The cellular supply-side economics for phospholipids.

Choline is an essential nutrient, but how cells acquire it was not known. Two studies by Kenny et al. and Tsuchiya et al. identified the plasma membrane proteins FLVCR1 and FLVCR2 to be the bona fide choline transporters mediating choline uptake for de novo synthesis of phospholipids in all cells.

Pharmacoeconomic evaluation of different doses of Curosurf for treating neonatal acute respiratory distress syndrome.

Neonatal acute respiratory distress syndrome (ARDS) is a serious stage of acute lung injury (ALI) which can be treated by exogenous surfactant. The aim of this study was to explore the clinical efficacy of two different doses of Poractant alfa (Curosurf®) for treating neonatal ARDS and to perform an economic evaluation. Fifty-four patients were divided into Group A (high dose) and Group B (low dose). Pharmacoeconomic evaluation was performed on the two groups regarding the treatment expenses, and the output was the cure rate and complication rate. There were significant differences between Group A and Group B for the duration of receiving oxygen therapy in moderate cases (6.4±3.5d:8.9±2.6d) (P<0.05) and severe cases (10.0±2.6d:14.8±1.3d) (P<0.05). There were significant differences between them for the duration of undergoing mechanical ventilation in severe cases (1.7±2.3d:5.5±2.4d) (P=0.01). There was a significant difference between Group A and Group B for hospitalization expenses in severe cases (P<0.05). There were no significant differences between them in all types of cases for the cure rate (P>0.05). A high dose of Curosurf had an advantage in treating neonatal ARDS, especially in severe cases, with lower final costs and better effects.

Validation of dynamic contrast-enhanced ultrasound in predicting outcomes of antiangiogenic therapy for solid tumors: the French multicenter support for innovative and expensive techniques study.

OBJECTIVES: Dynamic contrast-enhanced ultrasound (DCE-US) has been used in single-center studies to evaluate tumor response to antiangiogenic treatments: the change of area under the perfusion curve (AUC), a criterion linked to blood volume, was consistently correlated with the Response Evaluation Criteria in Solid Tumors response. The main objective here was to do a multicentric validation of the use of DCE-US to evaluate tumor response in different solid tumor types treated by several antiangiogenic agents. A secondary objective was to evaluate the costs of the procedure. MATERIALS AND METHODS: This prospective study included patients from 2007 to 2010 in 19 centers (8 teaching hospitals and 11 comprehensive cancer centers). All patients treated with antiangiogenic therapy were eligible. Dynamic contrast-enhanced ultrasound examinations were performed at baseline as well as on days 7, 15, 30, and 60. For each examination, a perfusion curve was recorded during 3 minutes after injection of a contrast agent. Change from baseline at each time point was estimated for each of 7 fitted criteria. The main end point was freedom from progression (FFP). Criterion/time-point combinations with the strongest correlation with FFP were analyzed further to estimate an optimal cutoff point. RESULTS: A total of 1968 DCE-US examinations in 539 patients were analyzed. The median follow-up was 1.65 years. Variations from baseline were significant at day 30 for several criteria, with AUC having the most significant association with FFP (P = 0.00002). Patients with a greater than 40% decrease in AUC at day 30 had better FFP (P = 0.005) and overall survival (P = 0.05). The mean cost of each DCE-US was 180&OV0556;, which corresponds to $250 using the current exchange rate. CONCLUSIONS: Dynamic contrast-enhanced ultrasound is a new functional imaging technique that provides a validated criterion, namely, the change of AUC from baseline to day 30, which is predictive of tumor progression in a large multicenter cohort. Because of its low cost, it should be considered in the routine evaluation of solid tumors treated with antiangiogenic therapy.

Contrast-enhanced ultrasound using SonoVue® (sulphur hexafluoride microbubbles) compared with contrast-enhanced computed tomography and contrast-enhanced magnetic resonance imaging for the characterisation of focal liver lesions and detection of liver metastases: a systematic review and cost-effectiveness analysis.

