Cost effectiveness of an outpatient multidisciplinary pulmonary rehabilitation programme

BACKGROUND: Pulmonary rehabilitation programmes improve the health of patients disabled by lung disease but their cost effectiveness is unproved. We undertook a cost/utility analysis in conjunction with a randomised controlled clinical trial of pulmonary rehabilitation versus standard care. METHODS: Two hundred patients, mainly with chronic obstructive pulmonary disease, were randomly assigned to either an 18 visit, 6 week rehabilitation programme or standard medical management. The difference between the mean cost of 12 months of care for patients in the rehabilitation and control groups (incremental cost) and the difference between the two groups in quality adjusted life years (QALYs) gained (incremental utility) were determined. The ratio between incremental cost and utility (incremental cost/utility ratio) was calculated. RESULTS: Each rehabilitation programme for up to 20 patients cost pound 12,120. The mean incremental cost of adding rehabilitation to standard care was pound -152 (95% CI -881 to 577) per patient, p=NS. The incremental utility of adding rehabilitation was 0.030 (95% CI 0.002 to 0.058) QALYs per patient, p=0.03. The point estimate of the incremental cost/utility ratio was therefore negative. The bootstrapping technique was used to model the distribution of cost/utility estimates possible from the data. A high likelihood of generating QALYs at negative or relatively low cost was indicated. The probability of the cost per QALY generated being below pound 0 was 0.64. CONCLUSIONS: This outpatient pulmonary rehabilitation programme produces cost per QALY ratios within bounds considered to be cost effective and is likely to result in financial benefits to the health service.     

Hypertension and albuminuria in chronic kidney disease mapped to a mouse chromosome 11 locus

Chronic kidney disease (CKD) is a key cause of hypertension and a potent independent risk for cardiovascular disease. Epidemiological studies suggest a strong genetic component determining susceptibility for renal disease and, by inference, the associated cardiovascular risk. With a subtotal nephrectomy model of kidney disease, we found the 129S6 mouse strain to be very susceptible to the development of hypertension, albuminuria, and kidney injury, whereas the C57BL/6 strain is relatively resistant. Accordingly, we set out to map quantitative trait loci conferring susceptibility to hypertension and albuminuria using this model with F2 mice. We found significant linkage of the blood pressure trait to two loci. At D11Mit143, mice homozygous for the 129S6 allele had significantly higher systolic blood pressure than mice heterozygous or homozygous for the C57BL/6 allele. Similarly, at D1Mit308, there was an excellent correlation between genotype and the blood pressure phenotype. The effect of the chromosome 11 locus was verified with a separate cohort of F2 mice. For the albuminuria trait, a significant locus was found at D11Mit143, which overlaps the blood pressure trait locus. Our studies have identified a region spanning approximately 8 cM on mouse chromosome 11 that is associated with susceptibility to hypertension and albuminuria in CKD.     

Increased nitric oxide production during acute rejection in kidney transplantation: a useful marker to aid in the diagnosis of rejection

BACKGROUND: The diagnosis of acute rejection (AR) relies on biopsy (Bx), with all the noninvasive tests failing to show satisfactory predictive value. Nitric oxide (NO) has been shown to play a role in AR. The aim of this study is to analyze the relationship between NO and (1) biopsy-proven allograft rejection and (2) other reasons of allograft dysfunction. PATIENTS AND METHODS: Fifty consecutive renal allograft recipients ages 23-72 yrs who were transplanted were prospectively recruited. Blood samples were collected for 3 months. Endogenous serum nitrate (SNO(3)) levels were measured with Griess reagent in 1178 samples. Biopsies were performed as clinically indicated. Tacrolimus levels, urinary cultures, and renal function tests were done as per unit protocol. RESULTS: Fifty recipients (mean+/-SD age 45.2+/-2.18 yrs, 24 men and 6 women) underwent 68 biopsies. Forty-five Bx (66.2%) showed AR in 19 recipients (mean age 47+/-8) and 23 (33.8%) Bx in 13 recipients (mean age 43+/-12) showed no AR. SNO(3) in AR was (73+/-8.89 micromol/L) compared with negative Bx (45+/-4.5 micromol/L; P<0.05). There was also a significant difference in SNO(3) during AR and other causes of allograft dysfunction; delayed graft function (54+/-7.8 micromol/L), urinary tract infection (44+/-2.9 micromol/L), tacrolimus toxicity (51+/-2.86 micromol/L), and increase in serum creatinine (44+/-2.36 micromol/L). CONCLUSION: There is a significant increase of serum nitrate with episodes of acute rejection compared with other causes of renal dysfunction. SNO(3) can therefore aid in the diagnosis of acute rejection.     

