Cost-effectiveness of 7-day-Holter monitoring alone or in combination with transthoracic echocardiography in patients with cerebral ischemia

Background and purpose

Prolonged Holter monitoring of patients with cerebral ischemia increases the detection rate of paroxysmal atrial fibrillation (PAF); this leads to improved antithrombotic regimens aimed at preventing recurrent ischemic strokes. The aim of this study was to compare a 7-day-Holter monitoring (7-d-Holter) alone or in combination with prior selection via transthoracic echocardiography (TTE) to a standard 24-h-Holter using a cost-utility analysis.

Methods

Lifetime cost, quality-adjusted life years (QALY), and incremental cost-effectiveness ratios (ICER) were estimated for a cohort of patients with acute cerebral ischemia and no contraindication to oral anticoagulation. A Markov model was developed to simulate the long-term course and progression of cerebral ischemia considering the different diagnostic algorithms (24-h-Holter, 7-d-Holter, 7-d-Holter after preselection by TTE). Clinical data for these algorithms were derived from the prospective observational Find-AF study (ISRCTN 46104198).

Results

Predicted lifelong discounted costs were 33,837 € for patients diagnosed by the 7-d-Holter and 33,852 € by the standard 24-h-Holter. Cumulated QALYs were 3.868 for the 7-d-Holter compared to 3.844 for the 24-h-Holter. The 7-d-Holter dominated the 24-h-Holter in the base-case scenario and remained cost-effective in extensive sensitivity analysis of key input parameter with a maximum of 8,354 €/QALY gained. Preselecting patients for the 7-d-Holter had no positive effect on the cost-effectiveness.

Conclusions

A 7-d-Holter to detect PAF in patients with cerebral ischemia is cost-effective. It increases the detection which leads to improved antithrombotic regimens; therefore, it avoids recurrent strokes, saves future costs, and decreases quality of life impairment. Preselecting patients by TTE does not improve cost-effectiveness.     

How much does it cost to care for survivors of colorectal cancer? Caregiver’s time, travel and out-of-pocket costs

Purpose

Cancer treatment is increasingly delivered in an outpatient setting. This may entail a considerable economic burden for family members and friends who support patients/survivors. We estimated financial and time costs associated with informal care for colorectal cancer.

Methods

Two hundred twenty-eight carers of colorectal cancer survivors diagnosed on October 2007–September 2009 were sent a questionnaire. Informal care costs included hospital- and domestic-based foregone caregiver time, travel expenses and out-of-pocket (OOP) costs during two phases: diagnosis and treatment and ongoing care (previous 30 days). Multiple regression was used to determine cost predictors.

Results

One hundred fifty-four completed questionnaires were received (response rate?=?68 %). In the diagnosis and treatment phase, weekly informal care costs per person were: hospital-based costs, incurred by 99 % of carers, mean?=?€393 (interquartile range (IQR), €131–€541); domestic-based time costs, incurred by 85 %, mean?=?€609 (IQR, €170–€976); and domestic-based OOP costs, incurred by 68 %, mean?=?€69 (IQR, €0–€110). Ongoing costs included domestic-based time costs incurred by 66 % (mean?=?€66; IQR, €0–€594) and domestic-based OOP costs incurred by 52 % (mean?=?€52; IQR, €0–€64). The approximate average first year informal care cost was €29,842, of which 85 % was time costs, 13 % OOP costs and 2 % travel costs. Significant cost predictors included carer age, disease stage, and survivor age.

Conclusion

Informal caregiving associated with colorectal cancer entails considerable time and OOP costs. This burden is largely unrecognised by policymakers, service providers and society in general. These types of studies may facilitate health decision-makers in better assessing the consequences of changes in cancer care organisation and delivery.     

C-QUALITY: Cost and Quality-of-Life Pharmacoeconomic Analysis of Antidepressants in Major Depressive Disorder in Italy

Introduction

Major depressive disorder (MDD) is a common and disabling condition across the world. Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are the most commonly used antidepressants. The objective of this study was to assess the cost-effectiveness [€ per quality-adjusted life year (QALY)] of all SSRIs and all SNRIs for the treatment of MDD in Italy.