BACKGROUND: Medical imaging techniques are important in the management of many patients with liver disease. Unenhanced ultrasound examinations sometimes identify focal abnormalities in the liver that may require further investigation, primarily to distinguish liver cancers from benign abnormalities. One important factor in selecting an imaging test is the ability to provide a rapid diagnosis. Options for additional imaging investigations include computed tomography (CT) and/or magnetic resonance imaging (MRI) and biopsy when the diagnosis remains uncertain. CT and MRI usually require referral with associated waiting time and are sometimes contraindicated. The use of contrast agents may improve the ability of ultrasound to distinguish between liver cancer and benign abnormalities and, because it can be performed at the same appointment as unenhanced ultrasound, more rapid diagnoses may be possible. OBJECTIVE: To compare the clinical effectiveness and cost-effectiveness of contrast-enhanced ultrasound (CEUS) using SonoVue(®) with that of contrast-enhanced computed tomography (CECT) and contrast-enhanced magnetic resonance imaging (CEMRI) for the assessment of adults with focal liver lesions (FLLs) in whom previous liver imaging is inconclusive. DATA SOURCES: Eight bibliographic databases including MEDLINE, EMBASE, Cochrane Database of Systematic Reviews and Database of Abstracts of Reviews of Effects were searched from 2000 to September/October 2011. Research registers and conference proceedings were also searched. REVIEW METHODS: Systematic review methods followed published guidance. Risk of bias was assessed using a modified version of the QUADAS-2 tool. Results were stratified by clinical indication for imaging (characterisation of FLLs detected on ultrasound surveillance of cirrhosis patients, detection of liver metastases, characterisation of incidentally detected FLLs, assessment of treatment response). For incidental FLLs, pooled estimates of sensitivity and specificity, with 95% CIs, were calculated using a random-effects model. For other clinical indications a narrative summary was used. The cost-effectiveness of CEUS was modelled separately for the three main clinical applications considered [characterisation of FLLs detected on ultrasound surveillance of cirrhosis patients, detection of liver metastases in patients with colorectal cancer (CRC), characterisation of incidentally detected FLLs]. RESULTS: Of the 854 references identified, 19 (describing 18 studies) were included in the review. Hand searching of conference proceedings identified a further three studies. Twenty of the 21 studies included in the systematic review were diagnostic test accuracy studies. Studies in cirrhosis patients reported varying estimates of test performance. There was no consistent evidence of a significant difference in performance between imaging modalities. It was unclear whether or not CEUS alone is adequate to rule out hepatocellular carcinoma (HCC) for FLLs of < 30 mm; one study indicated that CEUS may be better at ruling out HCC for FLLs of 11-30 mm [very small FLLs (< 10 mm) excluded]. There was no consistent evidence of a difference in test performance between imaging modalities for the detection of metastases; CEUS alone may be adequate to rule out liver metastases in colorectal cancer. In patients with incidentally detected FLLs, the pooled estimates of sensitivity for any malignancy using CEUS and CECT were 95.1% and 94.6%, respectively, and the corresponding specificity estimates were 93.8% and 93.1% respectively. One study comparing CEUS with CEMRI reported similar sensitivity and lower specificity for both modalities. In the surveillance of cirrhosis, CEUS was as effective as but £379 less costly than CECT. CEMRI was £1063 more costly than CEUS and gained 0.022 QALYs. In the detection of liver metastases from CRC, CEUS cost £1 more than CECT, and at a lifetime time horizon they yielded equal QALYs. CEMRI was dominated by CECT. In the characterisation of incidentally detected FLLs, CEUS was slightly more effective than CECT and CEMRI (by 0.0002 QALYs and 0.0026 QALYs respectively) and less costly (by £52 and £131 respectively). LIMITATIONS: There were a number of methodological issues specific to the studies included in this review. The main indication for liver imaging in the populations considered is likely to be to rule out primary liver cancer or metastases. Therefore, patient-level analyses of test performance are of particular interest. Some of the studies included in this review reported per-patient analyses; however, no study clearly stated how results were defined (e.g. was the presence of any positive lesion regarded as a positive test for the whole patient). In addition, a number of studies reported data for one lesion per patient (treated as per-patient data in this assessment). These studies generally selected the largest lesion or the lesion 'most suspicious for malignancy' for inclusion in analyses, with the consequence that estimates of test performance may have been exaggerated. The applicability of studies included in this review may be limited, as the majority of imaging studies were interpreted by multiple, experienced operators and the prevalence of malignancy in included studies appeared higher than might be expected in clinical practice. The cost-effectiveness analyses did not take into account the potential benefits of reduced anxiety that may arise from potentially shorter waiting times associated with SonoVue CEUS. CONCLUSIONS: SonoVue CEUS could provide similar diagnostic performance to other imaging modalities (CECT and CEMRI) for the assessment of FLLs. Economic analyses indicated that CEUS was a cost-effective replacement for CEMRI. The use of CEUS instead of CECT was considered cost-effective in the surveillance of cirrhosis and the characterisation of incidentally detected FLLs, with similar costs and effects for the detection of liver metastases from CRC. Further research is needed to compare the effects of different imaging modalities (SonoVue CEUS, CECT, CEMRI) on therapeutic planning, treatment and clinical outcomes. Future test accuracy studies should provide standardised definitions of a positive imaging test, and compare all three imaging modalities in the same patient group. STUDY REGISTRATION: PROSPERO: CRD42011001694. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

