A cost-effectiveness analysis of caspofungin vs. liposomal amphotericin B for treatment of suspected fungal infections in the UK

Objective: To evaluate the cost-effectiveness of caspofungin vs. liposomal amphotericin B in the treatment of suspected fungal infections in the UK.Methods: The cost-effectiveness of caspofungin vs. liposomal amphotericin B was evaluated using a decision-tree model. The decision tree was populated using both data and clinical definitions from published clinical studies. Model outcomes included success in terms of resolution of fever, baseline infection, absence of breakthrough infection, survival and quality adjusted life years (QALYs) saved. Discontinuation due to nephrotoxicity or other adverse events were included in the model. Efficacy and safety data were based on additional analyses of a randomised, double blind, multinational trial of caspofungin compared with liposomal amphotericin B. Information on life expectancy, quality of life, medical resource consumption and costs were obtained from peer-reviewed published data.Results: The caspofungin mean total treatment cost was £9762 (95% uncertainty interval 6955–12 577), which was £2033 (−2489; 6779) less than liposomal amphotericin B. Treatment with caspofungin resulted in 0.40 (−0.12; 0.94) additional QALYs saved in comparison with liposomal amphotericin B. Probabilistic sensitivity analysis found a 95% probability of the incremental cost per QALY saved being within the generally accepted threshold for cost-effectiveness (£30 000). Additional analyses with varying dose of caspofungin and liposomal amphotericin B confirmed these findings.Conclusion: Given the underlying assumptions, caspofungin is cost-effective compared with liposomal amphotericin B in the treatment of suspected fungal infections in the UK.<br/

Dallas with balls: televized sport, soap opera and male and female pleasures

Two of the most popular of television genres, soap opera and sports coverage have been very much differentiated along gender lines in terms of their audiences. Soap opera has been regarded very much as a 'gynocentric' genre with a large female viewing audience while the audiences for television sport have been predominantly male. Gender differentiation between the genres has had implications for the popular image of each. Soap opera has been perceived as inferior; as mere fantasy and escapism for women while television sports has been perceived as a legitimate, even edifying experience for men. In this article the authors challenge the view that soap opera and television sport are radically different and argue that they are, in fact, very similar in a number of significant ways. They suggest that both genres invoke similar structures of feeling and sensibility in their respective audiences and that television sport is a 'male soap opera'. They consider the ways in which the viewing context of each genre is related to domestic life and leisure, the ways in which the textual structure and conventions of each genre invoke emotional identification, and finally, the ways in which both genres re-affirm gender identities

New data on wild grey mullet (mugil cephalus linnaeus, 1758) myxosporean (myxobolus episquamalis egusa et al., 1990) in the black sea

Flathead grey mullet, Mugil cephalus, with mass whitish cystlike plasmodia on their scales were collected at Kerchensky preglass of the Black Sea in 2015. The prevalence of infected fish varied from 15% in spring, reached 100% in summer, and declined to 2.5% in autumn. No fish mortality was detected. The spores were oval in frontal view, tapering to a blunt apex. Two unequal polar capsules were pyriform and extended over the anterior half of spore. Spores were 8.2\ub10.03 \u3bcm (7.9-8.4) long, 5.9\ub10.23 \u3bcm (5.2-7.3) wide, and 4.4\ub10.17 \u3bcm (4.0-4.7) thick. Two pyriform and unequal polar capsules were observed (4.0\ub10.07 \u3bcm (3.3-4.5) long, and 1.5\ub10.24 \u3bcm (1.1-1.8) wide). The investigation of nucleotide sequences of the 18S rDNA gene of the myxosporean spores from scales with universal primer A (5\u2032-ACCTGGTTGATCCTGCCAGT-3\u2032) and B (5\u2032-TGATCCTTCTGCAGGTTCACCTAC-3\u2032) showed 100% identity with episquamalis, and 99 % with M. bizerti, M. ichkeulensis, M. spinacurvata and Myxobolus sp. previously detected in mullets. The results obtained from the present study reveal that M. episquamalis, found on the scales of M. cephalus from Kerchensky preglass of the Black Sea, is new record for Russian waters

Enantiomeric conformation controls rate and yield of photoinduced electron transfer in DNA sensitized by Ru(II) Dipyridophenazine complexes

Photosensitized oxidation of guanine is an important route to DNA damage. Ruthenium polypyridyls are very useful photosensitizers as their reactivity and DNA-binding properties are readily tunable. Here we show a strong difference in the reactivity of the two enantiomers of [Ru(TAP)2(dppz)]2+, by using time-resolved visible and IR spectroscopy. This reveals that the photosensitized one-electron oxidation of guanine in three oligonucleotide sequences proceeds with similar rates and yields for bound delta-[Ru(TAP)2(dppz)]2+, whereas those for the lambda enantiomer are very sensitive to base sequence. It is proposed that these differences are due to preferences of each enantiomer for different binding sites in the duplex

Monitoring guanine photo-oxidation by enantiomerically resolved Ru(II) dipyridophenazine complexes using inosine-substituted oligonucleotides

