Impact of high-cost drugs for individual patient use

To document and describe the individual patient use (IPU) scheme at St Vincent's Hospital, Sydney in terms of submissions and approvals and assess the financial impact of the scheme on the hospital drug expenditure. Method: All submissions for IPU approvals received between January 1997 and December 2001 were reviewed. Submissions were collected on a calendar year basis. Data collection and analysis included identification of approved medication and indication, off- label or approved indication, prescriber, ward, outcome of therapy, person deciding the approval, approval date duration and expiry, amount of medication dispensed and the cost of therapy. The annual cost and proportion of overall drug expenditure for each approval was calculated. Results: The number of approvals had a trend to increase each year. 67.1% of the IPU approvals were for off-label indications. Requested feedback on clinical outcomes was provided only in 18% of cases. The drug acquisition cost of the IPU scheme more than doubled in the period between 1999 and 2001. Similarly the proportion of the drug expenditure on IPU drugs increased significantly (p<0.001) from 1.6% in 1999 to 3.6% in 2001. Conclusion: The results indicated that the number of approvals and submissions for IPU had a tendency to increase. The financial impact of the IPU scheme increased over the years reviewed

Non-radial null geodesics in spherical dust collapse

The issue of the local visibility of the shell-focussing singularity in marginally bound spherical dust collapse is considered from the point of view of the existence of future-directed null geodesics with angular momentum which emanate from the singularity. The initial data (i.e. the initial density profile) at the onset of collapse is taken to be of class $C^3$. Simple necessary and sufficient conditions for the existence of a naked singularity are derived in terms of the data. It is shown that there exist future-directed non-radial null geodesics emanating from the singularity if and only if there exist future-directed radial null geodesics emanating from the singularity. This result can be interpreted as indicating the robustness of previous results on radial geodesics, with respect to the presence of angular momentum.Comment: 26 pages, 1 figur

A Characterisation of Strong Wave Tails in Curved Space-Times

A characterisation of when wave tails are strong is proposed. The existence of a curvature induced tail (i.e. a Green's function term whose support includes the interior of the light-cone) is commonly understood to cause backscattering of the field governed by the relevant wave equation. Strong tails are characterised as those for which the purely radiative part of the field is backscattered. With this definition, it is shown that electromagnetic waves in asymptotically flat space-times and fields governed by tail-free propagation have weak tails, but minimally coupled scalar fields in a cosmological scenario have strong tails.Comment: 17 pages, Revtex, to appear in Classical and Quantum Gravit

Co-designing drug alerts for health and community workers for an emerging early warning system in Victoria, Australia

Background: Alerts about changes in unregulated drug markets may be useful for supporting health and community workers to anticipate, prevent, and respond to unexpected adverse drug events. This study aimed to establish factors influencing the successful design and implementation of drug alerts for use in clinical and community service settings in Victoria, Australia. Methods: An iterative mixed methods design was used to co-produce drug alert prototypes with practitioners and managers working across various alcohol and other drug services and emergency medicine settings. A quantitative needs-analysis survey (n = 184) informed five qualitative co-design workshops (n = 31). Alert prototypes were drafted based on findings and tested for utility and acceptability. Applicable constructs from the Consolidated Framework for Implementation Research helped to conceptualise factors that impact successful alert system design. Results: Timely and reliable alerts about unexpected drug market changes were important to nearly all workers (98%) yet many reported insufficient access to this kind of information (64%). Workers considered themselves ‘conduits’ for information-sharing and valued alerts for increasing exposure to drug market intelligence; facilitating communication about potential threats and trends; and improving capacity for effective responding to drug-related harm. Alerts should be ‘shareable’ across a range of clinical and community settings and audiences. To maximise engagement and impact, alerts must command attention, be easily recognisable, be available on multiple platforms (electronic and printable formats) in varying levels of detail, and be disseminated via appropriate notification mechanisms to meet the needs of diverse stakeholder groups. Three drug alert prototypes (SMS prompt, summary flyer, and a detailed poster) were endorsed by workers as useful for supporting their work responding to unexpected drug-related harms. Discussion: Alerts informed by coordinated early warning networks that offer close to real-time detection of unexpected substances can provide rapid, evidence-based drug market intelligence to inform preventive and responsive action to drug-related harm. The success of alert systems requires adequate planning and resourcing to support design, implementation, and evaluation, which includes consultation with all relevant audiences to understand how to maximise engagement with information, recommendations, and advice. Our findings about factors impacting successful alert design have utility to inform the development of local early warning systems

Yang's gravitational theory

Yang's pure space equations (C.N. Yang, Phys. Rev. Lett. v.33, p.445 (1974)) generalize Einstein's gravitational equations, while coming from gauge theory. We study these equations from a number of vantage points: summarizing the work done previously, comparing them with the Einstein equations and investigating their properties. In particular, the initial value problem is discussed and a number of results are presented for these equations with common energy-momentum tensors.Comment: 28 pages, to appear in Gen. Rel. Gra

The Central Singularity in Spherical Collapse

The gravitational strength of the central singularity in spherically symmetric space-times is investigated. Necessary conditions for the singularity to be gravitationally weak are derived and it is shown that these are violated in a wide variety of circumstances. These conditions allow conclusions to be drawn about the nature of the singularity without having to integrate the geodesic equations. In particular, any geodesic with a non-zero amount of angular momentum which impinges on the singularity terminates in a strong curvature singularity.Comment: 17 pages; revised and corrected with improved result

