Anti-inflammatory bowel effect of industrial orange by-products in DSS-treated mice.

This work addresses the role of different by-products derived from the industrial extraction of orange juice in a possible anti-inflammatory effect in mice with colitis induced by dextran sulfate sodium (DSS). Fresh orange residue (FOR), dry orange residue (DOR), orange liqueur (OL) and animal feed (AF), as well as commercial citrus pectin (CP), were administered to C57BL/6J mice for 15 days before starting the DSS treatment. Analysis of macroscopic parameters such as the Disease Activity Index (DAI) and the colonic weight/length ratio revealed an anti-inflammatory effect following intake of FOR, AF or CP. Moreover, q-PCR of RNA from colonic tissue indicated measurable changes in the expression of TNF-α, IL-1ß, iNOS, and intercellular adhesion molecules ICAM I, as well as in intestinal barrier proteins such as MUC-3, occludin, and ZO-1. Pectin, phenolic compounds and/or Maillard reaction products formed at initial steps were identified as relevant components exerting the ascribed beneficial effects. Our findings could open up the further application of a variety of orange by-products as food supplements in the potential amelioration of inflammatory bowel diseases.

Economic assessment of actual prescription of drugs for treatment of atopic dermatitis: Differences between dermatology and pediatrics in large-scale receipt data.

Using large-scale receipt data, we analyzed the differences in the prescription of drugs and their costs between dermatology and pediatrics in the treatment of atopic dermatitis (AD) in children. Between August 2010 and July 2011, 50 706 patients were diagnosed as having AD, and the data of 21 075 (15 257 dermatology, 5818 pediatric) patients aged 0-14 years were included in this study. The use of classes I (strongest), II (very strong), and III (strong) topical corticosteroids and tacrolimus was significantly higher in dermatology than in pediatrics (class I, 2.88% vs 0.76%; class II, 27.68% vs 8.32%; class III, 52.53% vs 39.88%; tacrolimus, 5.05% vs 2.82%; all P < 0.05). Although total drug costs were higher in dermatology than in pediatrics, mean drug costs per person were significantly higher in pediatrics. Moisturizers and protective agents had the highest cost (~ ¥690 million). The introduction rate of generic drugs was low at 8.3% among classes I-V. The introduction rate of moisturizers and protective agents, for which costs were the highest, was approximately 9%. The prescription of generic classes II-V topical corticosteroids and moisturizers and protective agents was also significantly higher in dermatology than in pediatrics (P < 0.05). Among patients younger than 2 years, 4405 received drugs for AD; classes I and II topical corticosteroids and tacrolimus (against the guidelines) were administrated in 35 (0.8%), 474 (10.8%) and 29 patients (0.7%), respectively. The introduction of generic drugs is still low, and the use of generic moisturizers and protective agents should be addressed further.

Physicochemical properties and intestinal protective effect of ultra-micro ground insoluble dietary fibre from carrot pomace.

Carrot pomace is an abundant, but underutilized, byproduct from the juice industry. In this study, the insoluble dietary fiber from carrot pomace was treated using an ultra-microgrinding process, and the resulting changes in its physicochemical properties and intestinal protective effect against heavy metal damage were examined. The SEM and fluorescence microscopy results showed that the grinding process could significantly decrease the particle size of carrot insoluble dietary fibre and increase its Brunauer-Emmett-Teller surface area from 0.374 to 1.835 m(2) g(-1). Correspondingly, the water-holding capacity, swelling capacity, and oil-holding capacity increased by 62.09%, 49.25% and 45.45%, respectively. The glucose-, nitrite-, and lead ion-adsorbing abilities also improved significantly compared with the raw samples. In addition, apoptosis assessment by AO/EB revealed that the ground fibre could effectively protect Caco-2 cells from lead ion damage. The MTT assay showed that carrot insoluble dietary fibre has no toxicity for Caco-2 cells at a concentration of 10.0 mg L(-1). The findings of this study highlighted the potential of the ultra-microgrinding process to produce a high added-value fibre ingredient from carrot residues.

[Pharmacoeconomic Analysis of the Use of Hepatoprotectors in Management of Drug-Associated Liver Injury Due to Hodgkin's Lymphoma Chemotherapy].

The data on the pharmacoeconomic research of the use of Remaxol in treatment of drug-associated liver injury due to the chemotherapy in cancer patients are presented. The costs-efficiency method was applied to two groups of the patients with drug-associated liver injury treated according to different schemes. The research showed economical benefits of the Remaxol use.

[Clinical and economic analysis of the feasibility of using Dicarbamine for the prevention of the toxic effects of antineoplastic chemotherapy].

