Gilbert L’Italien

Multicountry burden of chronic hepatitis C viral infection among those aware of their diagnosis: a patient survey.

Background The World Health Organization has called for global and regional assessments of the burden of hepatitis C (HCV) along with country-specific patient profiles to better inform healthcare policy. The present investigated the characteristics and burden of patients reporting a diagnosis of HCV infection in the US, France, Germany, Italy, Spain, the UK, urban China, and Japan using a consistent methodology of patient-reported surveys. Methods The 2010 5EU (N = 57,805), 2009 US (N = 75,000), 2008/2009 Japan (N = 37,683), and 2009/2010 urban China (N = 33,261) waves of the National Health and Wellness Survey were used as the data source. Within each country, patients with a self-reported diagnosis of HCV were compared with those who did not report a diagnosis of HCV on sociodemographics, health behaviors, comorbidities, and health outcomes (e.g., Short Form-12v2). The effect of HCV was examined using regression analysis applying sampling weights. Results The prevalence of HCV ranged from 0.26% (China) to 1.42% (Italy). Patients in Japan and Italy (61.60 and 61.02 years, respectively) were the oldest, while patients in the US were the most likely to be obese (39.31%) and have concomitant anxiety (38.43%) and depression (46.05%) compared with other countries. Pooling countries and adjusting for sociodemographics, health behaviors, and comorbidities, HCV was associated with significantly lower physical component summary scores (b = −2.51) and health utilities (b = −0.04) and greater overall work impairment (b = 8.79), physician visits (b = 2.91), and emergency department visits (b = 0.30) (all p<.05). The effects on health status were strongest in the US and UK while the effects on healthcare resource use were strongest in Japan. Conclusions HCV was associated with a significant humanistic and economic burden. These results suggest that the manifestation of the HCV burden, and the profile of the patients themselves, varied dramatically by country. Successful disease management should be cognizant of region-specific unmet needs.

Renal function following living, standard criteria deceased and expanded criteria deceased donor kidney transplantation: impact on graft failure and death

We examined United States Renal Data System (USRDS) data for adult kidney transplant recipients in 1995–2003 (n = 87 575) to investigate associations of 12‐month renal function with long‐term clinical outcomes. Estimated glomerular filtration rate (eGFR) was computed by the Modification of Diet in Renal Disease (MDRD) equation. Associations of eGFR at the first transplant anniversary with graft and patient‐survival in years 1–9 post‐transplant were evaluated by multivariate nonlinear regression with spline forms, adjusted for recipient, donor, and transplant factors. Regardless of donor type, the likelihood of graft failure and death increased significantly with lower eGFR. The impact of poor eGFR was more pronounced for graft failure than death. Relative effects were similar across donor types, but were strongest among living‐donor recipients. For example, compared with reference eGFR of 80 ml/min/1.73 m2, 1‐year eGFR of 20 ml/min/1.73 m2 was associated with adjusted hazards ratios for subsequent death‐censored graft failure of 9.2 in living, 8.9 in standard criteria deceased, and 5.9 in expanded criteria deceased‐donor recipients. First‐year renal function after kidney transplantation has strong, nonlinear associations with subsequent allograft and patient survival regardless of donor type. Post‐transplant eGFR may be a useful end‐point for discriminating benefits of care strategies that differentially affect renal function.

Cost-effectiveness of atypical antipsychotics for the management of schizophrenia in the UK .

