Combinations of QT-prolonging drugs: towards disentangling pharmacokinetic and pharmaco-dynamic effects in their potentially additive nature.

Background: Whether arrhythmia risks will increase if drugs with electrocardiographic (ECG) QT-prolonging properties are combined is generally supposed but not well studied. Based on available evidence, the Arizona Center for Education and Research on Therapeutics (AZCERT) classification defines the risk of QT prolongation for exposure to single drugs. We aimed to investigate how combining AZCERT drug categories impacts QT duration and how relative drug exposure affects the extent of pharmacodynamic drug–drug interactions. Methods: In a cohort of 2558 psychiatric inpatients and outpatients, we modeled whether AZCERT class and number of coprescribed QT-prolonging drugs correlates with observed rate-corrected QT duration (QTc) while also considering age, sex, inpatient status, and other QTc-prolonging risk factors. We concurrently considered administered drug doses and pharmacokinetic interactions modulating drug clearance to calculate individual weights of relative exposure with AZCERT drugs. Because QTc duration is concentration-dependent, we estimated individual drug exposure with these drugs and included this information as weights in weighted regression analyses. Results: Drugs attributing a ‘known’ risk for clinical consequences were associated with the largest QTc prolongations. However, the presence of at least two versus one QTc-prolonging drug yielded nonsignificant prolongations [exposure-weighted parameter estimates with 95% confidence intervals for ‘known’ risk drugs + 0.93 ms (–8.88;10.75)]. Estimates for the ‘conditional’ risk class increased upon refinement with relative drug exposure and coadministration of a ‘known’ risk drug as a further risk factor. Conclusions: These observations indicate that indiscriminate combinations of QTc-prolonging drugs do not necessarily result in additive QTc prolongation and suggest that QT prolongation caused by drug combinations strongly depends on the nature of the combination partners and individual drug exposure. Concurrently, it stresses the value of the AZCERT classification also for the risk prediction of combination therapies with QT-prolonging drugs

Composition-structure-property relationships of commercial polyurethane foams for mattresses

Three commercial flexible polyurethane foams used for mattress have been submitted to chemical-physical analyses, water vapor permeability and compression mechanical tests, in order to understand the relationships among their composition, structure, and some functional properties of interest for bedding applications. The results demonstrated that all the three foams have open cell morphology and similar cell structure, with average cell diameters ranging from 430 to 510 micron and wide cell size distribution. As a consequence, they also show comparable water vapor transport behavior. On the contrary, their mechanical response, in terms of hysteresis loss, surface firmness and resistance to bottoming out, was found strongly dependent on their chemical structure and molecular mobility, as inferred from infrared spectroscopy analysis

Disuse osteoporosis and hip prosthesis: Surgical implications, a case report

In this paper, the authors present a case of osteo-arthtritis of the hip secondary to a septic event which was surgically treated with a hip prosthesis and complicated by intraoperative fracture due to a localized disuse osteoporosis. Disuse osteoporosis is an induced rapid bone loss in human skeleton that occurs mostly after a cord injury or muscle paralysis. Hypodynamia can also be a risk factor for osteoporosis. In this case the author describe the onset of a femoral intraoperative fragility fracture in a 58 year old woman affected by an erosive septic osteoarthritis. Our case suggest that disuse osteoporosis presence should be diagnosed and treated before surgery to help prevent major surgical or post-operative complications beginning a pharmacological antiresorptive treatment before the surge

TiO2 nanocrystals grafted on macroporous silica: A novel hybrid organic–inorganic sol–gel approach for the synthesis of highly photoactive composite material

TiO2–SiO2 composite materials with photocatalytic properties similar to those of slurry powdered TiO2 is obtained by a novel sol–gel synthetic strategy involving the hydrolysis/condensation of TMOS assisted by PEG as templating agent and the grafting of preformed titania nanocrystals onto the macropore walls of the silica matrix. In order to anchor TiO2 particles to the surface of SiO2, avoiding their embedding into silica matrix, functionalization with carboxylic acid or amine derivatives was carried out. The functionalization induces the confinement of titania nanocrystals in PEG, during the silica formation, and allows their dispersion on the silica surface. TiO2–SiO2 materials exhibit high thermal and chemical stability and a photocatalytic activity in the phenol mineralization comparable to that of powder TiO2 in slurry (half degradation time 120 min). These results suggest that the immobilization procedure here reported provides high accessibility of the catalyst active sites preserving the functional properties of the photoactive catalyst