Donor history of asthma is not a contraindication to lung transplantation: 12-year single-center experience.

BACKGROUND: Donor asthma has been regarded as a contraindication to lung transplantation (LTx) because of concerns that pre-existing airway inflammation will predispose to early and late graft dysfunction. The aim of this study was to describe LTx outcomes in which lungs had been transplanted from donors with a history of asthma. METHODS: A retrospective chart review was undertaken of 743 consecutive donor lung referrals to the Alfred Hospital between 1990 and September 2002. Seventy-four were noted to have a history of asthma, including 18 in whom asthma was the cause of death. Twenty-seven patients became lung donors, of whom 16 were on asthma treatment (on-treatment group) and 11 were not (no-treatment group). RESULTS: From 27 lung donors, 35 LTx procedures were performed (16 double LTx [DLTx], 19 single LTx [SLTx]). Five recipients died at <30 days (including 3 of early graft failure in the no-treatment group), and 7 died at >30 days (only 1 due to BOS). The 30-day, 1-year and 5-year survival rates in the on- and no-treatment donor groups were 90% vs 76%, 74% vs 69% and 74% vs 60%, respectively, and were not significantly different from our overall LTx survival rates. There were no significant differences in percent predicted forced expiratory volume in 1 second, ICU stay or hospital stay overall, or when analyzed according to on treatment vs no treatment and SLTx vs DLTx. Only 2 procedures LTx were performed from fatal asthma donors, both of whom had subsequent graft dysfunction and died on Days 73 and 484, respectively. CONCLUSIONS: The use of lungs from carefully selected lung donors with a history of asthma may increase the donor pool with acceptable long-term outcomes. The use of fatal asthma donors remains problematic.     

k-space filtering in 2D gradient-echo breath-hold hyperpolarized 3He MRI: spatial resolution and signal-to-noise ratio considerations.

In this work some of the factors that can influence the signal-to-noise ratio (SNR) and spatial resolution in MR images of inhaled hyperpolarized gases are systematically addressed. In particular, the effects of RF depletion of longitudinal polarization and image gradient diffusion dephasing were assessed in terms of their contribution to a k-space filter. By means of theoretical simulations and a novel method of experimental validation using a variable transverse magnetization of the 1H signal, systematic quantitative and qualitative investigations of the effects of k-space filtering intrinsic to imaging of hyperpolarized gas were made. A 2D gradient-echo image is considered for a range of flip angles with centric, sequential, and half-Fourier Cartesian phase-encoding strategies, and the results are assessed in terms of SNR and spatial resolution in the reconstructed images. Centric phase encoding was found to give the best SNR at higher flip angles, with a trade-off in spatial resolution compared to sequential phase encoding. A half-Fourier approach potentially offers increased SNR through the use of higher flip angles without compromising the spatial resolution, which is comparable to that achieved with sequential encoding.     

