The effects of long-term total parenteral nutrition on gut mucosal immunity in children with short bowel syndrome: a systematic review

BACKGROUND: Short bowel syndrome (SBS) is defined as the malabsorptive state that often follows massive resection of the small intestine. Most cases originate in the newborn period and result from congenital anomalies. It is associated with a high morbidity, is potentially lethal and often requires months, sometimes years, in the hospital and home on total parenteral nutrition (TPN). Long-term survival without parenteral nutrition depends upon establishing enteral nutrition and the process of intestinal adaptation through which the remaining small bowel gradually increases its absorptive capacity. The purpose of this article is to perform a descriptive systematic review of the published articles on the effects of TPN on the intestinal immune system investigating whether long-term TPN induces bacterial translocation, decreases secretory immunoglobulin A (S-IgA), impairs intestinal immunity, and changes mucosal architecture in children with SBS. METHODS: The databases of OVID, such as MEDLINE and CINAHL, Cochran Library, and Evidence-Based Medicine were searched for articles published from 1990 to 2001. Search terms were total parenteral nutrition, children, bacterial translocation, small bowel syndrome, short gut syndrome, intestinal immunity, gut permeability, sepsis, hyperglycemia, immunonutrition, glutamine, enteral tube feeding, and systematic reviews. The goal was to include all clinical studies conducted in children directly addressing the effects of TPN on gut immunity. RESULTS: A total of 13 studies were identified. These 13 studies included a total of 414 infants and children between the ages approximately 4 months to 17 years old, and 16 healthy adults as controls; and they varied in design and were conducted in several disciplines. The results were integrated into common themes. Five themes were identified: 1) sepsis, 2) impaired immune functions: In vitro studies, 3) mortality, 4) villous atrophy, 5) duration of dependency on TPN after bowel resection. CONCLUSION: Based on this exhaustive literature review, there is no direct evidence suggesting that TPN promotes bacterial overgrowth, impairs neutrophil functions, inhibits blood's bactericidal effect, causes villous atrophy, or causes to death in human model. The hypothesis relating negative effects of TPN on gut immunity remains attractive, but unproven. Enteral nutrition is cheaper, but no safer than TPN. Based on the current evidence, TPN seems to be safe and a life saving solution

Cost-minimization analysis of alemtuzumab compared to fingolimod and natalizumab for the treatment of active relapsing-remitting multiple sclerosis in the Netherlands

Aim: In active relapsing remitting multiple sclerosis (RRMS) patients requiring second-line treatment, the Dutch National Health Care Institute (ZiN) has not stated a preference for either alemtuzumab, fingolimod, or natalizumab. The aim was to give healthcare decision-makers insight into the differences in cost accumulation over time between alemtuzumab—with a unique, non-continuous treatment schedule—and fingolimod and natalizumab for second-line treatment of active RRMS patients in the Netherlands. Methods: In line with ZiN’s assessment, a cost-minimization analysis was performed from a Dutch healthcare perspective over a 5-year time horizon. Resource use was derived from hospital protocols and summaries of product characteristics, and validated by two MS specialists. Unit costs were based on national tariffs and guidelines. Robustness of the base case results was verified with multiple sensitivity and scenario analyses. Results: Alemtuzumab results in cost savings compared to fingolimod and natalizumab from, respectively, 3.3 and 2.8 years since treatment initiation onwards. At 5 years, total discounted costs per patient of alemtuzumab were €79,717, followed by fingolimod with €110,044 and natalizumab with €122,238, resulting in cost savings of €30,327 and €42,522 for alemtuzumab compared to fingolimod and natalizumab, respectively. Key drivers of the model are drug acquisition costs and the proportions of patients that do not require further alemtuzumab treatment after either two, three, or four courses. Limitations: No treatment discontinuation and associated switching between treatments were incorporated. Consequences of JC virus seropositivity while continuing natalizumab treatment (e.g. additional monitoring) were omitted from the base case. Conclusion: The current cost-minimization analysis demonstrates that, from the Dutch healthcare perspective, treating active RRMS patients with alemtuzumab results in cost savings compared to second-line alternatives fingolimod and natalizumab from ∼3 years since treatment initiation onwards. After 5 years, alemtuzumab’s cost savings are estimated at €30k compared to fingolimod and €43k compared to natalizumab