Methods

A decision analytic model was adapted from the Swedish Dental and Pharmaceutical Benefits agency model to reflect current clinical practice in the treatment of MDD in the largest Italian regions. This adaptation was possible thanks to the collaboration of an expert panel of Italian psychiatrists and health economists. The model evaluated patients with a first diagnosis of MDD and initiating an SSRI or an SNRI for the first time. The time horizon was 12 months. Efficacy and utility data for the model were retrieved from the literature and validated by the expert panel. Local data were considered for resource utilization and for treatment costs based on each regional health service perspective. Population-weighted regional data were used to define a national model. Scenario simulations, one-way sensitivity analyses, and Monte Carlo simulations were performed to test the robustness of the model.

Results

The base case analysis showed that escitalopram was associated with a lower total cost (€ 1,562) and a larger health gain (QALYs) at 1 year (0.732) per patient and dominated the other treatment strategies since more QALYs were achieved at a lower total cost. Sensitivity analyses support the robustness of the model.

Conclusion

The results indicate that escitalopram is the most cost-effective pharmacological treatment strategy for the Italian health service compared with other SSRIs and all SNRIs used in the first-line treatment of MDD.     

A Trial-Based Economic Evaluation Comparing Spinal Cord Stimulation With Best Medical Treatment in Painful Diabetic Peripheral Neuropathy

The objective was to perform an economic evaluation comparing spinal cord stimulation (SCS) in combination with best medical treatment (BMT) with BMT in painful diabetic peripheral neuropathy patients. Alongside a prospective 2-center randomized controlled trial, involving 36 painful diabetic peripheral neuropathy patients with severe lower limb pain not responding to conventional therapy, an economic evaluation was performed. Incremental cost-effectiveness ratios were based on: 1) societal costs and quality-adjusted life years (QALYs), and 2) direct health care costs and the number of successfully treated patients, respectively, both with a time horizon of 12 months. Bootstrap and secondary analyses were performed to address uncertainty. Total societal cost amounted to €26,539.18 versus €5,313.45 per patient in the SCS and BMT group, respectively. QALYs were .58 versus .36 and the number of successfully treated patients was 55% versus 7% for the SCS and BMT group, respectively. This resulted in incremental cost-effectiveness ratios of €94,159.56 per QALY and €34,518.85 per successfully treated patient, respectively. Bootstrap analyses showed that the probability of SCS being cost-effective ranges from 0 to 46% with willingness to pay threshold values ranging between €20,000 and €80,000 for a QALY. Secondary analyses showed that cost-effectiveness of SCS became more favorable after correcting for baseline cost imbalance between the 2 groups, extending the depreciation period of SCS material to 4 years, and extrapolation of the data up to 4 years. Although SCS was considerably more effective compared with BMT, the substantial initial investment that is required resulted in SCS not being cost-effective in the short term. Cost-effectiveness results were sensitive to baseline cost imbalances between the groups and the depreciation period of the SCS material.

Hemoglobin level at initiation of darbepoetin alfa: impact on need for transfusion and associated costs in chemotherapy-induced anemia treatment in Europe

Purpose

Erythropoiesis-stimulating agents can reduce red blood cell transfusion rates in patients developing anemia while receiving chemotherapy. We investigated potential cost savings from reduced transfusion rates in patients starting darbepoetin alfa (DA) at higher versus lower hemoglobin (Hb) levels.

Methods

Two systematic literature reviews were performed: transfusion outcomes in patients receiving DA stratified by baseline Hb level and costs of transfusion in Europe. Potential cost savings were calculated by multiplying the difference in transfusion rates between Hb levels by the midpoint of transfusion costs.

Results

Despite differences in baseline characteristics, treatment duration and analysis technique, the clinical studies (n?=?8) showed that fewer transfusions were required when DA was initiated at higher versus lower Hb levels. The economic studies (n?=?9) showed that 1 unit of transfusion ranged from €130 to €537 (2010-adjusted values). Cost savings from initiating DA at higher versus lower Hb levels were €503–2,226 (2 units transfused) and €880–3,895 (3.5 units) per ten patients.

Conclusions

Transfusion incidence increases with DA initiation at lower Hb levels. Potential cost savings depend on the number of units transfused and cost items included. DA initiation according to guidelines can reduce transfusions and potentially reduce transfusion-associated costs.     

Health-related outcomes of critically ill patients with and without sepsis

Purpose

To determine differences in health-related quality of life (HRQoL), survival and healthcare resource use of critically ill adults with and without sepsis.

