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L D Sharples

Publications and source records attributed to L D Sharples.

At least 19 recordsLinked to original sources
PubMed2007

Flexible random-effects models using Bayesian semi-parametric models: applications to institutional comparisons.

Random effects models are used in many applications in medical statistics, including meta-analysis, cluster randomized trials and comparisons of health care providers. This paper provides a tutorial on the practical implementation of a flexible random effects model based on methodology developed in Bayesian non-parametrics literature, and implemented in freely available software. The approach is applied to the problem of hospital comparisons using routine performance data, and among other benefits provides a diagnostic to detect clusters of providers with unusual results, thus avoiding problems caused by masking in traditional parametric approaches. By providing code for Winbugs we hope that the model can be used by applied statisticians working in a wide variety of applications.

Bayes Theorem↗
PubMed2006

Bayesian evidence synthesis to extrapolate survival estimates in cost-effectiveness studies.

This paper is concerned with survival extrapolation that represents an integral part of cost-effectiveness analysis. In the absence of long-term survival estimates from randomized clinical trials or meta-analysis we show how age-sex matched U.K. population data can additionally be used to estimate survival patterns. We adopt a Bayesian approach and we synthesize evidence from different sources such as patient registries, U.K. population statistics and meta-analyses. We also present methodology for Bayesian analysis of the additive hazards model and we show how to apply the techniques using freely available software. The methods are illustrated using data from a cohort of cardiac arrhythmia patients.

Aged↗
PubMed2006

Double-blind, randomised, controlled trial assessing controller medications in asthma.

BACKGROUND: The motive behind conducting this study was to determine if better control of asthma can be achieved by adding a second controller medication and to assess its use to reduce the dose of inhaled steroids. OBJECTIVES: The study aimed to determine whether either oral sustained-release theophylline or montelukast added to inhaled steroids improved clinical symptoms and pulmonary function test parameters when compared to high-dose steroids alone. METHODS: Ninety patients with incompletely controlled asthma were allocated, in a randomised, double-blind fashion, to one of three treatment groups: group A: double dose of inhaled budesonide (400 microg b.i.d.), group B: 400 mg oral sustained-release theophylline plus budesonide (200 microg b.i.d.) and group C: 10 mg montelukast plus budesonide (200 microg b.i.d.). The primary endpoints were forced expiratory volume in 1 s (FEV(1)) and mean morning peak expiratory flow rate (PEFR). RESULTS: All three groups had improved FEV(1) and PEFR at 8 weeks (p < 0.001). Group C increased their PEFR by 18.7 l/min (95% confidence interval, CI, 12.4-25.1) more than group A and by 19.8 l/min (95% CI 13.4-26.1) more than group B (both p = 0.001). Similarly, group C had a 114 ml (95% CI 45-183 ml) greater improvement in FEV(1) than group A and a 95 ml (95% CI 26-164 ml) greater improvement than group B (both p = 0.01). CONCLUSIONS: Addition of montelukast to budesonide is safe and results in greater improvement in pulmonary function test parameters than high-dose budesonide treatment or addition of theophylline.

Acetates↗
PubMed2005

Comparison of shuttle walk with measured peak oxygen consumption in patients with operable lung cancer.

BACKGROUND: The relationship between the shuttle walk test and peak oxygen consumption in patients with lung cancer has not previously been reported. A study was undertaken to examine this relationship in patients referred for lung cancer surgery to test the hypothesis that the shuttle walk test would be useful in this clinical setting. METHODS: 125 consecutive patients with potentially operable lung cancer were prospectively recruited. Each performed same day shuttle walking and treadmill walking tests. RESULTS: Shuttle walk distances ranged from 104 m to 1020 m and peak oxygen consumption ranged from 9 to 35 ml/kg/min. The shuttle walk distance significantly correlated with peak oxygen consumption (r = 0.67, p<0.001). All 55 patients who achieved more than 400 m on the shuttle test had a peak oxygen consumption of at least 15 ml/kg/min. Seventy of 125 patients failed to achieve 400 m on the shuttle walk test; in 22 of these the peak oxygen consumption was less than 15 ml/kg/min. Nine of 17 patients who achieved less than 250 m had a peak oxygen consumption of more than 15 ml/kg/min. CONCLUSION: The shuttle walk is a useful exercise test to assess potentially operable lung cancer patients with borderline lung function. However, it tends to underestimate exercise capacity at the lower range compared with peak oxygen consumption. Our data suggest that patients achieving 400 m on the shuttle walk test do not require formal measurement of oxygen consumption. In patients failing to achieve this distance we recommend assessment of peak oxygen consumption, particularly in those unable to walk 250 m, because a considerable proportion would still qualify for surgery as they had an acceptable peak oxygen consumption.

