International longitudinal registry of patients with atrial fibrillation and treated with rivaroxaban: RIVaroxaban Evaluation in Real life setting (RIVER)

Background Real-world data on non-vitamin K oral anticoagulants (NOACs) are essential in determining whether evidence from randomised controlled clinical trials translate into meaningful clinical benefits for patients in everyday practice. RIVER (RIVaroxaban Evaluation in Real life setting) is an ongoing international, prospective registry of patients with newly diagnosed non-valvular atrial fibrillation (NVAF) and at least one investigator-determined risk factor for stroke who received rivaroxaban as an initial treatment for the prevention of thromboembolic stroke. The aim of this paper is to describe the design of the RIVER registry and baseline characteristics of patients with newly diagnosed NVAF who received rivaroxaban as an initial treatment. Methods and results Between January 2014 and June 2017, RIVER investigators recruited 5072 patients at 309 centres in 17 countries. The aim was to enroll consecutive patients at sites where rivaroxaban was already routinely prescribed for stroke prevention. Each patient is being followed up prospectively for a minimum of 2-years. The registry will capture data on the rate and nature of all thromboembolic events (stroke / systemic embolism), bleeding complications, all-cause mortality and other major cardiovascular events as they occur. Data quality is assured through a combination of remote electronic monitoring and onsite monitoring (including source data verification in 10% of cases). Patients were mostly enrolled by cardiologists (n = 3776, 74.6%), by internal medicine specialists 14.2% (n = 718) and by primary care/general practice physicians 8.2% (n = 417). The mean (SD) age of the population was 69.5 (11.0) years, 44.3% were women. Mean (SD) CHADS2 score was 1.9 (1.2) and CHA2DS2-VASc scores was 3.2 (1.6). Almost all patients (98.5%) were prescribed with once daily dose of rivaroxaban, most commonly 20 mg (76.5%) and 15 mg (20.0%) as their initial treatment; 17.9% of patients received concomitant antiplatelet therapy. Most patients enrolled in RIVER met the recommended threshold for AC therapy (86.6% for 2012 ESC Guidelines, and 79.8% of patients according to 2016 ESC Guidelines). Conclusions The RIVER prospective registry will expand our knowledge of how rivaroxaban is prescribed in everyday practice and whether evidence from clinical trials can be translated to the broader cross-section of patients in the real world

Bacterial Nosocomial Pneumonia in Paediatric Intensive Care Unit

AIMS: To determine the incidence, risk factors, mortality and organisms causing nosocomial pneumonia (NP) in intubated patients in Paediatric Intensive Care Unit (PICU). Materials & Methods: All patients with endotracheal (ET) tube with or without mechanical ventilation (MV) in a PICU of a tertiary care teaching hospital were included in this prospective study. Clinical parameters and investigations were evaluated in patients who developed nosocomial pneumonia (NP). Colonisation of the ET tube tip was studied by culture and the antibiotic susceptibility pattern of the isolates was determined. Results: Sixty-nine patients had an ET tube inserted and fifty-nine of these underwent MV. ET tube tip colonisation was seen in 70 out of 88 ET tubes inserted. The incidence of NP in patients with ET tube was 27.54% (7.96/100 days of ET intubation). NP developed only in patients undergoing MV. The main risk factors for developing NP were - duration of MV and duration of stay in the PICU. Age, sex, immunocompromised status and altered sensorium did not increase the risk of NP. The mortality in cases with NP was 47.37%. E. coli and Klebsiella were the commonest organisms isolated from the ET tube tip cultures with maximum susceptibility to amikacin and cefotaxime. Conclusions: NP developed only in patients undergoing MV. Duration of MV and duration of stay in the PICU increased the risk of developing NP

Pre-transplant emotional support is associated with longer survival after allogeneic hematopoietic stem cell transplantation

Emerging evidence suggests that psychosocial factors pre-transplant predict survival in cancer patients undergoing hematopoietic stem cell transplantation (HSCT). These studies, however, typically have small sample sizes, short-term follow ups or a limited panel of medical covariates. We extend this research in a large, well-characterized sample of transplant patients, asking whether patients' perceived emotional support and psychological distress predict mortality over 2 years. Prior to transplant, 400 cancer patients (55.5% males; 82.8% White; M =50.0 years; 67.0% leukemia, 20.0% lymphoma) were interviewed by a social caseworker, who documented the patients' perceived emotional support and psychological distress. Subsequently, patients received an allogeneic HSCT (51.0% matched-related donor, 42.0% matched-unrelated donor and 7.0% cord blood). HSCT outcomes were obtained from medical records. Controlling for demographic characteristics (age, sex, race/ethnicity and marital status) and medical confounders (disease type, conditioning regimen, remission status, cell dosage, donor and recipient CMV seropositivity, donor sex, comorbidities and disease risk), ratings of good emotional support pre-transplant predicted longer overall survival (hazard ratio (HR)=0.61, 95% confidence interval (CI), 0.42-0.91; P=0.013). Pre-transplant psychological distress was unrelated to survival, however (Ps>0.58). Emotional support was marginally associated with lower rates of treatment-related mortality (HR=0.58, CI, 0.32-1.05; P=0.073). These findings are consistent with the hypothesis that emotional support contributes to better outcomes following HSCT. Future studies should examine whether intervention efforts to optimize emotional resources can improve survival in cancer patients

The influence of sodium carboxymethylcellulose on drug release from polyethylene oxide extended release matrices

Anionic polymer sodium carboxymethylcellulose (CELLOGEN® HP-HS and/or HP-12HS)was investigated for its ability to influence the release of three model drugs propranolol hydrochloride, theophylline and ibuprofen from polyethylene oxide (POLYOX™ WSR 1105 and/or Coagulant) hydrophilic matrices. For anionic ibuprofen and non-ionic theophylline, no unusual/unexpected release profiles were obtained from tablets containing a mixture of two polymers. However, for cationic propranolol HCl, a combination of polyethylene oxide (PEO) with sodium carboxymethylcellulose (NaCMC) produced a significantly slower drug release compared to the matrices with single polymers. The potential use of this synergistic interaction can be a design of new extended release pharmaceutical dosage forms with a more prolonged release (beyond 12 h) using lower polymer amount, which could be particularly beneficial for freely water-soluble drugs, preferably for once daily oral administration. In order to explain changes in the obtained drug release profiles, Fourier transform infrared absorption spectroscopy was performed. A possible explanation for the more prolonged propranolol HCl release from matrices based on both PEO and NaCMC may be due to a chemical bond(i.e. ionic/electrostatic intermolecular interaction) between amine group of the cationic drug and carboxyl group of the anionic polymer, leading to a formation of a new type/form of the active (i.e. salt) with sustained release pattern