Methods

We conducted a primary propensity score matched analysis of patients with and without sepsis enrolled in a large multicentre clinical trial. Outcomes included HRQoL at 6 months, survival to 2 years, length of ICU and hospital admission and cost of ICU and hospital treatment to 2 years.

Results

We obtained linked data for 3442 (97.3%) of 3537 eligible patients and matched 806/905 (89.0%) patients with sepsis with 806/2537 (31.7%) without. After matching, there were no significant differences in the proportion of survivors with and without sepsis reporting problems with mobility (37.8% vs. 38.7%, p?=?0.86), self-care (24.7% vs. 26.0%, p?=?0.44), usual activities (44.5% vs. 46.8%, p?=?0.28), pain/discomfort (42.4% vs. 41.6%, p?=?0.54) and anxiety/depression (36.9% vs. 37.7%, p?=?0.68). There was no significant difference in survival at 2 years: 482/792 (60.9%) vs. 485/799 (60.7%) (HR 1.01, 95% CI 0.86–1.18, p?=?0.94). The initial ICU and hospital admission were longer for patients with sepsis: 10.1?±?11.9 vs. 8.0?±?9.8 days (p?<?0.0001) and 22.8?±?21.2 vs. 19.1?±?19.0 days, (p?=?0.0003) respectively. The cost of ICU admissions was higher for patients with sepsis: A$43,345?±?46,263 (€35,109?±?35,043) versus 34,844?±?38,281 (€28,223?±?31,007), mean difference $8501 (€6885), 95% CI $4342–12,660 (€3517?±?10,254), p?<?0.001 as was the total cost of hospital treatment to 2 years: A$74,120?±?60,750 (€60,037?±?49,207) versus A$65,806?±?59,856 (€53,302?±?48,483), p?=?0.005.

Conclusions

Critically ill patients with sepsis have higher healthcare resource use and costs but similar survival and HRQoL compared to matched patients without sepsis.

     

Analyzing Health-Related Quality of Life Data to Estimate Parameters for Cost-Effectiveness Models: An Example Using Longitudinal EQ-5D Data from the SHIFT Randomized Controlled Trial

Introduction

The aim of this article is to discuss methods used to analyze health-related quality of life (HRQoL) data from randomized controlled trials (RCTs) for decision analytic models. The analysis presented in this paper was used to provide HRQoL data for the ivabradine health technology assessment (HTA) submission in chronic heart failure.

Methods

We have used a large, longitudinal EuroQol five-dimension questionnaire (EQ-5D) dataset from the Systolic Heart Failure Treatment with the I _f Inhibitor Ivabradine Trial (SHIFT) (clinicaltrials.gov: NCT02441218) to illustrate issues and methods. HRQoL weights (utility values) were estimated from a mixed regression model developed using SHIFT EQ-5D data (n = 5313 patients). The regression model was used to predict HRQoL outcomes according to treatment, patient characteristics, and key clinical outcomes for patients with a heart rate ≥75 bpm.

Results

Ivabradine was associated with an HRQoL weight gain of 0.01. HRQoL weights differed according to New York Heart Association (NYHA) class (NYHA I–IV, no hospitalization: standard care 0.82–0.46; ivabradine 0.84–0.47). A reduction in HRQoL weight was associated with hospitalizations within 30 days of an HRQoL assessment visit, with this reduction varying by NYHA class [?0.07 (NYHA I) to ?0.21 (NYHA IV)].

Conclusion

The mixed model explained variation in EQ-5D data according to key clinical outcomes and patient characteristics, providing essential information for long-term predictions of patient HRQoL in the cost-effectiveness model. This model was also used to estimate the loss in HRQoL associated with hospitalizations. In SHIFT many hospitalizations did not occur close to EQ-5D visits; hence, any temporary changes in HRQoL associated with such events would not be captured fully in observed RCT evidence, but could be predicted in our cost-effectiveness analysis using the mixed model. Given the large reduction in hospitalizations associated with ivabradine this was an important feature of the analysis. Funding: The Servier Research Group.

