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Objectives: This study aims to determine the usage pattern, effectiveness and safety of oral tramadol 75 mg and dexketoprofen trometamol 25 mg fixed-dose combination (TRAM/DKP FDC) in the short-term treatment of moderate-to-severe acute pain in real-world clinical practice in Asia., Design: Real-world, prospective, multicentre, observational, phase IV study., Setting: 13 tertiary-care hospital sites across the Philippines, Thailand, Malaysia and Singapore., Participants: Adult patients aged 18-80 years prescribed TRAM/DKP FDC for the short-term (up to 5 days) treatment of moderate-to-severe acute pain., Main Outcome Measures: Primary endpoints were the proportion of patients prescribed TRAM/DKP FDC with different types of postsurgical and non-surgical treatments, and the average dosing frequency and duration of TRAM/DKP FDC treatment. Secondary endpoints were the proportion of patients achieving ≥30% pain reduction at 8 hours post the first dose (pain severity was assessed using the 11-point Numeric Pain Rating Scale); patient satisfaction at the end of treatment (based on a 5-point Patient Global Evaluation Scale (PGE)) and safety including the incidence of adverse drug reactions (ADRs)., Results: Among 599 patients (median age 44 years, 61.3% female) enrolled in this study, 68.61% (n=411) were postsurgical and 31.39% (n=188) were non-surgical patients. TRAM/DKP FDC was prescribed in a diverse group of postsurgical patients (eg, orthopaedic, general and cancer surgery) as well as in non-surgical conditions (eg, lower back pain and musculoskeletal pain). In the majority of patients, TRAM/DKP FDC was prescribed every 8 hours (65.94%) and for 5 days (78.80%). There was a significant reduction in pain intensity throughout the study and 65% of patients achieved ≥30% pain reduction from baseline at 8 hours post the first dose of TRAM/DKP FDC on day 1. 95.69% of patients were satisfied with the treatment (rated good, very good and excellent on the PGE scale). Overall, 13.9% of patients reported ADRs; most were mild to moderate in severity. The most common ADRs were nausea, vomiting and dizziness., Conclusion: This study showed that TRAM/DKP FDC was used in diverse types of postsurgical and non-surgical patients in the real-world setting in Asia. It effectively reduced pain and was well tolerated with a high level of patient satisfaction., Competing Interests: Competing interests: BG, AG and DN are employees of A. Menarini Asia-Pacific Holdings Pte. Ltd., Singapore. All other authors report receiving investigator fees for this study from the sponsor., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Long bone fractures (LBF) often cause severe pain, impacting patients' quality of life. This prospective, randomized, double-blind study aimed to compare the analgesic efficacy of dexketoprofen (Dex) and ibuprofen (Ibu) in LBF patients in the emergency department., Methods: Conducted between August 10, 2023, and January 17, 2024, the study included 100 eligible patients randomized into Dex and Ibu groups. Visual analog scale (VAS) scores were measured at baseline and at 30, 60, and 120 min. DeltaVAS (ΔVAS) values and ΔVAS percentages (ΔVAS%) were calculated. Primary endpoints were ΔVAS scores (ΔVAS 30-60-120) and ΔVAS% for comparative analysis., Results: Statistical analysis showed no significant difference in ΔVAS30 (p = 0.359). However, ΔVAS60 exhibited a significant difference (p = 0.027), as did ΔVAS120 (p = < 0.001). ΔVAS%30 showed no significance (p = 0.224), but ΔVAS%60 and ΔVAS%120 were clinically and statistically significant (p = 0.017 and p = < 0.001, respectively)., Conclusion: Ibuprofen 800 mg demonstrated superior analgesic efficacy at 60 and 120 min compared to Dex in long bone fractures. These findings suggest ibuprofen's potential as an effective pain management option in emergency departments., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

The worldwide prevalence of uncomplicated lower urinary tract infections (uUTIs) caused by multidrug-resistant Escherichia coli is increasing. To address this emergency, international guidelines recommend reducing administration of fluoroquinolones, in the context of growing resistance and the long-lasting and potentially disabling side effects of these drugs. The favoured drug to replace fluoroquinolones is fosfomycin trometamol (FT), a well-known derivate of phosphonic acid with broad-spectrum activity against Gram-negative and Gram-positive bacteria, including multidrug-resistant (MDR) strains. The European Committee on Antimicrobial Susceptibility Testing (EUCAST) recently reduced the susceptibility breakpoint for E. coli from 32 mg/L to 8 mg/L regarding FT used for uUTIs. This might lead to increased appropriate use of oral fosfomycin target therapy against E. coli and other microorganisms, and may be associated with a high likelihood of success. For species such as Klebsiella spp, particularly MDR strains, the absence of clinical breakpoints might lead to reduced use of oral fosfomycin, particularly if minimum inhibitory concentration is not available. To address this issue, this review presents an overview of the preclinical evidence on the activity of FT, and a systematic review of the clinical activity of FT in uUTIs in women, and in the prevention of infectious complications after prostate biopsy. The findings indicate that the safety and microbiological and clinical effectiveness of a single oral dose of FT are similar to that for comparator regimens with longer treatment schedules in women with uUTI, and FT can be considered a viable alternative to fluoroquinolones for antimicrobial prophylaxis in prostate biopsy. These observations and a broad clinical experience support the empirical use of FT for treating uUTI and indicate that FT is a promising candidate to effectively counteract antibiotic-resistant uUTIs throughout Europe., (Copyright © 2023 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)

Background: Fosfomycin is a potentially attractive option as step-down therapy for bacteraemic urinary tract infections (BUTI), but available data are scarce. Our objective was to compare the effectiveness and safety of fosfomycin trometamol and other oral drugs as step-down therapy in patients with BUTI due to MDR Escherichia coli (MDR-Ec)., Methods: Participants in the FOREST trial (comparing IV fosfomycin with ceftriaxone or meropenem for BUTI caused by MDR-Ec in 22 Spanish hospitals from June 2014 to December 2018) who were stepped-down to oral fosfomycin (3 g q48h) or other drugs were included. The primary endpoint was clinical and microbiological cure (CMC) 5-7 days after finalization of treatment. A multivariate analysis was performed using logistic regression to estimate the association of oral step-down with fosfomycin with CMC adjusted for confounders., Results: Overall, 61 patients switched to oral fosfomycin trometamol and 47 to other drugs (cefuroxime axetil, 28; amoxicillin/clavulanic acid and trimethoprim/sulfamethoxazole, 7 each; ciprofloxacin, 5) were included. CMC was reached by 48/61 patients (78.7%) treated with fosfomycin trometamol and 38/47 (80.9%) with other drugs (difference, -2.2; 95% CI: -17.5 to 13.1; P = 0.38). Subgroup analyses provided similar results. Relapses occurred in 9/61 (15.0%) and 2/47 (4.3%) of patients, respectively (P = 0.03). The adjusted OR for CMC was 1.11 (95% CI: 0.42-3.29, P = 0.75). No relevant differences in adverse events were seen., Conclusions: Fosfomycin trometamol might be a reasonable option as step-down therapy in patients with BUTI due to MDR-Ec but the higher rate of relapses would need further assessment., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

In recent years, the harmonization of domestic and foreign clinical recommendations for the treatment of cystitis has been achieved. Nitrofurans and fosfomycin trometamol are recommended as first line therapy antibiotics, and oral 3rd generation of cephalosporins are recommended as alternative antibiotics; fluoroquinolones are excluded from the recommended medications due to an unfavorable safety profile. The main rationale for inclusion of antibiotics in the recommendations as a first line therapy of cystitis is the level of resistance of uropathogens to antibiotics, primarily Escherichia coli. Stable low level of resistance of E. coli in Russia was noted to nitrofurans and fosfomycin (5%), higher to cephalosporins. Among nitrofurans, furazidine is characterized by higher activity against E. coli compared to nitrofurantoin. The potassium salt of furazidine in dosage form with magnesium carbonate is preferred, since it is characterized by higher bioavailability and provides a therapeutic level of concentrations in urine above the MIC during the entire dosing period. Due to the global increase in the resistance of uropathogens observed in recent years, experts have begun to pay more and more attention to the ecological safety of antimicrobial therapy in order to minimize the risk of concomitant (collateral) damage, contributing to the selection of multi-drug resistant strains of microorganisms. In the latest WHO document of 2021, experts divided antibiotics into three groups (ACCESS, WATCH, RESERVE) according to the priority of choice. The ACCESS group of drugs for the treatment of cystitis includes nitrofurantoin and furazidine as agents with minimal collateral effect, while fosfomycin trometamol and cephalosporins are listed in the WATCH group. Thus, from the standpoint of ecological safety, WHO experts recommend prescribing nitrofurans in the treatment of cystitis in the first line of therapy.

