hemorroides desde septiembre de 2018 hasta mayo de 2022.INTERVENCIÓN:Programa de recuperación acelerada multimodal que incluye analgesia no opioide pre y posoperatoria con paracetamol oral, gabapentina y ketoloraco.PRINCIPALES MEDIDAS DE RESULTADO:El resultado principal fue el uso de opioides orales durante la primera semana postoperatoria. Los resultados secundarios incluyeron puntuaciones máximas de dolor y náuseas, eventos adversos e ingresos a la sala de emergencias o al hospital durante los primeros 30 días después de la operación.RESULTADOS:De los 109 pacientes incluidos, 20 se perdieron durante el seguimiento. Los 89 pacientes restantes tenían una mediana de edad de 38 (rango, 20-67) años e incluían 41 (46%) mujeres. No hubo diferencias significativas entre los grupos del protocolo de recuperación acelerada (Grupo E) y del protocolo de recuperación no acelerada (Grupo NE) en términos de características preoperatorias y quirúrgicas. El resultado principal del estudio, el uso de MME oral durante la primera semana, fue significativamente mayor entre los pacientes del grupo NE (79 mg; rango: 0-600) que los pacientes del grupo E (8 mg; rango: 0-390) ( p = 0,002). En el análisis de subgrupos, los pacientes de cirugía de fístula y hemorroides asignados al grupo NE tomaron MME oral significativamente más alto en la primera semana que los pacientes del grupo E. No hubo diferencias significativas en los resultados secundarios.LIMITACIONES:Los pacientes y proveedores no fueron cegados. Nuestros hallazgos se limitan a la cirugía de hemorroides y fístulas y pueden no ser aplicables a otros procedimientos anorrectales.CONCLUSIONES:Se deben utilizar protocolos de recuperación acelerada que incluyan analgesia multimodal en la cirugía electiva de fístula anal y hemorroides para disminuir el uso posoperatorio de opioides. (Traducción- Dr. Francisco M. Abarca-Rendon )CLINICAL TRIAL REGISTRATION:ClinicalTrials.gov ID NCT03738904., (Copyright © The ASCRS 2024.)

Introduction: The effect of individual non-narcotic analgesics in cystectomy enhanced recovery after surgery (ERAS) is unknown. Additionally, many non-narcotic medications are associated with side effects pertinent to the cystectomy population. To better understand the actual use and utility of these medications, we sought to characterize the association between non-narcotic medications and milligram morphine equivalent (MME) narcotic score during the postoperative inpatient stay., Methods: We reviewed 260 consecutive ERAS cystectomy patients. The MME impact of non-narcotic compliance and cumulative dose of medication received was evaluated separately with general linear models. We also assessed relationship of non-narcotic compliance to patient reported pain score, length of stay (LOS), and time to return of bowel function (ROBF) and performed manual review of postoperative documentation to identify reasons for medication noncompliance., Results: Compliance with postoperative acetaminophen, gabapentin, and ketorolac was low. There was an inverse relationship between ketorolac dose and MME on postoperative day 1 (-0.026 MME/mg; P = 0.004) and postoperative day 2 (-0.33 MME/mg; P < 0.001). Compliance with ketorolac was associated with lower MME on postoperative day 1 (26.1 MME v. 33.6 MME; P = 0.023). There were no such associations identified with gabapentin or acetaminophen. Gabapentin compliance was associated with earlier ROBF (3.7 days v. 4.3 days; P = 0.006). Ketorolac compliance was associated with lower pain score on POD1 (3.25 VAS v. 4.07 VAS; P = 0.019) and POD2 (3.05 VAS v. 3.85 VAS; P = 0.040) There was no association between medication compliance and LOS. The most common reasons identified for non-compliance with gabapentin and ketorolac were renal function concerns (38% and 40% respectively), bleeding concerns with ketorolac (20%) and concerns for neurologic adverse effect with gabapentin (16%)., Conclusion: Compliance with non-narcotic medications in our ERAS cystectomy protocol was poor. There was a modest association with ketorolac and postoperative MME but no association with gabapentin or acetaminophen. Further study will clarify the role of these medications for cystectomy patients. Component specific analysis of protocolized care is valuable and may alter care pathways., Competing Interests: Declaration of competing interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Purpose: Opioids remain the mainstay of analgesia for critically ill patients, but its exposure is associated with negative effects including persistent use after discharge. Nonsteroidal anti-inflammatory drugs (NSAIDs) may be an effective alternative to opioids with fewer adverse effects. We aimed to describe beliefs and attitudes towards the use of NSAIDs in adult intensive care units (ICUs)., Methods: Our survey of Canadian ICU physicians was conducted using a web-based platform and distributed through the Canadian Critical Care Society (CCCS) email distribution list. We used previously described survey development methodology including question generation and reduction, pretesting, and clinical sensibility and pilot testing., Results: We received 115 completed surveys from 321 CCCS members (36%). Nonsteroidal anti-inflammatory drugs use was most described as "rarely" (59 respondents, 51%) with the primary concern being adverse events (acute kidney injury [108 respondents, 94%] and gastrointestinal bleeding [92 respondents, 80%]). The primary preferred analgesic was acetaminophen (75 respondents, 65%) followed by opioids (40 respondents, 35%). Most respondents (91 respondents, 80%) would be willing to participate in a randomized controlled trial examining NSAID use in critical care., Conclusions: In our survey, Canadian critical care physicians did not mention commonly using NSAIDs primarily because of concerns about adverse events. Nevertheless, respondents were interested in further studying ketorolac, a commonly used NSAID outside of the ICU, in critically ill patients., (© 2024. Canadian Anesthesiologists' Society.)

Background: A randomized trial suggested that treatment with metoclopramide reduces the risk of pneumonia in patients with acute stroke and a nasogastric tube. We assessed whether this finding could be replicated in a post hoc analysis of the randomized PRECIOUS trial (Prevention of Complications to Improve Outcome in Elderly Patients With Acute Stroke)., Methods: PRECIOUS was an international, 3×2 partial-factorial, randomized controlled, open-label clinical trial with blinded outcome assessment assessing preventive treatment with metoclopramide, paracetamol, and ceftriaxone in patients aged ≥66 years with acute ischemic stroke or intracerebral hemorrhage and a National Institutes of Health Stroke Scale score ≥6. In the present study, we analyzed patients who had a nasogastric tube within 24 hours after randomization. Patients who were allocated to metoclopramide (10 mg TID) were compared with patients who were not. Treatment was started within 24 hours after symptom onset and continued for 4 days or until discharge if earlier. The primary outcome was pneumonia in the first week after stroke. The score on the modified Rankin Scale after 90 days was a secondary outcome and analyzed with ordinal logistic regression., Results: From April 2016 through June 2022, a total of 1493 patients were enrolled with 1376 included in this analysis, of whom 1185 (86%) had ischemic stroke and 191 (14%) had intracerebral hemorrhage. The first day after randomization, 329 (23.9%) patients had a nasogastric tube, of whom 156 were allocated to metoclopramide and 173 to standard care. Metoclopramide was not associated with a reduction of pneumonia (41.0% versus 35.8%; adjusted odds ratio, 1.35 [95% CI, 0.79-2.30]) or with poor functional outcome (adjusted odds ratio, 1.07 [95% CI, 0.71-1.61])., Conclusions: In patients with stroke who had a nasogastric tube shortly after stroke onset, metoclopramide for 4 days did not reduce pneumonia or have an effect on the functional outcome., Competing Interests: Drs Sluis, de Jonge, and Reinink all report grants from the European Union, all paid to their institution. Dr Bath reports having received grants from the UK National Institutes of Health Research and fees as a consultant from CoMind, DiaMedica, Phagenesis, and Roche. In addition, he reports compensation from World Stroke Organisation and the Stroke Association for other services and has stock options in CoMind. Dr van de Beek reports having received research grants from the European Union, The Netherlands Organisation for Health Research and Development, ItsMe Foundation, AMC Foundation, and Roche, none related. Dr van der Worp reports having received grants from the European Union, the Dutch Heart Foundation, and Stryker for research and funding for consultancy from Bayer and TargED, all paid to his institution. The other authors report no conflicts.