     

The impact of chemotherapy-induced side effects on medical care usage and cost in German hospital care — an observational analysis on non-small-cell lung cancer patients

Purpose

To evaluate frequency and severity of adverse drug reactions (ADRs) and its economic consequences after standard dose (immuno-)chemotherapy (CT) of non-small-cell lung cancer (NSCLC).

Patients and methods

Subanalysis of a prospective, multicentre, longitudinal, observational cohort study; data were collected from patient interviews and pre-planned chart reviews. Costs were aggregated per CT line and presented from provider perspective.

Results

A total of 120 consecutive NSCLC patients (mean age, 63.0?±?8.4 (SD) years; men, 64.2 %; ECOG (Eastern Cooperative Oncology Group) performance status <2, 84.3 %; tumour stage III/IV, 85 %; history of comorbidity, 93.3 %) receiving 130 CT lines were evaluated. 80 % of CT lines were associated with grade 3 or 4 ADRs, 22.3 % developed potential life-threatening complications, 77.7 % were associated with at least one hospital stay (inpatient, 63.9 %; outpatient/day clinic 39.2 %, ICU 6.9 %), with a mean cumulative number of 12.8 (±14.0 SD) hospital days. Mean (median) toxicity management costs per CT line (TMC-TL) amounted to €3,366 (€1,406) and were found to be higher for first-line compared to second-line treatment: €3,677 (€1,599) vs. €2,475 (€518). TMC-TL were particularly high in CT lines with ICU care €12,207 (€9,960). Eight out of 11 ICU stays were associated with grade 3 or 4 infections. Nine CT lines with ICU care accounted for 25 % of total expenses (€109,861 out of €437,580).

Conclusions

In first-line NSCLC treatment, in particular, CT toxicity management is expensive. Asymmetric cost distribution seems to be triggered by infection associated ICU care. Its avoidance should reduce patients' clinical burden and have considerable economic implications. Nevertheless, comparative observational studies have to confirm estimated savings.     

SuPAR and PAI-1 in critically ill, mechanically ventilated patients

Purpose

SuPAR (soluble urokinase plasminogen activator receptor) and PAI-1 (plasminogen activator inhibitor 1) are active in the coagulation-fibrinolysis pathway. Both have been suggested as biomarkers for disease severity. We evaluated them in prediction of mortality, acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), sepsis and renal replacement therapy (RRT) in operative and non-operative ventilated patients.

Methods

We conducted a prospective, multicenter, observational study. Blood samples and data of intensive care were collected. Mechanically ventilated patients with baseline suPAR and PAI-1 measurements were included in the analysis, and healthy volunteers were analysed for comparison. Receiver operating characteristics (ROC), logistic regression, likelihood ratios and Kaplan–Meier analysis were performed.

Results

Baseline suPAR was 11.6 ng/ml (quartiles Q1–Q3, 9.6–14.0), compared to healthy volunteers with suPAR of 0.6 ng/ml (0.5–11.0). PAI-1 concentrations were 2.67 ng/ml (1.53–4.69) and 0.3 ng/ml (0.3–0.4), respectively. ROC analysis for suPAR 90-day mortality areas under receiver operating characteristic curves (AUC) 0.61 (95 % confidence interval (CI): 0.55–0.67), sepsis 0.68 (0.61–0.76), ALI/ARDS 0.64 (0.56–0.73) and RRT 0.65 (0.56–0.73). Patients with the highest quartile of suPAR concentrations had an odds ratio of 2.52 (1.37–4.64, p = 0.003) for 90-day mortality and 3.16 (1.19–8.41, p = 0.02) for ALI/ARDS. In non-operative patients, the AUC’s for suPAR were 90-day mortality 0.61 (0.54–0.68), RRT 0.73 (0.64–0.83), sepsis 0.70 (0.60–0.80), ALI/ARDS 0.61 (0.51–0.71). Predictive value of PAI-1 was negligible.

Conclusions

In non-operative patients, low concentrations of suPAR were predictive for survival and high concentrations for RRT and mortality. SuPAR may be used for screening for patients with potentially good survival. The association with RRT may supply an early warning sign for acute renal failure.     

Accuracy of plasma neutrophil gelatinase-associated lipocalin in the early diagnosis of contrast-induced acute kidney injury in critical illness

Purpose

Neutrophil gelatinase-associated lipocalin (NGAL) is a promising biomarker for acute kidney injury (AKI). We evaluated the diagnostic and prognostic accuracies of plasma NGAL (pNGAL) for contrast-induced AKI (CI-AKI) in critically ill patients.

