The effects on waiting times of expanding provider choice:evidence from a policy experiment

Long waiting times for inpatient treatment in the UK National Health Service have long been a source of great popular and political concern, and therefore a target for policy initiatives. One such is the London Patient Choice Project, under which patients at risk of breaching inpatient waiting time targets were offered the choice of an alternative hospital with a guaranteed shorter wait. This paper uses a difference in difference econometric methodology to infer the impact of the choice project on ophthalmology waiting times. In line with our theoretical predictions, it finds that the project led to lower average waiting times in the London region and a convergence in waiting times amongst London hospitals.

Spectral fundus autofluorescence peak emission wavelength in ageing and AMD

Purpose To investigate the spectral characteristics of fundus autofluorescence (FAF) in AMD patients and controls. Methods Fundus autofluorescence spectral characteristics was described by the peak emission wavelength (PEW) of the spectra. Peak emission wavelength (PEW) was derived from the ratio of FAF recordings in two spectral channels at 500-560 nm and 560-720 nm by fluorescence lifetime imaging ophthalmoscopy. The ratio of FAF intensity in both channels was related to PEW by a calibration procedure. Peak emission wavelength (PEW) measurements were done in 44 young (mean age: 24.0 ± 3.8 years) and 18 elderly (mean age: 67.5 ± 10.2 years) healthy subjects as well as 63 patients with AMD (mean age: 74.0 ± 7.3 years) in each pixel of a 30° imaging field. The values were averaged over the central area, the inner and the outer ring of the ETDRS grid. Results There was no significant difference between PEW in young and elderly controls. However, PEW was significantly shorter in AMD patients (ETDRS grid centre: 571 ± 26 nm versus 599 ± 17 nm for elderly controls, inner ring: 596 ± 17 nm versus 611 ± 11 nm, outer ring: 602 ± 16 nm versus 614 ± 11 nm). After a mean follow-up time of 50.8 ± 10.8 months, the PEW in the patients decreased significantly by 9 ± 19 nm in the inner ring of the grid. Patients, showing progression to atrophic AMD in the follow up, had significantly (p ≤ 0.018) shorter PEW at baseline than non-progressing patients. Conclusions Peak emission wavelength (PEW) is related to AMD pathology and might be a diagnostic marker in AMD. Possibly, a short PEW can predict progression to retinal and/or pigment epithelium atrophy

Care for chronic illness in Australian general practice – focus groups of chronic disease self-help groups over 10 years: implications for chronic care systems reforms

Background: Chronic disease is a major global challenge. However, chronic illness and its care, when intruding into everyday life, has received less attention in Asia Pacific countries, including Australia, who are in the process of transitioning to chronic disease orientated health systems. Aim: The study aims to examine experiences of chronic illness before and after the introduction of Australian Medicare incentives for longer consultations and structured health assessments in general practice. Methods: Self-help groups around the conditions of diabetes, epilepsy, asthma and cancer identified key informants to participate in 4 disease specific focus groups. Audio taped transcripts of the focus groups were coded using grounded theory methodology. Key themes and lesser themes identified using a process of saturation until the study questions on needs and experiences of care were addressed. Thematic comparisons were made across the 2002/3 and 1992/3 focus groups. Findings: At times of chronic illness, there was need to find and then ensure access to 'the right GP'. The 'right GP or specialist' committed to an in-depth relationship of trust, personal rapport and understanding together with clinical and therapeutic competence. The 'right GP', the main specialist, the community nurse and the pharmacist were key providers, whose success depended on interprofessional communication. The need to trust and rely on care providers was balanced by the need for self-efficacy 'to be in control of disease and treatment' and 'to be your own case manager'. Changes in Medicare appeared to have little penetration into everyday perceptions of chronic illness burden or time and quality of GP care. Inequity of health system support for different disease groupings emerged. Diabetes, asthma and certain cancers, like breast cancer, had greater support, despite common experiences of disease burden, and a need for research and support programs. Conclusion: Core themes around chronic illness experience and care needs remained consistent over the 10 year period. Reforms did not appear to alleviate the burden of chronic illness across disease groups, yet some were more privileged than others. Thus in the future, chronic care reforms should build from greater understanding of the needs of people with chronic illness

Developing new approaches to measuring NHS outputs and productivity

The Centre for Health Economics and National Institute of Economic and Social Research have recently completed a project funded by the Department of Health to improve measurement of the productivity of the NHS. The researchers have suggested better ways of measuring both outputs and inputs to improve estimates of productivity growth. Past estimates of NHS output growth have not taken account of changes in quality. The CHE/NIESR team conclude that the routine collection of health outcome data on patients is vital to measure NHS quality. They also propose making better use of existing data to quality adjust output indices to capture improvements in hospital survival rates and reductions in waiting times. With these limited adjustments the team estimate that annual NHS output growth averaged 3.79% between 1998/99 and 2003/04.The research team has also developed improved ways of measuring NHS inputs, particularly by drawing on better information about how many people are employed in the NHS and by recognising that staff are becoming increasingly better qualified. There have been substantial increases in staffing levels, pharmaceutical use and investment in equipment and buildings since 1998/99. The net effect of this growth in both outputs and inputs is that, according to the research team’s estimates, NHS productivity declined by about 1.59% a year since 1998/99. This is not out of line with estimates of growth rates in other UK and US service sectors, including insurance and business services. Nor is it surprising that recent years have seen negative growth in the NHS. There are at least two reasons. First, there has been an unprecedented increase in NHS expenditure. The NHS has had to employ more staff to meet the requirements of the European Working Time Directive and hospital consultants and general practitioners, in particular, have benefited from new pay awards.Second, the NHS collects very little information about what actually happens to patients as a result of their contact with the health service. Until there is routine collection of health outcomes data, measurement of the quality of NHS output will remain partial and productivity growth is likely to be underestimated.

