The Model of Mortality with Incident Cirrhosis (MoMIC) and the model of Long-term Outlook of Mortality in Cirrhosis (LOMiC).

The purpose of this study was to produce two statistical survival models in those with cirrhosis utilising only routine parameters, including non-liver-related clinical factors that influence survival. The first model identified and utilised factors impacting short-term survival to 90-days post incident diagnosis, and a further model characterised factors that impacted survival following this acute phase. Data were from the Clinical Practice Research Datalink linked with Hospital Episode Statistics. Incident cases in patients ≥18 years were identified between 1998 and 2014. Patients that had prior history of cancer or had received liver transplants prior were excluded. Model-1 used a logistic regression model to predict mortality. Model-2 used data from those patients who survived 90 days, and used an extension of the Cox regression model, adjusting for time-dependent covariables. At 90 days, 23% of patients had died. Overall median survival was 3.7 years. Model-1: numerous predictors, prior comorbidities and decompensating events were incorporated. All comorbidities contributed to increased odds of death, with renal disease having the largest adjusted odds ratio (OR = 3.35, 95%CI 2.97-3.77). Model-2: covariables included cumulative admissions for liver disease-related events and admissions for infections. Significant covariates were renal disease (adjusted hazard ratio (HR = 2.89, 2.47-3.38)), elevated bilirubin levels (aHR = 1.38, 1.26-1.51) and low sodium levels (aHR = 2.26, 1.84-2.78). An internal validation demonstrated reliability of both models. In conclusion: two survival models that included parameters commonly recorded in routine clinical practice were generated that reliably forecast the risk of death in patients with cirrhosis: in the acute, post diagnosis phase, and following this critical, 90 day phase. This has implications for practice and helps better forecast the risk of mortality from cirrhosis using routinely recorded parameters without inputs from specialists.

Evaluation of the cost-effectiveness of rifaximin-α for the management of patients with hepatic encephalopathy in the United Kingdom.

OBJECTIVE: Rifaximin-α 550 mg twice daily plus lactulose has demonstrated efficacy in reducing recurrence of episodes of overt hepatic encephalopathy (OHE) and the risk of hepatic encephalopathy (HE)-related hospitalizations compared with lactulose alone. This analysis estimated the cost effectiveness of rifaximin-α 550 mg twice daily plus lactulose versus lactulose alone in United Kingdom (UK) cirrhotic patients with OHE. METHOD: A Markov model was built to estimate the incremental cost-effectiveness ratio (ICER). The perspective was that of the UK National Health Service (NHS). Clinical data was sourced from a randomized controlled trial (RCT) and an open-label maintenance study in cirrhotic patients in remission from recurrent episodes of OHE. Health-related utility was estimated indirectly from disease-specific quality of life RCT data. Resource use data describing the impact of rifaximin-α on hospital admissions and length of stay for cirrhotic patients with OHE was from four single-center UK audits. Costs (2012) were derived from published sources; costs and benefits were discounted at 3.5%. The base-case time horizon was 5 years. RESULTS: The average cost per patient was £22,971 in the rifaximin-α plus lactulose arm and £23,545 in the lactulose arm, a saving of £573. The corresponding values for benefit were 2.35 quality adjusted life years (QALYs) and 1.83 QALYs per person, a difference of 0.52 QALYs. This translated into a dominant base-case ICER. Key parameters that impacted the ICER included number of hospital admissions and length of stay. CONCLUSION: Rifaximin-α 550 mg twice daily in patients with recurrent episodes of OHE was estimated to generate cost savings and improved clinical outcomes compared to standard care over 5 years.

Cost-effectiveness of tapentadol prolonged release compared with oxycodone controlled release in the UK in patients with severe non-malignant chronic pain who failed 1st line treatment with morphine.