First-line treatments for mild to moderate psoriasis are typically topical formulations containing corticosteroids, however, the therapeutic efficacy of these formulations is compromised by limited penetration and skin retention. Even more challenging, off-target corticosteroids are known to adversely affect healthy skin, including induction of epidermal and dermal atrophy. Here, we report a nanoparticle-based topical formulation that cures psoriasis in a single dose, but leaves healthy skin intact. Specifically, we developed tris(hydroxymethyl)aminomethane-modified bioadhesive nanoparticles (Tris-BNPs) that exploit the high permeability characteristic of psoriasis to penetrate only psoriatic skin but not the healthy skin. Furthermore, as Tris-BNPs diffuse and penetrate into the epidermis, the Tris molecules slowly diffuse away, exposing the aldehyde groups of BNPs, which can bind to amine groups present within lesional skin, leading to long local retention of BNPs in lesions of psoriatic skin. The accumulated BNPs within lesions release corticosteroids over a ~ 3 day period to maintain local drug concentration above the therapeutic level. In addition to deeper penetration and longer retention compared with commercial psoriasis treatments, the topical applied Tris-BNPs were not affected by sweating, humidity, or active wiping due to their preferential accumulation between the stratum corneum and the basal cells of the epidermis. Overall, Tris-BNP as a topical formulation hold promise to overcome the limitations of current psoriasis treatment., Competing Interests: Declaration of Competing Interest Authors declare that they have no competing interests., (Copyright © 2022. Published by Elsevier B.V.)

The aim of the study was to examine the severity of clinical symptoms of acute cystitis and the level bacteriuria in female patients who underwent to laparoscopic surgery followed by a postoperative administration of dienogest 2 mg and combined oral contraceptives pills (COCP). One hundred and forty five women who had a laparoscopic surgery prospectively were enrolled. Criteria inclusions were the age from 30 to 45 years old; body mass index (BMI) absence of previous hormonal therapy at least 6 month and recent performed a laparoscopy surgery for endometriosis. The women ( n  = 35) who had uterine myoma, abnormal coagulation profile; concomitant neoplastic diseases; chronic pelvic inflammatory disease and chronic recurrent cystitis were excluded from study. The female patients were assigned into both groups treatment: group I ( n  = 54) and group II (control, n  = 56) who received dienogest 2 mg once daily and COCP, respectively. During follow-up three female patients of group I were withdrawn due to prolonged genital bleedings. The final analysis included 105 women. The patients of both groups had a low level of bacteriuria <10 3 CFU/ml without clinical symptoms of acute cystitis before treatment. The level of bacteriuria in-group I significantly increased from 10 2 to 10 6 CFU/ml whereas in-group II did not exceed 10 2 CFU/ml during 4 weeks of hormonal treatment. The differences of values of acute cystitis symptom score (ACSS) for differential, typical, quality of life domains were statistically significant after 4, 8 and 12 weeks of therapy in-group I compared with group II. During 3 months of hormonal treatment with dienogest 2 mg in group I, the acute cystitis developed in 10 (18.5%), in 19 (38%) and in 34 (68%) women at 4, 8 and 12 weeks of follow-up, respectively. All cases of acute cystitis in-group I were successfully treated with fosfomycin trometamol 3 g single dose or nitrofurantoin 50 mg four times a day during 5 days. We concluded that the dienogest might increase the level bacteriuria and severity of clinical symptoms of acute cystitis during a postoperative prophylaxis of endometriosis.Impact statement What is already known on this subject? Dienogest is a 19-nortestosterone derivative progestogen that is highly selective for progesterone receptors with high efficacy for reducing endometriosis-related pelvic pain syndrome. The administration of dienogest is a standard treatment option after laparoscopic excision of endometrial heterotopic tissue with prophylactic purpose. However, there are some adverse events, which are a cause for discontinuation. What do the results of this study add? Despite the low incidence of urinary tract infection (1-5.4%) reported in different studies this study has shown that there was a significant increase of level bacteriuria and severity of clinical symptoms of cystitis in the dienogest group. What are the implications of these findings for clinical practice and/or further research? The implications of these findings are that the administration of dienogest may lead to enhancing of clinical symptoms of cystitis and increasing bacteriuria in some women after operative treatment of endometriosis.

Dexketoprofen is an enantiomer of ketoprofen (S+) that belongs to nonsteroidal anti-inflammatory drugs and has analgesic, anti-inflammatory, and antipyretic properties. Dexketoprofen has a stronger effect than ketoprofen, which makes it a readily used preparation. The review aims to find in recent original publications data about dexketoprofen and its comparison with other painkilling medications. The systematic literature review was conducted in November 2021 (2018 onwards). We selected 12 articles from PubMed, Google Scholar, Medline Complete databases. In the last 4 years, there have been many publications that shed a new light on dexketoprofen. The article is a comparative analysis of dexketoprofen's action vs other nonsteroidal anti-inflammatory drugs and the combination of dexketoprofen with tramadol vs paracetamol with tramadol. The findings of the review confirm that dexketoprofen is a very good pain reliever more potent than paracetamol. Dexketoprofen produces similar effects to lidocaine and dexmedetomidine. Complex preparations containing dexketoprofen and tramadol are very effective painkilling tandem and are more effective than tramadol and paracetamol therapy in the treatment of acute pain., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Purpose: Although different forms of lidocaine are used for migraine attack headaches, the effect of intravenous lidocaine is still limited. This study aimed to investigate the effects of intravenous lidocaine infusion for the treatment of migraine attack headaches., Methods: A hundred patients with migraine attacks, aged between 18 and 65, were randomly divided into two groups. The lidocaine group (n = 50) received a 1.5 mg/kg lidocaine bolus and a 1 mg/kg infusion (first 30 min), followed by a 0.5 mg/kg infusion for a further 30 min intravenously. The non-steroidal anti-inflammatory drug (NSAID) group (n = 50) received 50 mg dexketoprofen trometamol and saline at the same volume as the lidocaine at the same time intervals intravenously. The Visual Analog Scale (VAS) pain scores, additional analgesia requirement, side effects, and revisits to the emergency department were recorded., Results: The VAS score was significantly lower in the lidocaine group than in the NSAID group for the first 20th and 30th minutes (p = 0.014 and p = 0.024, respectively). There was no difference between the VAS scores for the remaining evaluation times (p > 0.05). In terms of secondary outcomes, rescue medication requirement was not different between the two groups at both the 60th and 90th minutes (p > 0.05). However, the number of patients revisiting ED within 48-72 h was statistically less in the lidocaine group than in the NSAID group (1/50 vs. 8/50; p = 0.031)., Conclusion: Intravenous lidocaine may be an alternative treatment method for patients with migraine attack headaches in the emergency department., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Aim: Dexketoprofen trometamol is one of the most commonly used anti-inflammatory analgesic agents for pain control. This study aims to investigate the effect of dexketoprofen on penicillin-induced epileptiform activity in rats., Method: In this study, 28 male Wistar rats weighing 220-240 g were used. Tripolar electrodes were implanted under urethane anesthesia. Epileptiform activity was induced by micro-injection of 500 units (IU) penicillin into the rats' left somatomotor cortex. Dexketoprofen (5, 25, and 50 mg/kg) was administrated intraperitoneally after 30 min of penicillin injection. Epileptiform activity was evaluated by electrocorticography (ECoG)., Results: The low dose of dexketoprofen administration (5 mg/kg) reduced the mean spike frequency of epileptiform activity 60 min after its injection. However, 25 and 50 mg/kg dexketoprofen significantly reduced the mean spike frequency 30 min after the dexketoprofen injection compared to the control group (p < 0.05). The amplitudes of epileptiform discharges in all groups were unaffected (p > 0.05)., Conclusion: This study revealed that dexketoprofen had a significant anti-seizure effect when applied at 5 mg/kg, 25 mg/kg, and 50 mg/kg (especially at 25 and 50 mg/kg), in the penicillin-induced seizure model. The obtained data revealed that dexketoprofen might play an essential role against epileptic seizures., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Purpose: To evaluate preoperative asymptomatic bacteriuria (ASB) treatment to reduce early-periprosthetic joint infections (early-PJIs) after hip hemiarthroplasty (HHA) for fracture., Methods: Open-label, multicenter RCT comparing fosfomycin-trometamol versus no intervention with a parallel follow-up cohort without ASB., Primary Outcome: early-PJI after HHA., Results: Five hundred ninety-four patients enrolled (mean age 84.3); 152(25%) with ASB (77 treated with fosfomycin-trometamol/75 controls) and 442(75%) without. Despite the study closed without the intended sample size, ASB was not predictive of early-PJI (OR: 1.06 [95%CI: 0.33-3.38]), and its treatment did not modify early-PJI incidence (OR: 1.03 [95%CI: 0.15-7.10])., Conclusions: Neither preoperative ASB nor its treatment appears to be risk factors of early-PJI after HHA. ClinicalTrials.gov Identifier: Eudra CT 2016-001108-47., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Aim: Low back pain (LBP) is a common musculoskeletal complaint among emergency department (ED) admissions. In this study, it was aimed to compare the effectiveness of systemic treatment with intradermal sterile water injection (ISWI) treatment protocol combined with systemic therapy in patients with LBP of unclear chronicity., Methods: A prospective randomized, unblinded, controlled clinical study was conducted on patients admitted to the ED for LBP of unclear chronicity. One hundred twelve patients were randomly assigned to two groups; Group ISWI (n = 56) administered ISWI in the LBP region of patients along with systemic intravenous dexketoprofen therapy, while the other group (n = 56) received only systemic intravenous dexketoprofen therapy. The treatment methods' effectiveness was compared by measuring the pain intensity with the Visual Analog Scale (VAS) at admission, 10th minutes, 20th minutes, 30th minutes, and 24 h later. Also, opioid and analgesic consumptions in 24 h after treatment and patient satisfactions were compared., Results: In the treatment of LBP, ISWI treatment was found to be more effective in relieving pain than systemic therapy alone (p < 0.001). Also, it was observed that opioid consumption in the ED and analgesic consumption within 24 h after treatments were decreased in the ISWI group (p < 0.001). The patient satisfaction in the ED was statistically increased (p < 0.001)., Discussion: In this unblinded study, ISWI with systemic therapy improved pain outcomes more than systemic therapy alone. Further research is needed to determine whether this was due entirely to placebo effect., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to declare., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Competing Interests: Declaration of competing interest The authors declare no competing interests to disclose.