The intercalating [Ru(TAP)2(dppz)]2+ complex can photo-oxidise guanine in DNA, although in mixed-sequence DNA it can be difficult to understand the precise mechanism due to uncertainties in where and how the complex is bound. Replacement of guanine with the less oxidisable inosine (I) base can be used to understand the mechanism of electron transfer (ET). Here the ET has been compared for both L- and D-enantiomers of [Ru(TAP)2(dppz)]2+ in a set of sequences where guanines in the readily oxidisable GG step in {TCGGCGCCGA}2 have been replaced with I. The ET has been monitored using picosecond and nanosecond transient absorption and ps-time-resolved IR spectroscopy. In both cases inosine replacement leads to a diminished yield, but the trends are strikingly different for L- and D-complexes

Hahn-Steinthal fracture: a case report

Isolated fracture of the capitellum is rare. We present clinical and radiological data on a single case of a fracture of capitellum. We came across a 31 year old woman who sustained an isolated Hahn Steinthal type of fracture. It was treated operatively by open reduction and internal fixation using mini fragment screws. The elbow was immobilized for 4 weeks. The patient regained full range of movement at 12 weeks post operatively. We reiterate that anatomical reduction and fixation is the right way to treat this injury

Reversal of a single base pair step controls guanine photo-oxidation by an intercalating Ru(II) dipyridophenazine complex

Small changes in DNA sequence can often have major biological effects. Here the rates and yields of guanine photo-oxidation by Λ [Ru(TAP)2(dppz)]2+ have been compared in 5′-{CCGGATCCGG}2 and 5′-{CCGGTACCGG}2 using ps/ns transient visible and time-resolved IR (TRIR) spectroscopy. The inefficiency of electron transfer in the TA sequence is consistent with the 5′-TA-3′ vs. 5′-AT-3′ binding preference predicted by X-ray crystallography. The TRIR spectra also reveal the differences in binding sites in the two oligonucleotides

Inosine can increase DNA's susceptibility to photo-oxidation by a Ru(II) complex due to structural change in the minor groove

Key to the development of DNA-targeting phototherapeutic drugs is determining the interplay between the photoactivity of the drug and its binding preference for a target sequence. For the photo- oxidising lambda-[Ru(TAP)2(dppz)]2+ (Ʌ-1) complex bound to either d{T1C2G3G4C5G6C7C8G9A10}2 (G9) or d{TCGGCGCCIA}2 (I9), the X- ray crystal structures shows the dppz intercalated at the terminal T1C2;G9A10 step or T1C2;I9A10 step. Thus substitution of the G9 nucleobase by inosine does not affect intercalation in the solid state although with I9 the dppz is more deeply inserted. In solution it is found that the extent of guanine photo-oxidation, and the rate of back electron transfer, as determined by ps and ns time-resolved infrared and transient visible absorption spectroscopy, is enhanced in I9, despite it containing the less oxidisable inosine. This is attributed to the nature of the binding in the minor groove due to the absence of an NH2 group. Similar behaviour and the same binding site in the crystal.are found for d{TTGGCGCCAA}2 (A9), In solution we propose that intercalation occurs at the C2G3;C8I9 or T2G3;C8A9 steps, respectively, with G3 the likely target for photo-oxidation. This demonstrates how changes in the minor groove (in this case removal of an NH2 group) can facilitate binding of Ru(II)dppz complexes and hence influence any sensitised reactions occurring at these sites. No similar enhancement of photooxidation on binding to I9 is found for the delta enantiomer

Direct observation by time-resolved infrared spectroscopy of the bright and the dark excited states of the [Ru(phen)2(dppz)]2+ light-switch compound in solution and when bound to DNA

The [Ru(phen)2(dppz)]2+ complex (1) is non-emissive in water but is highly luminescent in organic solvents or when bound to DNA, making it a useful probe for DNA binding. To date, a complete mechanistic explanation for this “light-switch” effect is still lacking. With this in mind we have undertaken an ultrafast time resolved infrared (TRIR) study of 1 and directly observe marker bands between 1280–1450 cm-1, which characterise both the emissive “bright” and the non-emissive “dark” excited states of the complex, in CD3CN and D2O respectively. These characteristic spectral features are present in the [Ru(dppz)3]2+ solvent light-switch complex but absent in [Ru(phen)3]2+, which is luminescent in both solvents. DFT calculations show that the vibrational modes responsible for these characteristic bands are predominantly localised on the dppz ligand. Moreover, they reveal that certain vibrational modes of the “dark” excited state couple with vibrational modes of two coordinating water molecules, and through these to the bulk solvent, thus providing a new insight into the mechanism of the light-switch effect. We also demonstrate that the marker bands for the “bright” state are observed for both L- and D enantiomers of 1 when bound to DNA and that photo-excitation of the complex induces perturbation of the guanine and cytosine carbonyl bands. This perturbation is shown to be stronger for the L enantiomer, demonstrating the different binding site properties of the two enantiomers and the ability of this technique to determine the identity and nature of the binding site of such intercalators