OBJECTIVES: The aim of this analysis was to assess the cost-effectiveness of tapentadol PR (prolonged release) compared with oxycodone CR (controlled release) in severe non-malignant chronic pain patients in whom controlled release morphine was ineffective or not tolerated. METHODS: A Markov model was developed to assess costs and benefits over a 1-year time horizon from the National Health Service perspective in the UK. Patients could either continue on 2nd line therapy or switch to 3rd line opioid due to lack of efficacy or poor tolerability. Patients failing also 3rd line therapy entered the final absorbing health state (4th line). Data on tolerability, efficacy, and utilities for tapentadol and oxycodone were obtained from the three comparative phase III clinical trials. Costs of resource consumption associated with opioid treatment were derived from a retrospective database analysis of anonymized patient records. RESULTS: The model results predicted that initiating 2nd line therapy with tapentadol leads to higher effectiveness and lower costs vs oxycodone. For the overall population included in the clinical trials, mean annual costs per patient when treated with tapentadol and oxycodone were £3543 and £3656, respectively. Treatment with tapentadol, while cheaper than oxycodone, was more effective (0.6371 vs 0.6237 quality-adjusted life years (QALYs) for tapentadol and oxycodone, respectively), meaning that tapentadol dominated oxycodone. For the sub-group of opioid-experienced patients with severe pain at baseline the ranking in terms of costs and QALYs remained unchanged. Extensive sensitivity analyses showed that conclusions about the cost-effectiveness are consistent. CONCLUSIONS: The cost-effectiveness study suggested that initiating 2nd line treatment in patients with severe non-malignant chronic pain in the UK with tapentadol instead of oxycodone improves patients' quality-of-life and is less costly. Key limitations when interpreting the results are the use of different sources to populate the model and restricted generalizability due to data extrapolation.

The relationship between self-reported severe pain and measures of socio-economic disadvantage.

AIMS: To determine the association of severe pain with socioeconomic characteristics. METHODS: Data was extracted from the Health Survey for England (HSE), 2005. The HSE is a series of annual cross-sectional surveys designed to describe the health of people living in private homes in England, from a random sample of 720 postcode sectors. Interviewees were ≥ 16 years. Pain severity was characterised by the EQ-5D. Socioeconomic status was classified by ability to work, social security benefits, the National Statistics Socio-economic Classification (NS-SEC) and the Index of Multiple Deprivation (IMD). RESULTS: Pain status was recorded for 9419 subjects of whom 431 (4.6%) reported severe pain. 156 of those reporting severe pain were of working age. Of these 68 (43.6%) stated they were unable to work due to sickness or disability and 64 (41.0%) claimed a state benefit. After adjusting for disease and demographic variables, severe pain was associated with the IMD with an odds ratio of 1.65 (95% CI 1.16-2.34, p=0.005), NS-SEC (OR=2.94; 95% CI 1.76-4.91) and equivalised household income (lowest versus highest quintile; OR=2.58 (95% CI 1.46-4.57, p=0.001). CONCLUSIONS: This study demonstrated significant associations between pain and socio-economic disadvantage. Apart from the direct impact upon the individual, this clearly has wider societal implications in terms of additional health and social care costs for affected people.

Descriptive epidemiology of hospitalisation for psoriasis.

BACKGROUND: The epidemiology and outcome of people hospitalised with a primary diagnosis of psoriasis has never been characterised previously in the United Kingdom. The aim of the study was to characterise the epidemiology of people admitted to hospital with a primary diagnosis of psoriasis. METHODS: Routine hospital data from a large urban area of South Wales, UK (with a population of approximately 435,000) were record-linked using probability matching algorithms to mortality data from the Office of National Statistics (1991-2005). Relative survival was compared using Cox proportional hazards models. Patients were selected with a primary diagnosis of psoriasis. Admission rates were calculated as a proportion (%) of admissions and a crude population rate. RESULTS: It was possible to identify 1935 hospital admissions from 1038 subjects; 49% male. The mean age at first admission was 44 years (SD 20). The minimum, crude prevalence of people hospitalised with psoriasis at some time was 0.23%. These admissions represented 0.13% of all hospital admissions. The crude admission rate with a primary diagnosis of psoriasis was 2.9 per 10,000 population per year. The proportion of subjects who had only one admission ranged between 65% and 77%. The median time between the first admission and the second admission was 1.4 years (IQR 0.5-3.1). The mean length of hospital stay was 16.8 days (median 15; IQR 8-23). There were 55 deaths in total in this group. Ten year survival was 92.7%. Following standardisation, people admitted more than once had increased risk of all cause mortality (hazard ratio 2.71; 95% CI 1.39-5.31). CONCLUSION: This study provides useful background intelligence on the most severe psoriasis patients identified by their admission to hospital with the condition. The proportion of psoriasis patients admitted was estimated to be about one in six people. Those with more than one admission with psoriasis--greater psoriasis severity--were associated with increased risk of all-cause mortality.

