The incidence and nature of in-hospital adverse events: a systematic review

INTRODUCTION: Adverse events in hospitals constitute a serious problem with grave consequences. Many studies have been conducted to gain an insight into this problem, but a general overview of the data is lacking. We performed a systematic review of the literature on in-hospital adverse events. METHODS: A formal search of Embase, Cochrane and Medline was performed. Studies were reviewed independently for methodology, inclusion and exclusion criteria and endpoints. Primary endpoints were incidence of in-hospital adverse events and percentage of preventability. Secondary endpoints were adverse event outcome and subdivision by provider of care, location and type of event. RESULTS: Eight studies including a total of 74 485 patient records were selected. The median overall incidence of in-hospital adverse events was 9.2%, with a median percentage of preventability of 43.5%. More than half (56.3%) of patients experienced no or minor disability, whereas 7.4% of events were lethal. Operation- (39.6%) and medication-related (15.1%) events constituted the majority. We present a summary of evidence-based interventions aimed at these categories of events. CONCLUSIONS: Adverse events during hospital admission affect nearly one out of 10 patients. A substantial part of these events are preventable. Since a large proportion of the in-hospital events are operation- or drug-related, interventions aimed at preventing these events have the potential to make a substantial differenc

Heating mechanisms in radio frequency driven ultracold plasmas

Several mechanisms by which an external electromagnetic field influences the temperature of a plasma are studied analytically and specialized to the system of an ultracold plasma (UCP) driven by a uniform radio frequency (RF) field. Heating through collisional absorption is reviewed and applied to UCPs. Furthermore, it is shown that the RF field modifies the three body recombination process by ionizing electrons from intermediate high-lying Rydberg states and upshifting the continuum threshold, resulting in a suppression of three body recombination. Heating through collisionless absorption associated with the finite plasma size is calculated in detail, revealing a temperature threshold below which collisionless absorption is ineffective.Comment: 14 pages, 7 figure

Microbunching instability characterization via temporally modulated laser pulses

High-brightness electron bunches, such as those generated and accelerated in free-electron lasers (FELs), can develop small-scale structure in the longitudinal phase space. This causes variations in the slice energy spread and current profile of the bunch which then undergo amplification, in an effect known as the microbunching instability. By imposing energy spread modulations on the bunch in the low-energy section of an accelerator, using an undulator and a modulated laser pulse in the center of a dispersive chicane, it is possible to manipulate the bunch longitudinal phase space. This allows for the control and study of the instability in unprecedented detail. We report measurements and analysis of such modulated electron bunches in the 2D spectrotemporal domain at the Fermi FEL, for three different bunch compression schemes. We also perform corresponding simulations of these experiments and show that the codes are indeed able to reproduce the measurements across a wide spectral range. This detailed experimental verification of the ability of codes to capture the essential beam dynamics of the microbunching instability will benefit the design and performance of future FELs

Microbunching instability characterization via temporally modulated laser pulses

High-brightness electron bunches, such as those generated and accelerated in free-electron lasers (FELs), can develop small-scale structure in the longitudinal phase space. This causes variations in the slice energy spread and current profile of the bunch which then undergo amplification, in an effect known as the microbunching instability. By imposing energy spread modulations on the bunch in the low-energy section of an accelerator, using an undulator and a modulated laser pulse in the centre of a dispersive chicane, it is possible tomanipulate the bunch longitudinal phase space. This allows for the control and study of the instability in unprecedented detail. We report measurements and analysis of such modulated electron bunches in the 2Dspectro-temporal domain at the FERMI FEL, for three different bunch compression schemes. We also perform corresponding simulations of these experiments and show that the codes are indeed able to reproduce the measurements across a wide spectral range. This detailed experimental verification of the ability of codes to capture the essential beam dynamics of the microbunching instability will benefit the design and performance of future FELs

Paclitaxel alters the expression and specific activity of deoxycytidine kinase and cytidine deaminase in non-small cell lung cancer cell lines

