Targeted therapies and adverse drug reactions in oncology: the role of clinical pharmacist in pharmacovigilance.

Background The majority of adverse drug reactions (ADRs) reported in the summary of product characteristics (SPCs) are based on pivotal clinical trials, performed under controlled conditions and with selected patients. Objectives (1) to observe ADRs in the real-world setting and to evaluate if the supervision of the pharmacist impacts on the management of ADRs and on the satisfaction of patients; (2) to sensitise health professionals and patients on the need to increase the reporting of ADRs, in compliance with Pharmacovigilance. Setting CRO Aviano, Italian National Cancer Institute. Method From February 2013 to April 2015, we conducted an observational study enrolling 154 patients (≥ 18 years) undergoing treatment with at least one of ten targeted-therapies included in the study. Main outcome ADR reporting in the real-world setting. Patient satisfaction with clinical pharmacist support. Results Reported ADRs in the real setting do not always correspond with data described in the respective SPCs. Unknown ADRs were also identified such as hyperglycaemia with lenalidomide and sorafenib; and hypomagnesaemia with bevacizumab. We also observed a 124.3% increase in spontaneous reports. Conclusion This study shows the high value of active pharmacovigilance programs, and our results might be a starting point for developing a randomised trial which should aim to demonstrate the impact of the pharmacist on improving patient's adherence and in measuring the difference in ADRs reports in the different arms followed or not by the pharmacist.

Nucleation and growth of epitaxial metal-oxide films based on polymer-assisted deposition.

Polymer-assisted deposition (PAD) is one of the chemical solution deposition methods which have been successfully used to grow films, form coatings, and synthesize nanostructured materials. In comparison with other conventional solution-based deposition techniques, PAD differs in its use of water-soluble polymers in the solution that prevent the metal ions from unwanted chemical reactions and keep the solution stable. Furthermore, filtration to remove non-coordinated cations and anions in the PAD process ensures well controlled nucleation, which enables the growth of high quality epitaxial films with desired structural and physical properties. The precursor solution is prepared by mixing water-soluble polymer(s) with salt(s). Thermal treatment of the precursor films in a controlled environment leads to the formation of desired materials. Using BaTiO3 grown on SrTiO3 and LaMnO3 on LaAlO3 as model systems, we show the effect of filtration on the nucleation and growth of epitaxial complex metal-oxide films based on the PAD process.

Modular instrument mounting system for variable environment in operando X-ray experiments.

In the growing field of in operando and in situ X-ray experiments, there exists a large disparity in the types of environments and equipment to control them. This situation makes it challenging to conduct multiple experiments with a single mechanical interface to the diffractometer. Here, we describe the design and implementation of a modular instrument mounting system that can be installed on a standard six-circle diffractometer (e.g., 5021 Huber GmbH). This new system allows for the rapid changeover of different chambers and sample heaters and permits accurate sample positioning (x, y, z, and azimuthal rotation) without rigid coupling to the chamber body. Isolation of the sample motion from the chamber enclosure is accomplished through a combination of custom rotary seals and bellows. Control of the pressure and temperature has been demonstrated in the ranges of 10(-6)-10(3) Torr and 25°C-900°C, respectively. We have utilized the system with several different modular instruments. As an example, we provide in situ sputtering results, where the growth dynamics of epitaxial LaGaO3 thin films on (001) SrTiO3 substrates were investigated.

Application of breast tomosynthesis in screening: incremental effect on mammography acquisition and reading time.

OBJECTIVE: The aim of this study was to supplement the paucity of information available on logistical aspects of the application of three-dimensional (3D) mammography in breast screening. METHODS: We prospectively examined the effect on radiographers' and radiologists' workload of implementing 3D mammography in screening by comparing image acquisition time and screen-reading time for two-dimensional (2D) mammography with that of combined 2D+3D mammography. Radiologists' accuracy was also calculated. RESULTS: Average acquisition time (measured from start of first-view breast positioning to compression release at completion of last view) for seven radiographers, based on 20 screening examinations, was longer for 2D+3D (4 min 3 s; range 3 min 53 s-4 min 18 s) than 2D mammography (3 min 13 s; range 3 min 0 s-3 min 26 s; p<0.01). Average radiologists' reading time per screening examination (three radiologists reading case-mix of 100 screens: 10 cancers, 90 controls) was longer for 2D+3D (77 s; range 60-90 s) than for 2D mammography (33 s; range 25-46 s; p<0.01). 2D+3D screen-reading was associated with detection of more cancers and with substantially fewer recalls than 2D mammography alone. CONCLUSION: Relative to standard 2D mammography, combined 2D+3D mammography prolongs image acquisition time and screen-reading time (at initial implementation), and appears to be associated with improved screening accuracy. ADVANCES IN KNOWLEDGE: These findings provide relevant information to guide larger trials of integrated 3D mammography (2D+3D) and its potential implementation into screening practice.

Laparoscopic partial nephrectomy with "on-demand" clamping reduces warm ischemia time.