Background: Postoperative pain is an important problem for patients undergoing shoulder surgery. Our study investigated analgesic efficacy, duration of analgesia, postoperative analgesic use and patient satisfaction with the use of preemptive intravenous dexketoprofen for interscalene block in addition to general anesthesia in arthroscopic shoulder surgery. Methods: 60 patients, scheduled for arthroscopic shoulder surgery were randomized (30 patients each) into either: - control group (Group1) or dexketoprofen group (Group 2). Patients were followed for 48 hours to compare both groups for; post-operative pain scores, effectiveness of postoperative analgesia, duration of analgesia, and analgesia consumption. Duration of postoperative sensory block of the shoulder joint was defined as time to onset of pain at the incision site. Duration of postoperative motor block of the shoulder joint was defined as time to onset of first shoulder movement. Results: While no significant difference was determined for motor block time, sensory block time was significantly longer in the dexketoprofen group ( p  < 0.05).VAS scores were significantly lower at all times in the dexketoprofen group ( p  < 0.05).Total PCA fentanyl consumption was 274.16 ± 314.89 (μg) in the dexketoprofen group, and 490.00 ± 408.98 (μg) in the control group, the difference was statistically significant ( p  < 0.05). No significant difference was observed between the groups' demographic and hemodynamic data. Conclusion: Pre-emptive IV dexketoprofen may be a good option for arthroscopic shoulder surgery and provides effective analgesia.

Objectives: The increasing incidence of fluoroquinolones (FQ) resistance may lower its efficacy in preventing UTI following transrectal ultrasound-guided prostate biopsy (TRUS-PB). We assessed the efficacy and safety of FQ and fosfomycin-trometamol (FT) in patients undergoing TRUS-PB., Methods: A prospective observational study was conducted between April 2017 and June 2019 and enrolled men undergoing TRUS-PB and receiving a single-dose of FQ (FQ-arm) or FT (FT-arm) for UTI prophylaxis per physician's choice. The primary efficacy endpoint was self-reported TRUS-PB UTI. We assessed baseline factors associated with UTI with logistic regression., Results: A total of 222 men were enrolled, 141/222 (64%) received FQ, and 81/222 (36%) FT. The median age was 67.6 years [IQR, 61.4-72.1] and the Charlson score was 3 [IQR, 3-5]. The overall incidence of self-reported TRUS-PB UTI was 12% (24/197, (95%CI, 8%-17%)): 15% (17/116, (95% CI, 10%-17%)) in FQ-arm, versus 9% (7/81, 95% CI (5%-13%)) in FT-arm (RR = 0.55 (95% CI, 0.22-1.40), p-value = 0.209). No baseline characteristic was significantly associated with TRUS-PB UTI. Safety was similar between the arms: the rate of the reported adverse event was 31% (36/116, (95% CI, 25%-37%) in the FQ-arm versus 36% (28/81, (95% CI, 28%-41%)) in the FT-arm (RR = 1.17 (95% CI, 0.64-2.15), p = 0.602)., Conclusions: TRUS-PB UTI prophylaxis with FT and FQ has similar efficacy and safety. A randomized comparison of these two antibiotics is warranted., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To assess whether mild thrombocytopenia (platelet count 100-149 k/microliter) is associated with an increased risk of postpartum hemorrhage., Methods: Nulliparous women with term, singleton, vertex pregnancies undergoing labor at our institution between August 2016 and September 2017 were included. The primary exposure was mild thrombocytopenia, defined as platelet count 100-149 k/microliter, and the comparator was normal platelet count (150 k/microliter or greater). Those with severe thrombocytopenia (platelet count less than 100 k/microliter) were excluded from analysis. The primary outcome was postpartum hemorrhage, determined by International Classification of Diseases, Tenth Revision codes and the hospital discharge problem list. Secondary outcomes included use of uterotonic agents (methylergonovine maleate or carboprost tromethamine), total blood loss 1,000 mL or greater, and blood transfusion. Data were analyzed by t test, χ or Fisher exact test, and multivariable logistic regression, with significance at α <0.05., Results: We evaluated 2,845 eligible women, of whom 2,579 (90.2%) had normal platelet count 150 k/microliter or greater, 266 (9.3%) had platelet count 100-149 k/microliter (mild thrombocytopenia), and 13 (0.5%) had platelet count less than 100 k/microliter (severe thrombocytopenia). Compared with women with normal platelet count, those with mild thrombocytopenia had a higher rate of postpartum hemorrhage (16.9% vs 8.5%, P<.001) and were more likely to have total blood loss 1,000 mL or greater (4.5% vs 1.7%, P=.002) and receive methylergonovine maleate (10.5% vs 5.9%, P=.003) or carboprost tromethamine (6.0% vs 1.6%, P<.001) or both (3.8% vs 1.0%, P<.001), but rates of blood transfusion were no different (1.9% vs 1.5%, P=.59). The association between mild thrombocytopenia and postpartum hemorrhage persisted after multivariable adjustment for potential confounders (adjusted odds ratio 2.2, 95% CI 1.5-3.2, P<.001)., Conclusion: Among nulliparous women with term, singleton, vertex pregnancies undergoing labor, those with mild thrombocytopenia (platelet count 100-149 k/microliter) had a twofold greater likelihood of postpartum hemorrhage compared with those with normal platelet count.

Currently, the optimal resuscitation fluid remains debatable. Therefore, in the present study, we designed a trometamol-balanced solution (TBS) for use as a resuscitation fluid for hemorrhagic shock. Hemorrhagic shock was induced in 18 male Wistar-Kyoto rats, which were assigned to normal saline (NS), Ringer's solution (RS), and TBS groups. During the hemorrhagic state, their hemodynamic parameters were recorded using an Abbott i-STAT analyzer with the CG4+ cartridge (for pH, pressure of carbon dioxide, pressure of oxygen, total carbon dioxide, bicarbonate, base excess, oxygen saturation, and lactate), the CG6+ cartridge (for sodium, potassium, chloride, blood glucose, blood urea nitrogen, hematocrit, and hemoglobin), and enzyme-linked immunosorbent assay kits (calcium, magnesium, creatinine, aspartate aminotransferase, alanine aminotransferase, bilirubin, and albumin). Similar trends were found for the parameters of biochemistries, electrolytes, and blood gas, and they revealed no significant changes after blood withdrawal-induced hemorrhagic shock. However, the TBS group showed more effective ability to correct metabolic acidosis than the NS and RS groups. TBS was a feasible and safe resuscitation solution in this study and may be an alternative to NS and RS for resuscitation in hemorrhagic shock patients without liver damage., Competing Interests: The authors declare no conflicts of interest., (© 2020 The Korean Society of Veterinary Science.)