We analyzed data from positively tested COVID-19 outpatients to describe self-medication with OTC drugs and use of other remedies against symptoms of SARS-CoV-2 infection. We specifically considered their type and frequency, as well as associations with patient characteristics, and reasons for use. Data were collected between May 1, 2020 and February 22, 2021 with two questionnaires in an observational cohort study with PCR-confirmed SARS-CoV-2-positive adult outpatients in the district of Western Pomerania in Germany. 523 out of 710 outpatients (74%; 340 women and 183 men) reported using drugs and other remedies to relieve COVID-19-symptoms. Overall, participants reported utilization of 1282 finished dosage products or remedies, including 213 different ingredients. In the population of 710 outpatients, utilization of ibuprofen (26%), acetaminophen (21%), metamizole (14%), and acetylsalicylic acid (10%) was most commonly reported. Phytopharmaceuticals, herbal and animal products as well as vitamins and minerals were also frequently reported. Among the 523 participants who used drugs and other remedies, most commonly mentioned reasons for use were headache (40%), other kinds of pain (e.g. myalgia; 37%), fever (24%) and cough (16%). Our analysis showed that a majority of the participants tried to alleviate COVID-19-symptoms using drugs and other remedies. Especially analgesic and antipyretic agents, followed by herbal medicines, were used very frequently.Trial registration: German Register for Clinical Studies DRKS00021672, first registration on December 1st, 2020., (© 2024. The Author(s).)

Background: Postoperative pain delays ambulation, extends hospital stay, reduces the probability of recovery, and increases risk of long-term functional impairment. Pain management in hip fractured patients poses a challenge to the healthcare teams. Older adults are more vulnerable to opioid-associated side effect and it is primordial to minimize their exposure to opioids. Acetaminophen is associated with reduced opioid use so we need to focus on acetaminophen use in first-line analgesia., Methods: We conducted a controlled before/after study to assess the ability of an audit and feedback (A&F) intervention built with nurses to improve the quality of perioperative pain management in older patients hospitalized for hip fracture in an orthogeriatric unit (experimental group) versus a conventional orthopedic unit (no A&F intervention). The primary endpoint was the percentage of patients who received 3 g/day of acetaminophen during the three postoperative days, before and after the A&F intervention. Secondary endpoints included nurses' adherence to medical prescriptions, clinical data associated with patients and finally factors associated with intervention. The significative level was set at 0.05 for statistical analysis., Results: We studied data from 397 patients (mean age 89 years, 75% female). During the postoperative period, 16% of patients from the experimental group received 3 g/day of acetaminophen before the A&F intervention; the percentage reached 60% after the intervention. The likelihood of receiving 3 g/day of acetaminophen during the postoperative period and adhering to the medical prescription of acetaminophen were significantly increased in the experimental group as compared with the control group. The patient's functional status at discharge (assessed by Activities of Daily Living scores) was significantly better and the length of hospital stay significantly reduced after the A&F intervention., Conclusion: Our controlled before/after study showed that an A&F intervention significantly improved perioperative pain management in older adults hospitalized for hip fracture. Involving teams in continuous education programs appears crucial to improve the quality of pain management and ensure nurses' adherence to medical prescriptions., (© 2024. The Author(s).)

Background: Post-dural puncture headache (PDPH) is the most common complication following spinal anesthesia among parturients undergoing cesarean section surgery. The purpose of this study was to evaluate the effectiveness of acetaminophen and caffeine in preventing PDPH., Methods: This double-blind, randomized clinical trial was conducted on 96 obstetric women, who were candidates for elective cesarean section. Following the randomization of participants into two groups, participants in the intervention group received tablets of acetaminophen (500 mg)+caffeine (65 mg), and participants in the control group received placebo tablets orally 2 hours before spinal anesthesia induction and then every 6 hours after surgery up to 24 hours. All parturients were evaluated for frequency and intensity of PDPH every 6 hours until 24 hours after surgery and then 48 and 72 hours after surgery. Overall satisfaction during the first 72 hours of postpartum was evaluated. The data were analyzed using SPSS software. P<0.05 was considered statistically significant., Results: Participants in the intervention group were 70% less likely to experience PDPH after spinal anesthesia (OR=0.31 P=0.01, 95% CI [0.12-0.77]). They also experienced significantly milder headaches 18 hours, 48 hours, and 72 hours later. Participants in the intervention group reported higher levels of satisfaction at the end of the study (P=0.01). No side effects related to the intervention were reported., Conclusion: Prophylactic administration of acetaminophen+caffeine decreases 70% the risk of PDPH and significantly attenuates pain intensity in obstetric patients who underwent spinal anesthesia for cesarean section., Competing Interests: Mohammad Ali Sahmeddini and Naeimehossadat Asmarian, as the Editorial Board Members, were not involved in any stage of handling this manuscript. A team of independent experts was formed by the Editorial Board to review the article without their knowledge., (Copyright: © Iranian Journal of Medical Sciences.)

Objectives: Acetaminophen is the most widely antipyretic analgesic medicine used in adults and children worldwide. Rectal acetaminophen is widely used in children who resist or cannot take oral medications. This study was designed to compare the efficacy of rectal and IV acetaminophen in children with fever and mild to moderate pain., Patients and Methods: Total 60 children aged six months to 6 years, with fever and pain, that were treated with rectal or intravenous acetaminophen were selected and assigned in two groups. The IV group received 10mg/kg paracetamol as an IV infusion, and the rectal group received a 15mg/kg dose immediately after admission. Pain score was calculated using the FLACC method, and the axillary temperature was recorded at baseline and then 0.5, 1, 2, 4, and 6hours after drug administration. Blood samples were collected at baseline and then at 30min-intervals for the first 90minutes., Results: The trend of changes in mean pain score at different time intervals was significantly different between the two groups. Body temperature decrease was more prominent in the IV group. The plasma concentration increased in both groups significantly with time. This increase was sharper in the IV group, just in the first 60minutes after drug administration., Conclusions: IV acetaminophen has more rapid onset of action, while rectal dosage form control fever and pain for longer duration. Considering its favorable effects with ease of administration and lower cost, rectal acetaminophen can be a reasonable option in selected patients with pain or fever., (Copyright © 2024 Académie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.)