Combined experimental and simulation studies of crosslinked polymer brushes under shear

We have studied the effect of crosslinking on the tribological behavior of polymer brushes using a combined experimental and theoretical approach. Tribological and indentation measurements on poly(glycidyl methacrylate) brushes and gels in the presence of dimethylformamide solvent were obtained by means of atomic force microscopy. To complement experiments, we have performed corresponding molecular-dynamics (MD) simulations of a generic bead-spring model in the presence of explicit solvent and crosslinkers. Our study shows that crosslinking leads to an increase in friction between polymer brushes and a counter-surface. The coefficient of friction increases with increasing degree of crosslinking and decreases with increasing length of the crosslinker chains. We find that the brush-forming polymer chains in the outer layer play a significant role in reducing friction at the interface

Molecular Mechanisms for Drug Hypersensitivity Induced by the Malaria Parasite's Chloroquine Resistance Transporter

Mutations in the Plasmodium falciparum ‘chloroquine resistance transporter’ (PfCRT) confer resistance to chloroquine (CQ) and related antimalarials by enabling the protein to transportthese drugs away from their targets within the parasite’s digestive vacuole (DV). However, CQ resistance-conferring isoforms of PfCRT (PfCRTCQR) also render the parasite hypersensitive to a subset of structurally-diverse pharmacons. Moreover, mutations in PfCRTCQR that suppress the parasite’s hypersensitivity to these molecules simultaneously reinstate its sensitivity to CQ and related drugs. We sought to understand these phenomena by characterizing the functions of PfCRTCQR isoforms that cause the parasite to become hypersensitive to the antimalarial quinine or the antiviral amantadine. We achieved this by measuring the abilities of these proteins to transport CQ, quinine, and amantadine when expressed in Xenopus oocytes and complemented this work with assays that detect the drug transport activity of PfCRT in its native environment within the parasite. Here we describe two mechanistic explanations for PfCRT-induced drug hypersensitivity. First, we show that quinine, which normally accumulates inside the DV and therewithin exerts its antimalarial effect, binds extremely tightly to the substrate-binding site of certain isoforms of PfCRTCQR. By doing so it likely blocks the normal physiological function of the protein, which is essential for the parasite’s survival, and the drug thereby gains an additional killing effect. In the second scenario, we show that although amantadine also sequesters within the DV, the parasite’s hypersensitivity to this drug arises from the PfCRTCQR-mediated transport of amantadine from the DV into the cytosol, where it can better access its antimalarial target. In both cases, the mutations that suppress hypersensitivity also abrogate the ability of PfCRTCQR to transport CQ, thus explaining why rescue from hypersensitivity restores the parasite’s sensitivity to this antimalarial. These insights provide a foundation for understanding clinically-relevant observations of inverse drug susceptibilities in the malaria parasite

The 'permeome' of the malaria parasite: an overview of the membrane transport proteins of Plasmodium falciparum

BACKGROUND: The uptake of nutrients, expulsion of metabolic wastes and maintenance of ion homeostasis by the intraerythrocytic malaria parasite is mediated by membrane transport proteins. Proteins of this type are also implicated in the phenomenon of antimalarial drug resistance. However, the initial annotation of the genome of the human malaria parasite Plasmodium falciparum identified only a limited number of transporters, and no channels. In this study we have used a combination of bioinformatic approaches to identify and attribute putative functions to transporters and channels encoded by the malaria parasite, as well as comparing expression patterns for a subset of these. RESULTS: A computer program that searches a genome database on the basis of the hydropathy plots of the corresponding proteins was used to identify more than 100 transport proteins encoded by P. falciparum. These include all the transporters previously annotated as such, as well as a similar number of candidate transport proteins that had escaped detection. Detailed sequence analysis enabled the assignment of putative substrate specificities and/or transport mechanisms to all those putative transport proteins previously without. The newly-identified transport proteins include candidate transporters for a range of organic and inorganic nutrients (including sugars, amino acids, nucleosides and vitamins), and several putative ion channels. The stage-dependent expression of RNAs for 34 candidate transport proteins of particular interest are compared. CONCLUSION: The malaria parasite possesses substantially more membrane transport proteins than was originally thought, and the analyses presented here provide a range of novel insights into the physiology of this important human pathogen

A lactate and formate transporter in the intraerythrocytic malaria parasite, Plasmodium falciparum

The intraerythrocytic malaria parasite relies primarily on glycolysis to fuel its rapid growth and reproduction. The major byproduct of this metabolism, lactic acid, is extruded into the external medium. In this study, we show that the human malaria parasite Plasmodium falciparum expresses at its surface a member of the microbial formate-nitrite transporter family (PfFNT), which, when expressed in Xenopus laevis oocytes, transports both formate and lactate. The transport characteristics of PfFNT in oocytes (pH-dependence, inhibitor-sensitivity and kinetics) are similar to those of the transport of lactate and formate across the plasma membrane of mature asexual-stage P. falciparum trophozoites, consistent with PfFNT playing a major role in the efflux of lactate and hence in the energy metabolism of the intraerythrocytic parasite.This work was supported by grants from the Australian National Health and Medical Research Council (NHMRC; 316933 and 525428 to K.K. and 1007035 to R.E.M.), and by the L’Ore´al Australia For Women in Science programme (R.E.M.). A.M.L. was supported by an NHMRC Overseas Biomedical Fellowship (585519) and R.E.M. was supported by NHMRC Australian Biomedical Fellowships (520320 and 1053082)