The Global Drug Facility as an intervention in the market for tuberculosis drugs

Objective

To investigate funding for the Global Drug Facility since 2001 and to analyse the facility’s influence on the price of high-quality tuberculosis drugs.

Methods

Data on the price of tuberculosis drugs were obtained from the Global Drug Facility for 2001 to 2012 and, for the private sector in 15 countries, from IMS Health for 2002 to 2012. Data on funding of the facility were also collected.

Findings

Quality-assured tuberculosis drugs supplied by the Global Drug Facility were generally priced lower than drugs purchased in the private sector. In 2012, just three manufacturers accounted for 29.9 million United Stated dollars (US$) of US$ 44.5 million by value of first-line drugs supplied. The Global Fund to Fight AIDS, Tuberculosis and Malaria provided 73% (US$ 32.5 million of US$ 44.5 million) and 89% (US$ 57.8 million of US $65.2 million) of funds for first- and second-line drugs, respectively. Between 2010 and 2012, the facility’s market share of second-line tuberculosis drugs increased from 26.1% to 42.9%, while prices decreased by as much as 24% (from US$ 1231 to US$ 939). Conversely, the facility’s market share of first-line drugs fell from 37.2% to 19.2% during this time, while prices increased from US$ 9.53 to US$ 10.2.

Conclusion

The price of tuberculosis drugs supplied through the facility was generally less than that on the private market. However, to realize its full potential and meet the needs of more tuberculosis patients, the facility requires more diverse and stable public funding and greater flexibility to participate in the private market.     

Unifying the spatial epidemiology and molecular evolution of emerging epidemics

We introduce a conceptual bridge between the previously unlinked fields of phylogenetics and mathematical spatial ecology, which enables the spatial parameters of an emerging epidemic to be directly estimated from sampled pathogen genome sequences. By using phylogenetic history to correct for spatial autocorrelation, we illustrate how a fundamental spatial variable, the diffusion coefficient, can be estimated using robust nonparametric statistics, and how heterogeneity in dispersal can be readily quantified. We apply this framework to the spread of the West Nile virus across North America, an important recent instance of spatial invasion by an emerging infectious disease. We demonstrate that the dispersal of West Nile virus is greater and far more variable than previously measured, such that its dissemination was critically determined by rare, long-range movements that are unlikely to be discerned during field observations. Our results indicate that, by ignoring this heterogeneity, previous models of the epidemic have substantially overestimated its basic reproductive number. More generally, our approach demonstrates that easily obtainable genetic data can be used to measure the spatial dynamics of natural populations that are otherwise difficult or costly to quantify.     

Impact of cross-protective vaccines on epidemiological and evolutionary dynamics of influenza

Large-scale immunization has profoundly impacted control of many infectious diseases such as measles and smallpox because of the ability of vaccination campaigns to maintain long-term herd immunity and, hence, indirect protection of the unvaccinated. In the case of human influenza, such potential benefits of mass vaccination have so far proved elusive. The central difficulty is a considerable viral capacity for immune escape; new pandemic variants, as well as viral escape mutants in seasonal influenza, compromise the buildup of herd immunity from natural infection or deployment of current vaccines. Consequently, most current influenza vaccination programs focus mainly on protection of specific risk groups, rather than mass prophylactic protection. Here, we use epidemiological models to show that emerging vaccine technologies, aimed at broad-spectrum protection, could qualitatively alter this picture. We demonstrate that sustained immunization with such vaccines could--through potentially lowering transmission rates and improving herd immunity--significantly moderate both influenza pandemic and seasonal epidemics. More subtly, phylodynamic models indicate that widespread cross-protective immunization could slow the antigenic evolution of seasonal influenza; these effects have profound implications for a transition to mass vaccination strategies against human influenza, and for the management of antigenically variable viruses in general.     