Objective: Following recent changes to the German Narcotics Act, this article examines prehospital analgesia by paramedics using piritramide vs. nalbuphine + paracetamol., Material and Methods: Prehospital analgesia administered by paramedics from the Fulda (piritramide) and Gütersloh (nalbuphine + paracetamol) emergency services was compared regarding pain intensity at the beginning and end of the mission, measured using the numeric rating scale (NRS). Additionally, an analysis of the resulting complications was carried out., Results: In this study 2429 administrations of analgesia were evaluated (nalbuphine + paracetamol: 1635, 67.3%, initial NRS: 8.0 ± 1.4, end of NRS: 3.7 ± 2.0; piritramide: 794, 32.7%, initial NRS: 8.5 ± 1.1, end of NRS: 4.5 ± 1.6). Factors influencing NRS change were initial NRS (regression coefficient, RC: 0.7075, 95% confidence interval, CI: 0.6503-0.7647, p < 0.001), treatment with nalbuphine + paracetamol (RC: 0.6048, 95% CI: 0.4396-0.7700, p < 0.001). Treatment with nalbuphine + paracetamol (n = 796 (48.7%)) compared to piritramide (n = 190 (23.9%)) increased the odds of achieving NRS < 4 (odds ratio, OR: 2.712, 95% CI: 2.227-3.303, p < 0.001). Complications occurred in n = 44 (5.5%) with piritramide and in n = 35 (2.1%) with nalbuphine + paracetamol. Risk factors for complications were analgesia with piritramide (OR: 2.699, 95% CI: 1.693-4.301, p < 0.001), female sex (OR: 2.372, 95% CI: 1.396-4.029, p = 0.0014), and age (OR: 1.013, 95% CI: 1.002-1.025, p = 0.0232)., Conclusion: Compared with piritramide, prehospital analgesia with nalbuphine + paracetamol has favorable effects in terms of analgesic efficacy and complication rates and should therefore be considered in future recommendations for paramedics., (© 2024. The Author(s).)

Background: Parenteral ketorolac and intravenous (IV) acetaminophen have been used for prehospital analgesia, yet limited data exist on their comparative effectiveness., Study Objectives: To evaluate the comparative effectiveness of IV acetaminophen and parenteral ketorolac for analgesia in the prehospital setting., Methods: We conducted a retrospective cross-sectional evaluation of patients receiving IV acetaminophen or parenteral ketorolac for pain management in a large suburban EMS system between 1/1/2019 and 11/30/2021. The primary outcome was change in first to last pain score. Subgroup analysis was performed on patients with traumatic pain. We used inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) to estimate the treatment effect of acetaminophen versus ketorolac among all patients and the subgroup of those with traumatic pain., Results: Of 2178 patients included, 856 (39.3%) received IV acetaminophen and 1322 (60.7%) received parenteral ketorolac. The unadjusted mean change in pain score was -1.9 (SD 2.4) for acetaminophen group and -2.4 (SD 2.4) for ketorolac. In the propensity score analyses, there was no statistically significant difference in pain score change for the acetaminophen group versus ketorolac among all patients (mean difference, IPTW: 0.11, 95% confidence interval [CI] -0.16, 0.37; PSM: 0.15, 95% CI -0.13, 0.43) and among those with traumatic pain (unadjusted: 0.18, 95% CI -0.35, 0.72; IPTW: 0.23, 95% CI -0.25, 0.71; PSM: -0.03, 95% CI -0.61, 0.54)., Conclusions: We found no statistically significant difference in mean pain reduction of IV acetaminophen and parenteral ketorolac for management of acute pain., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: There is no non-invasive treatment to prevent aneurysmal subarachnoid hemorrhage (ASAH) caused by intracranial aneurysm (IA) rupture. We aimed to identify drug classes that may affect liability to IA using a genetic approach., Patients and Methods: Using genome-wide association summary statistics we calculated genetic correlation between unruptured IA ( N  = 2140 cases), ASAH ( N  = 5140) or the combined group, and liability to drug usage from 23 drug classes ( N up to 320,000) independent of the risk factor high blood pressure. Next, we evaluated the causality and therapeutic potential of correlated drug classes using three different Mendelian randomization frameworks., Results: Correlations with IA were found for antidepressants, paracetamol, acetylsalicylic acid, opioids, beta-blockers, and peptic ulcer and gastro-esophageal reflux disease drugs. MR showed no evidence that genetically predicted usage of these drug classes caused IA. Genetically predicted high responders to antidepressant drugs were at higher risk of IA (odds ratio [OR] = 1.61, 95% confidence interval (CI) = 1.09-2.39, p  = 0.018) and ASAH (OR = 1.68, 95% CI = 1.07-2.65, p  = 0.024) if they used antidepressant drugs. This effect was absent in non-users. For beta-blockers, additional analyses showed that this effect was not independent of blood pressure after all. A complex and likely pleiotropic relationship was found between genetic liability to chronic multisite pain, pain medication usage (paracetamol, acetylsalicylic acid, and opioids), and IA., Conclusions: We did not find drugs decreasing liability to IA and ASAH but found that antidepressant drugs may increase liability. We observed pleiotropic relationships between IA and other drug classes and indications. Our results improve understanding of pathogenic mechanisms underlying IA., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: Tension-type headache is the most common type of primary headache and results in a huge socioeconomic burden. This network meta-analysis (NMA) aimed to compare the efficacy and safety of simple analgesics for the treatment of episodic tension-type headache (ETTH) in adults., Methods: We searched the Cochrane Library, PubMed, Web of Science, Embase, Chinese BioMedical Literature database and International Clinical Trials Registry Platform databases for eligible randomized clinical trials reporting the efficacy and/or safety of simple analgesics. A Bayesian NMA was performed to compare relative efficacy and safety. The surface under the cumulative ranking curve (SUCRA) was calculated to rank interventions. PROSPERO registration number: CRD42018090554., Results: We highlighted six studies including 3507 patients. For the 2 h pain-free rate, the SUCRA ranking was ibuprofen > diclofenac-K > ketoprofen > acetaminophen > naproxen > placebo. All drugs except naproxen reported a higher 2 h pain-free rate than placebo, with a risk ratio (RR) of 2.86 (95% credible interval, CrI: 1.62-5.42) for ibuprofen and 2.61 (1.53-4.88) for diclofenac-K. For adverse events rate, the SUCRA ranking was: metamizol > diclofenac-K > ibuprofen > lumiracoxib > placebo > aspirin > acetaminophen > naproxen > ketoprofen. The adverse event rates of all analgesics were no higher than those of placebo, except for ketoprofen. Moreover, all drugs were superior to placebo in the global assessment of efficacy. In particular, the RR of lumiracoxib was 2.47 (1.57-4.57). Global heterogeneity I 2 between the studies was low., Conclusions: Simple analgesics are considered more effective and safe as a placebo for ETTH in adults. Our results suggest that ibuprofen and diclofenac-K may be the two best treatment options for patients with ETTH from a comprehensive point of view (both high-quality evidence).