The association between C-reactive protein and the likelihood of progression to joint replacement in people with rheumatoid arthritis: a retrospective observational study.

BACKGROUND: This study sought to evaluate the association between systemic inflammation as measured by C-reactive protein and total joint replacement and the association between change in CRP status (low, < or = 10 mg/L and high, >10 mg/L) measured over one year and total joint replacement in patients diagnosed with rheumatoid arthritis. METHODS: A cohort of patients was selected from The Health Improvement Network (THIN) dataset of anonymised patient-level data from UK general practice with a confirmed chronic rheumatic diagnosis. Surgery-free survival was evaluated using Cox proportional hazards regression models (CPHM). RESULTS: 2,421 cases had at least one CRP measurement of which 125 cases (5.2%) had at least one major joint replacement. In CPHM, each additional unit increase in log mean CRP (range 1 to 6) was associated with a hazard ratio (HR) for major orthopaedic surgery of 1.36 (95% CI 1.10 to 1.67; p = 0.004), after controlling for age at first rheumatoid presentation and average body mass index over the same observation period. Repeated CRP observations around one year apart were recorded in 1,314 subjects. After controlling for confounding factors, in cases whose CRP remained high (>10 mg/L), the HR for joint replacement increased more than two-fold (p = 0.040) relative to cases whose CRP remained low. In patients whose CRP increased from low to high, the HR was 1.86 compared to those who remained in a low state (p = 0.217). By comparison, among those subjects whose CRP was reduced from a high to low state, the hazard ratio was more than halved (1.46) from to those who remained high (p = 0.441). Although underpowered, the trend evident from CRP change corroborates the association of TJR progression with mean CRP. CONCLUSION: CRP level predicts progression to major joint replacement after standardisation for relevant risk factors as did change in CRP status between low and high states observed over one year.

An evaluation of the association between systemic inflammation--as measured by C-reactive protein--and hospital resource use.

OBJECTIVE: To evaluate the association between inflammatory status, as measured by C-reactive protein (CRP), during inpatient admission and subsequent inpatient outcome and associated resource use. METHODS: Probabilistic record linkage was used to match hospital episode data, laboratory reports and mortality statistics in a large urban population of 424,000 people in South Wales, UK. Inpatient mortality, length of stay, emergency readmissions and subsequent 1-year hospital bed day occupancy were assessed as a function of CRP status. RESULTS: Between 2001 and 2005, in total there were 432,272 CRP observations from 98,505 people; 69,593 admissions had at least one CRP measurement, affecting 47,100 individual patients. Across all ICD-10 primary diagnoses, CRP was acutely high (> 10 mg/L) in three-quarters of admissions. Acutely high CRP was associated with an eight-fold increase in risk of hospital mortality (p < 0.001) and a doubling of length of stay (p < 0.001) compared to normal CRP levels, after standardising for age and gender. Across the range of observed maximum CRP values measured during admissions (1 mg/L to > 400 mg/L) the likelihood of emergency readmission within 28 days of discharge increased by 50% (p < 0.001), and the predicted number of subsequent bed days occupied in the year following discharge increased by 30-58% across the range of CRP measurement (p = 0.004). CONCLUSIONS: CRP has been found to be clearly associated with hospital resource use. Furthermore, CRP also predicted in-hospital mortality. This may imply that better management of systemic inflammation would result in resource savings in inflammatory diseases such as rheumatoid arthritis.

Evaluation of the cost effectiveness of sirolimus versus tacrolimus for immunosuppression following renal transplantation in the UK.