<p>Abstract</p> <p>Background</p> <p>We observed that paclitaxel altered the pharmacokinetic properties of gemcitabine in patients with non-small cell lung cancer (NSCLC) and limited the accumulation of gemcitabine and its metabolites in various primary and immortalized human cells. Therefore, we classified the drug-drug interaction and the effects of paclitaxel on deoxycytidine kinase (dCK) and cytidine deaminase (CDA) in three NSCLC cell lines. These enzymes are responsible for the metabolism of gemcitabine to its deaminated metabolite dFdU (80% of the parent drug) and the phosphorylated metabolites dFdCMP, dFdCDP and dFdCTP. These metabolites appear to relate to sensitivity and tolerability of gemcitabine based on previous animal and laboratory studies.</p> <p>Methods</p> <p>Three immortalized human cells representative of the most common histological subtypes identified in patients with advanced NSCLC were exposed to the individual drugs or combinations to complete a multiple drug effect analysis. These same cell lines were exposed to vehicle-control or paclitaxel and the mRNA levels, protein expression and specific activity of dCK and CDA were compared. Comparisons were made using a two-tailed paired t-test or analysis of variance with a P value of < 0.05 considered significant.</p> <p>Results</p> <p>The multiple drug effect analysis indicated synergy for H460, H520 and H838 cells independent of sequence. As anticipated, paclitaxel-gemcitabine increased the number of G2/M cells, whereas gemcitabine-paclitaxel increased the number of G0/G1 or S cells. Paclitaxel significantly decreased dCK and CDA mRNA levels in H460 and H520 cells (40% to 60%, P < 0.05) and lowered dCK protein (24% to 56%, P < 0.05) without affecting CDA protein. However, paclitaxel increased both dCK (10% to 50%) and CDA (75% to 153%) activity (P < 0.05). Paclitaxel caused substantial declines in the accumulation of the deaminated and phosphorylated metabolites in H520 cells (P < 0.05); the metabolites were not measurable in the remaining two cell lines. The ratio of dCK to CDA mRNA levels corresponded to the combination index (CI) estimated for sequential paclitaxel-gemcitabine.</p> <p>Conclusion</p> <p>In summary, paclitaxel altered the mRNA levels and specific activity of dCK and CDA and these effects could be dependent on histological subtype. More cell and animal studies are needed to further characterize the relationship between mRNA levels and the overall drug-drug interaction and the potential to use histological subtype as a predictive factor in the selection of an appropriate anticancer drug regimen.</p

Patient safety in elderly hip fracture patients: design of a randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>The clinical environment in which health care providers have to work everyday is highly complex; this increases the risk for the occurrence of unintended events. The aim of this randomised controlled trial is to improve patient safety for a vulnerable group of patients that have to go through a complex care chain, namely elderly hip fracture patients.</p> <p>Methods/design</p> <p>A randomised controlled trial that consists of three interventions; these will be implemented in three surgical wards in Dutch hospitals. One surgical ward in another hospital will be the control group. The first intervention is aimed at improving communication between care providers using the SBAR communication tool. The second intervention is directed at stimulating the role of the patient within the care process with a patient safety card. The third intervention consists of a leaflet for patients with information on the most common complications for the period after discharge. The primary outcome measures in this study are the incidence of complications and adverse events, mortality rate within six months after discharge and functional mobility six months after discharge. Secondary outcome measures are length of hospital stay, quality and completeness of information transfer and patient satisfaction with the instruments.</p> <p>Discussion</p> <p>The results will give insight into the nature and scale of complications and adverse events that occur in elderly hip fracture patients. Also, the implementation of three interventions aimed at improving the communication and information transfer provides valuable possibilities for improving patient safety in this increasing patient group. This study combines the use of three interventions, which is an innovative aspect of the study.</p> <p>Trial registration</p> <p>The Netherlands National Trial Register <a href="http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=1562">NTR1562</a></p

Vinflunine: a new active drug for second-line treatment of advanced breast cancer. Results of a phase II and pharmacokinetic study in patients progressing after first-line anthracycline/taxane-based chemotherapy

To evaluate the single agent activity, pharmacokinetics and tolerability of the novel tubulin targeted agent vinflunine (VFL) (320 mg m−2 q 21 days) as second-line chemotherapy in patients with metastatic breast carcinoma (MBC). All patients had disease progression after anthracycline/taxane (A/T) therapy. They could have received a nonanthracycline adjuvant treatment and subsequently received a first-line A/T combination for advanced/metastatic disease; or relapsed >6 months after completion of adjuvant A/T therapy and were subsequently treated with the alternative agent; or relapsed within 6 months from an adjuvant A/T combination. Objective response was documented in 18 of 60 patients enrolled (RR: 30% (95% confidence interval (CI): 18.9–43.2%)). Among the responders, seven patients had relapsed during a period of <3 months from taxane-based regimen yielding a RR of 33.3%. The median duration of response was 4.8 months (95% CI: 4.2–7.2), median progression-free survival was 3.7 months (95% CI: 2.8–4.2) and median overall survival was 14.3 months (95% CI: 9.2–19.6). The most frequent adverse event was neutropenia (grade 3 in 28.3% and grade 4 in 36.7% of patients). No febrile neutropenia was observed. Fatigue (grade 3 in 16.7% of patients) and constipation (grade 3 in 11.7% of patients) were also common; these were non-cumulative and manageable permitting achievement of a good relative dose intensity of 93.5%. Vinflunine is an active agent with acceptable tolerance in the management of MBC patients previously treated with (A/T)-based regimens. These encouraging phase II results warrant further investigation of this novel agent in combination with other active agents in this setting or in earlier stages of disease