Introduction: Acute musculoskeletal injuries are one of the most common painful presentation when admission to the emergency department. The aim of the study is to compare the tenoxicam mesotherapy with intravenous dexketoprofen in pain control in patients with acute musculoskeletal injury., Methods: This parallel randomized controlled trial was conducted with the patients admitted to the emergency department with musculoskeletal injury. Intravenous dexketoprofen was administered to the control group, and mesotherapy treatment was performed to the other group. Differences between 10th, 30th, 60th and 120th minutes VAS scores and on the admission VAS score, clinically meaningful change in pain intensity, and adverse effect of the procedures were compared among groups., The Results: The differences in VAS scores and the presence of clinically meaningful change in pain intensity were statistically significantly higher in mesotherapy group than the systemic therapy group in all time periods. During one-week follow-up period, there was no reported adverse effect neither in mesotherapy group nor in the systemic therapy group., Conclusions: The mesotherapy treatment may be superior than the systemic therapy for pain relief in musculoskeletal injury in short term follow-up in emergency department settings., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: Dexketoprofen trometamol is a modified non-selective COX inhibitor with a rapid onset of action that is available as both oral and parenteral formulations. The aim of this narrative review was to assess the efficacy and tolerability/safety of dexketoprofen trometamol in acute pain states using the best available published scientific evidence (randomized controlled clinical trials and systematic reviews/meta-analyses)., Methods: Literature retrieval was performed via Medline, Embase and the Cochrane Library (from inception up to March 2017) using combinations of the terms "randomized controlled trials", "dexketoprofen", "celecoxib", "etoricoxib", "parecoxib" and "acute pain"., Results: Single-dose dexketoprofen trometamol provides effective analgesia in the treatment of acute pain, such as postoperative pain (dental and non-dental surgery), renal colic, acute musculoskeletal disorders and dysmenorrhea, and reduces opioid consumption in the postoperative setting. It has a rapid onset of action (within 30 minutes) and is well tolerated during short-term treatment. Direct comparisons with COX-2 inhibitors are lacking; however, the efficacy and tolerability of single-dose dexketoprofen trometamol appears to be consistent with that seen with celecoxib, etoricoxib and parecoxib in the acute pain setting., Conclusion: In conclusion, dexketoprofen trometamol appears to provide similar analgesic efficacy to COX-2 inhibitors when used to treat acute pain, has a rapid onset of action, is well tolerated, and has an opioid-sparing effect when used as part of a multimodal regimen in the acute pain setting.

Introduction: Acute cystitis is the most common type of uncomplicated urinary tract infection. A choice of antibiotics for the treatment depends not only on the spectrum of antimicrobial activity against pathogens, but also on the pharmacokinetic properties, due to high urine concentration after single or double use is needed. In addition, high safety profile and acceptable cost are important. Fosfomycin is one of the drugs whose efficiency in treating of patients with lower urinary tract infection is proved. It has been on the pharmaceutical market for a long time and is widely used in urologic practice. There is a risk of a decreasing of efficiency of fosfomycin, considering sustained downward trend in the sensitivity of uropathogens. This causes a need to monitor the resistance of main uropathogens to fosfomycin. In this article our experience of using of fosfomycin for the treatment of women with acute uncomplicated cystitis is presented., Aim: to evaluate an efficiency of fosfomycin trometamol for treatment of women with acute uncomplicated cystitis., Materials and Methods: During the period from September to November 2018, we performed an examination and treatment of 57 women with acute uncomplicated cystitis aged from 19 to 40 years. All patients were prescribed 1 sachet of Fosfomycin Esparma (fosfomycin trometamol) after urination. The examinations were carried out on the 1st, 3rd and 7th day, including an evaluation of urination frequency, urgency, nocturia and pain intensity. In addition, urinalysis and urine culture using solid media with determination of the type of pathogens, sensitivity to antibiotics and the level of bacteriuria were also performed., Results: Baseline, all patients had complaints of pain in the bladder, urethral discomfort and frequent urination, but passing only small amount of urine. All women had leucocyturia and bacteriuria. By the 3rd day after receiving fosfomycin, urinary disturbances persisted in 22.8% patients and 17.5% of women still described pain. Mild leucocyturia was determined in 42% cases. Urine culture was negative. By the 7th day after the start of therapy, all clinical and laboratory data were returned to the normal values in all patients., Conclusion: Based on the results of our study, we recommend the fosfomycin as the first-line treatment of uncomplicated lower urinary tract infection due to broad spectrum, low resistance of uropathogens, high safety profile and good compliancy.

Purpose: Pain has a negative impact on life satisfaction (LS). Our primary aims were to compare LS in on-opioid and opioid-naïve spine surgery patients and to evaluate whether surgery affects LS during the first 3 weeks after surgery., Methods: After informed consent 200 patients (99 on-opioid, 101 opioid-naïve; 112 male; aged 23-71 years) having elective spine surgery were enrolled. Their LS was evaluated using a four-item Life Satisfaction Scale (4-20, lower score more satisfied) and pain interference using Brief Pain Inventory (BPI)-questionnaire (0-10, lower score, less interference) before and 21 days after surgery., Results: At baseline LS was lower in the ON-OPIOID-group, mean LS-score 10.6 (SD 3.9), than that in the OPIOID-NAÏVE-group, 9.3 (3.0) (p = .027). At 3 weeks after surgery LS had increased in both groups compared to baseline (p < .001). However, LS was still lower in the ON-OPIOID-group, 9.1 (3.7) than that in the OPIOID-NAÏVE-group, 7.6 (2.7) (p = .005). Patients with lower LS experienced more pain interference pre- and post-operatively (p < .001). At 3 weeks the pain interference had decreased in both groups, in the ON-OPIOID-group from mean BPI-score 5.1 (2.0) to 3.0 (2.0) (p < .001) and in the OPIOID-NAÏVE-group from 4.0 (2.1) to 2.4 (2.3) (p < .001), but BPI-score was still higher in the ON-OPIOID-group (p = .045)., Conclusion: Life satisfaction increased and pain interference decreased in both groups after spine surgery. However, LS was lower and pain interference was more significant in on-opioid patients than that in opioid-naïve patients.

Within the developed countries, low back pain and related ailments represent one of the most relevant conditions, affecting both health and socio-economic systems. Non-specific acute low back pain (nsALBP) could represent either an isolated event or the presenting symptom of an underlying condition. Its management is usually medical and radiological investigations should be avoided. However, a general agreement on the best pharmacological treatment is still missing. In the present study, we retrospectively collected patients' data from the institutional database. Two different medical treatments were recognized and groups consequently set. Outcomes were the clinical status, measured using the visual analogue scale (VAS) score for back pain, the use rate of rescue drugs, side effects related to medical treatment, compliance to the treatment, and global satisfaction. The pharma blending of Tramadol 75 mg and Dexketoprofen 25 mg (available blended in a single tablet), resulted effective in the nsALBP management, with less side effects and rescue-drug use along with a higher compliance. Furthermore, patient satisfaction in this treatment group was significatively higher. Many different medical treatments have been investigated and reported in nsALBP management during the last decades. Associations of different drugs are the most common protocols, even though there is no general agreement. Tramadol and Dexketoprofen provide a good clinical result, fewer side effects and a long-lasting and more effective painkiller action, reducing the use of rescue drugs. Moreover, our results suggest that a single tab may provide a higher compliance rate.

Carboprost tromethamine is a synthetic prostaglandin derivative, which can effectively promote law contraction of the uterus and significantly reduce the amount of bleeding during and after delivery. In this study, we explored the effect of carboprost tromethamine on the prevention of postpartum hemorrhage after cesarean section and the effect on coagulation function and hemodynamics. At the same time, the effects of oxytocin and carboprost tromethamine were studied in different groups. The results showed that the amount of 2h bleeding (256.7±65.21) mL and the amount of 24h hemorrhage (308.3±78.3) after the operation were significantly decreased, and the difference was statistically significant (P<0.05). After the operation, the levels of APTT, TT and Fib in the two groups were significantly lower than those before the operation. The levels of SBP (119.4±8.24) mmHg and DBP (79.6±6.21) mmHg in the experimental group were significantly higher than those of the control group. In summary, carboprost tromethamine has a significant effect on the prevention of postpartum hemorrhage in cesarean section, and has a significant effect on improving the state of hypercoagulable blood and maintaining the stable hemodynamic state, which has clinical a value.