INTRODUCTION: Immunosuppressive therapy is required to prevent graft rejection. Calcineurin inhibitors such as tacrolimus are paradoxically toxic to the kidney, whereas sirolimus (rapamycin; Rapamune) is not generally associated with the nephrotoxicity of CNIs. The purpose of this study was to evaluate the relative cost utility of sirolimus versus tacrolimus for the primary prevention of graft rejection in renal transplant recipients in the UK. METHODS: A stochastic simulation model was constructed using clinical trial and observational data comparing the two treatments. Time duration was up to 20 years. Costs were from a UK NHS perspective, valued at 2003 prices and discounted at 6%. Benefits were discounted at 1.5%. Simulated events included patient and graft survival, haemodialysis, peritoneal dialysis, re-transplants and acute rejection. Costs were summed for events and various maintenance therapies. Utility was differentially accredited depending upon survival and using the alternative renal replacement therapies. Outcome was predicted using post-transplant creatinine levels up to 3 years. Extensive statistical economic and sensitivity analyses were undertaken. RESULTS: Over the 10-year horizon, sirolimus gained 0.72 years (discounted) of functioning graft over tacrolimus, resulting in an incremental cost per year of functioning graft that was dominant. Over a 20-year time horizon, the cost effectiveness of sirolimus over tacrolimus further improved with an average discounted gain in years of a functioning graft of 1.8 years, resulting in an incremental cost-utility ratio that was also dominant. The number of haemodialysis events was 48,243 for sirolimus recipients versus 127,829 for those receiving tacrolimus and peritoneal dialysis events 40,872 versus 105,249, respectively. Similar values were obtained when real-life observational data on tacrolimus use in Cardiff, Wales were entered into the model. Using data from Cardiff, sirolimus remained dominant over tacrolimus under all scenarios. CONCLUSION: Our study suggests that sirolimus may be more cost effective than tacrolimus for the primary prevention of graft rejection in renal transplant recipients in the UK. Sirolimus was economically 'dominant' under almost all scenarios investigated. This finding was robust using statistical economic analysis and univariate sensitivity analysis.

Evaluation of the cost-effectiveness of sirolimus versus cyclosporin for immunosuppression after renal transplantation in the United Kingdom.

OBJECTIVE: The purpose of this study was to evaluate the cost-effectiveness of sirolimus compared with cyclosporin for the postsurgical management of renal transplant recipients, from the perspective of the UK National Health Service and the Personal Social Service. METHODS: A discrete event stochastic simulation model was developed to evaluate both cost-effectiveness and cost utility over 10 and 20 years after transplant using historical data on 937 renal transplant recipients from the University Hospital of Wales in Cardiff, United Kingdom. The simulation was designed to forecast the incidence of acute rejection events, graft failure, retransplant, frequency of hemodialysis (HD) and peritoneal dialysis (PD), and death. Cox proportional hazard models were derived from historical transplant data, in which 1-, 2-, and 3-year post-transplant serum creatinine levels were used as the key drivers for predicting graft success and survival. Costs were reported as year-2003 UK pounds sterling (1 UK pound = US $1.76). Probabilistic sensitivity analysis was conducted and results reported with particular attention to 2 threshold values, 30,000/QALY and 20,000/QALY RESULTS: Over a 10-year time horizon, treatment with sirolimus was projected to produce a gain of 0.60 discounted year of functioning graft with a cost savings of 276 UK pounds per patient. Over a 20-year time horizon these benefits increased to 1.59 discounted years of functioning graft and a cost savings of 7405 UK pounds per patient. Using sensitivity analysis of the 10-year model, the only factors found to cause the probability of exceeding a 30,000 ceiling to be >5% were the proportion of subjects maintaining continuous graft function and the use of low-dose cyclosporin. With the 20-year model, sirolimus maintained cost-effectiveness across most scenarios in sensitivity analysis. CONCLUSIONS: In this model analysis, sirolimus was cost-effective compared with cyclosporin for 10 to 20 years after renal transplantation in the United Kingdom, from the perspective of the UK National Health Service and Personal Social Service.

Characterisation and comparison of health-related quality of life for patients with renal failure.

OBJECTIVE: The objective of this study was to assess the health related quality of life (HRQOL) in patients with kidney failure who had received renal transplants compared to those receiving haemodialysis, peritoneal dialysis or were waiting to start dialysis. RESEARCH DESIGN AND METHODS: The study was conducted at the University Hospital of Wales, Cardiff. HRQOL was measured using the EQ-5D, SF-36 and the Kidney Disease Quality of life questionnaire (KDQOL). Patients with kidney failure were identified from the renal unit departmental database and were surveyed by postal questionnaire or during their treatment. RESULTS: Of 1251 people surveyed, 416 valid returns were received, a response rate of 33%. For renal transplant patients the mean EQ-5Dindex was 0.712 (SD 0.272), significantly higher than those in the other treatment groups (haemodialysis mean = 0.443 (SD 317), p < 0.001; peritoneal dialysis mean = 0.569 (SD 329), p < 0.001). This difference remained after controlling for age and co-morbidity. With the exception of pain, the SF-36 showed significantly higher scores across all domains for transplant patients compared to both dialysis groups. From the KDQOL there were significantly lower scores compared with the transplant patients for both groups of dialysis patients for the effects and burden of kidney disease and general symptoms and problems. However, overall health scores were significantly higher for dialysis patients compared with transplant patients. CONCLUSION: Kidney failure has a high cost in terms of health related quality of life. There was a large difference between patients who have received a functioning graft following kidney transplant versus the alternative methods of renal replacement therapy, that is, peritoneal dialysis and haemodialysis. Kidney transplant should be the treatment of choice, and every effort should be made to increase the availability of kidneys for transplantation.