The aim of the study was to conduct clinical and economic analysis of the feasibility of using Dicarbamine for the prevention of toxic effects of chemotherapy. There were compared the direct medical costs on prevention and treatment of febrile neutropenia in 2 groups of breast cancer patients: chemotherapy alone in TAC mode or chemotherapy in the same way against oral Dicarbamine. Total costs due to hematologic toxicity were 1003945 rubles in the control group (22817 rubles on average by 1 patient) and 658980 rubles in the group treated with Dicarbamine (14 644 rubles on average by 1 patient). Also, the study found that in the group treated by Dicarbamine there were lower rates of dose reduction and delay of the next course of chemotherapy, which might have an impact on other costs arising from cancer. The results of this study demonstrate the clinical and economic feasibility of using Dicarbamine for the prevention of hematotoxic complications of chemotherapy.

[Effectiveness of the hepatoprotective activity of reamberine, remaxol, and ademethionine and risk assessment in their use in patients with respiratory tuberculosis and drug-induced liver injury].

AIM: To comparatively evaluate the hepatoprotective activity of reamberine, remaxol, and exogenous ademethionine and a risk for unfavorable/favorable outcomes of their use in patients with liver injury during antituberculosis chemotherapy. SUBJECTS AND METHODS: One hundred and eighty patients with new-onset respiratory tuberculosis were examined and divided into 4 groups (45 patients in each group): Study Group 1 (SG1): patients who took reamberine; Study Group 2 (SG2): those who received remaxol; Study Group 3 (SG3): those who had ademethionine; and a Comparative Group (CG): those who received 5% glucose solution. The test drugs were intravenously administered in a dropwise manner once daily for 10 days. The laboratory hepatic injury severity index (LHISI) was estimated according to the method described by T.N. Kalachnyuk and the risk for a favorable/unfavorable outcome was assessed, by calculating the average cost of the used hepatotropic agents. RESULTS: LHISI increased statistically significantly with the development of liver injury induced by antituberculosis agents. There was a statistically significant reduction in LHISI during therapy with the test hepatotropic agents versus glucose solution, the most pronounced activity being shown by remaxol. Relative risk (RR) and odds ratio (OR) assessments revealed the high likelihood of a favorable outcome (a reduction in LHISI) when each of the 3 test drugs versus glucose solution was administered; the highest RR and OR were also found in the use of remaxol. Estimation of costs and the number of patients to be treated (NPBT) in order to avoid a case of none LHLIS reduction could reveal the highest efficacy of remaxol. CONCLUSION: The test agents (reamberine, remaxol, and ademethionine) are effective in treating tuberculosis patients with drug-induced liver injury. The administration of remaxol demonstrated the highest positive effect (as estimated by LHISI) in terms of both RR and NPBT.

Cost-utility analysis of proton pump inhibitors and other gastro-protective agents for prevention of gastrointestinal complications in elderly patients taking nonselective nonsteroidal anti-inflammatory agents.

BACKGROUND: The use of proton pump inhibitors (PPIs) among elderly patients using nonselective nonsteroidal anti-inflammatory drugs (nsNSAIDs) has increased; the price of PPIs is higher than that of majority of alternative treatment strategies. AIM: To evaluate the cost-effectiveness of nsNSAIDS + PPIs relative to alternative gastroprotective regimens in the prevention of GI complications among elderly patients (aged > or = 65 years). METHODS: An incremental cost-utility analysis, comparing PPIs with alternative gastroprotective regimens was conducted using a decision analytical model. Clinical outcomes, costs and utilities were derived from recently published studies. Probabilistic and deterministic sensitivity analyses were performed to test the robustness of the results to variation in model inputs and assumptions. RESULTS: The incremental cost-utility ratio (ICUR) of PPIs, relative to nsNSAID alone, was $206,315 per QALY gained or were more costly and less effective. Other co-prescribed treatment options had higher costs per QALY gained. In patients with a history of a complicated or uncomplicated ulcer, PPIs had ICURs of $24,277 and $40,876, respectively. CONCLUSIONS: Use of PPIs in all elderly patients taking nsNSAIDs is unlikely to represent an efficient use of finite healthcare resources. Co-prescribing PPIs, however, to elderly patients taking nsNSAIDs who have a history of complicated or uncomplicated ulcers appears to be economically attractive.

Docetaxel in combination with doxorubicin and cyclophosphamide as adjuvant treatment for early node-positive breast cancer: a cost-effectiveness and cost-utility analysis.

