We compared the pharmacokinetic (PK) profiles of co-crystal of tramadol-celecoxib (CTC) vs. each reference product (alone and in open combination) after single (first dose) and multiple dosing.

The effect of the use of immunomodulatory drugs on the risk of developing hospital-acquired bloodstream infection (BSI) in patients with COVID-19 has not been specifically assessed. We aim to identify risk factors for, and outcomes of, BSI among hospitalized patients with severe COVID-19 pneumonia.

The profiles of patients with COVID-19 have been widely studied, but little is known about differences in baseline characteristics and in outcomes between subjects with a ceiling of care assigned at hospital admission and subjects without a ceiling of care. The aim of this study is to compare, by ceiling of care, clinical features and outcomes of hospitalized subjects during four waves of COVID-19 in a metropolitan area in Catalonia.

Opioids are the most effective painkillers, but their benefit-risk balance often hinder their therapeutic use. WLB-73502 is a dual, bispecific compound that binds sigma-1 (S1R) and mu-opioid (MOR) receptors. WLB-73502 is an antagonist at the S1R. It behaved as a partial MOR agonist at the G-protein pathway and produced no/unsignificant β-arrestin-2 recruitment, thus demonstrating low intrinsic efficacy on MOR at both signalling pathways. Despite its partial MOR agonism, WLB-73502 exerted full antinociceptive efficacy, with potency superior to morphine and similar to oxycodone against nociceptive, inflammatory and osteoarthritis pain, and superior to both morphine and oxycodone against neuropathic pain. WLB-73502 crosses the blood-brain barrier and binds brain S1R and MOR to an extent consistent with its antinociceptive effect. Contrary to morphine and oxycodone, tolerance to its antinociceptive effect did not develop after repeated 4-week administration. Also, contrary to opioid comparators, WLB-73502 did not inhibit gastrointestinal transit or respiratory function in rats at doses inducing full efficacy, and it was devoid of proemetic effect (retching and vomiting) in ferrets at potentially effective doses. WLB-73502 benefits from its bivalent S1R antagonist and partial MOR agonist nature to provide an improved antinociceptive and safety profile respect to strong opioid therapy.

Individuals with IPF who follow a MUFA diet report a lower incidence of pirfenidone gastrointestinal adverse events than those that follow a SFA diet, which could explain the different prevalence in GI pirfenidone AEs reported by countries in IPF cohorts https://bit.ly/3LuzAUJ

Treatment failure occurs in about 25% of patients with methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia. We assessed whether cloxacillin plus fosfomycin achieves better treatment success than cloxacillin alone in hospitalized adults with MSSA bacteremia. We conducted a multicenter, open-label, phase III-IV superiority randomized clinical trial. We randomly assigned patients (1:1) to receive 2 g of intravenous cloxacillin alone every 4 h or with 3 g of intravenous fosfomycin every 6 h for the initial 7 days. The primary endpoint was treatment success at day 7, a composite endpoint with the following criteria: patient alive, stable or with improved quick Sequential Organ Failure Assessment score, afebrile and with negative blood cultures for MSSA, adjudicated by an independent committee blinded to treatment allocation. We randomized 215 patients, of whom 105 received cloxacillin plus fosfomycin and 110 received cloxacillin alone. We analyzed the primary endpoint with the intention-to-treat approach in 214 patients who received at least 1 day of treatment. Treatment success at day 7 after randomization was achieved in 83 (79.8%) of 104 patients receiving combination treatment versus 82 (74.5%) of 110 patients receiving monotherapy (risk difference 5.3%; 95% confidence interval (CI), -5.95-16.48). Secondary endpoints, including mortality and adverse events, were similar in the two groups except for persistent bacteremia at day 3, which was less common in the combination arm. In a prespecified interim analysis, the independent committee recommended stopping recruitment for futility prior to meeting the planned randomization of 366 patients. Cloxacillin plus fosfomycin did not achieve better treatment success at day 7 of therapy than cloxacillin alone in MSSA bacteremia. Further trials should consider the intrinsic heterogeneity of the infection by using a more personalized approach. ClinicalTrials.gov registration: NCT03959345 .

This trial assessed the efficacy of MR309 (a novel selective sigma-1 receptor ligand previously developed as E-52862) in ameliorating oxaliplatin-induced peripheral neuropathy (oxaipn). A discontinuous regimen of MR309 (400 mg/day, 5 days per cycle) was tested in patients with colorectal cancer receiving FOLFOX in a phase II, randomized, double-blind, placebo-controlled, multicenter clinical trial. Outcome measures included changes in 24-week quantitative measures of thermal sensitivity and total neuropathy score. In total, 124 patients were randomized (1:1) to MR309 or placebo. Sixty-three (50.8%) patients withdrew prematurely before completing 12 planned oxaliplatin cycles. Premature withdrawal because of cancer progression was less frequent in the MR309 group (7.4% vs 25.0% with placebo; p = 0.054). MR309 significantly reduced cold pain threshold temperature [mean treatment effect difference (SE) vs placebo: 5.29 (1.60)°C; p = 0.001] and suprathreshold cold stimulus-evoked pain intensity [mean treatment effect difference: 1.24 (0.57) points; p = 0.032]. Total neuropathy score, health-related quality-of-life measures, and nerve-conduction parameters changed similarly in both arms, whereas the proportion of patients with severe chronic neuropathy (National Cancer Institute Common Terminology Criteria for Adverse Events ≥ 3) was significantly lower in the MR309 group (3.0% vs 18.2% with placebo; p = 0.046). The total amount of oxaliplatin delivered was greater in the active arm (1618.9 mg vs 1453.8 mg with placebo; p = 0.049). Overall, 19.0% of patients experienced at least 1 treatment-related adverse event (25.8% and 11.9% with MR309 and placebo, respectively). Intermittent treatment with MR309 was associated with reduced acute oxaipn and higher oxaliplatin exposure, and showed a potential neuroprotective role for chronic cumulative oxaipn. Furthermore, MR309 showed an acceptable safety profile.