Relevance: Acute uncomplicated lower urinary tract infections (AULUTI) are one of the most common diseases in urological practice. The management of cystitis is commonly based on antibacterial therapy. Despite the high efficiency, inadequate prescription of antibiotics leads to an increase in microorganisms resistance. In light of these matters, the selection of antibacterial agents to which the sensitivity of bacteria is the highest is becoming increasingly challenging., Aim: To estimate the spectrum and local sensitivity of E. coli in patients with AULUTI., Materials and Methods: The present study analyzed the results of bacterial culture sampled from 45 patients with AULUTI. The mean age of the patients was 44+/-17 years. All bacterial cultures were obtained in out-patient settings in the framework of a multicenter initiative study on the prevention of recurrent AULUTI with d-mannose., Results: Microbiological studies of the urine of patients with AULUTI revealed the growth of E. coli in concentrations ranging from 104 to 107 CFU/ml. Assessment of sensitivity demonstrated 100% sensitivity of Escherichia coli to fosfomycin trometamol., Conclusion: According to the findings of microbiological studies, the patients with the AULUTI retain the highest sensitivity level of E.coli to phosphomycin trometamol, which allows it to be used as a first-line drug.

No single analgesic provides effective pain relief in all patients and increasing the dose of an analgesic may increase its unwanted effects.1 In addition, pain frequently results from multiple mechanisms that may respond to different pharmacological interventions.2 One suggested approach is to combine analgesics with different modes of action, with the aim of delivering better analgesia using lower doses of each drug.1 Skudexa (A. Menarini Farmaceutica Internazionale SRL), a combination of tramadol hydrochloride (a synthetic opioid analgesic that is a partial agonist at the μ, δ and κ opioid receptors) and dexketoprofen (a NSAID), is licensed for short term treatment of moderate to severe acute pain in adults.1-4 Here, we consider the evidence for this product and how it fits with current guidance on the management of pain., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Nanoparticulate systems have been receiving a significant attention especially for the treatment of cancer but one of the main hurdles is to produce these developed and high-tech nanosystems in large quantities. Anticancer drug formulations are generally designed for parenteral administrations but oral administration is still the most convenient route. In this study, orally applicable nano-sized chitosan nanoparticles (NPs) were successfully prepared using Nano Spray Dryer. It is possible to produce these NPs in large quantities by simply increasing the processing time using the machine without changing any parameter. A chemotherapeutic agent (imatinib mesylate; IMA) and nonsteroidal anti-inflammatory drug (dexketoprofen trometamol) were loaded together in these NPs. NPs were also functionalized with polyethylene glycol and folic acid to obtain long circulating NPs and tumor targeting. The antitumoral activities of formulations showed that these developed NPs can enhance the effectiveness. Animal experiments were performed on fibrosarcoma-bearing mice model, and the treatment with 0.8 mg/μL/kg IMA-loaded chitosan NPs was found to be successful to slow down the growth of tumors. The tumor tissues were removed from the animals and enzymatic activities were evaluated. The inhibitory effect of tyrosine kinase was found to be enhanced from 36.4% to 68.4% when IMA was used in combination with dexketoprofen trometamol. Furthermore, all dried NPs were found to be stable for more than a year at 25°C. Presented results show that these developed combinatorial drug-loaded NPs can be used for the treatment of fibrosarcoma, and these data can provide an insight, new strategies for productions or alternatives in cancer treatment., (Copyright © 2018 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

Post-Market Research Clinical evidence supports the use of dexketoprofen trometamol (DEX) to manage acute postoperative pain. However, controversies surround the impact of the use of this drug in preoperative analgesic protocols. The aim of the present meta-analysis was to evaluate the effectiveness of the preoperative administration of DEX under postoperative pain conditions. Electronic and manual searches were conducted through diverse electronic databases. A systematic review and meta-analysis to evaluate the analgesic efficacy of the preoperative administration of DEX was performed including Randomized Clinical Trials (RCTs) published between 2002 and 2017. Suitable individual studies were evaluated through a quality system, and the data were extracted and analyzed. Fourteen RTCs were included (12 parallel trials and 2 cross-over trials), published in the English and Turkish languages. Follow-up periods ranged from 4, 6, 8, 24, and 48 hr. All trials measured the outcome result as Acute Pain Level (APL) (VAS, NRS, VRS), time to requiring a second dose of DEX or analgesic emergency and consumption of opioids via patient-controlled analgesia. When the comparators were other drugs - paracetamol, Lornoxicam or placebo during the preoperative time, preoperative administration of DEX was superior. When the comparison comprised preoperative and postoperative DEX, both alternatives exhibited comparable analgesic effects. The analgesic efficacy of the preoperative administration of DEX when compared to placebo, lornoxicam, and paracetamol on postoperative pain was evident. Preoperative administration of DEX compared to its immediate postoperative administration showed a similar analgesic effect., (© 2017 Wiley Periodicals, Inc.)

Objective: This study compares the efficacy in post-operative pain control of the intraarticular catheter compared to the epidural catheter after primary total knee arthroplasty., Material and Method: Randomised clinical trial consisting of two groups of patients. A control group with intradural anaesthesia and an intraoperative epidural catheter (ropivacaine) and an intervention group using the same anaesthetic technique and an intraarticular catheter with an elastomeric pump (ropivacaine+dexketoprofen). Data such as demographic, anaesthetic and surgical variables, pain intensity according to Verbal Rating Scale, opioid use and complications, joint balance, onset of walking and hospital stay were recorded., Results: A lower incidence and severity on Verbal Rating Scale and a better control of postoperative pain (p<.0014) were observed in the intervention group. Joint balance also presented significant results in flexion and 74% of these patients started walking before the first 36h and the control group had not yet done so. Regarding patient satisfaction, 54.1% of the patients were "very satisfied" with the use of the catheter (p>.001). Finally, the hospital stay decreased significantly, with 33.3% of intervention group patients discharged within the first 48h compared to none of the control group., Discussion and Conclusions: The use of the intraarticular catheter as postoperative analgesia is a useful and safe alternative. It reduces the possibility of side effects. It helps in early improvement of joint balance, onset of walking and control of pain. All of which increase patient satisfaction and result in a shorter period of hospitalisation., (Copyright © 2017 SECOT. Publicado por Elsevier España, S.L.U. All rights reserved.)

Introduction: This randomized, controlled, Phase III non-inferiority clinical trial aimed to determine whether herbal therapy with Canephron® N (BNO 1045) is non-inferior to fosfomycin trometamol (FT) in treating acute lower uncomplicated urinary tract infections (uUTIs)., Materials and Methods: Women aged 18-70 years with typical symptoms of newly diagnosed acute lower uUTIs were randomized to BNO 1045 (n = 325) or FT (n = 334), with corresponding matched placebo. The primary endpoint was the proportion of patients who received additional antibiotics (ABs) to treat uUTIs between Days 1 and 38 ±3., Results: Between Days 1 and 38, 238 (83.5%) patients in the BNO 1045 group and 272 (89.8%) patients in the FT group received no additional ABs. At a 15% non-inferiority margin, BNO 1045 was non-inferior to FT in treating uUTIs (non-AB rate difference: -6.26%; 95% CI -11.99 to -0.53%; 2-sided p = 0.0014). Adverse event rates were similar between groups, with higher rates of gastrointestinal disorders in the FT group and pyelonephritis in the BNO 1045 group. During the trial, no patient died or discontinued due to a treatment-related adverse event., Conclusions: BNO 1045 has the potential to reduce outpatient use of ABs for uUTIs and thus may have a significant impact on antimicrobial stewardship strategies., Trial Registration: NCT02639520, EudraCT number 2013-004529-99., (The Author(s). Published by S. Karger AG, Basel.)

Background: Non-steroidal anti-inflammatory drugs (NSAIDs) may act through others mechanisms, in addition to inhibition of prostaglandin synthesis. These includes cholinergic, NO, serotonergic and opioids pathways., Methods: The aim of this work was to evaluate the effect of systemic action of (S)-+-ketoprofen (dexketoprofen, DEX) on pain behaviors using the orofacial formalin test in mice and the potential involvement of cholinergic, NO, serotonergic and opioids pathways., Results: The pretreatment of the mice with 1mg/kg ip of atropine or opoid antagonists: 1mg/kg, ip of NTX or 1mg/kg ip of NTI or 1mg/kg of NOR-BNI ip, did not produce significant change in the ED 50 values of the antinociception to orofacial test induced by DEX. The pretreatment of the mice with 0.5mg/kg ip tropisetron, increased in a significant fashion the values of ED 50 of DEX. When the mice were treated with 5mg/kg ip of L-NAME or 25mg/kg ip of aminoguanidine or 50mg/kg ip of 7-nitroindazole reversed the antinociception of DEX., Conclusion: The findings of this study demonstrate activation of NO and 5-HTpathways play important roles in the systemic antinociceptive effect of DEX in a murine model of inflammatory pain., (Copyright © 2016. Published by Elsevier Urban & Partner Sp. z o.o.)