PURPOSE: To estimate the cost effectiveness of TAC (docetaxel, doxorubicin, and cyclophosphamide) compared with FAC (fluorouracil, doxorubicin, and cyclophosphamide) when administered as adjuvant therapy to women with node-positive early breast cancer in the United Kingdom (UK), both with and without primary prophylaxis with granulocyte colony-stimulating factor (G-CSF). METHODS: A standard health economic Markov model estimated the cost and outcome for node-positive early breast cancer patients, from initiation of adjuvant chemotherapy to death. Patient-level data were used from the Breast Cancer International Research Group (BCIRG) 001 trial for estimates of the effect of chemotherapy on toxicity and outcome, and an observational data set collected from a UK university hospital provided estimates of resource use and outcome for patients with relapsed disease. RESULTS: Over a 10-year analysis timeframe, the incremental cost per life-year saved associated with the use of TAC rather than FAC was estimated as pound 15,418 (95% CI, pound 13,734 to pound 17,997) and the incremental cost per quality-adjusted life-year gained (IC/QALY) was pound 18,188 (95% CI, pound 14,161 to pound 32,422). The addition of primary G-CSF (lenograstim or filgrastim) to the TAC regimen resulted in an IC/QALY of pound 20,432. The results were most sensitive to the quality-of-life (QOL) score for patients in remission postchemotherapy. However, even if QOL was assumed to be as poor as for patients with metastatic disease, the IC/QALY estimate rose only to pound 32,430. CONCLUSION: The use of adjuvant TAC rather than FAC for node-positive early breast cancer patients is cost effective, despite the increased drug and toxicity treatment costs, and when primary G-CSF prophylaxis is given to all patients.

Utilization and cost comparison of current and optimal prescribing of nonsteroidal antiinflammatory drugs in Quebec, Canada.

OBJECTIVE: Clinical practice guidelines recommend prophylactic use of gastroprotective agents (GPA) with nonselective nonsteroidal antiinflammatory drugs (nsNSAID) for patients at risk of gastrointestinal (GI) complications. We estimated the costs of cyclooxygenase-2 selective inhibitors, nsNSAID, and concurrent GPA prescribed in 2002 in Quebec, Canada, and compared these to estimated costs if prescribing followed guideline recommendations. METHODS: We used the Quebec government medical and pharmaceutical claims database (RAMQ). All prescriptions for NSAID and concurrent GPA dispensed between January 1 and December 31, 2002, were evaluated for continuously covered beneficiaries 18 years of age or older. Prescriptions were stratified by patient GI risk factors determined at the dispensing date of each prescription into low-, moderate-, elevated-, and high-risk categories. Five scenarios of "appropriate" NSAID therapy were identified using clinical practice guidelines. The potential effect on the prescription drug budget of implementing each of these scenarios was estimated. RESULTS: In total, 503,671 patients filled 1,863,171 prescriptions for NSAID, representing 41.1 million days of treatment with total expenditures of about dollar 94 million CDN for NSAID and concurrent GPA. Average actual daily costs for coxibs (rofecoxib and celecoxib), celecoxib, nsNSAID, and concurrent GPA were dollar 1.94, dollar 2.06, dollar 1.19, and dollar 2.30, respectively. Prescribing nsNSAID with GPA to all patients at moderate and elevated risks while prescribing NSAID without GPA to patients at low risk, and celecoxib with a GPA to patients at very high risk would have cost dollar 36.4 million more, mainly due to the additional cost of GPA. CONCLUSION: Compared to actual prescribing patterns, a prescribing strategy consistent with clinical practice guidelines can increase drug acquisition costs to the healthcare payer.

Clinical and cost effectiveness of a cleanser protectant lotion for treatment of perineal skin breakdown in low-risk patients with incontinence.

Perineal dermatitis due to urinary and/or fecal incontinence is a common problem. A multicenter, open label, phase II product evaluation was conducted to determine the effectiveness of a new cleanser protectant lotion in reducing perineal erythema and pain in patients at low-risk for perineal dermatitis and to compare the cost of this product to standard protocols of care. Nineteen elderly patients (14 male, 5 female, mean age 73.1 years) participated in the study. Average baseline scores for erythema and pain were 2.3 (+/- 0.5) and 1.5 (+/- 1.0), respectively (scale 0 to 4). After 7 days, both scores were significantly lower (mean scores 0.6 +/- 0.8 and 0.3 +/- 0.8, respectively; P < 0.01). Based on an average of 2.6 perineal episodes per day, the one-step product evaluated would cost $136 per patient/year less than standard protocols of care while reducing caregiver time (average 23 seconds per episode of care). Optimal perineal care may reduce the incidence of complications; studies to ascertain the safety and effectiveness of commonly used products and procedures are needed.

Diclofenac/misoprostol. Pharmacoeconomic implications of therapy.