A woman in her mid-60s who is a high hypermetrope presented with bilateral eye pain and headache approximately 1 hour after taking a single dose of a widely available decongestant containing paracetamol, guaifenesin and phenylephrine hydrochloride for coryzal symptoms. She had previous successful bilateral peripheral iridotomies performed for narrow angles. At presentation, her intraocular pressures (IOPs) were significantly raised at 72 mm Hg and 66 mm Hg in the right and left eye, respectively, with bilateral corneal oedema. Her IOP was normalised with urgent treatment using 500 mg intravenous acetazolamide, pilocarpine 2%, dexamethasone 0.1% and IOP-lowering drops. She was listed for cataract surgery and was advised to avoid the precipitating agent and other over-the-counter decongestants. This is the first reported case of bilateral angle closure triggered by a decongestant with such a combination of ingredients. Clinicians should be aware of this rare side effect for prompt diagnosis and management., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Importance: Acetaminophen (paracetamol) has many pharmacological effects that might be beneficial in sepsis, including inhibition of cell-free hemoglobin-induced oxidation of lipids and other substrates., Objective: To determine whether acetaminophen increases days alive and free of organ dysfunction in sepsis compared with placebo., Design, Setting, and Participants: Phase 2b randomized, double-blind, clinical trial conducted from October 2021 to April 2023 with 90-day follow-up. Adults with sepsis and respiratory or circulatory organ dysfunction were enrolled in the emergency department or intensive care unit of 40 US academic hospitals within 36 hours of presentation., Intervention: Patients were randomized to 1 g of acetaminophen intravenously every 6 hours or placebo for 5 days., Main Outcome and Measures: The primary end point was days alive and free of organ support (mechanical ventilation, vasopressors, and kidney replacement therapy) to day 28. Treatment effect modification was evaluated for acetaminophen by prerandomization plasma cell-free hemoglobin level higher than 10 mg/dL., Results: Of 447 patients enrolled (mean age, 64 [SD, 15] years, 51% female, mean Sequential Organ Failure Assessment [SOFA] score, 5.4 [SD, 2.5]), 227 were randomized to acetaminophen and 220 to placebo. Acetaminophen was safe with no difference in liver enzymes, hypotension, or fluid balance between treatment arms. Days alive and free of organ support to day 28 were not meaningfully different for acetaminophen (20.2 days; 95% CI, 18.8 to 21.6) vs placebo (19.6 days; 95% CI, 18.2 to 21.0; P = .56; difference, 0.6; 95% CI, -1.4 to 2.6). Among 15 secondary outcomes, total, respiratory, and coagulation SOFA scores were significantly lower on days 2 through 4 in the acetaminophen arm as was the rate of development of acute respiratory distress syndrome within 7 days (2.2% vs 8.5% acetaminophen vs placebo; P = .01; difference, -6.3; 95% CI, -10.8 to -1.8). There was no significant interaction between cell-free hemoglobin levels and acetaminophen., Conclusions and Relevance: Intravenous acetaminophen was safe but did not significantly improve days alive and free of organ support in critically ill sepsis patients., Trial Registration: ClinicalTrials.gov Identifier: NCT04291508.

Opioids are frequently used first line to manage acute pain in a variety of settings; however, the use of nonprescription analgesics for acute pain is recognized by experts as a practical and effective opioid-sparing strategy. Variations in dosages and formulations and a lack of standardization in reporting clinical data hinder the awareness of nonprescription treatments and recommendation of their use before opioids and other prescription options. A fixed-dose combination (FDC) of two common nonprescription analgesics, ibuprofen (IBU) and acetaminophen (APAP), is an appealing alternative to opioids in acute pain settings with a range of potential benefits. This narrative review evaluates the evidence in support of IBU/APAP FDCs containing IBU (≤1200 mg/day) and APAP (≤4000 mg/day), the nonprescription maximum daily doses in Canada and the United States, as alternatives to opioids and as a means to reduce the need for rescue opioid medication in acute pain management. A literature search was performed to identify clinical studies that directly compared IBU/APAP FDCs with opioids or nonopioids and measured the need for opioid rescue therapy in acute pain. Across studies, IBU/APAP FDCs consistently demonstrated pain relief similar to or better than opioid and nonopioid comparators and reliably reduced the use of rescue opioids with fewer adverse events. Based on these data, healthcare clinicians should consider FDC nonprescription analgesics as a potential first-line option for the management of acute pain.

Objective: To investigate the effects of pregabalin combined with tramadol/paracetamol on acute pain in patients with CT-guided puncture localization of pulmonary nodules., Materials and Methods: In this randomized, placebo-controlled and single-center study, 120 patients were allocated randomly to four groups: the control group (Group P), the pregabalin-placebo group (Group BP), the tramadol/paracetamol-placebo group (Group AP), and the pregabalin-tramadol/paracetamol group (Group AB). The primary outcome was the NRS (Numerical Rating Scale) score. Other outcomes included systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), pulse oxygen saturation (SpO 2 ), the incidence of moderate to severe pain, the analgesia recovery ratio, the incidence of adverse drug reactions and patients' satisfaction., Results: No significant interaction was detected between the interventions (P = 0.752). The NRS score of the Taking pregabalin group and the Taking tramadol/paracetamol group were significantly lower than those of the Not-taking pregabalin group and the Not-taking tramadol/paracetamol group respectively (P < 0.05). There was significant difference in the NRS scores among the four groups (P < 0.001). The NRS score of Group AB was significantly lower than that of Group P (P < 0.001), Group BP (P < 0.001) and Group AP (P = 0.001). At the same time, the NRS scores of Group BP (P < 0.001) and Group AP (P < 0.001) were significantly lower than those of Group P, but there was no significant difference between Group BP and Group AP (P = 1.000). The SBP, DBP, HR, the incidence of moderate to severe pain and the analgesia recovery ratio of Group AB were significantly lower than those of Group P (P < 0.05), while the SpO 2 and the number of people who were very satisfied were significantly higher than those of Group P (P < 0.05). There was no significant difference in the incidence of adverse drug reactions among the four groups (P = 0.272)., Conclusions: The combination or single use of pregabalin and tramadol/paracetamol can effectively relieve the acute pain after localization. Pregabalin combined with tramadol/paracetamol has the best analgesic effect and significantly reduces the hemodynamic fluctuations, with high safety and low incidence of adverse drug reactions, which has a certain clinical popularization and application value., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Aims: The use of multimodal non-opioid analgesia in hip fractures, specifically acetaminophen combined with non-steroidal anti-inflammatory drugs (NSAIDs), has been increasing. However, the effectiveness and safety of this approach remain unclear. This study aimed to compare postoperative outcomes among patients with hip fractures who preoperatively received either acetaminophen combined with NSAIDs, NSAIDs alone, or acetaminophen alone., Methods: This nationwide retrospective cohort study used data from the Diagnosis Procedure Combination database. We included patients aged ≥ 18 years who underwent surgery for hip fractures and received acetaminophen combined with NSAIDs (combination group), NSAIDs alone (NSAIDs group), or acetaminophen alone (acetaminophen group) preoperatively, between April 2010 and March 2022. Primary outcomes were in-hospital mortality and complications. Secondary outcomes were opioid use postoperatively; readmission within 90 days, one year, and two years; and total hospitalization costs. We used propensity score overlap weighting models, with the acetaminophen group as the reference group., Results: We identified 93,018 eligible patients, including 13,068 in the combination group, 29,203 in the NSAIDs group, and 50,474 in the acetaminophen group. Propensity score overlap weighting successfully balanced patient characteristics among the three groups, with no significant difference in in-hospital mortality rates observed among the groups (combination group risk difference 0.0% (95% CI -0.5 to 0.4%); NSAIDs group risk difference -0.2% (95% CI -0.5 to 0.2%)). However, the combination group exhibited a significantly lower risk of in-hospital complications than the acetaminophen group (risk difference -1.9% (95% CI -3.2 to -0.6%)) as well as a significantly lower risk of deep vein thrombosis (risk difference -1.4% (95% CI -2.2 to -0.7%)). Furthermore, total hospitalization costs were higher in the NSAIDs group than in the acetaminophen group (difference USD $438 (95% CI 249 to 630); p < 0.001). No significant differences in other secondary outcomes were observed among the three groups., Conclusion: The combination of acetaminophen with NSAIDs appears to be safe and advantageous in terms of reducing in-hospital complications., Competing Interests: H. Yasanaga reports an institutional grant from The Ministry of Health, Labour and Welfare, Japan (23AA2003 and 22AA2003)., (© 2024 The British Editorial Society of Bone & Joint Surgery.)