Migraine is a common neurovascular disorder, affecting millions of people worldwide. Current guidelines recommend triptans as first-line treatment for moderate-to-severe migraine attacks. Frovatriptan is a second-generation triptan with a longer terminal elimination half-life in blood than other triptans (~26 hours). Three double-blind, randomized crossover preference studies have been recently conducted, assessing efficacy and safety of frovatriptan versus rizatriptan, zolmitriptan, and almotriptan, respectively. Frovatriptan showed favorable tolerability and sustained effect, with a significantly lower rate of relapse over 48 hours versus the other triptans. These findings were confirmed in a series of analyses of patient subsets from the three studies, including patients with menstrually related and oral contraceptive-induced migraine, hypertension, obesity, weekend migraine, as well as patients with migraine with aura. In all patient subsets analyzed, lower headache recurrence rates were observed versus the comparator triptans, indicating a more sustained pain-relieving effect on migraine symptoms. A further randomized, double-blind study demonstrated that frovatriptan given in combination with the fast-acting cyclooxygenase inhibitor dexketoprofen provided improved migraine pain-free activity at 2 hours, and gave more sustained pain-free activity at 24 hours, versus frovatriptan alone. These benefits were observed both when the combination was administered early (<1 hour after symptom onset) or late (>1 hour after onset). Different pharmacokinetic, but synergistic, properties between frovatriptan and dexketoprofen may make the combination of these agents particularly effective in migraine treatment, with rapid onset of action and sustained effect over 48 hours. These benefits, together with potential cost-effectiveness advantages versus other triptans could drive selection of the most appropriate treatment for acute migraine attacks., Competing Interests: Both authors have occasionally served as scientific consultants for manufacturers of frovatriptan. The authors report no other conflicts of interest in this work.

Study Objective: The aim of this study is to compare the effects of intravenous single-dose dexketoprofen trometamol and diclofenac sodium 30 minutes before the end of the surgery on relief of postoperative pain in patients undergoing laparoscopic cholecystectomy., Design: A randomized fashion., Setting and Patients: Sixty (American Society of Anesthesiologist class I-II) patients undergoing laparoscopic cholecystectomy were divided into 2 groups, Intervention: Patients in group DT received 50 mg dexketoprofen trometamol, whereas patients in group DS received 75 mg diclofenac sodium, intravenously 30 minutes before the end of surgery., Measurements: Postoperative pain intensity, morphine consumption with patient-controlled analgesia, time to first analgesic requirement, complications, rescue analgesic (intravenous tenoxicam 20 mg) requirement, and duration of hospital stay were recorded., Main Results: Postoperative pain visual analog scale scores were similar in the follow-up periods (P > .05). Patient-controlled analgesia morphine consumption was significantly less in group DT compared with group DS in all postoperative follow-up periods (2 and 4 hours: P < .01; 8, 12, 18, and 24 hours: P < .001). In the postoperative period, the first analgesic requirement time was significantly longer in group DT compared with group DS (P < .01). In addition, the number of patients requiring rescue analgesic was higher in group DS compared with group DT (P < .01). Other follow-up parameters were similar., Conclusion: In our study, administration of intravenous single-dose dexketoprofen trometamol 30 minutes before the end of surgery provided effective analgesia with reduced consumption of opioids and requirement for rescue analgesic compared with diclofenac sodium in patients undergoing laparoscopic cholecystectomy. For this reason, we believe that, as a part of multimodal analgesia, dexketoprofen trometamol provides more effective analgesia than diclofenac sodium in patients undergoing laparoscopic cholecystectomy., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: This study is designed to investigate the effect of three different analgesics, used to treat pain in AP, on oxidative stress, DNA damage in mononuclear leukocytes, and on oxidative status., Methods: This parallel design randomized controlled trial is composed of three treatment arms, intravenous paracetamol, intravenous dexketoprofen, and intravenous tramadol., Results: A total of 107 patients were diagnosed with acute pancreatitis within the study period in the ED. Seventyseven of them were included in the study; 26 patients for the paracetamol group, 24 patients for the dexketoprofen group, and 27 patients for the tramadol group. The mean age of study subjects was 52.73 ± 15.38 and 66% (n = 51) of them were men. At the beginning of the study (before treatment), mean levels of DNA damage, TOS, and OSI levels were significantly higher and TAS was significantly lower in the acute pancreatitis groups than in the control group. DNA damage and OSI in HAPS-positive patients were found to be significantly greater than HAPS-negative patients (p = 0.046). DNA damage and oxidative stress were compared between the three groups. There were no differences between the groups in terms of DNA damage (p = 0.42) and also for the oxidatif stress parameters (OSI,TAS,TOS had p-values of p = 0.26, p = 0.78, p = 0.35, respectively)., Conclusions: There is no difference between the effects of paracetamol, dexketoprofen, and tramadol, which are commonly used to manage acute pain in AP, on DNA damage in human T-lymphocytes and on serine parameters of oxidative status.

We report 2 cases of recurrent Campylobacter coli enteritis caused by macrolide- and fluoroquinolone-resistant strains in 2 patients with hypogammaglobulinemia, successfully treated with a prolonged course of fosfomycin-tromethamine with no side effects. Fosfomycin-tromethamine may be a feasible alternative therapy for recurrent enteritis caused by Campylobacter species resistant to first-line drugs., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)

Thirty-two dogs were used in this prospective, randomized, clinical and double-blinded study. Dexmedetomidine was administered at 1 μg/kg IV, and randomly each dog received dexketoprofen 1 mg/kg IV (group DK) or methadone 0.2 mg/kg IV (group M). Dogs were induced with propofol and maintained with isoflurane in 100% oxygen. During surgery, the isoflurane concentration was changed depending on clinical signs of depth of anesthesia. Fentanyl and propofol could be used as required. Qualities of sedation and recovery were evaluated. A generalized linear mixed model or Mann-Whiney U test was used, and P<0.05 was considered statistically significant. No significant differences were observed between groups in the qualities of sedation and recovery, isoflurane concentration and in the total amount of fentanyl and propofol used intraoperatively. This study shows that the administration of dexketoprofen at 1 mg/kg IV at premedication required a similar isoflurane concentration to maintain anesthesia as methadone at 0.2 mg/kg IV during orthopedic surgery in dogs. Further analgesia is recommended intraoperatively, because of the need of fentanyl and propofol in same animals in both groups., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Objective: To determine whether dexketoprofen administered by phonophoresis or iontophoresis is more effective for the treatment of subacromial impingement syndrome (SIS) than conventional ultrasound therapy., Design: Randomised clinical trial., Setting: University hospital., Participants: Ninety-nine participants with SIS without a complete tear of the rotator cuff were assigned at random to three intervention groups., Intervention Groups: Participants received ultrasound (n=32), phonophoresis with dexketoprofen (50mg/session) (n=33) or iontophoresis with dexketoprofen (50mg/session) (n=34). All participants completed 20 treatment sessions plus exercise therapy and cryotherapy., Outcome Measures: A visual analogue scale (VAS), the Constant-Murley Scale (CMS) and the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire were administered pre-treatment (baseline), post-treatment and 1 month post-treatment., Results: At baseline, there were no differences between the groups. Post-treatment, VAS score improved by -1.2 points and CMS score improved by 8.9 points in the ultrasound group compared with the iontophoresis group [95% confidence interval (CI) -0.2 to -2.2 and 95% CI 17.0 to 0.7, respectively]. CMS score improved by 7.1 points in the phonophoresis group compared with the iontophoresis group (95% CI 14.8 to -0.7). At 1 month post-treatment, no significant differences were detected between the groups. VAS, CMS and DASH scores of all groups improved post-treatment and at 1 month post-treatment., Conclusion: Ultrasound, iontophoresis with dexketoprofen and phonophoresis with dexketoprofen can improve pain, shoulder function, and physical functioning and symptoms in the upper limb in patients with SIS without a complete tear of the rotator cuff. CLINICAL TRIALS., Gov Registration Number: NCT01748188., (Copyright © 2015 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.)