Adult↗
PubMed2005

Octogenarians undergoing cardiac surgery outlive their peers: a case for early referral.

OBJECTIVE: To examine short and long term outcomes of octogenarians having heart operations and to analyse the interaction between patient and treatment factors. METHODS: Multivariate analysis of prospectively collected data and a survival comparison with an age and sex matched national population. The outcomes were base in-hospital mortality, risk stratified by logistic EuroSCORE (European system for cardiac operative risk evaluation), and long term survival. RESULTS: 12,461 consecutive patients (706 over 80 years) operated on between 1996 and 2003 in a regional UK unit were studied. Octogenarians more often had impaired ventricular function, pulmonary hypertension, and valve operations. They also included a higher proportion of women, had a higher serum creatinine concentration, and had a trend towards more unstable angina. Younger patients had a higher prevalence of previous cardiac operation, previous myocardial infarction, and diabetes. The in-hospital mortality rate was 3.9% for all patients (EuroSCORE predicted 6.1%, p < 0.001) and 9.8% for octogenarians (predicted 14.1%, p = 0.002). Long bypass time and non-elective surgery increased the risk of death above EuroSCORE prediction in both groups. A greater proportion of octogenarians stayed in intensive care more than 24 hours (37% v 23%, p < 0.001). Long term survival was significantly better in the study patients than in a general population with the same age-sex distribution (survival rate at five years 82.1% v 55.9%, p < 0.001). CONCLUSIONS: Cardiac surgery in a UK population of octogenarians produced excellent results. Elective referrals should be encouraged in all age groups.

Age Factors↗
PubMed2005

Extended ganciclovir prophylaxis in lung transplantation.

BACKGROUND: Positive cytomegaloviral status of the donor or of the recipient adversely affects survival and enhances the development of bronchiolitis obliterans syndrome (BOS) in lung transplant recipients. The role of ganciclovir prophylaxis in cytomegalovirus infection in respect to obliterative bronchiolitis or to BOS development is not known. METHODS: From the Papworth transplant database, we identified 146 patients who received organs from cytomegalovirus-positive donors. We classified patients into 3 groups as follows: Group 1 consisted of 42 patients who underwent transplantation between 1990 and 1992 when no prophylaxis was given; Group 2 consisted of 49 patients who underwent transplantation between 1992 and 1995 when 4 weeks of IV ganciclovir was given as prophylaxis; and Group 3 consisted of 55 patients who underwent transplantation between 1995 and 1998 when cytomegalovirus prophylaxis consisted of IV (1 week) followed by oral ganciclovir for a total of 3 months. Donor management, recipient management during and after surgery, and pharmacotherapy were uniform during the study period. We used survival and regression methods to compare these groups, adjusting for the transplantation type (single lung, double lung, or heart-lung) and for HLA typing. RESULTS: We found a significant difference among all 3 groups in numbers of cytomegaloviral disease episodes in the 1st year after transplantation. The number of rejection episodes in the 3 groups during the 1st post-transplant year gradually decreased from Group 1 to Group 3. We identified no statistically significant benefit in the time to BOS occurrence or in actuarial survival. CONCLUSION: Extended prophylaxis with IV and oral ganciclovir practically abolishes cytomegaloviral disease and is related to a decreased incidence of rejection episodes. However, ganciclovir prophylaxis is not related to a decreased incidence or progression of BOS or survival.

Adult↗
PubMed2004

Inflammatory related changes in bone mineral content in adults with cystic fibrosis.