Comparative cost-effectiveness of focal and total salvage (125)I brachytherapy for recurrent prostate cancer after primary radiotherapy

PURPOSE: Focal salvage (FS) iodine 125 ((125)I) brachytherapy could be an effective treatment for locally radiorecurrent prostate cancer (PCa). Toxicity is often reduced compared to total salvage (TS) while cancer control can be maintained, which could increase cost-effectiveness. The current study estimates the incremental cost per quality-adjusted life year (QALY) of FS compared to TS. MATERIAL AND METHODS: A decision analytic Markov model was developed, which compares costs and QALYs associated with FS and TS. A 3-year time horizon was adopted with six month cycles, with a hospital perspective on costs. Probabilities for genitourinary (GU) and gastrointestinal (GI) toxicity and their impact on health-related quality of life (SF-36) were derived from clinical studies in the University Medical Center Utrecht (UMCU). Probabilistic sensitivity analysis, using 10,000 Monte Carlo simulations, was performed to quantify the joint decision uncertainty up to the recommended maximum willingness-to-pay threshold of €80,000/QALY. RESULTS: Focal salvage dominates TS as it results in less severe toxicity and lower treatment costs. Decision uncertainty is small, with a 97-100% probability for FS to be cost-effective compared to TS (€0-€80,000/QALY). Half of the difference in costs between FS and TS was explained by higher treatment costs of TS, the other half by higher incidence of severe toxicity. One-way sensitivity analyses show that model outcomes are most sensitive to utilities and probabilities for severe toxicity. CONCLUSIONS: Focal salvage (125)I brachytherapy dominates TS, as it has lower treatment costs and leads to less toxicity in our center. Larger comparative studies with longer follow-up are necessary to assess the exact influence on (biochemical disease free) survival and toxicity

Comparative cost-effectiveness of focal and total salvage (125)I brachytherapy for recurrent prostate cancer after primary radiotherapy

PURPOSE: Focal salvage (FS) iodine 125 ((125)I) brachytherapy could be an effective treatment for locally radiorecurrent prostate cancer (PCa). Toxicity is often reduced compared to total salvage (TS) while cancer control can be maintained, which could increase cost-effectiveness. The current study estimates the incremental cost per quality-adjusted life year (QALY) of FS compared to TS. MATERIAL AND METHODS: A decision analytic Markov model was developed, which compares costs and QALYs associated with FS and TS. A 3-year time horizon was adopted with six month cycles, with a hospital perspective on costs. Probabilities for genitourinary (GU) and gastrointestinal (GI) toxicity and their impact on health-related quality of life (SF-36) were derived from clinical studies in the University Medical Center Utrecht (UMCU). Probabilistic sensitivity analysis, using 10,000 Monte Carlo simulations, was performed to quantify the joint decision uncertainty up to the recommended maximum willingness-to-pay threshold of €80,000/QALY. RESULTS: Focal salvage dominates TS as it results in less severe toxicity and lower treatment costs. Decision uncertainty is small, with a 97-100% probability for FS to be cost-effective compared to TS (€0-€80,000/QALY). Half of the difference in costs between FS and TS was explained by higher treatment costs of TS, the other half by higher incidence of severe toxicity. One-way sensitivity analyses show that model outcomes are most sensitive to utilities and probabilities for severe toxicity. CONCLUSIONS: Focal salvage (125)I brachytherapy dominates TS, as it has lower treatment costs and leads to less toxicity in our center. Larger comparative studies with longer follow-up are necessary to assess the exact influence on (biochemical disease free) survival and toxicity