Methods

In a prospective observational study in two adult intensive care units in a university hospital, 100 consecutive critically ill patients with stable serum creatinine concentrations up to 48 h before contrast medium (CM) injection were enrolled. Serial blood sampling for pNGAL analysis was performed at enrolment, 2, 6, and 24 h after CM injection. The primary outcome was CI-AKI, defined by AKIN criteria, within the first 72 h following CM injection. Secondary outcomes were the need for renal replacement therapy (RRT) and mortality.

Results

Of the 98 patients analyzed, 30 developed CI-AKI. The pNGAL levels did not differ in patients with or without CI-AKI, and were higher in septic patients compared to nonseptic patients, and in patients with AKI preceding CM injection. The discriminative value of pNGAL to predict CI-AKI and mortality was poor; although, it did predict the need for RRT requirement after CM injection (area under receiver-operating characteristic curve, 0.85, 0.80, 0.83 and 0.86 at H0, H2, H6 and H24, respectively).

Conclusion

CI-AKI was common in critically ill patients. pNGAL levels were higher in patients with sepsis or previous AKI, but did not help to diagnose CI-AKI any earlier than serum creatinine after CM injection. However, pNGAL could be of interest to detect patients at risk of subsequent RRT requirement.     

Cost-Effectiveness of Primary Prevention with Statin Treatment for Chinese Patients with Type 2 Diabetes

Introduction

Statins can reduce the risk of cardiovascular events in patients with diabetes. The objective of this analysis was to evaluate whether primary prevention with statin treatment is cost-effective for newly diagnosed type 2 diabetes mellitus (T2DM) patients in the Chinese context.

Methods

An economic analysis of primary prevention with statin treatment was conducted using the Chinese Outcomes Model for T2DM with a time horizon of a lifetime, which was developed and validated based on the Chinese population. Clinical costs and utility inputs were gathered from published sources. Lifetime discounted quality-adjusted life-years (QALYs), costs, and the incremental cost-effectiveness ratio (ICER) were measured. The uncertainty was evaluated by one-way and probabilistic sensitivity analyses.

Results

Statin treatment with atorvastatin 10 mg could add 0.08 QALYs with an additional $1676 compared with that of no statin management (control strategy) over a lifetime horizon, which led to an ICER of $21,924 per QALY gained. At a willingness-to-pay threshold of $27,351 per QALY gained, there was an approximately 80% probability of statin treatment being cost-effective compared with the control strategy. The model outcomes were most sensitive to the length of the expected life and age at the T2DM diagnosis.

Conclusions

Statin treatment with atorvastatin is most likely cost-effective for primary prevention in Chinese patients newly diagnosed with type 2 diabetes.

Funding

Partially funded by Pfizer Inc.

     

Generic and disease-specific health-related quality of life in patients with chronic systolic heart failure: impact of depression

Aims

Heart failure is known to profoundly affect health-related quality of life (HRQoL). We aimed to describe both generic and disease-specific HRQoL in a large community-based sample of patients with systolic heart failure (SHF) and to identify important somatic and psychosocial correlates.

Methods and results

Seven hundred and two patients, 67 ± 12 years old, 71 % men, with distributions of New York Heart Association (NYHA) functional classes I/II/III/IV of 2/55/39/4 % were included in this cross-sectional analysis. Generic HRQoL was measured with the SF-36 health survey, disease-specific HRQoL with the Kansas City Cardiomyopathy Questionnaire, and depression with the self-reported Patient Health Questionnaire (PHQ-9). Both generic- and disease-specific HRQoL measurements indicated moderate to poor HRQoL. The KCCQ scores demonstrated higher sensitivity to the varying levels of heart failure severity as compared to the SF-36 scores. Patients with either a minor (15 %) or a major depression (24 %) reported significantly and substantially lower HRQoL (p < .001) than patients without depression did. In multivariable regression analyses, depression accounted for the largest part of the variance of both generic and specific HRQoL (12 and 36 %, respectively), whereas most biomedical variables had no or only a marginal influence.

Conclusion

Patients with SHF suffer from severe limitations of HRQoL. Depression was the most important correlate of both generic and disease-specific HRQoL.     