Objective: We aimed to compare the analgesic effectiveness of intranasal tapentadol nasal spray 44.5 mg and intravenous (IV) paracetamol 1 gm during the postoperative period in patients undergoing lower limb orthopedic surgeries under spinal anesthesia., Methods: This prospective, randomized, single-blind clinical trial was carried out in a tertiary care teaching hospital. Patients aged between 18 and 60 years of physical status ASA grade 1-3 were included in the study. Postoperative pain scores were measured using the visual analog scale (VAS) in centimeters (cm) every 12 hours in 37 patients per group. The patients were administered either intranasal tapentadol or IV paracetamol every 6 hours for 72 hours, beginning 3 hours after surgery., Results: There was a significant group by intervention effect favoring intranasal tapentadol, suggesting a greater reduction in VAS pain scores after the intervention at 72 hours (estimate: -1.58 cm; SE:0.2; P<0.001). Group by time effect for all the measured time frames, except for 36 hours, favored intranasal tapentadol with estimated values for greater reduction in VAS pain scores ranging from -0.8 cm to -1.6 cm., Discussion: The results of the present study suggests that intranasal tapentadol results in a greater reduction of postoperative pain compared with IV paracetamol in lower limb orthopedic surgeries. The ease of administration of tapentadol may make it a preferred option over IV paracetamol in such surgeries., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: Substantial interindividual variability characterizes osteoarthritis (OA) pain. Previous findings identify quantitative sensory testing (QST), psychological factors, and health-related quality of life as contributors to OA pain and predictors of treatment outcomes. This exploratory study aimed to explain baseline OA pain intensity and predict OA pain after administration of a nonsteroidal anti-inflammatory drug in combination with paracetamol for 3 weeks. The Knee Injury and Osteoarthritis Outcome Score (KOOS) pain score was used to estimate OA pain presentation. One hundred one patients were assessed at baseline and follow-up using QST (pressure pain thresholds and temporal summation of pain [TSP]), symptoms of depression and anxiety, pain catastrophizing scales (PCSs), and health-related quality of life. Linear regression with backward selection identified that PCS significantly explained 34.2% of the variability in baseline KOOS pain, with nonsignificant contributions from TSP. Pain catastrophizing score and TSP predicted 29.3% of follow-up KOOS pain, with nonsignificant contributions from symptoms of anxiety. When assessed separately, PCS was the strongest predictor (32.2% of baseline and 24.1% of follow-up pain), but QST, symptoms of anxiety and depression, PCS, and quality of life also explained some variability in baseline and follow-up knee OA pain. Further analyses revealed that only TSP and PCS were not mediated by any other included variables, highlighting their role as unique contributors to OA pain presentation. This study emphasizes the importance of embracing a multimodal approach to OA pain and highlights PCS and TSP as major contributors to the baseline OA pain experience and the OA pain experience after OA treatment., (Copyright © 2024 International Association for the Study of Pain.)

Background: Multiple medications are more effective than single agents for postoperative pain management. We investigated the analgesic effects of an intravenous combination of acetaminophen and ibuprofen immediately after thyroidectomy., Methods: In this double-blind clinical trial, 62 patients who underwent thyroidectomies were randomized to either the treatment (1000 mg acetaminophen, 300 mg ibuprofen) or control (1000 mg acetaminophen) group. Postoperative pain intensity was assessed using the visual analog scale (VAS) 0, 15, and 30 min after recovery room admission. Opioid rescue consumption was also recorded., Results: The VAS scores were significantly lower in the treatment than in the control group 15 [3 (2-4.3) vs. 5 (3-6); p = 0.015] and 30 [3 (2-4.3) vs. 4 (3-5); p = 0.018] min after recovery room admission, as were the opioid rescue dose requirements (p = 0.033)., Conclusions: Combined intravenous acetaminophen and ibuprofen may be better than acetaminophen alone for immediately acute postoperative pain after thyroidectomy., (© 2024 Wiley Periodicals LLC.)

Introduction: Low back pain is a common reason for presentation to the Emergency Department (ED). However, there are limited large-scale, recent data on the epidemiology, disposition, and medication administration for this condition. The objective of this was to assess the incidence, admission rates, medication administrations, and discharge prescriptions among ED visits for low back pain in the United States., Methods: This was a cross-sectional study of ED presentations for low back pain from 1/1/2016 to 12/31/2023 using the Epic Cosmos database. All ED visits for adults with low back pain identified by ICD-10 codes were included. Outcomes included admission rates, distribution of opioid, benzodiazepine, (non-benzodiazepine) muscle relaxant, acetaminophen, NSAID, and corticosteroid medications administered in the ED, and distribution of opioid, benzodiazepine, muscle relaxant, and corticosteroid medications given upon discharge. Subgroup analyses were performed by specific medication., Results: Of 207,154,419 ED encounters, 12,241,240 (5.9%) were due to back pain with 1,957,299 of these (16.0%) admitted. The admission rate increased over time from 12.8% to 17.1%. The most common medication given in the ED was opioids (40.7%), followed by acetaminophen (37.8%), NSAIDs (22.6%), muscle relaxants (18.4%) benzodiazepines (12.8%), and corticosteroids (5.5%). The most common medications prescribed upon discharge were muscle relaxants (32.1%), followed by opioids (23.2%), corticosteroids (12.2%), and benzodiazepines (3.0%)., Conclusion: Low back pain represents a common reason for presentation to the ED, and admissions have been increasing over time. Opioids remain the most common ED medication, whereas muscle relaxants have arisen as the most common discharge prescription. These findings can help inform health policy decisions, resource allocation, and evidence-based interventions for medication administration., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Acetaminophen and 5-hydroxytryptamine type 3 (5-HT3) receptor antagonists are administered as standard prophylaxes for postoperative pain, nausea, and vomiting. Preclinical studies, however, suggest that 5-HT3 antagonists may compromise acetaminophen's analgesic effect. This hospital registry study investigates whether 5-HT3 antagonists mitigate the analgesic effect of prophylactic acetaminophen in a perioperative setting., Methods: This study included 55,016 adult patients undergoing general anesthesia for ambulatory procedures at a tertiary healthcare center in Massachusetts from 2015 to 2022. Using binary exposure variables and a comprehensive selection of preplanned patient- and procedure-related covariates for confounder control, the authors investigated whether intraoperative 5-HT3 antagonists affected the association between pre- or intraoperative acetaminophen and postoperative opioid consumption, gauged by opioid dose in milligram oral morphine equivalents (OME) administered in the postanesthesia care unit. A multivariable, zero-inflated negative binomial regression model was applied., Results: A total of 3,166 patients (5.8%) received only acetaminophen, 15,438 (28.1%) only 5-HT3 antagonists, 31,850 (57.9%) both drugs, and 4,562 (8.3%) neither drug. The median postanesthesia care unit opioid dose was 7.5 mg OME (interquartile range, 7.5 to 14.3 mg OME) among 16,640 of 55,016 (30.2%) patients who received opioids, and the mean opioid dose was 3.2 mg OME across all patients (maximum cumulative dose, 20.4 mg OME). Acetaminophen administration was associated with a -5.5% (95% CI, -9.6 to -1.4%; P = 0.009; adjusted absolute difference, -0.19 mg OME; 95% CI, -0.33 to -0.05; P = 0.009) reduction in opioid consumption among patients who did not receive a 5-HT3 antagonist, while there was no effect in patients who received a 5-HT3 antagonist (adjusted absolute difference, 0.00 mg OME; 95% CI, -0.06 to 0.05; P = 0.93; P for interaction = 0.013)., Conclusions: A dose-dependent association of pre- or intraoperative acetaminophen with decreased postoperative opioid consumption was not observed when 5-HT3 antagonists were coadministered, suggesting that physicians might consider reserving 5-HT3 antagonists as rescue medication for postoperative nausea or vomiting when acetaminophen is administered for pain prophylaxis., (Copyright © 2024 American Society of Anesthesiologists. All Rights Reserved.)

