Budget impact of optimizing rifaximin-alpha use for the prevention of recurrent hepatic encephalopathy in The Netherlands

Aims Rifaximin-alpha as an adjunct to lactulose is reimbursed in the Netherlands for prevention of the third and subsequent episodes of overt Hepatic Encephalopathy (HE) in cirrhotic patients. However, use of rifaximin-alpha remains limited. This study evaluates the clinical and economic impact of treating all patients eligible under Dutch reimbursement conditions with rifaximin-alpha as an adjunct to lactulose for the prevention of overt HE in the Netherlands from a hospital and healthcare payer's perspective. Materials and methods A budget impact analysis was performed following national and international guidelines. Resource use was based on Dutch real-world data. HE-related cost inputs were based on the declaration codes, Dutch cost manual, and actual drug list prices. Several sensitivity and scenario analyses were conducted to assess model robustness. Results Treating eligible HE patients with rifaximin-alpha in addition to lactulose saves euro4,487 and costs euro249 per patient over a 5-year period compared with lactulose monotherapy from hospital and healthcare payer's perspectives, respectively. In the Netherlands, an estimated 38% of the 2,567 eligible patients are currently being treated with rifaximin-alpha. Optimizing rifaximin-alpha use by treating all eligible patients with the rifaximin-alpha + lactulose could save more than 3,000 hospital admissions, almost 15,000 hospital bed days, and 300 deaths over a 5-year period. Despite increased drug costs, treatment is estimated to result in potential cost savings over a 5-year period of 7.2 million euros from a Dutch hospital perspective. The budget impact is 397,770 euros from a healthcare payer's perspective. Conclusions Next to a clinical perspective, also from an economic perspective, wider prescription of rifaximin-alpha adhering to guidelines could be beneficial to reduce costs from a hospital perspective. From a healthcare payer's perspective, costs increase with addition of rifaximin-alpha due to relative better survival causing relatively higher drug and liver transplantation-related costs.Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Hepatitis e virus shows more genomic alterations in cell culture than in vivo

Hepatitis E Virus (HEV) mutations following ribavirin treatment have been associated with treatment non-response and viral persistence, but spontaneous occurring genomic variations have been less well characterized. We here set out to study the HEV genome composition in 2 patient sample types and 2 infection models. Near full HEV genome Sanger sequences of serum- and feces-derived HEV from two chronic HEV genotype 3 (gt3) patients were obtained. In addition, viruses were sequenced after in vitro or in vivo expansion on A549 cells or a humanized mouse model, respectively. We show that HEV acquired 19 nucleotide mutations, of which 7 nonsynonymous amino acids changes located in Open Reading Frame 1 (ORF1), ORF2, and ORF3 coding regions, after prolonged in vitro culture. In vivo passage resulted in selection of 8 nucleotide mutations with 2 altered amino acids in the X domain and Poly-proline region of ORF1. Intra-patient comparison of feces- and serum-derived HEV gt3 of two patients showed 7 and 2 nucleotide mutations with 2 and 0 amino acid changes, respectively. Overall, the number of genomic alterations was up to 1.25× per 1000 nucleotides or amino acids in in vivo samples, and up to 2.84× after in vitro expansion of the same clinical HEV strain. In vitro replication of a clinical HEV strain is therefore associated with more mutations, compared to the minor HEV genomic alterations seen after passage of the same strain in an immune deficient humanized mouse; as well as in feces and blood of 2 immunosuppressed chronically infected HEV patients. These data suggest that HEV infected humanized mice more closely reflect the HEV biology seen in solid organ transplant recipients

Cost-utility of liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based urine analyses to improve adherence to antihypertensive treatment

Objectives: In the UK, over 28% of the population are estimated to suffer from hypertension. A high systolic blood pressure (SBP) increases the risk for cardiovascular disease (CVD). While antihypertensive medications, along with lifestyle changes, are deemed effective in combatting hypertension, adherence to drug treatment may not be optimal. Data from UK patient samples show that discussion of the results from LC-MS/MS-based urine analyses with patients can improve adherence significantly. The objective of this study was to determine whether performing LC-MS/ MS-based urine analyses is cost-effective by improving adherence in hypertensive patients. Methods: Cost-utility analysis was performed from a UK healthcare payer perspective over a lifetime horizon. A Markov model was adapted from an existing published model in a UK setting. Hypertensive patients entered the model event-free, but at risk for cardiovascular events. Effectiveness of urine analysis was modelled by lowering the probability of having an event, as a consequence of lowered SBP by improved adherence to drug treatment, as found in the empirical study. Cost and utilities were derived from literature. The base case cohort consisted of males aged 65. Further analysis varied sex and age of the population. Subgroup analysis concerned those with resistant hypertension, and univariate and probabilistic sensitivity analyses were also performed. Results: The intervention resulted in an incremental health benefit of 0.020 quality-adjusted life-years (QALYs) per patient, and incremental cost was -£867 per patient, i.e. the intervention strategy is dominant compared to care as usual. Sensitivity analyses showed that targeting younger patients (aged 45) or only patients with resistant hypertension would increase cost savings and QALY gains. Conclusions: Using LC-MS/MS-based urine analyses to improve adherence in hypertensive patients is an effective and cost-saving strategy, especially in patients with resistant hypertension, since nonadherence is found to be higher in this population

Swarm Intelligence-Enhanced Detection of Non-Small-Cell Lung Cancer Using Tumor-Educated Platelets

Contains fulltext : 177967.pdf (Publisher’s version ) (Open Access)Blood-based liquid biopsies, including tumor-educated blood platelets (TEPs), have emerged as promising biomarker sources for non-invasive detection of cancer. Here we demonstrate that particle-swarm optimization (PSO)-enhanced algorithms enable efficient selection of RNA biomarker panels from platelet RNA-sequencing libraries (n = 779). This resulted in accurate TEP-based detection of early- and late-stage non-small-cell lung cancer (n = 518 late-stage validation cohort, accuracy, 88%; AUC, 0.94; 95% CI, 0.92-0.96; p < 0.001; n = 106 early-stage validation cohort, accuracy, 81%; AUC, 0.89; 95% CI, 0.83-0.95; p < 0.001), independent of age of the individuals, smoking habits, whole-blood storage time, and various inflammatory conditions. PSO enabled selection of gene panels to diagnose cancer from TEPs, suggesting that swarm intelligence may also benefit the optimization of diagnostics readout of other liquid biopsy biosources