A Cost-Effectiveness Analysis of Clopidogrel for Patients with Non-ST-Segment Elevation Acute Coronary Syndrome in China

Introduction

There are a number of economic evaluation studies of clopidogrel for patients with non-ST-segment elevation acute coronary syndrome (NSTEACS) published from the perspective of multiple countries in recent years. However, relevant research is quite limited in China. We aimed to estimate the long-term cost effectiveness for up to 1-year treatment with clopidogrel plus acetylsalicylic acid (ASA) versus ASA alone for NSTEACS from the public payer perspective in China.

Methods

This analysis used a Markov model to simulate a cohort of patients for quality-adjusted life years (QALYs) gained and incremental cost for lifetime horizon. Based on the primary event rates, adherence rate, and mortality derived from the CURE trial, hazard functions obtained from published literature were used to extrapolate the overall survival to lifetime horizon. Resource utilization, hospitalization, medication costs, and utility values were estimated from official reports, published literature, and analysis of the patient-level insurance data in China. To assess the impact of parameters’ uncertainty on cost-effectiveness results, one-way sensitivity analyses were undertaken for key parameters, and probabilistic sensitivity analysis (PSA) was conducted using the Monte Carlo simulation.

Results

The therapy of clopidogrel plus ASA is a cost-effective option in comparison with ASA alone for the treatment of NSTEACS in China, leading to 0.0548 life years (LYs) and 0.0518 QALYs gained per patient. From the public payer perspective in China, clopidogrel plus ASA is associated with an incremental cost of 43,340 China Yuan (CNY) per QALY gained and 41,030 CNY per LY gained (discounting at 3.5% per year). PSA results demonstrated that 88% of simulations were lower than the cost-effectiveness threshold of 150,721 CYN per QALY gained. Based on the one-way sensitivity analysis, results are most sensitive to price of clopidogrel, but remain well below this threshold.

Conclusion

This analysis suggests that treatment with clopidogrel plus ASA for up to 1 year for patients with NSTEACS is cost effective in the local context of China from a public payers’ perspective.

Funding

Sanofi China.

     

Cost-Effectiveness of Different Strategies for the Prevention of Venous Thromboembolism After Total Hip Replacement in China

Introduction

The aim of this study was to evaluate the cost-effectiveness of rivaroxaban and apixaban versus enoxaparin for the universal prophylaxis of venous thromboembolism (VTE) and associated long-term complications in Chinese patients after total hip replacement (THR).

Methods

A decision model, which included both acute VTE (represented as a decision tree) and the long-term complications of VTE (represented as a Markov model), was developed to assess the economic outcomes of the three prophylactic strategies for Chinese patients after THR. Transition probabilities for acute VTE were derived from two randomized controlled studies, RECORD1 and ADVANCE3, of patients after THR. The transition probabilities of long-term complications after acute VTE, utilities, and costs were derived from the published literature and local healthcare settings. One-way and probabilistic sensitivity analyses (PSA) were performed to test the uncertainty concerning the model parameters. The quality-adjusted life years (QALYs) and direct medical costs were reported over a 5-year horizon, and incremental cost-effectiveness ratios (ICERs) were also calculated.

Results

Thromboprophylaxis with apixaban was estimated to have a higher cost (US $178.70) and more health benefits (0.0025 QALY) than thromboprophylaxis with enoxaparin over a 5-year time horizon, which resulted in an ICER of US $71,244 per QALY gained and was more than three times the GDP per capita of China in 2014 (US $22,140). Owing to the higher cost and lower generated QALYs, rivaroxaban was inferior to enoxaparin among post-THR patients. The sensitivity analyses confirmed these results.

Conclusions

The analysis found that apixaban was not cost-effective and that rivaroxaban was inferior to enoxaparin. This finding indicates that compared with enoxaparin, the use of apixaban for VTE prophylaxis after THR does not represent a good value for the cost at the acceptable threshold in China; in addition, the cost of rivaroxaban was higher with lower QALYs.

     

Effect of general symptom level, specific adverse events, treatment patterns, and patient characteristics on health-related quality of life in patients with multiple myeloma: results of a European, multicenter cohort study

Purpose

Novel multiple myeloma (MM) therapies have increased patient longevity but are often associated with notable symptom burden. This study quantified the effect of general symptom level, specific symptoms, and treatment-related adverse events (AEs) on MM patients’ health-related quality of life (HRQoL).