Surprises in the Orbital Magnetic Moment and g-Factor of the Dynamic Jahn-Teller Ion C_{60}^-

We calculate the magnetic susceptibility and g-factor of the isolated C_{60}^- ion at zero temperature, with a proper treatment of the dynamical Jahn-Teller effect, and of the associated orbital angular momentum, Ham-reduced gyromagnetic ratio, and molecular spin-orbit coupling. A number of surprises emerge. First, the predicted molecular spin-orbit splitting is two orders of magnitude smaller than in the bare carbon atom, due to the large radius of curvature of the molecule. Second, this reduced spin-orbit splitting is comparable to Zeeman energies, for instance, in X-band EPR at 3.39KGauss, and a field dependence of the g-factor is predicted. Third, the orbital gyromagnetic factor is strongly reduced by vibron coupling, and so therefore are the effective weak-field g-factors of all low-lying states. In particular, the ground-state doublet of C_{60}^- is predicted to show a negative g-factor of \sim -0.1.Comment: 19 pages RevTex, 2 postscript figures include

Haemoglobin mass and running time trial performance after recombinant human erythropoietin administration in trained men

&lt;p&gt;Recombinant human erythropoietin (rHuEpo) increases haemoglobin mass (Hbmass) and maximal oxygen uptake (v˙ O2 max).&lt;/p&gt; &lt;p&gt;Purpose: This study defined the time course of changes in Hbmass, v˙ O2 max as well as running time trial performance following 4 weeks of rHuEpo administration to determine whether the laboratory observations would translate into actual improvements in running performance in the field.&lt;/p&gt; &lt;p&gt;Methods: 19 trained men received rHuEpo injections of 50 IUNkg21 body mass every two days for 4 weeks. Hbmass was determined weekly using the optimized carbon monoxide rebreathing method until 4 weeks after administration. v˙ O2 max and 3,000 m time trial performance were measured pre, post administration and at the end of the study.&lt;/p&gt; &lt;p&gt;Results: Relative to baseline, running performance significantly improved by ,6% after administration (10:3061:07 min:sec vs. 11:0861:15 min:sec, p,0.001) and remained significantly enhanced by ,3% 4 weeks after administration (10:4661:13 min:sec, p,0.001), while v˙ O2 max was also significantly increased post administration (60.765.8 mLNmin21Nkg21 vs. 56.066.2 mLNmin21Nkg21, p,0.001) and remained significantly increased 4 weeks after rHuEpo (58.065.6 mLNmin21Nkg21, p = 0.021). Hbmass was significantly increased at the end of administration compared to baseline (15.261.5 gNkg21 vs. 12.761.2 gNkg21, p,0.001). The rate of decrease in Hbmass toward baseline values post rHuEpo was similar to that of the increase during administration (20.53 gNkg21Nwk21, 95% confidence interval (CI) (20.68, 20.38) vs. 0.54 gNkg21Nwk21, CI (0.46, 0.63)) but Hbmass was still significantly elevated 4 weeks after administration compared to baseline (13.761.1 gNkg21, p&#60;0.001).&lt;/p&gt; &lt;p&gt;Conclusion: Running performance was improved following 4 weeks of rHuEpo and remained elevated 4 weeks after administration compared to baseline. These field performance effects coincided with rHuEpo-induced elevated v˙ O2 max and Hbmass.&lt;/p&gt

A review of the methodological features of systematic reviews in maternal medicine

Background In maternal medicine, research evidence is scattered making it difficult to access information for clinical decision making. Systematic reviews of good methodological quality are essential to provide valid inferences and to produce usable evidence summaries to guide management. This review assesses the methodological features of existing systematic reviews in maternal medicine, comparing Cochrane and non-Cochrane reviews in maternal medicine. Methods Medline, Embase, Database of Reviews of Effectiveness (DARE) and Cochrane Database of Systematic Reviews (CDSR) were searched for relevant reviews published between 2001 and 2006. We selected those reviews in which a minimum of two databases were searched and the primary outcome was related to the maternal condition. The selected reviews were assessed for information on framing of question, literature search and methods of review. Results Out of 2846 citations, 68 reviews were selected. Among these, 39 (57%) were Cochrane reviews. Most of the reviews (50/68, 74%) evaluated therapeutic interventions. Overall, 54/68 (79%) addressed a focussed question. Although 64/68 (94%) reviews had a detailed search description, only 17/68 (25%) searched without language restriction. 32/68 (47%) attempted to include unpublished data and 11/68 (16%) assessed for the risk of missing studies quantitatively. The reviews had deficiencies in the assessment of validity of studies and exploration for heterogeneity. When compared to Cochrane reviews, other reviews were significantly inferior in specifying questions (OR 20.3, 95% CI 1.1–381.3, p = 0.04), framing focussed questions (OR 30.9, 95% CI 3.7- 256.2, p = 0.001), use of unpublished data (OR 5.6, 95% CI 1.9–16.4, p = 0.002), assessment for heterogeneity (OR 38.1, 95%CI 2.1, 688.2, p = 0.01) and use of meta-analyses (OR 3.7, 95% CI 1.3–10.8, p = 0.02). Conclusion This study identifies areas which have a strong influence on maternal morbidity and mortality but lack good quality systematic reviews. Overall quality of the existing systematic reviews was variable. Cochrane reviews were of better quality as compared to other reviews. There is a need for good quality systematic reviews to inform practice in maternal medicine