ABSTRACT Objective: To evaluate the cost-effectiveness of atypical antipsychotic treatment sequences for the management of stable schizophrenia in the UK. Research design and methods: A Markov model was developed to assess the cost per quality-adjusted life year (QALY) gained from 12 alternative treatment sequences each containing two of four atypical antipsychotics (aripiprazole, olanzapine, quetiapine and risperidone), followed by clozapine. The main model parameters were populated with data from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study and a recent trial comparing aripiprazole with olanzapine. Patients enter the model with stable schizophrenia and may relapse, discontinue or continue and experience adverse events (AEs), or develop diabetes. Population mortality was adjusted for schizophrenia and diabetes. Utility decrements applied to stable schizophrenia, relapse, diabetes and treatment-related AEs were taken from a direct UK utility elicitation study. Resource use and unit costs were taken from published sources. A time horizon of 10 years was adopted. Results are based on 10,000 probabilistic iterations of the model. Results: Aripiprazole followed by risperidone produced the greatest number of QALYs, an additional 0.03 compared with risperidone followed by olanzapine, at an incremental cost of £257 (incremental cost/QALY: £9,440). Aripiprazole followed by risperidone had the greatest probability among evaluated sequences of being cost-effective at a threshold of >£10,000/QALY. All other strategies were dominated by at least one of these strategies. The impact of lower pricing for risperidone (based on generic availability) did not impact results. Conclusions: Modelling the cost-effectiveness of different treatment sequences for stable schizophrenia is appropriate given that patients rarely remain on one treatment for long periods. The treatment sequence aripiprazole followed by risperidone was the most cost-effective option for patients with stable schizophrenia in the UK.

The cost implications of first anniversary renal function after living, standard criteria deceased and expanded criteria deceased donor kidney transplantation

Abstract Objectives: To quantify relationships of post-transplant renal function with healthcare costs after kidney transplantation. Methods: Clinical and billing records for Medicare-insured kidney transplant recipients (1995–2003) were drawn from the US Renal Data System. Estimated glomerular filtration rate (eGFR) at 1-year post-transplant was computed with the abbreviated Modification of Diet in Renal Disease equation. Associations of eGFR with total Medicare payments in the second and third post-transplant years were examined by multivariate non-linear regression with spline forms. Adjustment covariates were drawn from the survival prediction model developed by the UNOS Kidney Allocation Review Committee. Results: The sample comprised 7103 living donor (LD), 22,110 standard criteria deceased (SCD), and 2594 expanded criteria deceased (ECD) donor transplant recipients. Regardless of donor type, lower 1-year eGFR was associated with significantly increased expenditures during the second and the third years post-transplant. Marginal costs began to increase as eGFR fell below 45 mL/min/1.73 m2 and rose in an accelerating manner. Compared to a reference eGFR of 75 mL/min/1.73 m2, 1-year eGFR of 20 ml/min/1.73 m2 in SCD recipients was associated with ∼ 

Projecting Long-Term Graft and Patient Survival after Transplantation

17,500 and

The Patient-Related Burden of Pegylated-Interferon-α Therapy and Adverse Events among Patients with Viral Hepatitis C in Japan☆

18,200 higher adjusted payments in the second and third post-transplant years, respectively. Patterns were similar among recipients of LD and ECD transplants. Limitations: The study sample was limited to Medicare beneficiaries who survived with allograft function to the first transplant anniversary, which may limit generalizability of the findings. eGFR is a surrogate measure of renal function. The design is retrospective and changes in post-transplant management may alter long-term cost implication of renal function. Conclusions: Decreased renal function is significantly associated with higher healthcare expenditures following kidney transplantation. Post-transplant eGFR may be a useful metric for discriminating the economic impact of care strategies that differentially affect renal function.

A Glycomarker for Short-term Prediction of Hepatocellular Carcinoma: A Longitudinal Study With Serial Measurements

OBJECTIVE In spite of increases in short-term kidney transplant survival rates and reductions in acute rejection rates, increasing long-term graft survival rates remains a major challenge. The objective here was to project long-term graft- and survival-related outcomes occurring among renal transplant recipients based on short-term outcomes including acute rejection and estimated glomerular filtration rates observed in randomized trials. METHODS We developed a two-phase decision model including a trial phase and a Markov state transition phase to project long-term outcomes over the lifetimes of hypothetical renal graft recipients who survived the trial period with a functioning graft. Health states included functioning graft stratified by level of renal function, failed graft, functioning regraft, and death. Transitions between health states were predicted using statistical models that accounted for renal function, acute rejection, and new-onset diabetes after transplant and for donor and recipient predictors of long-term graft and patient survival. Models were estimated using data from 38,015 renal transplant recipients from the United States Renal Data System. The model was populated with data from a 3-year, randomized phase III trial comparing belatacept to cyclosporine. RESULTS The decision model was well calibrated with data from the United States Renal Data System. Long-term extrapolation of Belatacept Evaluation of Nephroprotection and Efficacy as Firstline Immunosuppression Trial was projected to yield a 1.9-year increase in time alive with a functioning graft and a 1.2 life-year increase over a 20-year time horizon. CONCLUSIONS This is the first long-term follow-up model of renal transplant patients to be based on renal function, acute rejection, and new-onset diabetes. It is a useful tool for undertaking comparative effectiveness and cost-effectiveness studies of immunosuppressive medications.

