Economic Evaluation of Varicella Vaccination Programmes: A Review of the Literature

Chickenpox, Cost-analysis, Herpes-zoster, Varicella-vaccines

Validation of Health Economic Models: The Example of EVITA

AbstractObjectivesThe credibility of models rests on their validity. An age-structured decision analytic model, Economic Varicella VaccInation Tool for Analysis (EVITA), has been developed to examine the epidemiologic and economic effects of universal varicella (chicken pox) vaccination in Germany. EVITA combines a varicella transmission module describing the spread of infection in a population over time with a second module describing the course of disease in case of an infection. Any vaccination strategy can be assessed dependent on coverage levels and targeted age group. Model input data include epidemiologic, clinical, and economic information, which were mainly derived from actual varicella cases (retrospective survey). The objective of this study was to illustrate the efforts undertaken to validate the EVITA model.MethodsWe assess the descriptive validity, i.e., whether the model provides an adequate picture of the reality and covers all relevant aspects of the spread of varicella and the course of disease. Analyzing the consistency of the model results with observable data does technical verification. Face validity, i.e., the consistency with the underlying theoretical basis of the spread of varicella, is analyzed with respect to results on possible age shifts and elimination of varicella. Tests of corroboration, or convergent validity, are performed by comparisons with other models.ResultsWithout vaccination, the EVITA model predicts undiscounted, indirect costs of €154 million, nearly 40,000 complications and 5,700 hospitalizations per year owing to varicella. These results, especially the distribution of complications and hospitalizations, fit well with population-based survey data. The development of the EVITA model is based on an established epidemiologic model and on real-life data from the survey, ensuring descriptive validity. Results on age shifts and elimination show face validity. Although other models differ considerably with respect to methods applied, the economic results of EVITA, i.e., a benefit–cost ratio of 4.12 when vaccinating young children, lies in the range found in other studies. This underscores its convergent validity. Comparable with other studies, discount rates and price of vaccine proved to be most sensitive variables.ConclusionsEVITA provides a powerful tool to simulate the highly complex processes associated with varicella infections and the impact of vaccination. The results of EVITA provide a reliable tool for informed decision making and should enhance the acceptance of such models

The influence of measles vaccination on the incidence of otosclerosis in Germany

The pathologic process of otosclerosis is characterized by an inflammatory lytic phase followed by an abnormal bone remodeling at very specific sites of predilection. There is a clear genetic predisposition with about half of all cases occurring in families with more than one affected member. Females are affected more frequently than males with an approximate 2:1 ratio. N, H, and F measles proteins as well as measles virus RNA have been demonstrated in osteoblasts, chondroblasts, and macrophages of the inflammatory phase of the disease. These observations merely show an association between measles viruses and otosclerosis. In the present study, we tried to prove that there is a causal relationship: voluntary measles vaccination has been available in Germany since 1974. In the absence of official data, we reconstructed the rate of vaccination coverage between 1974 and 2004 using information from the Robert Koch Institute (RKI, Berlin) and from the literature. From the German Federal Office of Statistics, we received the data of 64,112 patients who had been hospitalized between 1993 and 2004 and in whom otosclerosis (ICD-9: 387; ICD-10: H80) had been confirmed. We calculated the effect of measles vaccination on the incidence of hospital treatments for otosclerosis in the period from 1993 to 2004 in Germany. For this purpose, we divided the female and male otosclerosis patients treated as inpatients each year in the observation period into two age groups: those up to 25 years, who had in most cases been vaccinated (designated below as "vaccinated patients") and those over 25 years who mostly could not have been vaccinated (designated below as "unvaccinated patients"). We calculated the incidence of otosclerosis requiring inpatient treatment for the two age groups in each year in the period of observation. For external validation of the study results, the same analysis was carried out in all patients who received inpatient treatment for otitis media in the same period. Between 1993 and 2004 the incidence of hospital treatments for otosclerosis decreased to a significantly greater extent in the vaccinated patients than in the unvaccinated patients. The decline is much greater in men than in women. A comparable effect cannot be demonstrated in patients with otitis media. The results indicate that measles vaccination in Germany has resulted in a significant reduction in the number of hospital treatments for otosclerosis in the vaccinated age groups. We conclude that there is a causal relationship between measles viruses and the development of otosclerosis

Susceptibility of murine induced pluripotent stem cell-derived cardiomyocytes to hypoxia and nutrient deprivation