OBJECTIVES: To investigate the impact of "on-demand" clamping during laparoscopic partial nephrectomy on warm ischemia time. METHODS: We retrospectively reviewed 39 consecutive patients with renal tumors who had undergone transperitoneal laparoscopic partial nephrectomy from April 2002 to May 2006. Median tumor size was 2.3 cm. In all cases, the hilum was dissected early and extracorporeal clamping performed. The pedicle was clamped only in case of excessive bleeding, and it was released immediately after the closure of the renal defect with knot-tying sutures over Surgicel bolsters. RESULTS: Median operative time was 120 min. Renal clamping was required in 31 of 39 patients and in this subgroup the median warm ischemia time was 9 min. Median operative blood loss was 150 ml. Eight patients required blood transfusion and among these two were converted to open surgery. Positive surgical margin was observed in one case. Renal cell carcinoma was present in 22 (54.4%) specimens. No recurrence was observed after a median follow-up of 15 mo. CONCLUSIONS: This novel technique using extracorporeal clamping significantly decreases warm ischemia time, avoiding clamping of the pedicle in selected cases. Our study underlines the feasibility of performing laparoscopic partial nephrectomy with extracorporeal hilar clamping, allowing the shortest ischemia time ever published.

Laparoscopic live donor right nephrectomy: a new technique to maximize the length of the renal vein using a modified Endo GIA stapler.

OBJECTIVES: To report the utilization of a modified Endo GIA vascular stapler to obtain the full length of the renal vein during transperitoneal laparoscopic live donor right nephrectomy. METHODS: We used a modified Endo GIA stapler, in which the triple staggered rows of staples were removed from the kidney donor side to obtain the full length of the right renal vein. This technique has currently been used in nine consecutive transperitoneal laparoscopic right donor nephrectomies. RESULTS: With this technique, the entire right renal vein length was harvested in all cases, without vascular complications. Mean renal warm ischemia time from clamping of the renal vessels to cold perfusion was 135s, and mean receptor postoperative glomerular filtration rate after 30 d was 67.3 ml/min. There were no graft losses. CONCLUSIONS: A novel technique for laparoscopic live donor right nephrectomy is described. It allows harvesting the full length of the right renal vein in a safe and feasible way without compromising warm ischemia time.

Antidepressants for patients with tinnitus.

BACKGROUND: Tinnitus is described as the perception of sound or noise in the absence of real acoustic stimulation. It has been compared with chronic pain, and may be associated with depression or depressive symptoms which can affect quality of life and the ability to work. Antidepressant drugs have been used to treat tinnitus in patients with and without depressive symptoms. OBJECTIVES: To assess the effectiveness of antidepressants in the treatment of tinnitus and to ascertain whether any benefit was due to a direct tinnitus effect or a secondary effect due to treatment of concomitant depressive states. SEARCH STRATEGY: We searched the Cochrane Ear, Nose and Throat Disorders Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) The Cochrane Library Issue 1, 2006); MEDLINE (January 1951 to 2006); EMBASE (1974 to 2006), CINAHL (to 2006), PSYCINFO (to 2006), LILACS (to 2006), and Cambridge Scientific Abstracts. The date of the most recent search was March 2006. SELECTION CRITERIA: Randomised controlled clinical studies of antidepressant drugs versus placebo in patients with tinnitus. DATA COLLECTION AND ANALYSIS: The studies retrieved were critically appraised and data extracted independently by two authors. Where necessary study authors were contacted for further information. MAIN RESULTS: Five trials involving 525 patients were included. Four of these trials looked at the effect of tricyclic antidepressants on tinnitus, investigating 405 patients. One trial investigated the effect of a selective serotonin reuptake inhibitor (SSRI) in a group of 120 patients. No trials involving other antidepressant agents met the inclusion criteria. Only the trial using the SSRI drug met the highest quality standard. None of the other included trials met the highest quality standard, due to use of inadequate outcome measures, large drop out rates or failure to separate the effects on tinnitus from the effects on symptoms of anxiety and depression. All the trials assessing tricyclic antidepressants suggested that there was a slight improvement in tinnitus but these effects may have been attributable to methodological bias. The trial that investigated the SSRI drug found no overall improvement in any of the validated outcome measures that were used in the study although there was possible benefit for a subgroup that received higher doses of the drug. This observation merits further investigation. Reports of side effects including sedation, sexual dysfunction and dry mouth were common. AUTHORS' CONCLUSIONS: There is insufficient evidence to say that antidepressant drug therapy improves tinnitus.

Cu2O island shape transition during Cu-Au alloy oxidation.

In situ transmission electron microscopy observations of the oxidation of (001) Cu-Au alloys indicate that the Cu2O islands that form undergo a remarkable transformation from an initially compact morphology to a dendritic structure as growth proceeds. Correspondingly, the surface composition becomes nonuniform and the fractal dimension associated with the islands evolves from 2.0 to a stable value of 1.87, indicating a transition in the rate-limiting mechanism of oxidation from oxygen surface diffusion to diffusion of copper through the increasingly gold-rich regions adjacent to the islands.

Origin of atomic clusters during ion sputtering.

Previous studies have shown that the size distributions of small clusters ( n < or = 40; n = number of atoms/cluster) generated by sputtering obey an inverse power law with an exponent between -8 and -4. Here we report electron microscopy studies of the size distributions of larger clusters ( n > or = 500) sputtered by high-energy ion impacts. These new measurements also yield an inverse power law, but one with an exponent of -2 and one independent of sputtering yield, indicating that the large clusters are produced when shock waves, generated by subsurface displacement cascades, ablate the surface.