Background: The aim was to evaluate the analgesic efficacy and safety of the dexketoprofen/tramadol 25 mg/75 mg fixed-dose combination vs dexketoprofen (25 mg) and tramadol (100 mg) in moderate-to-severe acute pain after total hip arthroplasty., Methods: This was a randomized, double-blind, parallel-group study in patients experiencing pain of at least moderate intensity on the day after surgery, compared with placebo at first administration to validate the pain model. The study drug was administered orally every 8 h throughout a 5 day period. Rescue medication, metamizole 500 mg, was available during the treatment period. The evaluation of efficacy was based on patient assessments of pain intensity and pain relief. The primary end point was the mean sum of the pain intensity difference values throughout the first 8 h (SPID8)., Results: Overall, 641 patients, mean age 62 (range 29-80) yr, were analysed; mean (sd) values of SPID8 were 247 (157) for dexketoprofen/tramadol, 209 (155) for dexketoprofen, 205 (146) for tramadol, and 151 (159) for placebo. The primary analysis confirmed the superiority of the combination over dexketoprofen 25 mg (P=0.019; 95% confidence interval 6.4-73) and tramadol 100 mg (P=0.012; 95% confidence interval 9.5-76). The single components were superior to placebo (P<0.05), confirming model sensitivity. Most secondary analyses supported the superiority of the combination. The incidence of adverse drug reactions was low and similar among active treatment groups., Conclusion: The efficacy results confirmed the superiority of dexketoprofen/tramadol over its single components, even at higher doses (tramadol), with a safety profile fully in line with that previously known for these agents in monotherapy., Clinical Trial Registration: EudraCT 2012-004548-31 (https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract&#95;number:2012-004548-31);ClinicalTrials.gov NCT01902134 (https://www.clinicaltrials.gov/ct2/show/NCT01902134?term=NCT01902134&rank=1)., (© The Author 2016. Published by Oxford University Press on behalf of the British Journal of Anaesthesia.)

Objective: Migraine is a leading headache etiology that frequently presents to the emergency department (ED). In the present study, we aimed to determine the efficacy of dexketoprofen in aborting migraine headaches in the ED., Methods: This prospective, randomized, double-blind study was conducted in an ED of a tertiary care hospital using allocation concealment. Patients were allocated into two arms to receive the study drug; 50 mg dexketoprofen in 50 ml saline and 50 ml saline as placebo. Change in pain intensity was measured by the visual analog scale at baseline, both at 30 and 45 minutes after the study medication was administered. Rescue medication requirement and pain relapse were also recorded by a telephone follow-up at 48 hours., Results: A total of 224 patients (112 in each group) were included into the final analysis. Mean age of the study participants was 37 ± 11 (SD) and 25% (n = 56) of them were male. The median pain improvement at 45 minutes for patients receiving dexketoprofen was 55 (IQR: 49 to 60) and 30 (IQR: 25 to 35) for those receiving placebo. The mean difference between the two groups at 45 minutes was 21.4 (95% CI: 14.4. to 28.5). Rescue drugs were needed in 22.3% of patients who received dexketoprofen compared to 55.4% in patients who received placebo (dif: 33.1%; 95% CI: 20% to 45%). There were no adverse events reported in either group during the study period., Conclusion: Intravenous dexketoprofen is superior to placebo in relieving migraine headaches in the ED. It may be a suitable therapy with minimum side effects in patients presenting with a migraine headache to the ED., (© International Headache Society 2015.)

Purpose: The effect of a single-dose of pre-emptive pregabalin is still unknown, although it is used as an adjuvant in controlling acute postoperative pain. The purpose of this study was to evaluate the effects of pre-emptive single-dose pregabalin on postoperative acute pain and 24-hour opioid consumption in patients who underwent double-jaw surgery., Patients and Methods: Forty patients (18 to 45 yr old; American Society of Anesthesiologists status I to II) for whom elective double-jaw surgery was planned under general anesthesia were included in this study, which had been planned as a prospective, randomized, and double-blinded study. Patients were randomly divided into 2 groups: the pregabalin group (n = 20) was given pregabalin 150 mg orally 1 hour before general anesthesia and the placebo group (n = 20) was given an oral placebo capsule. The groups were administered the routine general anesthesia protocol. Postoperative analgesia was performed intravenously in the 2 groups twice a day with dexketoprofen trometamol 50 mg and patient-controlled analgesia with fentanyl. Postoperative analgesia was evaluated using the visual analog scale (VAS). Fentanyl consumption, additional analgesia requirement, and side-effects were recorded during the first 24 hours after surgery. Descriptive and bivariate statistics were computed, and significance was set at a P value less than .05., Results: Compared with placebo, the VAS score was statistically lower in the pregabalin group during the early postoperative period (P < .05). The 24-hour opioid consumption was significantly higher in the placebo group compared with the pregabalin group (509.40 ± 261.56 vs. 260.10 ± 246.53 μq, respectively; P = .004). In addition, the analgesia requirement was statistically lower in the pregabalin group (P < .05). Nausea or vomiting was observed more often in the placebo group, whereas other side-effects were similar for the 2 groups., Conclusion: A single 150-mg dose of pre-emptive pregabalin decreased postoperative opioid consumption in the first 24 hours after double-jaw surgery. Multimodal analgesia techniques that contain pre-emptive analgesia can be used successfully in preventing postoperative pain caused by orthognathic surgery., (Copyright © 2016 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Introduction: Low tidal volume (VT) ventilation is recommended in patients with acute respiratory distress syndrome (ARDS). This may increase arterial carbon dioxide tension (PaCO2), decrease pH, and augment pulmonary vascular resistance (PVR). We hypothesized that Tris(hydroxymethyl)aminomethane (THAM), a pure proton acceptor, would dampen these effects, preventing the increase in PVR., Methods: A one-hit injury ARDS model was established by repeated lung lavages in 18 piglets. After ventilation with VT of 6 ml/kg to maintain normocapnia, VT was reduced to 3 ml/kg to induce hypercapnia. Six animals received THAM for 1 h, six for 3 h, and six serving as controls received no THAM. In all, the experiment continued for 6 h. The THAM dosage was calculated to normalize pH and exhibit a lasting effect. Gas exchange, pulmonary, and systemic hemodynamics were tracked. Inflammatory markers were obtained at the end of the experiment., Results: In the controls, the decrease in VT from 6 to 3 ml/kg increased PaCO2 from 6.0±0.5 to 13.8±1.5 kPa and lowered pH from 7.40±0.01 to 7.12±0.06, whereas base excess (BE) remained stable at 2.7±2.3 mEq/L to 3.4±3.2 mEq/L. In the THAM groups, PaCO2 decreased and pH increased above 7.4 during the infusions. After discontinuing the infusions, PaCO2 increased above the corresponding level of the controls (15.2±1.7 kPa and 22.6±3.3 kPa for 1-h and 3-h THAM infusions, respectively). Despite a marked increase in BE (13.8±3.5 and 31.2±2.2 for 1-h and 3-h THAM infusions, respectively), pH became similar to the corresponding levels of the controls. PVR was lower in the THAM groups (at 6 h, 329±77 dyn∙s/m(5) and 255±43 dyn∙s/m(5) in the 1-h and 3-h groups, respectively, compared with 450±141 dyn∙s/m(5) in the controls), as were pulmonary arterial pressures., Conclusions: The pH in the THAM groups was similar to pH in the controls at 6 h, despite a marked increase in BE. This was due to an increase in PaCO2 after stopping the THAM infusion, possibly by intracellular release of CO2. Pulmonary arterial pressure and PVR were lower in the THAM-treated animals, indicating that THAM may be an option to reduce PVR in acute hypercapnia.

Various drugs are known to cause pill esophagitis. Antimicrobial drugs and nonsteroidal anti-inflammatory drugs are the most common causes of pill-induced esophagitis. Most patients suffer only self-limiting pain, but serious complications can occur. A 21-year-old man was admitted to our outpatient clinic with retrosternal chest pain, dysphagia, and odynophagia complaints, which occurred within 2 weeks after starting dexketoprofen trometamol. An upper endoscopy system examination revealed three well-demarcated ulcers in the esophagus at 35 cm from the incisors. Dexketoprofen trometamol may cause esophageal lesions. This rare disorder should be considered in patients presenting with sudden-onset retrosternal pain in addition to dysphagia and odynophagia.