The combined formulation of diclofenac/misoprostol provides effective relief of pain and inflammation, with a 2- to 3-fold lower incidence of NSAID-associated gastroduodenal ulcers than diclofenac monotherapy. Both components of the combined formulation have been widely used and have well documented efficacy and tolerability profiles. Compared with other agents used as prophylaxis for NSAID-induced gastropathies, misoprostol is generally considered to have the most extensive outcomes data establishing its efficacy in preventing both gastric and duodenal ulcers associated with long term NSAID use. Economic analyses conducted to date have shown that diclofenac/misoprostol is associated with similar or lower total direct medical treatment costs compared with other NSAIDs (with or without coprescribed misoprostol or an alternate prophylactic agent). As with pharmacoeconomic studies of coprescribed misoprostol with NSAIDs, the most favourable results with the combined formulation of diclofenac/misoprostol appear to be in patients at high risk of developing NSAID-associated gastroduodenal ulcers (e.g. the elderly). Although economic analyses with diclofenac/misoprostol were conducted in several different countries using a variety of methodologies and employing a wide range of clinical and economic assumptions, results have been generally favourable for the combined formulation. However, as is the case with pharmacoeconomic analyses in general, results of individual studies with diclofenac/misoprostol may not be generalisable between countries and are subject to change over time. Overall, clinical and economic data suggest that the optimal and most cost-effective use of the combined formulation of diclofenac/misoprostol is in patients requiring long term NSAID therapy who are at increased risk of developing NSAID-induced gastropathy, such as elderly patients with rheumatoid arthritis or osteoarthritis.

Gastropathy induced by nonsteroidal anti-inflammatory drugs: prescribing patterns among geriatric practitioners.

The objective of this study was to determine patterns among geriatric practitioners in prescribing agents that protect the gastrointestinal tract when nonsteroidal anti-inflammatory drug (NSAID) treatment is started for elderly patients. A questionnaire describing five scenarios of elderly patients requiring NSAID therapy asked respondents to choose gastrointestinal-protective agents for each scenario. Respondents were then asked to what extent four established risk factors for NSAID gastropathy (age, previous peptic ulcer, previous gastrointestinal bleeding, and heart disease) affected their choices. The choice of gastrointestinal-protective agent was compared with the training and experience of the respondents. This self-administered survey was provided to 821 randomly selected physicians from the membership of the American Geriatrics Society throughout the United States and Puerto Rico. Statistical Package for the Social Sciences (SPSS), version 6.1.4, was used to obtain frequencies. Of 821 surveys, 229 (28%) were returned. It was found that well elderly patients and nursing home residents were not treated with any gastrointestinal-protective agent by 64% (well elderly patients) and 32% (nursing home residents) of respondents. Among respondents who would prescribe, about half would choose misoprostol for a well elderly patient or a nursing home resident, whereas half or more preferred histamine H2-receptor antagonists. Twenty-three percent would not prescribe misoprostol when NSAID therapy was resumed after an active ulcer had healed, and 68% preferred H2 antagonists in that setting. The difference in response attributable to training/experience was less than 9%. Factors that did not affect prescribing patterns included the patient's age (15% to 62%) and heart disease (44% to 50%). The study concluded that age and heart disease are risk factors to which physicians give less consideration when choosing gastrointestinal-protective agents. Although misoprostol is the only agent approved by the Food and Drug Administration for prophylaxis against NSAID gastropathy, 23% of respondents chose not to prescribe misoprostol when NSAID therapy was resumed after an active ulcer had healed. Histamine H2-receptor antagonists were preferred over misoprostol for well elderly patients and nursing home residents. Training and experience were not responsible for differences among respondents' prescribing patterns.

Pharmacoeconomics of amifostine in ovarian cancer.

Physicians are frequently pressured to make therapeutic decisions within a cost-effective framework to demonstrate value to managed care. Because cancer is a chronic disease, health care costs are known to be expensive and physicians must use their resources as efficiently as possible. Historically, economic analyses in oncology have emphasized survival as their clinical end point. Today, both government groups and professional organizations are moving toward making quality of life the clinical end point in determining the economics of chemotherapy. This report evaluates the cost and efficacy of amifostine (Ethyol; Alza Pharmaceuticals, Palo Alto, CA/US Bioscience, West Conshohocken, PA) use in the treatment of advanced ovarian cancer using two pharmacoeconomic analyses. A cost-utility analysis performed in the United States indicated that inclusion of amifostine therapy had both a favorable clinical and cost-utility profile compared with other medical therapies. A second cost-benefit analysis, conducted in Canada, suggested that use of amifostine in patients with advanced ovarian cancer would be cost saving. Amifostine is a novel agent that protects against both chemotherapy- and radiotherapy-induced toxicities, such as nephrotoxicity, neutropenia, thrombocytopenia, peripheral neuropathy, mucositis, and xerostomia. These toxicities are disturbing to both patients and physicians alike. The results of these studies support the use of amifostine as a valuable resource both economically and clinically.