UK cost-consequence analysis of aripiprazole in schizophrenia: diabetes and coronary heart disease risk projections (STAR study)

OBJECTIVES Pegylated-interferon-α (IFN-α)-based therapies for viral hepatitis C (HCV) are effective, but they are associated with several adverse events (AEs). The primary objectives of this study were to quantify the burden of IFN-α-based treatment and to measure the prevalence and burden of IFN-α-related AEs in Japan. METHODS A cross-sectional survey was administered online to patients with HCV in 2013. Patients who were currently taking IFN-α-based therapy (n = 188) were compared with patients who were taking a liver protectant but not IFN-α-based therapy (n = 180) and with patients who were untreated (n = 365) on measures of health-related quality of life (using the Hepatitis Quality of Life Questionnaire, version 2), work productivity, and health care resource use, controlling for sociodemographic characteristics and health history. Among patients taking IFN-α-based therapy, the prevalence and burden of AEs was examined on the same set of health outcomes as noted above along with treatment satisfaction and adherence. RESULTS Compared with untreated patients, patients using IFN-α reported poorer health-related quality of life (physical component summary score, 50.13 vs. 52.04; mental component summary score, 44.12 vs. 47.97), more overall work impairment (32.73 vs. 25.64), more physician visits in the past 6 months (14.51 vs. 8.36), and an increased likelihood of an emergency room visit (odds ratio = 7.25) and hospitalization (odds ratio = 4.05) (all P < 0.05). The mean number of AEs was 6.05 for patients using IFN-α. All AEs were associated with poorer health outcomes (particularly the mental component summary score), and most were also associated with lower treatment satisfaction and medication adherence. CONCLUSIONS A significant patient burden for IFN-α treatment itself and various AEs was observed. The results suggest that effective, non-IFN-α-based treatments may reduce the societal burden.

High hepatitis C viral load and genotype 2 are strong predictors of chronic kidney disease

Objectives: Wisteria floribunda agglutinin‐positive human Mac‐2‐binding protein (WFA+‐M2BP) is a glycomarker. The present community‐based long‐term follow‐up study repeatedly determined the serum WFA+‐M2BP level and examined its short‐ and long‐term associations with hepatitis C virus (HCV)‐related hepatocellular carcinoma (HCC). Methods: A total of 921 participants with antibodies against HCV seropositive, but seronegative for hepatitis B surface antigen were enrolled from seven townships in Taiwan during 1991–1992. The participants were regularly followed and their serum WFA+‐M2BP levels were measured at baseline and follow‐up. HCC was ascertained through active follow‐up and computerized data linkage with the National Cancer Registration System until December 31, 2013. Cox proportional hazards and logistic regression models were applied to estimate the magnitude of associations between serum WFA+‐M2BP levels and HCC. Results: During a median follow‐up of 21.7 years, 122 new‐onset HCC cases were identified. Elevated serum WFA+‐M2BP levels were associated with an increased risk of HCC (p < 0.001). Patients with increasing changes in serum WFA+‐M2BP levels, relative to their baseline levels, had a 4.36‐fold risk of HCC. The areas under receiver operating curves (AUROCs) of WFA+‐M2BP for predicting HCC showed that the prediction efficacy was significantly higher while closer to HCC diagnosis (p = 0.024). The AUROC was 0.91 for predicting HCC within 1 year by including the predictors of age, sex, alanine aminotransferase, alpha‐fetoprotein (AFP) and WFA+‐M2BP. Conclusions: Serum WFA+‐M2BP level may elevate before HCC onset and is a short‐term predictor of HCC among patients infected with HCV.