Background: Most methodologically rigorous, ED-based, comparative effectiveness analgesic studies completed in the last two decades failed to find a clinically important difference between the comparators. We believe that many of these comparative effectiveness studies were biased towards the null hypothesis because some ED patients with intense pain will respond to relatively mild interventions. We hypothesized that including a run-in period would alter the results of an acute pain RCT., Methods: We conducted a sequential, multiple-assignment, randomized study. Adults with acute moderate/severe musculoskeletal pain were randomized (3:1 ratio) to run-in period or no run-in. We administered 650 mg acetaminophen to run-in participants. Those run-in patients who reported insufficient relief one-hour later were randomized (1:1 ratio) to ibuprofen 800mg PO or ketorolac 20mg PO as were all participants randomized to no run-in. The primary outcome was achieving a clinically important improvement, defined as improvement ≥1.3 on a 0-10 scale. We built a logistic regression model including run-in/no run-in, ketorolac/ibuprofen, age and sex., Results: Of 307 participants who received acetaminophen, 100 (32.6%) reported inadequate relief and were randomized to an NSAID. Of the 100 patients randomized to no run-in, 84/100 (84%) achieved the primary outcome versus 246/287 (86%) run-in participants (95% CI for difference = 2%:-7,10%). Among run-in participants who received an NSAID, 82/99(83%) achieved the primary outcome versus 84/100(84%) no run-in participants (p = 0.82). Among all ibuprofen participants, 44/49(90%) randomized to run-in and 42/50(84%) randomized to no run-in achieved the primary outcome. Among all ketorolac participants, 38/50(76%) randomized to run-in and 42/50 (84%) randomized to no run-in achieved the primary outcome. We observed the following results in a multivariable analysis: OR for ketorolac versus ibuprofen:0.60 (95% CI: 0.28, 1.28); OR for run-in versus no run-in:0.91(95% CI: 0.43, 1.93)., Conclusions: Among patients with acute musculoskeletal pain, using an acetaminophen first strategy did not alter pain outcomes., Competing Interests: Declaration of competing interest None of the authors have any competing financial or intellectual interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The average rate of patient dissatisfaction following total knee arthroplasty (TKA) is 10%. Multi-modal analgesia is the present standard of pain management after TKA. Studies show that with multi-modal analgesia, approximately 60% of patients experience severe knee pain following surgery, while around 30% experience moderate pain. To date, there is no literature available on targeted pain management using bone cement., Objectives: To investigate the feasibility of incorporating anti-inflammatory medications and identify the analgesic with the best release pharmacokinetics from bone cement for application in pain management., Methods: In an in-vitro study, 100 mg of five drugs (aceclofenac, diclofenac, naproxen, paracetamol and methyl prednisolone) were incorporated into bone cement (Palacos). Cement cubes holding each drug were made and allowed to harden for 30 min. Each drug-containing cube was placed in a beaker with saline for 72 h. Fractions of 10 ml were collected at 0, 6, 24, 48 and 72 h and analysed using high-pressure liquid chromatography to measure the percentage release of the drug from bone cement., Results: Naproxen showed superior elution from bone cement, with 10.9% at 24 h and 9.08% at 72 h. Paracetamol showed 4.9% at 24 h and 3.78% at 72 h, aceclofenac 0.2% at 24 h and 0.4% at 72 h, diclofenac 3.03% at 24 h and 1.99% at 72 h, and methylprednisolone 0.26% at 24 h and 0.32% at 72 h., Conclusions: Polymethylmethacrylate bone cement can elute analgesics in vitro. Among the five drugs studied, naproxen had the best release kinematics from polymethylmethacrylate bone cement. Analgesic eluting bone cement is a novel approach for targeted postoperative pain management in TKA., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Medication use during pregnancy has increased in the United States despite the lack of safety data for many medications., Objective: This study aimed to inform research priorities by examining trends in medication use during pregnancy and identifying gaps in safety information on the most commonly prescribed medications., Study Design: We identified population-based cohorts of commercially (MarketScan 2011-2020) and publicly (Medicaid Analytic eXtract/Transformed Medicaid Statistical Information System Analytic Files 2011-2018) insured pregnancies ending in live birth from 2 health care utilization databases. Medication use was based on filled prescriptions between the date of last menstrual period through delivery, as well as the period before the last menstrual period and during specific trimesters. We also included a cross-sectional representative sample of pregnancies ascertained by the National Health and Nutrition Examination Survey (2011-2020), with information on prescription medication use during the preceding month obtained through maternal interviews. Teratogen Information System was used to classify the available evidence on teratogenic risk., Results: Among over 3 million pregnancies, the medications most commonly dispensed at any time during pregnancy were analgesics, antibiotics, and antiemetics. The top medications were ondansetron (16.8%), amoxicillin (13.5%), and azithromycin (12.4%) in MarketScan, nitrofurantoin (22.2%), acetaminophen (21.3%; mostly as part of acetaminophen-hydrocodone products), and ondansetron (19.5%) in Medicaid Analytic eXtract/Transformed Medicaid Statistical Information System Analytic Files, and levothyroxine (5.0%), sertraline (2.9%), and insulin (2.9%) in the National Health and Nutrition Examination Survey group. The most commonly dispensed suspected teratogens during the first trimester were antithyroid medications. The use of antidiabetic and psychotropic medications has continued to increase in the United States during the last decade, opioid dispensation has decreased by half, and antibiotics and antiemetics continue to be common. For one-quarter of medications, there is insufficient evidence available to characterize their safety profile in pregnancy., Conclusion: There is a need for more drug research in pregnant patients. Future research should focus on anti-infectives with high utilization and limited level of evidence on safety for use during pregnancy. Although lack of evidence is not evidence of safety concerns, it does not indicate risk either. In many instances, the benefits outweigh the risks when these medications are used clinically, and some of the medications with no proven safety may be necessary to treat patients., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Importance: A third of children who survive malaria with neurological involvement (central nervous system [CNS] malaria) develop sequelae. A higher maximum temperature (Tmax) and seizures are risk factors for sequelae., Objective: To compare aggressive antipyretic therapy using scheduled acetaminophen and ibuprofen vs usual care with acetaminophen alone given only for a temperature of 38.5 °C or higher., Design, Setting, and Participants: This randomized clinical trial was conducted at inpatient pediatric services of 1 tertiary care and 1 district hospital in Zambia and a tertiary care center in Malawi. Included were children aged 2 to 11 years with CNS malaria (excluding those with creatinine >1.2 mg/dL), who were enrolled from 2019 to 2022. Data analysis took place from December 2022 to April 2023., Intervention: The aggressive antipyretic group received acetaminophen (30 mg/kg load, then 15 mg/kg) plus ibuprofen, 10 mg/kg, every 6 hours, regardless of clinical temperature for 72 hours. The usual care group received 15 mg/kg of acetaminophen as needed every 6 hours for a temperature of 38.5 °C or higher., Main Outcomes and Measures: The primary outcome variable was Tmax over 72 hours, the total duration of follow-up. Secondary outcomes included seizures and parasite clearance., Results: Five hundred fifty-three patients were screened, 226 (40.9%) were ineligible, and 57 (10.3%) declined. A total 256 participants (n = 128/group) had a mean (SD) age of 4.3 (2.1) years; 115 (45%) were female, and 141 (55%) were male. The aggressive antipyretic group had a lower Tmax, 38.6 vs 39.2 °C (difference, -0.62 °C; 95% CI, -0.82 to -0.42; P < .001) and lower odds of experiencing multiple or prolonged seizures, 10 (8%) vs 34 children (27%) in the usual care group (odds ratio [OR], 0.26; 95% CI, 0.12 to 0.56). No group difference in parasite clearance time was detected. Severe adverse events occurred in 40 children (15%), 25 (20%) in the usual care group and 15 (12%) in the aggressive antipyretic group, including 13 deaths (10 [8%] and 3 [2%], respectively). Increased creatinine resulted in study drug discontinuation in 8 children (6%) in the usual care group and 13 children (10%) in the aggressive antipyretic group (OR, 1.74; 95% CI, 0.63 to 5.07)., Conclusions and Relevance: This study found that aggressive antipyretic therapy reduced mean Tmax to temperature levels comparable with the Tmax among children without neurological impairments in prior observational studies and improved acute seizure outcomes with no prolongation of parasitemia., Trial Registration: ClinicalTrials.gov Identifier: NCT03399318.