Methods

The European Organization for Research and Treatment of Cancer (EORTC) generic cancer questionnaire (Quality of Life Questionnaire Core 30) and MM-specific questionnaire (QLQ-MY20) were used in this study to assess patients’ HRQoL. Data were collected on sociodemographics, disease and treatment history, and the presence/severity of MM-related symptoms or treatment-related AEs from patients with MM in 11 UK and German centers. Multiple regression analyses were conducted.

Results

Of 154 patients (63 % male; mean age, 66.4 years; mean time since diagnosis, 3.7 years; 52 % currently on treatment; and 43 % with ≥1 prior MM therapy), 25, 32, 31, and 11 % were severely symptomatic, moderately symptomatic, mildly symptomatic, and asymptomatic, respectively. Fatigue (59 %), bone pain (51 %), sleepiness (36 %), hypoesthesia or paresthesia (33 %), and muscle cramps (31 %) were most commonly reported. Moderate and severe general symptom levels, bone symptoms, depression, and mental status changes were identified as strong determinants of HRQoL.

Conclusions

Severity, type of disease symptoms, and treatment-related AEs are important HRQoL determinants in patients with MM, allowing for targeted treatment.     

Cost-Effectiveness Analysis of Bezlotoxumab Added to Standard of Care Versus Standard of Care Alone for the Prevention of Recurrent <Emphasis Type="Italic">Clostridium difficile</Emphasis> Infection in High-Risk Patients in Spain

Introduction

Clostridium difficile infection (CDI) is the major cause of infectious nosocomial diarrhoea and is associated with considerable morbidity, mortality and economic impact. Bezlotoxumab administered in combination with standard of care (SoC) antibiotic therapy prevents recurrent CDI. This study assessed the cost-effectiveness of bezlotoxumab added to SoC, compared to SoC alone, to prevent the recurrence of CDI in high-risk patients from the Spanish National Health System perspective.

Methods

A Markov model was used to simulate the natural history of CDI over a lifetime horizon in five populations of patients at high risk of CDI recurrence according to MODIFY trials: (1)?≥?65 years old; (2) severe CDI; (3) immunocompromised; (4)?≥?1 CDI episode in the previous 6 months; and (5)?≥?65 years old and with?≥?1 CDI episode in the previous 6 months. The incremental cost-effectiveness ratio (ICER) expressed as cost per quality-adjusted life-year (QALY) gained was calculated. Deterministic (DSA) and probabilistic sensitivity analyses (PSA) were performed.

Results

In all patient populations (from 1 to 5), bezlotoxumab added to SoC reduced CDI recurrence compared to SoC alone by 26.4, 19.5, 21.2, 26.6 and 39.7%, respectively. The resulting ICERs for the respective subgroups were €12,724, €17,495, €9545, €7386, and €4378. The model parameters with highest impact on the ICER were recurrence rate (first), mortality, and utility values. The probability that bezlotoxumab was cost-effective at a willingness-to-pay threshold of €21,000/QALY was 85.5%, 54.1%, 86.0%, 94.5%, 99.6%, respectively.

Conclusion

The results suggest that bezlotoxumab added to SoC compared to SoC alone is a cost-effective treatment to prevent the recurrence of CDI in high-risk patients. The influence of changes in model parameters on DSA results was higher in patients ?≥?65 years old, with severe CDI and immunocompromised. Additionally, PSA estimated that the probability of cost-effectiveness exceeded 85% in most subgroups.

Funding

Merck Sharp & Dohme Corp.

     

Late initiation of renal replacement therapy is associated with worse outcomes in acute kidney injury after major abdominal surgery

Introduction

Abdominal surgery is probably associated with more likelihood to cause acute kidney injury (AKI). The aim of this study was to evaluate whether early or late start of renal replacement therapy (RRT) defined by simplified RIFLE (sRIFLE) classification in AKI patients after major abdominal surgery will affect outcome.