Size and complexity in model financial systems

The global financial crisis has precipitated an increasing appreciation of the need for a systemic perspective toward financial stability. For example: What role do large banks play in systemic risk? How should capital adequacy standards recognize this role? How is stability shaped by concentration and diversification in the financial system? We explore these questions using a deliberately simplified, dynamic model of a banking system that combines three different channels for direct transmission of contagion from one bank to another: liquidity hoarding, asset price contagion, and the propagation of defaults via counterparty credit risk. Importantly, we also introduce a mechanism for capturing how swings in “confidence” in the system may contribute to instability. Our results highlight that the importance of relatively large, well-connected banks in system stability scales more than proportionately with their size: the impact of their collapse arises not only from their connectivity, but also from their effect on confidence in the system. Imposing tougher capital requirements on larger banks than smaller ones can thus enhance the resilience of the system. Moreover, these effects are more pronounced in more concentrated systems, and continue to apply, even when allowing for potential diversification benefits that may be realized by larger banks. We discuss some tentative implications for policy, as well as conceptual analogies in ecosystem stability and in the control of infectious diseases.Although global financial systems have seen considerable growth in size, concentration, and complexity over the past few decades (1), our understanding of the dynamic behavior of such systems has not necessarily kept pace. Indeed, the current financial crisis has presented a stark demonstration of the potential for modern financial systems to amplify and disseminate financial distress on a global scale. From a regulatory perspective, these events have prompted fresh interest in understanding financial stability from a system level. In particular, although precrisis regulation (as typified by the Basel II accords) sought to minimize the risk of failure of individual banks irrespective of systemic importance, new regulation will seek to target the systemic consequences of bank collapse as well. To quote Haldane and May (2), “What matters is not a bank’s closeness to the edge of the cliff; it is the extent of the fall.”In this context, a clear feature of interest is the presence of large, highly connected banks. These banks have conceptual parallels in biology: simple models have been influential in underlining the importance of “superspreaders” in the spread and control of infectious diseases (3, 4), and “keystone” species are thought to serve a valuable role in ecosystem stability (5, 6). Here we develop dynamic models to apply and extend these lessons to financial systems. Our approach is theoretical, and our models necessarily oversimplified. Nonetheless, by considering transmission mechanisms specific to modern financial systems, our approach recognizes some important differences between these and other complex systems. We show how, even with such distinctions, the basic insights deriving from our model allow us to draw certain parallels with other situations where size and complexity are important.If financial crises may be compared with forest fires, causes for the initiating sparks pose important questions in their own right: for example, the role of excessive leverage and credit growth (7) or the pricing for complex financial instruments (8, 9). Here, however, our focus is on the role of large banks in the “flammability” of the system, or its capacity for amplification and propagation of an initiating shock. We ask the following questions: How does the impact of a bank’s collapse scale with its size? How might capital adequacy standards seek to mitigate this impact? More broadly, what is the effect of concentration and diversification on system stability?Network approaches (10–14) are well-suited for such questions, particularly in modeling contagion that is transmitted through linkages in the financial system. Here we adopt such an approach to bring together three important transmission channels into a unified framework: (i) liquidity hoarding, where banks cut lending to each other as a defensive measure (1, 15); (ii) asset price contagion linked to market illiquidity (16–18); and (iii) the propagation of defaults via counterparty credit risk (19–21).Although the network effects listed above act on defined webs of connectivity, confidence effects can operate more broadly, with the overall state of the system potentially influencing an individual bank’s actions, and vice versa. This motivates a special feature of our model, which explicitly integrates network dynamics with confidence effects.The interaction of such network and confidence effects arguably played a major role in the collapse of the interbank market (a network of lending exposures among banks) and global liquidity “freeze” that occurred during the crisis (22). Interbank loans have a range of maturities, from overnight to a matter of years, and may often be renewed, or rolled over, at the point of maturity. A pronounced feature of the 2007/2008 crisis was that, as the system deteriorated, banks stopped lending to each other at all but the shortest maturities (7, 29). The bankruptcy of Lehman Brothers in September 2008 transmitted distress further across the financial network, and signaled that there was no guarantee of government support for institutions in distress. The effects extended well beyond those institutions directly exposed to Lehman Brothers, with banks throughout the system withdrawing interbank lending outright and propagating distress to the real economy by sharply contracting household and corporate lending (23). At the time of writing, ongoing events illustrate the potential for similar dynamics in the context of sovereign and banking sector distress in some Eurozone countries.Several specific motivating factors have been proposed to explain “liquidity hoarding” (the maturity-shortening and ultimate withdrawal of interbank lending): precautionary measures by lending banks in anticipation of future liquidity shortfalls, counterparty concerns over specific borrowing banks, or collapses in overall system confidence (24, 25). Our framework parsimoniously incorporates all of these mechanisms, but also captures the idea that a bank’s distress may affect not just those directly exposed or linked to it, but also confidence in the market at large.In what follows we summarize essential features of the model structure, with details provided in Materials and Methods, and a summary of model parameters and their default values given in Table S1. We use this model to explore the impact of an initiating shock, with particular reference to the nonlinearities arising from each of the contagion channels modeled, the effects of size disparity among banks and system concentration, and the effects of diversification. We then outline tentative implications for regulatory capital requirements before discussing important caveats to our work. Throughout the paper, we abstract from extraordinary policy intervention in crisis, so that liquidity cannot be obtained more easily from the central bank than from the market, and failing institutions are not bailed out.     