Patterns of graft and patient survival following renal transplantation and evaluation of serum creatinine as a predictor of survival: a review of data collected from one clinical centre over 34 years.

BACKGROUND: The pattern of renal transplantation has never been described since the introduction of the technique. The purpose of this study was therefore to characterise the pattern of renal transplantation from 1967 to 2000, focusing on renal graft function as a predictor of survival. METHODS: This study was a retrospective analysis of an electronic database. The setting was a single renal transplant centre in the United Kingdom covering a population of 2.2 million and included patients who received at least one renal transplant over the study period (n = 1516). The main outcome measures were patient and graft survival, acute rejection episodes and patterns of graft function, as measure by creatinine levels. RESULTS: There were 559 (36.8%) female patients; 109 (7.2%) patients had pre-existing diabetes. Patient survival was adversely affected by increased age at transplant (p < 0.001): 5-year patient survival from first transplant was 82% for patients aged 0 to 17 years, 80% for 18 to 49 years and 61% for > 49 years. Pre-existing diabetes also adversely affected survival (p < 0.01): 5-year graft survival was 63% for patients with diabetes versus 74% for those without. Graft survival was significantly associated with serum creatinine levels recorded 1 year post-primary transplant (p < 0.001) and with three or more acute rejection episodes (p < 0.05). Neither gender nor diabetes status were statistically significant in predicting graft survival. The number of acute rejection episodes was significantly greater in patients with pre-existing diabetes than those without (61% versus 42%, respectively; p < 0.001). There were no differences in the number of acute rejection episodes occurring across age groups. CONCLUSION: Patient and graft survival improved markedly over the 34-year study period, although patient survival has changed little since 1990. Serum creatinine levels are a reliable predictor of graft survival.

Cost effectiveness of representatives of three classes of antidepressants used in major depression in the UK.

OBJECTIVE: To estimate the cost effectiveness of representatives of three different classes of antidepressants used in major depression in the UK NHS. DESIGN, PATIENTS AND INTERVENTIONS: A decision-tree model for the treatment of major depression was constructed by interviewing UK GPs and psychiatrists (as part of a Delphi panel). An important part of the tree was that patients in primary care were treated until remission (pre-morbid state). Three classes of antidepressants (serotonin and noradrenaline reuptake inhibitors [SNRIs; venlafaxine], selective serotonin reuptake inhibitors [SSRIs; fluoxetine, paroxetine and fluvoxamine] and tricyclic antidepressants [TCAs; amitriptyline]) were compared by populating the tree with clinical success rates determined by a meta-analysis and a clinical trial. Where there were insufficient data from clinical trials a Delphi panel was used. Costs within the tree were taken from UK data sources. Six-monthly costs and cost effectiveness were then calculated. MAIN OUTCOME MEASURES AND RESULTS: Treatment costs for 6 months were pound 1285 for venlafaxine, pound 1348 for SSRIs and pound 1385 for amitriptyline. Cost effectiveness as measured by cost per symptom-free day was pound 21 for venlafaxine, pound 26 for SSRIs and pound 32 for TCAs (2001 values). Incremental cost-effectiveness analyses showed a treatment strategy of using venlafaxine and switching if necessary to an SSRI was dominant over all other strategies considered. Sensitivity testing demonstrated that the cost of an SSRI could be reduced to 4 pence daily and amitriptyline to zero before the expected 6-monthly cost of venlafaxine ceased to be the lowest. CONCLUSION: The SNRI, venlafaxine, may be a cost-effective option compared with the SSRIs and TCAs when used as a first-line drug for depression in primary care in the UK. As this is a model, cost effectiveness can be suggested but not proven.