BACKGROUND: Proinflammatory cytokines stimulate osteoclast activity and this could lead to increased bone resorption in patients with cystic fibrosis. The aim of this study was to determine whether markers of systemic inflammation are related to changes in bone mineral content (BMC) in adults with cystic fibrosis. METHODS: Total body BMC was assessed by dual energy x ray absorptiometry in 100 patients (54 male) of mean (SD) age 25.6 (7.1) years and forced expiratory volume in 1 second (FEV(1)) 61.8 (24.1)% predicted on recruitment to the study and 1 year later. Blood was also taken at these time points to measure markers of systemic inflammation. RESULTS: After 1 year BMC had reduced by 16.1 (62.1) g, p = 0.01; (0.6 (2.8)%). The change in BMC was related to mean levels of interleukin (IL)-6 (r(s) = -0.39, p<0.001) and C reactive protein (r(s) = -0.34, p = 0.002), intravenous antibiotic use (r(s) = -0.27, p = 0.006) and oral corticosteroid use (r(s) = -0.20, p = 0.045). Urinary markers of osteoclast activity were also related to IL-6 (r(s) = 0.27, p = 0.02). Multiple linear regression revealed that IL-6 (coefficient -2.2 (95% CI -3.4 to -1.0) per pg/ml, p = 0.001), colonisation with Burkholderia cepacia (coefficient -46.8 (95% CI -75.5 to -18.1), p = 0.002), and annual change in BMI (coefficient 15.4 (95% CI 3.6 to 27.2) per kg/m(2), p = 0.011) were independently significant predictors of annual change in BMC. CONCLUSIONS: These data suggest a pathophysiological mechanism by which chronic pulmonary infection results in bone loss in patients with cystic fibrosis.

Absorptiometry, Photon↗
PubMed2003

Performance status score: do patients and their oncologists agree?

Oncologists traditionally assess their patients' ECOG performance status (PS), and few studies have evaluated the accuracy of these assessments. In this study, 101 patients attending a rapid access clinic at Papworth Hospital with a diagnosis of lung cancer were asked to assess their own ECOG PS score on a scale between 0 and 4. Patients' scores were compared to the PS assessment of them made by their oncologists. Of 98 patients with primary non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC), weighted kappa statistics showed PS score agreement between patient and oncologist of 0.45. Both patient- and oncologist-assessed scores reflected survival duration (in NSCLC and SCLC) as well as disease stage (in NSCLC), with oncologist-assessed scores being only marginally more predictive of survival. There was no sex difference in patient assessment of PS scores, but oncologists scored female patients more pessimistically than males. This study showed that, with few exceptions, patients and oncologists assessed PS scores similarly. Although oncologists should continue to score PS objectively, it may benefit their clinical practice to involve their patients in these assessments.

Adult↗
PubMed2003

The use of hospital admission data as a measure of outcome in clinical studies of heart failure.

AIM: To describe and evaluate the methods currently used to summarize, depict, and analyse hospitalization data in clinical studies of patients with heart failure. METHODS AND RESULTS: Studies published during 1999 and 2000 were reviewed if they reported hospitalization data collected during the follow-up of a defined group of adults who had been diagnosed as having heart failure. Of 130 studies identified, the majority considered only the first of any hospital admissions for each individual. When presented, statistical analyses in 70% of papers, and graphics in 75% of papers, were based purely on the first hospitalization. A minority of papers based analyses on the number of admissions (23%), or the amount of time spent in hospital by patients (14%) during the follow-up period. CONCLUSIONS: Data on the hospitalizations undergone by patients with heart failure are potentially informative about the disease burden to individuals and health services. The widespread practice of focussing a statistical analysis on the first admission a patient undergoes discards those aspects of hospitalization that are informative about disease burden: multiple admissions and length of stay. Statistical methods that incorporate these aspects appeared in a handful of papers, and the more widespread adoption of these is desirable.

Data Collection↗
PubMed2002

A randomised controlled crossover trial of nurse practitioner versus doctor led outpatient care in a bronchiectasis clinic.