Methods

A multicenter prospective observational study based on the NSARF (National Taiwan University Surgical ICU Associated Renal Failure) Study Group database. 98 patients (41 female, mean age 66.4 ± 13.9 years) who underwent acute RRT according to local indications for post-major abdominal surgery AKI between 1 January, 2002 and 31 December, 2005 were enrolled The demographic data, comorbid diseases, types of surgery and RRT, as well as the indications for RRT were documented. The patients were divided into early dialysis (sRIFLE-0 or Risk) and late dialysis (LD, sRIFLE -Injury or Failure) groups. Then we measured and recorded patients' outcome including in-hospital mortality and RRT wean-off until 30 June, 2006.

Results

The in-hospital mortality was compared as endpoint. Fifty-seven patients (58.2%) died during hospitalization. LD (hazard ratio (HR) 1.846; P = 0.027), old age (HR 2.090; P = 0.010), cardiac failure (HR 4.620; P < 0.001), pre-RRT SOFA score (HR 1.152; P < 0.001) were independent indicators for in-hospital mortality.

Conclusions

The findings of this study support earlier initiation of acute RRT, and also underscore the importance of predicting prognoses of major abdominal surgical patients with AKI by using RIFLE classification.     

Health-related quality of life, depression, and sexual function in testicular cancer survivors in a developing country: a Serbian experience

Purpose

The aims of this study were to assess health-related quality of life (HRQoL), depression, adverse physical symptoms, and sexual function within Serbian long-term testicular cancer survivors (TCS) and to address cultural specificity.

Methods

This is a cross-sectional study involving 202 TCS, followed up after platinum-based chemotherapy. The HRQoL was measured using the Short Form 36 and the European Organization for Research and Treatment of Cancer Quality of Life questionnaire. The Beck Depression Inventory (BDI) was used to explore general depressive status while sexual function was assessed using a nine-item questionnaire.

Results

The mean follow-up time since treatment was 47.3?±?26.8 months. The highest values of the SF-36 scales were obtained for physical functioning, and the lowest SF-36 values were obtained for vitality. Age of patients and BDI scores statistically significantly influenced total quality of life. The mean score of the whole sample on the BDI-II was 4.0. Age is the only statistically significant risk factor for the development of depression. A total of 27.3 % TCS reported decreased sexual function compared to the period before treatment. Any level of impairment of erectile function was reported by 20.8 % patients and problems with ejaculation by 25.7 % patients. Loss of desire was reported by 17.3 % TCS. The presence of sexual problems statistically significantly lowered scores of SF-36 domains.

Conclusion

Sexual problems seriously impaired HRQoL in TCS. Additionally, HRQoL was also affected by age, depression, and fatigue. Serbian TCS achieved high levels of SF-36 scores, and these results are comparable to studies conducted in developed countries.     

Choice of renal replacement therapy modality and dialysis dependence after acute kidney injury: a systematic review and meta-analysis

Purpose

Choice of renal replacement therapy (RRT) modality may affect renal recovery after acute kidney injury (AKI). We sought to compare the rate of dialysis dependence among severe AKI survivors according to the choice of initial renal replacement therapy (RRT) modality applied [continuous (CRRT) or intermittent (IRRT)].

Methods

Systematic searches of peer-reviewed publications in MEDLINE and EMBASE were performed (last update July 2012). All studies published after 2000 reporting dialysis dependence among survivors from severe AKI requiring RRT were included. Data on follow-up duration, sex, age, chronic kidney disease, illness severity score, vasopressors, and mechanical ventilation were extracted when available. Results were pooled using a random-effects model.

Results

We identified 23 studies: seven randomized controlled trials (RCTs) and 16 observational studies involving 472 and 3,499 survivors, respectively. Pooled analyses of RCTs showed no difference in the rate of dialysis dependence among survivors (relative risk, RR 1.15 [95 % confidence interval (CI) 0.78–1.68], I ² = 0 %). However, pooled analyses of observational studies suggested a higher rate of dialysis dependence among survivors who initially received IRRT as compared with CRRT (RR 1.99 [95 % CI 1.53–2.59], I ² = 42 %). These findings were consistent with adjusted analyses (performed in 7/16 studies), which found a higher rate of dialysis dependence in IRRT-treated patients [odds ratio (OR) 2.2–25 (5 studies)] or no difference (2 studies).

Conclusions

Among AKI survivors, initial treatment with IRRT might be associated with higher rates of dialysis dependence than CRRT. However, this finding largely relies on data from observational trials, potentially subject to allocation bias, hence further high-quality studies are necessary.