Objective: Emerging data indicate that acetaminophen may adversely affect lung health. We examined whether acetaminophen compared with cyclooxygenase (COX) inhibitor alone for patent ductus arteriosus (PDA) is associated with mortality or respiratory morbidity in extremely preterm infants., Methods: This is a retrospective cohort study using data from the National Institute of Child Health and Human Development Neonatal Research Network. Infants were born at 22 to 28 weeks' gestation or weighing 401 to 1000 g between 2016 and 2020 and received acetaminophen, ibuprofen, and/or indomethacin for PDA closure. The primary outcome was death or grade 2 to 3 bronchopulmonary dysplasia (BPD) at 36 weeks' postmenstrual age. Secondary outcomes included predischarge mortality and respiratory morbidities. Risk ratios were adjusted for baseline and early postnatal factors. Additional exploratory analyses were adjusted for later postnatal covariates., Results: Of 1921 infants, 627 (32.6%) received acetaminophen and 1294 (67.3%) received COX inhibitor only. Multidrug therapy (42.9% vs 4.7%) and surgical or catheter PDA closure (26.5% vs 19.9%) were more common among acetaminophen-exposed infants. Death or grade 2 to 3 BPD at 36 weeks' postmenstrual age was similar between infants treated with acetaminophen versus COX inhibitor only (57.1% vs 58.3%; adjusted relative risk [aRR] 0.96, 95% confidence interval [CI] 0.87-1.06). Acetaminophen was associated with increased risk of predischarge mortality (13.3% vs 10.0%) when adjusting for perinatal and early postnatal factors (aRR 1.42, 95% CI 1.02-1.93), but not in exploratory analyses that included later postnatal factors (aRR 1.28, 95% CI 0.91-1.82)., Conclusions: Treatment with acetaminophen versus COX inhibitor alone for PDA was not associated with the composite outcome of death or BPD in extremely preterm infants. Our results support further evaluation of whether acetaminophen for PDA increases mortality., (Copyright © 2024 by the American Academy of Pediatrics.)

Background: Because of the adverse effects of morphine and its derivatives, non-opioid analgesia procedures are proposed after outpatient surgery. Without opioids, the ability to provide quality analgesia after the patient returns home may be questioned. We examined whether an opioid-free strategy could ensure satisfactory analgesia after ambulatory laparoscopic colectomy., Methods: We performed a retrospective observational single-center study (of prospective collected database) including all patients eligible for scheduled outpatient colectomy. Postoperative analgesia was provided by paracetamol and nefopam. Postoperative follow-up included pain at mobilization (assessed by a numerical rating scale, NRS), hemodynamic variables, temperature, resumption of transit and biological markers of postoperative inflammation. The primary outcome was the proportion of patients with moderate to severe pain (NRS > 4) the day after surgery., Results: Data from 144 patients were analyzed. The majority were men aged 59 ± 12 years with a mean BMI of 27 [25-30] kg/m 2 . ASA scores were 1 for 14%, 2 for 59% and 3 for 27% of patients. Forty-seven patients (33%) underwent surgery for cancer, 94 for sigmoiditis (65%) and 3 (2%) for another colonic pathology. Postoperative pain was affected by time since surgery (Q3 = 52.4,p < 0.001) and decreased significantly from day to day. The incidence of moderate to severe pain at mobilization (NRS > 4) on the first day after surgery was (0.19; 95% CI, 0.13-0.27)., Conclusion: Non-opioid analgesia after ambulatory laparoscopic colectomy seems efficient to ensure adequate analgesia. This therapeutic strategy makes it possible to avoid the adverse effects of opioids., Trial Registration: The study was retrospectively registered and approved by the relevant institutional review board (CERAR) reference IRB 00010254-2018 - 188). All patients gave written informed consent for analysis of their data. The anonymous database was declared to the French Data Protection Authority (CNIL) (reference 221 2976 v0 of April 12, 2019)., (© 2024. The Author(s).)

Purpose: To compare compliance with the French national guidelines before and after the implementation (in 2018) of a new protocol on acute fracture pain management in the pediatric emergency department of a French university medical center., Methods: We conducted a retrospective, before-after study in patients aged below 16 years presenting at the pediatric emergency department with a fracture. We compared pain management before (in 2017) and after (in 2019 and 2020) implementation of the new procedure. The primary endpoint was appropriate pain management, defined as (i) an appropriate initial assessment of pain, (ii) appropriate treatment with analgesic drugs (acetaminophen for mild pain, acetaminophen and ibuprofen for moderate pain, ibuprofen and morphine for severe pain) and (iii) reassessment of the pain intensity., Results: 572 patients were included (mean age: 6.5 years; male: 60%). 190 in 2017 and 382 in 2019-2020. Pain management was appropriate for 40% of the patients in 2017 and 52% in 2019-2020 (p = 0.004). Pain was rated for 98% of patients in 2017 vs. 100% in 2019-2020 (p = 0.04). The frequency of appropriate treatment for mild pain and moderate pain increased significantly from 52 to 76% and from 0 to 44%, respectively. The administration of ibuprofen increased by 26% points (from 3 to 20 patients treated) and the administration of morphine increased by 29% points (from 1 to 17 patients treated). Pain reassessment rose significantly from 21 to 43%. Levels of compliance with the guidelines were similar in 2019 and 2020. Analgesia was significantly more effective in 2019-2020 than in 2017 (in 20% vs. 14% of the patients, respectively; p = 0.005)., Conclusion: After the implementation of a new protocol for the management of acute fracture pain, we observed an increase in compliance with the guidelines. Although the use of ibuprofen and morphine rose significantly as did the frequency of pain reassessment, further improvements are required., (© 2024. The Author(s).)

Objective: We evaluated ductal closure rates in preterm neonates with hemodynamically significant patent ductus arteriosus (hsPDA) who received paracetamol (PCM) as first-line therapy., Methods: In this retrospective chart review, we included inborn preterm (< 37 weeks) neonates (January 2017-December 2021) with hsPDA (ductal diameter > 1.5 mm and left atrium-to-aortic root ratio (La/Ao > 1.4) who were treated with oral or intravenous PCM. Primary outcome was hsPDA closure (defined as small or no PDA) following 3-day treatment. Secondary outcomes were need for retreatment and surgical ligation, pulmonary hypertension (PH), and in-hospital morbidities., Results: Out of 2784 preterm birth, 117 neonates were diagnosed with hsPDA. Out of 96 neonates who received PCM in the first course, 20 died before the completing the first course. The median (IQR) gestation and birth weight of neonates who received PCM were 28 (26, 29) weeks and 841 (714, 1039) g, respectively. Out of 76 neonates who completed treatment with first course of PCM (57 intravenous, 19 oral), 43 (56.6%) achieved successful closure and five (6.6%) developed PH. Out of 14 neonates who received a second course of PCM, 10 achieved closure of hsPDA while one neonate expired., Conclusion: Paracetamol is associated with successful closure of hsPDA in 56.6% of preterm neonates after one course and 70% of premies after two courses.