BACKGROUND: With the decrease in junior doctor hours, the advent of specialist registrars, and the availability of highly trained and experienced nursing personnel, the service needs of patients with chronic respiratory diseases attending routine outpatient clinics may be better provided by appropriately trained nurse practitioners. METHODS: A randomised controlled crossover trial was used to compare nurse practitioner led care with doctor led care in a bronchiectasis outpatient clinic. Eighty patients were recruited and randomised to receive 1 year of nurse led care and 1 year of doctor led care in random order. Patients were followed up for 2 years to ensure patient safety and acceptability and to assess differences in lung function. Outcome measures were forced expiratory volume in 1 second (FEV(1)), 12 minute walk test, health related quality of life, and resource use. RESULTS: The mean difference in FEV(1) was 0.2% predicted (95% confidence interval -1.6 to 2.0%, p=0.83). There were no significant differences in the other clinical or health related quality of life measures. Nurse led care resulted in significantly increased resource use compared with doctor led care (mean difference pound 1497, 95% confidence interval pound 688 to pound 2674, p<0.001), a large part of which resulted from the number and duration of hospital admissions. The mean difference in resource use was greater in the first year ( pound 2625) than in the second year ( pound 411). CONCLUSIONS: Nurse practitioner led care for stable patients within a chronic chest clinic is safe and is as effective as doctor led care, but may use more resources.

Ambulatory Care↗
PubMed2001

Heart-lung transplantation for Eisenmenger syndrome: early and long-term results.

BACKGROUND: Heart-lung transplantation (HLT) for Eisenmenger syndrome (ES) provides superior early and intermediate survival when compared with other forms of transplantation. The early risk factors and long-term outcome of HLT for ES are less well defined. METHODS: We analyzed 263 patients who had undergone HLT at our institution during more than 15 years. Fifty-one consecutive patients with ES who underwent HLT, 33 (65%) of which had simple anatomy, were compared with 212 cases having HLT for other indications (non-ES). RESULTS: Female sex and previous thoracotomy were more prevalent in the ES group. Patients with ES had greater postoperative blood loss and returned more frequently to the operating room for control of bleeding. There were 8 (16%) early deaths in the ES group compared with 27 (13%) in non-ES (p = 0.65). One-, 5-, and 10-year survival rates for ES were 72.6%, 51.3%, and 27.6%, respectively, compared with non-ES of 74.1%, 48.1%, and 26.0%, respectively, and there was no difference in survival overall (p = 0.54). Among ES patients, previous thoracotomy was a risk factor for hospital death. A subgroup analysis based on simple versus complex type of ES did not show statistically significant differences in terms of postoperative course or early or late survival. CONCLUSIONS: Heart-lung transplantation is a successful procedure for ES. Despite a greater frequency of risk factors and a more difficult operative course, early and late outcome with HLT is comparable to non-ES recipients.

Adult↗
PubMed2001

A UK trial-based cost--utility analysis of transmyocardial laser revascularization compared to continued medical therapy for treatment of refractory angina pectoris.

OBJECTIVE: Transmyocardial laser revascularization (TMLR) is used to treat patients with refractory angina considered unsuitable for conventional forms of revascularization. Using patient specific data from a single centre UK randomised-controlled trial, we aimed to determine whether, from a UK National Health Service (NHS) perspective, TMLR plus standard medical management is cost-effective when compared with standard medical management alone. METHODS: One hundred and eighty-eight patients assessed as having refractory angina, and not suitable for conventional forms of revascularization were randomized to receive TMLR and medical management (94) or medical management alone (94). Costs to the UK NHS of TMLR (where appropriate), and all secondary sector health care contacts and cardiac-related medication in the 12 months following randomization, were collected. Patient utility as measured using the EuroQol EQ-5D questionnaire was combined with 12-month survival data to generate quality adjusted life years (QALYs). RESULTS: The mean cost per patient over the year from hospitalization for TMLR was 11,470 pounds sterling and for medical management alone was 2586 pounds sterling, giving a cost difference of 8901 pounds sterling (95% confidence interval (CI) 7502 pounds sterling--10,008 pounds sterling: P < 0.0001). The mean QALY difference, in favour of TMLR was 0.039 (95% CI -0.033 to 0.113: P = 0.268). This gives an incremental cost per QALY of over 228,000 pounds sterling. Analysis of stochastic uncertainty and of sensitivity to gross changes in key parameters consistently produces very high costs per QALY. CONCLUSIONS: The policy implications are clear: for such patients TMLR is an inefficient use of UK health service resources. This conclusion would not be changed by considerable improvements in effectiveness or reductions in cost.

Aged↗
PubMed2001

A model for analyzing the cost of the main clinical events after lung transplantation.