Computed tomography perfusion imaging in acute stroke

The development of thrombolytic and neuroprotective agents for the treatment of acute stroke has created an imperative for improved imaging techniques in the assessment of acute stroke. Five cases are presented to illustrate the value of perfusion CT in the evaluation of suspected acute stroke. To obtain the perfusion data, a rapid series of images was acquired without table movement following a bolus of contrast medium. Cerebral blood flow, cerebral blood volume and mean transit time were determined by mathematically modelling the temporal changes in contrast enhancement in the brain and vascular system. Pixel-by-pixel analysis allowed generation of perfusion maps. In two cases, CT-perfusion imaging usefully excluded acute stroke, including one patient in whom a low-density area on conventional CT was subsequently proven to be tumour. Cerebral ischaemia was confirmed in three cases, one with an old and a new infarction, one with a large conventional CT abnormality but only a small perfusion defect, and one demonstrating infarct and penumbra. Perfusion CT offers the ability to positively identify patients with non-haemorrhagic stroke in the presence of a normal conventional CT, to select those cases where thrombolysis is appropriate, and to provide an indication for prognosis.     

Interleaved pulsed MAMBA: a new parallel slice imaging method.

A method of acquiring slices in parallel is described which uses interleaved sets of pulsed B(0) field coils to generate discrete regions of uniform field within the main magnetic field known as interleaved MAMBA (multiple acquisition micro B(0) array). Simulations of a number of coil designs were performed using the Biot-Savart law. A six-step coil was built and interfaced to a 0.17 T Niche MRI system and the field steps measured using an imaging technique. Measured field steps were in good agreement with the values predicted by simulation. The coil design was then scaled up by a factor of three, interfaced to a 1.5 T whole-body MRI system, and scans of the hands and arms of volunteers were acquired from up to four field steps using standard spin and gradient echo sequences. Images were also acquired simultaneously from two field steps with no frequency encode aliasing and one excitation. The one-dimensional interleaved pulsed MAMBA step field technique shows great promise for enabling many slices to be acquired simultaneously along the axis of the coil for rapid volumetric studies without the need for multiple shot Hadamard encoding. Extension of interleaved coil design to two or three dimensions is feasible, which could provide full spatial coverage combined with ultra-rapid data acquisition.     

105Changes in Nitric Oxide Levels After Deep Dermal injury in the Female,Red Duroc Pig (FRDP)

Introduction : Hypertrophic scar is a devastating sequel to burns and other tangential skin injuries. It follows deep dermal injuries and does not occur after superficial injuries. Nitric oxide (NO) plays many important roles in wound healing from inflammation to scar remodeling. Studies have shown that expression of nitric oxide synthase and nitric oxide production are decreased in human hypertrophic scar. However little is known about NO involvement in the early stages of hypertrophic scarring, because of the lack of an animal model. It was recently reported that the female red Duroc pig (FRDP) makes thick scar, which is similar to human hypertrophic scar. We hypothesized that NO production in wounds on the female, red Duroc pig is similar to that of human hypertrophic scar and that NO involvement in deep wounds is different from that in superficial wounds. Methods : Superficial (0.015” to 0.030”) and deep (0.045” to 0.060”) wounds were created on the backs of four FRDPs. Biopsies were collected at weeks 1.5, 4, 8 and 21 post wounding including samples of uninjured skin. Nitric oxide levels were measured with the Griess reaction assay and normalized with tissue protein level. Results : Superficial wounds healed with an invisible scar whereas the deep wounds healed with scar resembling mild hypertrophic scar. The thickness of the scars from the deep wounds was significantly greater than uninjured skin and healed superficial wounds (p < 0.01). NO levels were increased at 1.5 weeks in deep wounds compared to superficial wounds and uninjured skin (p < 0.05). At 8 weeks, NO levels in deep wounds had returned to the level of uninjured tissue and superficial wounds. By 21 weeks, NO levels had decreased significantly when compared to superficial wounds (p < 0.01). There were no differences in NO levels between uninjured skin and superficial wounds at any time point (p > 0.05). Conclusions : NO production is similar in late, deep wounds on the female, red Duroc pig to that reported in the literature for human hypertrophic scar further validating this animal model. NO production is quite different after deep wounds as compared to superficial wounds in the FRDP. Early elevation in nitric oxide production might account for excessive inflammation in deep wounds that become thick scars in the FRDP. Nitric oxide regulators and effects at early stages of scar formation should be elucidated further and the FRDP appears to be a useful model.