Marine by-product phospholipids as booster of medicinal compounds.

Marine phospholipids are defined as phospholipids containing docosahexaenoic acid (DHA) or eicosapentaenoic acid that would be more effective than fish oil, which is mostly composed of triacylglycerol, in exerting health benefits. Marine phospholipids would boost the effect of both the health-beneficial hydrophilic and the hydrophobic compounds such as cell differentiators, anticancer compounds, and antiobesity compounds. When marine phospholipids are served as liposomal drinks, they would be more effective than adding into solid foods or feeds. As long as the liposome bilayer is basically composed of marine phospholipids, they would promote the encapsulated functional compounds. And this is the principal advantage of choosing marine phospholipids as liposomal membrane. Bioconversion of marine phospholipid would also be advantageous in delivering DHA into the desired tissue. For example, lysophosphatidylserine obtained through phospholipase D-mediated transphosphatidylation and phospholipase A1 or sn-1 positional specific lipase-mediated partial hydrolysis seemed to be the most effective chemical form in delivering DHA into brain.

An evaluation of costs and effects of a nutrient-based skin care program as a component of prevention of skin tears in an extended convalescent center.

PURPOSE: A decision model was developed in a pilot study comparing a regimen using a skin care product line containing active ingredients and nutrients with a commercially available alternative skin care regimen in an elderly convalescent care hospital-based center. METHODS: Using a decision-tree model, skin treatment with a nutrient-based skin care (NBSC) formulation was compared with products without nutrients. The number of skin-tear-free days was the primary outcome measure. A cost-effectiveness ratio was calculated for each skin treatment as the average cost for reaching a particular outcome. Incidence of skin tear data was collected from residents in a convalescent center from 2004 to 2005. An independent t test was used to compare differences in the number of skin tears between periods when NBSC and other formulations were used. All costs in the decision model were adjusted to 2007 dollars. Sensitivity analysis was used to test uncertain data. RESULTS: The NBSC provided more skin-tear-free days and was less costly than the use of non-NBSC products. The expected skin-tear-free days for a patient in the model treated with NBSC were 179.7 days compared with 154.6 days for non-NBSC products, yielding an incremental effect of 25.1 days. The expected cost of preventing skin tears and treatment via skin treatment per patient in the NBSC group was $281.00 versus $324.10 for periods when other products were used. CONCLUSION: The NBSC had a lower projected cost for prevention of skin tears and more skin-tear-free days when compared with non-NBSC products.

Ammonium sulfate gradient loading of brucine into liposomes: effect of phospholipid composition on entrapment efficiency and physicochemical properties in vitro.

BACKGROUND: Brucine, the major active alkaloid constituent extracted from traditional Chinese herbal medicine Nux vomica, had been found to possess remarkable antitumor, analgesic, and anti-inflammatory activities. In this study, we attempted to encapsulate brucine into liposomes to improve its therapeutic effects. The entrapment efficiency (EE) and the stability of liposomes are two key factors associated with the therapeutic effects of liposomal drugs. We developed a novel liposome-based brucine formulation that was composed of soybean phosphatidylcholine (SPC) and hydrogenated soybean phosphatidylcholine (HSPC). METHOD: The liposomes with different phospholipid composition were characterized for their EE, vesicle size, drug release profile, and leakage in vitro. RESULTS: The molar ratio of HSPC/SPC = 1:9 was determined as the optimum ratio. Compared with conventional liposomes composed of only SPC or HSPC, EE of the brucine-loaded novel liposomes was increased markedly, especially at high drug/lipid molar ratios. The results of drug release showed that the novel liposomes were more stable than the conventional SPC liposomes in the presence of fetal calf serum. In addition, the results of the leakage experiments revealed that the novel liposomes also had better stability in phosphate buffer solution (PBS) with respect to drug retention. Although the conventional HSPC liposomes is more stable than the novel liposomes, the novel liposomes composed of 10% HSPC and 90% SPC may still have promising application potential because HSPC is much more expensive than SPC. CONCLUSION: Taken together, efficient encapsulation of brucine into the novel liposomes, their improved stability, and the price of phospholipids indicate that the novel liposomes may act as promising carriers for active alkaloids such as brucine.