INTRODUCTION: Induced pluripotent stem cell-derived cardiomyocytes (iPS-CMs) may be suitable for myocardial repair. While their functional and structural properties have been extensively investigated, their response to ischemia-like conditions has not yet been clearly defined. METHODS: iPS-CMs were differentiated and enriched from murine iPS cells expressing eGFP and puromycin resistance genes under the control of an alpha-MHC promoter. iPS-CMs maturity and function were characterized by microscopy, rt-PCR, calcium transient recordings, electrophysiology, and mitochondrial function assays, and compared to those from neonatal murine cardiomyocytes (N-CMs). iPS-CMs as well as N-CMs were exposed for 3 h to hypoxia (1% O2) and glucose/serum deprivation (GSD), and viability, apoptosis markers, reactive oxygen species (ROS), mitochondrial membrane potential (Deltapsim) and intracellular stress signaling cascades were investigated. Then, the iPS-CMs response to mesenchymal stromal cell-conditioned medium (MSC-CoM) was determined. RESULTS: iPS-CMs displayed key morphological and functional properties that were comparable to those of N-CMs, but several parameters indicated an earlier iPS-CMs maturation stage. During hypoxia/GSD, iPS-CMs exhibited a significantly higher proportion of poly-caspase-active, 7-AAD- and TUNEL-positive cells than N-CMs. The average mitochondrial membrane potential (Deltapsim) was reduced in "ischemic" iPS-CMs but remained unchanged in N-CMs, ROS production was only increased in "ischemic" iPS-CMs, and oxidoreductase activity in iPS-CMs dropped more rapidly than in N-CMs. In iPS-CMs, hypoxia/GSD led to upregulation of Hsp70 transcripts and decreased STAT3 phosphorylation and total PKCepsilon protein expression. Treatment with MSC-CoM preserved oxidoreductase activity and restored pSTAT3 and PKCepsilon levels. CONCLUSION: iPS-CMs appear to be particularly sensitive to hypoxia and nutrient deprivation. Counteracting the ischemic susceptibility of iPS-CMs with MSC-conditioned medium may help enhance their survival and efficacy in cell-based approaches for myocardial repair

Evaluation of the Hepa Wash® treatment in pigs with acute liver failure

BACKGROUND Mortality of patients with acute liver failure (ALF) is still unacceptably high. Available liver support systems are still of limited success at improving survival. A new type of albumin dialysis, the Hepa Wash® system, was newly introduced. We evaluated the new liver support system as well as the Molecular Adsorbent Recycling System (MARS) in an ischemic porcine model of ALF. METHODS In the first study animals were randomly allocated to control (n=5) and Hepa Wash (n=6) groups. In a further pilot study, two animals were treated with the MARS-system. All animals received the same medical and surgical procedures. An intraparenchymal intracranial pressure was inserted. Hemodynamic monitoring and goal-directed fluid therapy using the PiCCO system was done. Animals underwent functional end-to-side portacaval shunt and ligation of hepatic arteries. Treatment with albumin dialysis was started after fall of cerebral perfusion pressure to 45 mmHg and continued for 8 h. RESULTS All animals in the Hepa Wash group survived the 13-hour observation period, except for one that died after stopping treatment. Four of the control animals died within this period (p=0.03). Hepa Wash significantly reduced impairment of cerebral perfusion pressure (23±2 vs. 10±3 mmHg, p=0.006) and mean arterial pressure (37±1 vs. 24±2 mmHg, p=0.006) but had no effect on intracranial pressure (14±1 vs. 15±1 mmHg, p=0.72). Hepa Wash also enhanced cardiac index (4.94±0.32 vs. 3.36±0.25 l/min/m2, p=0.006) and renal function (urine production, 1850 ± 570 vs. 420 ± 180 ml, p=0.045) and eliminated water soluble (creatinine, 1.3±0.2 vs. 3.2±0.3 mg/dl, p=0.01; ammonia 562±124 vs. 1382±92 μg/dl, p=0.006) and protein-bound toxins (nitrate/nitrite 5.54±1.57 vs. 49.82±13.27 μmol/l, p=0.01). No adverse events that could be attributed to the Hepa Wash treatment were observed. CONCLUSIONS Hepa Wash was a safe procedure and improved multiorgan system failure in pigs with ALF. The survival benefit could be the result of ameliorating different organ functions in association with the detoxification capacity of water soluble and protein-bound toxins