Purpose: Postoperative shivering (POS) is a common and vital complication after anesthesia, which may result in serious consequences and uncomfortable experiences. Acetaminophen has been used to treat fever and mild to moderate pain. However, there is not enough evidence to prove its advantage for POS. This meta-analysis aimed to explore the prophylactic use of acetaminophen as a valid agent for POS., Methods: Two researchers independently searched PubMed, the Cochrane Library, and Embase for controlled clinical trials. The meta-analysis of randomized controlled trials (RCTs) was performed by Review Manager., Results: Nine trials with 856 patients were included in our meta-analysis. Acetaminophen significantly reduced POS compared with placebo (pooled risk ratio [RR]: 0.43, 95% confidence interval [CI]: 0.35-0.52). What is more, not only 15 mg/kg but also 1000 mg intravenous acetaminophen could reduce the incidence of shivering compared with placebo., Conclusion: Our present meta-analysis demonstrates that the intravenous prophylactic infusion of acetaminophen may prevent POS, and the results may provide new evidence to expand the clinical value of acetaminophen in addition to its routine usage., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Nefopam and propacetamol are the most commonly used analgesics in postoperative multimodal analgesic regimens. Distinct mechanisms are involved in each drug's anti-nociceptive effects. No studies have compared pain relief efficacy between the two drugs in patients undergoing transplantation surgery. Here, we investigated whether the administration of nefopam or propacetamol to healthy living kidney donors who underwent rectus sheath block (RSB) for parietal pain could reduce the subsequent opioid dose necessary to produce adequate analgesia., Methods: This prospective, randomized controlled trial included 72 donors undergoing elective hand-assisted living donor nephrectomy into two groups: propacetamol (n = 36) and nefopam (n = 36). Intraoperative RSB was performed in all enrolled donors. The primary outcome was the total volume of intravenous opioid-based patient-controlled analgesia (PCA) used on postoperative day 1 (POD 1). Additionally, the Numeric Rating Scale scores for flank (visceral) and umbilicus (parietal) pain at rest and during coughing were compared, and the Korean adaptation of the Quality of Recovery-15 Questionnaire (QoR-15 K) was evaluated on POD 1., Results: Both groups had similar preoperative and intraoperative characteristics. On POD 1, the total amount of PCA infusion was significantly lower in the nefopam group than in the propacetamol group (44.5 ± 19.3 mL vs. 70.2 ± 29.0 mL; p < 0.001). This group also reported lower pain scores at the flank and umbilical sites and required fewer rescue doses of fentanyl in the post-anesthesia care unit. However, pain scores and fentanyl consumption in the ward were comparable between groups. The QoR-15 K scores were similar between groups; there were substantial improvements in breathing, pain severity, and anxiety/depression levels in the nefopam group. The incidences of postoperative complications, including sweating and tachycardia, were similar between groups., Conclusion: Compared with propacetamol, nefopam provides a greater analgesic effect for visceral pain and enhances the effects of blocks that reduce the opioid requirement in living kidney donors with parietal pain managed by RSB., Trial Registration: The trial was registered prior to patient enrollment in the clinical trial database using the Clinical Research Information Service (registration no. KCT0007351 , Date of registration 03/06/2022)., (© 2024. The Author(s).)

Background: Septorhinoplasty is one the most common class of procedures performed worldwide, and opioids are frequently prescribed for post-operative pain [1]., Objective: The objective of this study was to examine the rate of post-operative opioid prescription refills following septorhinoplasty., Methods: This study was a case-control study of patients who underwent septoplasty and other secondary concomitant procedures., Results: Of the 249 patients included in this study, the majority of patients (94.8%) were prescribed 12 tablets of hydrocodone-acetaminophen 5 mg - 325 mg and only 31 patients (13.3%) received refills. The presence of osteotomies and history of prior opioid use were associated with refills. Nasal valve repair type, open versus closed approach, and presence of autologous auricular cartilage graft harvest were not., Discussion: Our study highlights factors that surgeons should consider when prescribing opioids after septorhinoplasty. Twelve tablets of an opioid are likely sufficient for the majority of patients, but if osteotomies are performed or the patient has a history of prior opioid use, more may be indicated to avoid the need for refills. Additional narcotics are not necessary for an open approach or for patients in which auricular cartilage is needed., Competing Interests: Declaration of competing interest The authors of this study do not have any conflicts of interest to disclose. This study received no specific grant from any funding agency in the public, commercial, or non-profit sectors., (Published by Elsevier Inc.)

Objective: To evaluate the opinions of university-level Health Sciences students about unused, leftover and expired medicine, as well as their disposal practices, and to classify the medicines., Methods: The cross-sectional study was conducted from April 1 to May 31, 2023, at the Faculty of Health Sciences, Burdur Mehmet Akif Ersoy University, Turkey, and comprised those studying at the Nursing, Nutrition Dietetics and Physical Therapy and Rehabilitation departments. Data was collected using Google Forms. The Anatomical Therapeutic Chemical classification was used for classifying pharmaceutical active ingredients. Data was analysed using SPSS 24., Results: Of the 373 participants, 272(73%) were females and 101(27%) were males. The overall mean age was 20.8±2.8 years. There were 348(93.3%) subejcts who reported having a total of 845 boxes of leftover and unused medicines in their homes (2.3±1.9 per capita), while 25(6.7%) participants had none. The medicines were stored in the kitchen 261(61.5%) as the storage area, and in the refrigerator 181(40.2%) as the storage unit. The expired medicine was disposed of in the garbage in 328(86.1%) cases. Self-medication was prevalent in 325(87.1%) cases. Anatomical Therapeutic Chemical classification analysis showed that paracetamol, acetylsalicylic acid, paracetamol+caffeine and metamizole sodium was the most common group of leftover and unused medicines 283(81.3%)., Conclusion: High prevalence of unused and leftover medicine, disposal of medicine in household garbage, and selfmedication behaviour indicated a serious public health and environmental problem.

Introduction: Most pain studies have been based on a postsurgical, third molar model using ibuprofen (IBU)/acetaminophen (APAP). Studies have found quicker onset of pain relief with a newer formulation of IBU - ibuprofen sodium dihydrate (ISD). The purpose of this study was to compare pain reduction of ISD/APAP to ISD in an acute endodontic pain model of untreated patients experiencing moderate to severe pain with symptomatic apical periodontitis., Methods and Materials: In this double-blind randomized study, 64 adult emergency patients in acute moderate to severe pain, a pulpal diagnosis of symptomatic irreversible pulpitis or necrosis, and symptomatic apical periodontitis participated. Each patient randomly received either one dose of 768 mg ISD/1000 mg APAP or one dose of 768 mg ISD. Pain intensity scores were recorded every 15 minutes over 240 minutes using the Heft-Parker VAS along with time to first sign of pain relief, time to meaningful pain relief, and time to 50% pain relief also recorded. The data were analyzed statistically., Results: Both ISD and ISD/APAP groups showed a progressive decrease in pain from baseline to 120 minutes after medication administration. Afterward, a relative plateau was seen in the patients' pain. There was no difference in the VAS scores between the ISD and ISD/APAP at any given time point, time to first sign of pain relief, time to meaningful pain relief, and time to 50% pain relief., Conclusions: The addition of APAP to ISD for pain control in an untreated endodontic pain model did not differ significantly from ISD alone., (Copyright © 2024 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)