Waiting time distribution in public health care: empirics and theory.

Excessive waiting times for elective surgery have been a long-standing concern in many national healthcare systems in the OECD. How do the hospital admission patterns that generate waiting lists affect different patients? What are the hospitals characteristics that determine waiting times? By developing a model of healthcare provision and analysing empirically the entire waiting time distribution we attempt to shed some light on those issues. We first build a theoretical model that describes the optimal waiting time distribution for capacity constraint hospitals. Secondly, employing duration analysis, we obtain empirical representations of that distribution across hospitals in the UK from 1997-2005. We observe important differences on the 'scale' and on the 'shape' of admission rates. Scale refers to how quickly patients are treated and shape represents trade-offs across duration-treatment profiles. By fitting the theoretical to the empirical distributions we estimate the main structural parameters of the model and are able to closely identify the main drivers of these empirical differences. We find that the level of resources allocated to elective surgery (budget and physical capacity), which determines how constrained the hospital is, explains differences in scale. Changes in benefits and costs structures of healthcare provision, which relate, respectively, to the desire to prioritise patients by duration and the reduction in costs due to delayed treatment, determine the shape, affecting short and long duration patients differently. JEL Classification I11; I18; H51.

Identifying the impact of government targets on waiting times in the NHS.

Waiting times for elective surgery are a key issue for the NHS. The principal policy response in the English NHS has been to introduce maximum waiting time targets against which performance is measured and rewarded. The aim of this paper is to identify the effect of government targets on the distribution of waiting times in the NHS. Specifically, we investigate the following questions: How does the probability of admission for any given patient vary during the time that they wait? How is the probability of admission for any given waiting time affected by the targets? Can variations in waiting times be explained by clinical, patient, or provider-level characteristics? What implications may be drawn from our results with respect to providers' managerial responses to the targets? This paper investigates these questions by applying duration analysis techniques to waiting time data from 2001/2002 and 2002/2003 for three specialties: general surgery, trauma & orthopaedics and ophthalmology. Estimation of survival functions reveals considerable variations in waiting times between specialties, operative procedures and hospitals. Hazard rates vary over time and peaks in them-high probabilities of admission-coincide with targets and change when targets change. Amongst patient characteristics, whether they are NHS or private and whether they are day or inpatient cases both influence waiting times, but other characteristics such as age, sex and ethnicity do not.

Public T cell receptor beta-chains are not advantaged during positive selection.

Studies of human and murine T cells have shown that public TCR beta-chain rearrangements can dominate the Ag-specific and naive repertoires of distinct individuals. We show that mouse T cells responding to the minor histocompatibility Ag HYDbSmcy share an invariant Vbeta8.2-Jbeta2.3 TCR gene rearrangement. The dominance of this rearrangement shows that it successfully negotiated thymic selection and was highly favored during clonal expansion in all animals examined. We hypothesized that such beta-chains are advantaged during thymic and/or peripheral selection and, as a result, may be over-represented in the naive repertoire. A sequencing study was undertaken to examine the diversity of Vbeta8.2-Jbeta2.3 CDR3 loops from naive T cell repertoires of multiple mice. Public TCR beta-chain sequences were identified across different repertoires and MHC haplotypes. To determine whether such public beta-chains are advantaged during thymic selection, individual chains were followed through T cell development in a series of novel bone marrow competition chimeras. We demonstrate that beta-chains were positively selected with similar efficiency regardless of CDR3 loop sequence. Therefore, the establishment and maintenance of public beta-chains in the periphery is predominantly controlled by post-thymic events through modification of the primary, thymus-derived TCR repertoire.

Expansion of CD8+ cytotoxic T cells in vitro and in vivo using MHC class I tetramers.

BACKGROUND: The expansion of cytotoxic CD8+ T lymphocytes (CTLs) which recognize peptide epitopes of tumour or viral origin has been a major aim of immunotherapy research for the past decade. Alongside the established dendritic cell-based methods, more recent approaches using recombinant MHC class I peptide complexes have been developed. METHODS: In this study we have explored the potential of a simplified system using soluble streptavidin-linked MHC class I tetramers to expand antigen-specific CTLs in vitro and in vivo. RESULTS: In vitro tetramer-mediated expansion of CD8+ CTLs recognizing HLA-2/Melan-A and HLA-A2/Gag complexes was demonstrated with PBMCs from healthy donors or HIV+ donors, respectively. With 3 weekly rounds of tetramer stimulation, cell numbers expanded 100-fold from 0.05 to 5.0%. The lytic function of HLA-A2/Melan-A-expanded cells was demonstrated in 51Cr release assays by specific killing of T2 cells pulsed with Melan-A, but not other peptides. Similarly, murine CD8+ T cells specific for the HY epitope H2-Db/Uty could be expanded in vitro over a wide range of tetramer concentrations (0.008-1.0 microg/ml), with a single exposure producing substantial T cell expansion from 0.11 to 36%. Intraperitoneal administration of H2-Db/Uty tetramers to primed C57BL/6 mice produced over 5-fold expansion of Db/Uty-specific CTL in vivo. CONCLUSION: The results in this paper demonstrate that simple, multimeric MHC complexes may be of value in expanding CTLs in vitro for adoptive immunotherapy and also potentially in vivo. Further studies will be necessary to clarify the optimum protocols and schedules of administration for T cell expansion using recombinant MHC multimers.