BACKGROUND: The aim of this project was to model clinically important events experienced by lung transplant patients (from the day after transplant to 5 years or death) and costs associated with these events, and to assess the economic impact of different immunosuppression therapies. METHODS: The population comprised 356 lung transplant patients (223 heart-lung, 102 single lung and 31 double lung) transplanted between April 1984 and December 1997. All patients received a cyclosporine-based triple-immunosuppression protocol. We designed a Markov model that included 3 time periods (0 to 6, 7 to 12, and 13 to 60 months), 5 clinical states (well, acute rejection, cytomegalovirus infection, non-cytomegalovirus infection and bronchiolitis obliterans syndrome), and death. For the well state, cost elements were immunosuppression, prophylaxis, and routine clinic visits. For all other states, cost elements were diagnosis, treatment, and bed days/visits. We excluded costs of the procedure. RESULTS: The monthly costs associated with the well state decreased over time, from pound sterlings 1,778 ($2,658) in the first 6 months to pound sterlings 503 ($752) in months 7 to 12 and pound sterlings 350 ($523) after the first 12 months. The cost per event of the acute states remained reasonably constant over the 3 periods: pound sterlings 1,850 ($2,766) for rejection, pound sterlings 3,380 ($5,053) for cytomegalovirus, and pound sterlings 2,790 ($4,171) for other infections. The average cost per patient, discounted at 6%, over 5 years was pound sterlings 35,429 ($52,966) (95% range, pound1,435 [$2,145] to pound67,079 [$100,283]). This estimate is most sensitive to changes in immunosuppression. Substituting tacrolimus for cyclosporine increased 5-year costs by 5%; substituting mycophenolate mofetil for azathioprine increased 5-year costs by 26%. CONCLUSIONS: This model is valuable in estimating the effect of new immunosuppression agents on the costs of follow-up care.

Adult↗
PubMed2001

A piecewise-homogeneous Markov chain process of lung transplantation.

BACKGROUND: Markov and semi-Markov models are increasingly used in clinical and public health epidemiology to represent disease processes. We present a Markov model of events following lung transplantation as a case study in clinical epidemiology. METHODS: A five-state discrete-time Markov model with two-way transitions between acute event states is applied to the analysis of 356 lung transplant patients. A two-state continuous time Markov model for chronic disease onset is fitted. Values of transition parameters are estimated by maximum likelihood using numerical methods. RESULTS: Accurate estimates of acute and chonic event rates, and survival probabilities are calculated from transition probabilities. Costs attributed to different acute and chronic states are calculated. CONCLUSIONS: Transition models provide a useful and flexible representation of acute and chronic events and can be used to explore the economic impact of changes in therapy.

Algorithms↗
PubMed2000

Randomized trial of blood eosinophil count monitoring as a guide to corticosteroid dosage adjustment after heart transplantation.

BACKGROUND: Increases in blood eosinophil counts (EOS) beyond 0.06 x 10(9)/liter precede treated heart allograft rejection. An oral prednisolone dose of 0.35 mg/kg/day usually suppresses EOS below this threshold. METHODS: We designed a randomized trial to compare our empirical protocol for steroid dose adjustment with a novel protocol guided by EOS monitoring during the first 3 months after heart transplantation. Eighty patients were randomized to either have their EOS reported and used for steroid dose adjustment (RG; n=40), or not reported (NG; n=40). RG patients had their steroid dosage increased if EOS exceeded 0.06 x 10(9)/liter. RESULTS: RG patients had an 83% lower risk of treated rejection (P=0.035) and lower median intravenous dose of methyl-prednisolone (P=0.017) than NG during the first 6 postoperative weeks. The proportion of diagnostic increases in EOS that were followed within 2 weeks by treated rejection was 42% greater in NG than RG (P=0.0001), compatible with a direct impact of EOS-guided prednisolone dose adjustment on the risk of subsequent rejection. Overall, RG had less than half the risk of rejection of any grade (P<0.001) and significantly more rejection-free biopsies than NG (P=0.001). The mean oral prednisolone dosage was significantly greater in RG than NG during the first (P=0.014) and second (P=0.001) 6 weeks of follow-up. This did not increase the incidence of serious steroid-related side effects. CONCLUSIONS: EOS monitoring is a simple, cheap, and effective means of optimizing steroid immunosuppression. Restriction of the EOS-guided steroid dosing protocol to periods of prolonged hospitalisation during the first 3 postoperative months should limit the requirement for higher prednisolone dosage without affecting immunosuppressive efficacy.

Adrenal Cortex Hormones↗