Simultaneous Intra-gastric Balloon Removal and Laparoscopic Sleeve Gastrectomy for the Super-Super Obese Patients—a Prospective Feasibility Study

Background

The aim of the study was to prospectively evaluate the feasibility and clinical efficacy of a strategy of performing simultaneous balloon removal and sleeve gastrectomy in the super-super obese patients.

Methods

Forty consecutive super-super obese patients underwent intra-gastric balloon insertion followed by simultaneous balloon removal and sleeve gastrectomy 6 months later.

Results

Balloon insertion resulted in a reduction in mean body mass index from 69.3?±?1.4 to 62.3?±?1.3 kg/m². Simultaneous balloon removal and sleeve gastrectomy was achieved in 39 cases. There were no operative mortality and no leaks. Six months following sleeve gastrectomy, the mean BMI of the cohort had fallen to 54.1?±?1.2 kg/m².

Conclusions

Simultaneous balloon removal and sleeve gastrectomy in the super-super obese patients is feasible as a single-stage procedure with good perioperative outcomes.     

Introduction of an enhanced recovery protocol for radical cystectomy

OBJECTIVE

To describe and assess an enhanced recovery protocol (ERP) for the peri‐operative management of patients undergoing radical cystectomy (RC), which was started at our institution on 1 October 2005, as RC is associated with increased morbidity and longer inpatient stays than other major urological procedures.

PATIENTS AND METHODS

An ERP was introduced in our institution that focused on reduced bowel preparation, and standardized feeding and analgesic regimens. In all, 112 consecutive patients were compared, i.e. 56 before implementing the ERP and 56 since introducing the ERP. The primary outcome measures were duration of total inpatient stay and interval from surgery to discharge, and the morbidity and mortality. Data were analysed retrospectively from cancer network and hospital records.

RESULTS

The demographics of the two groups showed no significant difference in age, gender distribution, American Society of Anesthesiologists grade, or type of urinary diversion. Re‐admission, mortality and morbidity rates showed no statistically significant difference between the groups. The median (interquartile range) duration of hospital stay was 17 (15–23) days in the no‐ERP group, and 13 (11–17) days in the ERP group (significantly different, P < 0.001, Wilcoxon rank‐sum test). The median duration of recovery after RC was 15 (13–21) days in the no‐ERP group and 12 (10–15) days in the ERP group (significantly different, P = 0.001, Wilcoxon rank‐sum test).

CONCLUSION

The introduction of an ERP was associated with significantly reduced hospital stay, with no deleterious effect on morbidity or mortality.