Objectives: The relationship between epilepsy and inflammation is known, and it has been reported that there is an increase in cyclooxygenase (COX) levels in epilepsy. We aim to reveal the anticonvulsant effects of dexketoprofen in pentylenetetrazol (PTZ)-induced seizures in rats., Materials and Methods: Forty-eight male Sprague-Dawley rats, 24 of them for EEG recording and 24 of them are for behavioral studies, were randomly divided in two groups: Group A for EEG recordings and Group B for behavioral assessment. A weight of 70 mg/kg PTZ was used for behavioral studies after dexketoprofen administration. Thirty-five milligrams per kilogram PTZ were used for EEG recording after dexketoprofen administration. The electrodes were implanted on dura over the left frontal cortex and the reference electrode was implanted over the cerebellum for EEG recording. The Racine convulsion scale (RCS), first myoclonic jerk (FMJ) onset time, and spike percentages were evaluated between the two groups., Results: There was a significant (P< 0·05) difference between the RCS, FMJ onset time (P< 0·001), and spike percentage (P< 0·05) between the groups (Group 2 compared with Groups 3 and 4)., Conclusion: Dexketoprofen has an antiepileptic feature and this effect increases as the dosage increases, however it is currently unknown through which mechanism this drug shows its anticonvulsant effect. Dexketoprofen, in the group of NSAIDs, shows an anticonvulsant effect on PTZ-induced epilepsy model. This study suggests that dexketoprofen can preferably be used with NSAIDs for epileptic patients in clinical practice.

Frovatriptan is a triptan characterized by a high affinity for 5-HT1B/1D receptors and a long half-life contributing to a more sustained and prolonged action than other triptans. Dexketoprofen is a nonsteroidal anti-inflammatory drug with a relatively short half-life and rapid onset of action, blocking the action of cyclo-oxygenase, which is involved in prostaglandins' production, thus reducing inflammation and pain. Both drugs have been successfully employed as monotherapies for the treatment of acute migraine attacks. The combination of these two drugs (frovatriptan 2.5 mg plus dexketoprofen 25 or 37.5 mg) has been tested in migraine sufferers, showing a rapid and good initial efficacy, with 2-h pain free rates of 51%, and a high persistence in the 48-h following the onset of pain: recurrence occurred in only 29% of attacks and sustained pain free rates were 43% at 24- and 33% at 48-h.

In this study, the analgesic effects of dexketoprofen trometamol and meperidine hydrochloride were compared in patients diagnosed with renal colic. This study was a prospective, randomized, double-blind study. Fifty-two patients, between the ages of 18 and 70 years who were diagnosed with renal colic, were enrolled in the study after obtaining ethics committee approval. Before drug injection, dexketoprofen trometamol and meperidine hydrochloride were placed in closed envelopes, and the patients were randomly given a single dose of intravenous infusion for 20 minutes. Severity of pain and symptoms was evaluated with the numerical rating scale and renal colic symptom score for each patient immediately before administration of drugs and 30 minutes after the end of the application. At the same time, systolic arterial blood pressure, diastolic arterial pressure, respiratory rate, heart rate, nausea, vomiting, and reactions due to drug administration were recorded before and after drug administration. In statistical methods, t test, analysis of variance, and repeated measure analysis were used for the analysis of normally distributed continuous variables and the Mann-Whitney U, Kruskal-Wallis and Friedman tests were used for analysis of not-normally distributed continuous variables. In the analysis of discrete variables, the χ test was used. In both groups, a significant decrease was found in numerical rating scale values measured 30 minutes after drug administration, but the decline in dexketoprofen trometamol group (P = 0.02) was found to be more. Although a significant decrease was found in the renal colic symptom score (P < 0.001) values measured after drug administration in the dexketoprofen trometamol group, no significant decrease was found in the meperidine HCl (P = 0.058) group. After drug administration, a statistically significant decrease was found in the systolic arterial blood pressure, heart rate, and respiratory rate in both groups. Also, a statistically significant decrease was found in the diastolic arterial pressure in the meperidine group. But these changes in vital findings were not serious enough to disrupt patients' clinical status. With this study, we concluded that dexketoprofen trometamol, from the nonsteroidal anti-inflammatory drug group, can be within the primary treatment options for renal colic because of better analgesic efficacy, being well tolerated by patients compared with meperidine hydrochloride.

Rocuronium is a non-depolarizing neuromuscular blocking agent which is associated with injection pain and induces withdrawal movement of the injected hand or arm or generalized movements of the body after intravenous injection. The aim of this randomized study was to compare the efficacy of pretreatment with oral dexketoprofen trometamol (Arvelles(®); Group A) with placebo (Group P) without tourniquet to prevent the withdrawal response caused by rocuronium injection. The study cohort comprised 150 American Society of Anaesthesiologists class I-III patients aged 18-75 years who were scheduled to undergo elective surgery with general anesthesia. The patients response to rocuronium was graded using a 4-point scale [0 = no response; 1 = movement/withdrawal at the wrist only, 2 = movement/withdrawal involving the arm only (elbow/shoulder); 3 = generalized response]. The overall incidence of withdrawal movement after rocuronium injection was significantly lower in Group A (30.1 %) than in Group P (64.6 %) (p < 0.001). The incidence of score 0 withdrawal movements was higher in Group A (69.9 %) than in Group P (35.4 %), that of score 1 withdrawal movements was similar between groups (Group A 21.9 %; Group B 26.1 %) (p = 0.560) and that of score 2 withdrawal movements was lower in Group A (8.2 %) than in Group P (38.5 %) (p < 0.001). There were no score 3 withdrawal movements in either group (p > 0.05). These results demonstrate that the preemptive administration of dexketoprofen trometamol can attenuate the degree of withdrawal movements caused by the pain of the rocuronium injection.

Early triptan use after headache onset may help improve the efficacy of acute migraine treatment. This may be particularly the case when triptan therapy is combined with a nonsteroidal anti-inflammatory drug (NSAID). The objective of this is to assess whether the combination of frovatriptan 2.5 mg + dexketoprofen 25 or 37.5 mg (FroDex25 and FroDex37.5) is superior to frovatriptan 2.5 mg alone (Frova) in the acute treatment of migraine attacks in patients who took the drug within 30 min from the onset of pain (early use) or after (late use). A total of 314 subjects with a history of migraine with or without aura were randomized into a double-blind, multicenter, parallel group, pilot study to Frova, FroDex25 or FroDex37.5 and were required to treat at least one migraine attack. In the present post hoc analysis, traditional migraine endpoints were compared across study drugs for subgroups of the 279 patients of the full analysis set according to early (n = 172) or late (n = 107) drug use. The proportion of patients pain free at 2 h in the early drug use subgroup was 33 % with Frova, 50 % with FroDex25 and 51 % with FroDex37.5 mg (p = NS combinations vs. monotherapy), while in the late drug use subgroup was 22, 51 and 50 % (p < 0.05 FroDex25 and FroDex37.5 vs. Frova), respectively. Pain-free episodes at 4 h were 54 % for early and 34 % for late use of Frova, 71 and 57 % with FroDex25 and 74 and 68 % with FroDex37.5 (p < 0.05 for early and p < 0.01 for late use vs. Frova). The proportion of sustained pain free at 24 h was 26 % under Frova, 43 % under FroDex25 mg and 40 % under FroDex37.5 mg (p = NS FroDex25 or 37.5 vs. Frova) in the early drug intake subgroup, while it was 19 % under Frova, 43 % under FroDex25 mg and 45 % under FroDex37.5 mg (p < 0.05 FroDex25 and FroDex37.5 vs. Frova) in the late drug intake subgroup. Risk of relapse at 48 h was similar (p = NS) among study drug groups (Frova: 25 %, FroDex25: 21 %, and FroDex37.5: 37 %) for the early as well as for the late drug use subgroup (14, 42 and 32 %). FroDex was found to be more effective than Frova taken either early or late. The intrinsic pharmacokinetic properties of the two single drug components made FroDex combination particularly effective within the 2-48-h window from the onset of the acute migraine attack. The efficacy does not seem to be influenced by the time of drug use relative to the onset of headache.

A randomised controlled trial was conducted to investigate efficacy of paracetamol and dexketoprofen trometamol for perineal pain relief after perineal repair. Subjects were randomly assigned to receive two doses of either 50 mg of intravenous dexketoprofen trometamol via slow i.v. infusion (Group I, n = 49) or 1,000 mg of paracetamol via intravenous infusion (Group II, n = 46). The main outcome measure was a VAS (visual analogue scale) for pain recorded at 1 h (VAS 1). A total of 82 patients were included in the final analysis (Group I, n = 41; Group II, n = 41). There was no difference among groups in terms of pain scores at the beginning (VAS 0). The pain was decreased in 70% of the patients in Group I and in 62% of the patients in Group II (p = 0.502). Both paracetamol and dexketoprofen are effective in perineal pain relief after episiotomy or perineal tear repair.