Effectiveness of fosfomycin trometamol as oral step-down therapy for bacteraemic urinary tract infections due to MDR Escherichia coli: a post hoc analysis of the FOREST randomized trial.

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.

Intravenous lidocaine vs. NSAIDs for migraine attack in the ED: a prospective, randomized, double-blind study.

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.

The dienogest-related cystitis in women with endometriosis: a prospective, controlled, comparative study.

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 <103 CFU/ml without clinical symptoms of acute cystitis before treatment. The level of bacteriuria in-group I significantly increased from 102 to 106 CFU/ml whereas in-group II did not exceed 102 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 statementWhat 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.

[Rationale for choosing an antibiotic for the treatment of cystitis: recommendations of clinical pharmacologists: A review].

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.

Role of asymptomatic bacteriuria on early periprosthetic joint infection after hip hemiarthroplasty. BARIFER randomized clinical trial.

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.

The effectiveness of intradermal sterile water injection for low back pain in the emergency department: A prospective, randomized controlled study.

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.

New Drugs 2021, Part 2.

ABSTRACT: The second of a two-part series, this article describes eight recently approved drugs, including the first drug approved for the treatment of SARS-CoV-2, a first-in-class HIV attachment inhibitor, and a new intravenous injection indicated for the treatment of acute pain in adults for whom other treatments are ineffective.

Intradermal mesotherapy versus systemic therapy in the treatment of musculoskeletal pain: A prospective randomized study.

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.

Medical management of acute non-specific low back pain: comparison of different medical treatments, one center's retrospective analysis.

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.

Life satisfaction and pain interference in spine surgery patients before and after surgery: comparison between on-opioid and opioid-naïve patients.

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.

Non-Antibiotic Herbal Therapy (BNO 1045) versus Antibiotic Therapy (Fosfomycin Trometamol) for the Treatment of Acute Lower Uncomplicated Urinary Tract Infections in Women: A Double-Blind, Parallel-Group, Randomized, Multicentre, Non-Inferiority Phase III Trial.

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.

Analgesic efficacy of preoperative dexketoprofen trometamol: A systematic review and meta-analysis.

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.

Effect of carboprost tromethamine in prevention of postpartum hemorrhage in cesarean section.

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.

[Efficiency of fosfomycin trometamol for treatment of acute uncomplicated cystitis].

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.

[Issues of spectrum and local sensitivity of E. coli in female patients with acute uncomplicated lower urinary tract infection a review of M. Seitz study and own observations].

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.

Potential Use of Fosfomycin-Tromethamine for Treatment of Recurrent Campylobacter Species Enteritis.

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.

Intravenous dexketoprofen vs placebo for migraine attack in the emergency department: A randomized, placebo-controlled trial.

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.

Randomized clinical trial of dexketoprofen/tramadol 25 mg/75 mg in moderate-to-severe pain after total hip arthroplasty.

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_number:2012-004548-31);ClinicalTrials.gov NCT01902134 (https://www.clinicaltrials.gov/ct2/show/NCT01902134?term=NCT01902134&rank=1).

Oxidative Status and DNA Damage Following Analgesic Treatment in Patients with Acute Pancreatitis.

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.