Contrast-enhanced ultrasonography in the characterization of benign focal liver lesions: activity-based cost analysis.

PURPOSE: The aim of this study was to perform a cost analysis of contrast-enhanced ultrasonography (CEUS) in the study of benign focal liver lesions (BFLL) with indeterminate appearance on ultrasonography (US). MATERIALS AND METHODS: A decision model of patients with suspected BFLL on baseline US who subsequently underwent CEUS between 2002 and 2005 was constructed. We analysed the cost effectiveness of CEUS, considering whether or not computed tomography (CT) was necessary for the diagnosis. There were 398 patients with 213 angiomas, 41 focal nodular hyperplasias (FNH) and 154 pseudolesions (focal fatty sparing, focal fatty areas). Each patient underwent CEUS, and 98 of them were also studied by CT. All lesions were followed up. RESULTS: The cost of a single CEUS examination was 101.51 euros, and that of a single CT scan was 211.48 euros. For diagnosis of haemangiomas, we saved 1,406.97 euros in 2002, 5,315.22 euros in 2003, 10,317.78 euros in 2004 and 9,536.13 euros in 2005. For diagnosis of focal nodular hyperplasias, we saved 781.65 euros in 2003, 781.65 euros in 2004 and 1,406.97 euros in 2005. For diagnosis of pseudolesions, we saved 2,813.94 euros in 2002, 5,158.89 euros in 2003, 5,158.89 euros in 2004 and 4,220.91 euros in 2005. In the period 2002-2005, the introduction of CEUS allowed us to save a total of 47,055.33 euros in the diagnosis of benign focal hepatic liver lesions. CONCLUSIONS: This cost analysis shows that CEUS is the least expensive second-line modality after baseline US for the diagnosis of BFLL.

Economic assessment of contrast-enhanced ultrasonography for evaluation of focal liver lesions: a multicentre Italian experience.

BACKGROUND: The aim of this study was to evaluate the clinical and economic consequences of the introduction of contrast-enhanced ultrasonography (CEUS) into the diagnostic clinical algorithm for the characterization of incidental focal liver lesions (FLLs). METHODS: This prospective study enrolled 485 subjects at three hospitals in Italy. Two diagnostic algorithms were utilized: (1) a classic patient work-up, which included baseline US followed by a CT or MR examination, and (2) a new patient management scheme in which, following the baseline US, a CEUS examination was performed. For each pathway, both direct and indirect health costs for the National Health System (NHS) at two of the three hospitals involved in the study were calculated. Clinical outcome was measured in terms of number of cases correctly diagnosed, using contrast-enhanced CT/contrast-enhanced MR as the reference standard. RESULTS: CEUS correctly differentiated (benign vs. malignant) 559 of 575 lesions (97.2%), with a sensitivity of 98.1% and a specificity of 95.7%. Histological characterization was correct in 502 of 575 lesions (87%) with a sensitivity of 90.5% and a specificity of 85.4%. In terms of cost, the conventional diagnostic algorithm incurred for the NHS a total cost of Euro 134.576,60 vs. Euro 55.674,30 with CEUS, for a saving of Euro 78.902 (Euro 162 per patient). For the hospitals, the total cost was Euro 147.045 without CEUS vs Euro 61.979 with CEUS, for a saving of Euro 85.065,96 or Euro 175,39 per patient. CONCLUSION: The routine use of CEUS for the characterization of FLLs provides significant cost savings, both for the NHS and for the hospital.

A comparison of Zenoderm with DuoDERM E in the treatment of split skin graft donor sites.

A prospective, randomised, controlled study compared Zenoderm (ZM) with DuoDERM E (DE) in the treatment of split skin graft donor areas in 64 patients. The donor site comfort was similar in the two groups. DE usage resulted in significantly faster healing but also a higher leakage rate than ZM. Two patients in the ZM group developed infection in their donor sites. The cost is significantly less with ZM than DE.