An increased fracture risk has been described as a complication of Type 2 diabetes mellitus (T2DM). Clinical prediction models for general population have a limited predictive accuracy for fractures in T2DM patients. The aim was to develop and validate a clinical prediction tool for the estimation of 5-year hip and major fracture risk in T2DM patients.

No abstract available

Stenosis is one of the most common complications in patients with Crohn's disease (CD). Endoscopic balloon dilation (EBD) is the treatment of choice for a short stenosis adjacent to the anastomosis from previous surgery. Self-expandable metal stents (SEMS) may be a suitable treatment option for longer stenoses. To date, however, there is no scientific evidence as to whether endoscopic (EBD/SEMS) or surgical treatment is the best approach for de novo or primary stenoses that are less than 10 cm in length.

Co-crystal of tramadol-celecoxib (CTC) is a novel co-crystal molecule containing two active pharmaceutical ingredients under development by Esteve (E-58425) and Mundipharma Research (MR308). This Phase I study compared single-dose pharmacokinetics (PK) of CTC with those of the individual reference products [immediate-release (IR) tramadol and celecoxib] alone and in open combination.

Acute cardiac events (ACEs) are increasingly being recognized as a major complication in pneumococcal community-acquired pneumonia (CAP). Information regarding host- and pathogen-related factors for ACEs, including pneumococcal serotypes and clonal complexes, is scarce.

Alzheimer's disease and its complications are the leading cause of death in adults with Down syndrome. Studies have assessed Alzheimer's disease in individuals with Down syndrome, but the natural history of biomarker changes in Down syndrome has not been established. We characterised the order and timing of changes in biomarkers of Alzheimer's disease in a population of adults with Down syndrome.

Enflicoxib is a non-steroidal anti-inflammatory drug of the coxib family characterized by a long-lasting pharmacological activity that has been attributed to its active metabolite E-6132.

COVID-19 infection is associated with a higher mortality rate in surgical patients, but surgical risk scores have not been validated in the emergency setting. We aimed to study the capacity for postoperative mortality prediction of the P-POSSUM score in COVID-19-positive patients submitted to emergency general and digestive surgery.

Staphylococcus aureus bloodstream infection (SABSI) arising from a urinary tract source (UTS) is poorly understood.

We investigated whether the difference of antigen tube 2 (TB2) minus antigen tube 1 (TB1) (TB2-TB1) of the QuantiFERON-TB gold plus test, which has been postulated as a surrogate for the CD8+ T-cell response, could be useful in identifying recent tuberculosis (TB) exposure. We looked at the interferon gamma (IFN-γ) responses and differences in TB2 and TB1 tubes for 686 adults with QFT-plus positive test results. These results were compared among groups with high (368 TB contacts), low (229 patients with immune-mediated inflammatory diseases [IMID]), and indeterminate (89 asylum seekers or people from abroad [ASPFA]) risks of recent TB exposure. A TB2-TB1 value >0.6 IU·ml-1 was deemed to indicate a true difference between tubes. In the whole cohort, 13.6%, 10.9%, and 11.2% of cases had a TB2>TB1 result in the contact, IMID, and ASPFA groups, respectively (P = 0.591). The adjusted odds ratios (aORs) for an association between a TB2-TB1 result of >0.6 IU·ml-1 and risk of recent exposure versus contacts were 0.71 (95% confidence interval [CI], 0.31 to 1.61) for the IMID group and 0.86 (95% CI, 0.49 to 1.52) for the ASPFA group. In TB contact subgroups, 11.4%, 15.4%, and 17.7% with close, frequent, and sporadic contact had a TB2>TB1 result (P = 0.362). The aORs versus the close subgroup were 1.29 (95% CI, 0.63 to 2.62) for the frequent subgroup and 1.55 (95% CI, 0.67 to 3.60) for the sporadic subgroup. A TB2-TB1 difference of >0.6 IU·ml-1 was not associated with increased risk of recent TB exposure, which puts into question the clinical potential as a proxy marker for recently acquired TB infection. IMPORTANCE Contact tuberculosis tracing is essential to identify recently infected people, who therefore merit preventive treatment. However, there are no diagnostic tests that can determine whether the infection is a result of a recent exposure or not. It has been suggested that by using the QuantiFERON-TB gold plus, an interferon gamma (IFN-γ) release assay, a difference in IFN-γ production between the two antigen tubes (TB2 minus TB1) of >0.6 IU·ml-1 could serve as a proxy marker for recent infection. In this large multinational study, infected individuals could not be classified according to the risk of recent exposure based on differences in IFN-γ in TB1 and TB2 tubes that were higher than 0.6 IU·ml-1. QuantiFERON-TB gold plus is not able to distinguish between recent and remotely acquired tuberculosis infection, and it should not be used for that purpose in contact tuberculosis tracing.

Surgical site infection (SSI) is one of the most frightening complications after surgery. Adhesive drapes (AD) are widely used as an infection prevention tool. They can be non-impregnated or iodophor-impregnated, although non-impregnated are less used as they might be related to higher number of infections. One of the most common ways to study their efficacy is by analyzing the intraoperative contamination, which is a useful primary endpoint as it does not need follow-up and it has been strongly associated with infections. Therefore, we believe a systematic review (SR) and meta-analysis is needed to determine which is the literature available about this topic and to explore their results.