Xylooligosaccharides: an economical prebiotic from agroresidues and their health benefits.

Oligosaccharides and dietary fibres are non-digestible food ingredients that preferentially stimulate the growth of prebiotic Bifidobacterium and other lactic acid bacteria in the gastro-intestinal tract. Xylooligosaccharides (XOS) provide a plethora of health benefits and can be incorporated into several functional foods. In the recent times, there has been an over emphasis on the microbial conversion of agroresidues into various value added products. Xylan, the major hemicellulosic component of lignocellulosic materials (LCMs), represents an important structural component of plant biomass in agricultural residues and could be a potent bioresource for XOS. On an industrial scale, XOS can be produced by chemical, enzymatic or chemo-enzymatic hydrolysis of LCMs. Chemical methods generate XOS with a broad degree of polymerization (DP), while enzymatic processes will be beneficial for the manufacture of food grade and pharmaceutically important XOS. Xylooligomers exert several health benefits, and therefore, have been considered to provide relief from several ailments. This review provides a brief on production, purification and structural characterization of XOS and their health benefits.

Computer-assisted management of unconsumed drugs as a cost-containment strategy in oncology.

BACKGROUND: Cost-containment strategies are required to deal with rising drug expenditure, also in oncology. Drug wastage related to the preparation of chemotherapy drugs for patients is costly, but solutions exist for optimizing the use of unconsumed anticancer drugs. OBJECTIVE: Our pharmacy department makes use of a computerized drug storage bank, which records stability data and the amounts of unconsumed drugs available, and is connected to prescription software via an interface. We aimed to evaluate the real cost savings generated by this system. METHOD: We assessed the cost savings achieved with this system, for 37 different anticancer drugs, over a 1-year period. French drug pricing and the amounts of drugs from the storage bank potentially re-used were assessed. RESULTS: The re-use of unconsumed anticancer drugs generated substantial cost savings, for nine drugs in particular: azacitidine, bevacizumab, bortezomib, cetuximab, docetaxel, liposomal doxorubicin, rituximab, topotecan and trastuzumab. Overall cost savings accounted for about 5 % of total anticancer drug expenditure at our hospital (8.5 M). CONCLUSION: In medical hematology-oncology, drug wastage reduction and a computerized physician order entry system could be applied in routine practice at centralized drug-processing units, with significant financial benefits.

[Aspirin and cancer: evidence of a prophylactic effect]. / Acetylsalicylzuur en kanker: aanwijzingen voor een preventief effect.

Due to increased life expectancy, the number of new patients diagnosed with cancer is also increasing; this requires effective and inexpensive strategies for preventing cancer. The concept of chemoprevention involves taking medication to reduce cancer risk. By re-assessing aspirin trials that were originally conducted to determine its effect on cardiovascular disease, it appeared that aspirin was associated with a reduction in the incidence of cancer as well as cancer-related mortality. The vascular benefits and risks associated with aspirin are only clinically relevant in the short term; its beneficial effects on cancer risk only become apparent after three years. Aspirin probably has a preventive effect on metastasis. These findings from randomised trials are consistent with results from methodologically rigorous observational studies. Until now, primary prevention in vascular disease has only proven to be cost-effective in certain risk groups. In future cost-effectiveness analyses, the beneficial effect of aspirin on cancer risk needs to be taken into account.

Aspirin as a chemoprevention agent for colorectal cancer.

Colorectal cancer (CRC) is one of the leading causes of mortality in the western world. It is widely accepted that neoplasms such as colonic polyps are precursors to CRC formation; with the polyp-adenoma-carcinoma sequences well described in medical literature [1, 2]. It has been shown that Aspirin and other non-steroid anti-inflammatory drugs (NSAID) have a negative effect on polyp and cancer formation. This review aims to describe some of the mechanism behind the chemoprotective properties of aspirin; COX 2 inhibition, regulation of proliferation and apoptosis and effects on the immune system and also the current evidence that supports its use as a chemoprevention agent against CRC. We will also aim to explore the side effects with the use of aspirin and the pitfalls of using aspirin routinely for primary prophylaxis against CRC.

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.

Projet pilote sur l'évaluation de quatre médicaments anticancéreux / Pilot project on the evaluation of four cancer drugs

INTRODUCTION: Le présent rapport fait suite à un entretien tenu avec le ministre de la Santé et des Services sociaux, le 12 octobre dernier, où il a été convenu que l'INESSS voit si certains paramètres de son évaluation de quatre médicaments refusés en 2011, pour des considérations essentiellement de nature pharmacoéconomique, pourraient plutôt être analysés en fonction de nouveaux principes théoriques émergeant de ses travaux en cours. En effet, peu après sa création, en janvier 2011, l'INESSS a mis en place un plan d'action visant une amélioration continue des façons de faire et une meilleure gestion de l'innovation, à l'instar d'autres organisations dans le monde qui font face à des défis similaires. Ce plan, appliqué ici aux médicaments anticancéreux, vise également à explorer de nouvelles approches qui pourraient procurer un meilleur accès aux médicaments pour les personnes affligées de maladies graves, dont le cancer, et ce, particulièrement dans un contexte de fin de vie, tout en garantissant un accès équitable et raisonnable aux médicaments requis par l'état de santé de l'ensemble de la population. Cela doit se faire en tenant compte de l'impératif d'assurer la pérennité du régime public d'assurance médicaments et du système de soins de santé québécois, comme sa mission, telle que définie par loi, demande à l'INESSS de le faire. Les principaux constats qui se dégagent des réflexions du groupe de travail ont permis au Comité scientifique permanent de l'évaluation des médicaments aux fins d'inscription (CSEMI) de réexaminer, selon la perspective d'un projet pilote et en fonction de nouveaux principes théoriques émergeant de ses travaux en cours, les recommandations de l'INESSS pour les quatre médicaments ayant fait l'objet d'un refus en 2011. Les recommandations pour les médicaments suivants ont donc été revues à la lumière de ces réflexions: AfinitorMC dans le traitement de deuxième intention du carcinome métastatique rénal; AlimtaMC dans le traitement d'entretien du cancer du poumon métastatique; IressaMC dans le traitement de première intention du cancer du poumon métastatique; TarcevaMC dans le traitement d'entretien du cancer du poumon métastatique. MÉTHODOLOGIE: Le plan d'action implique d'abord un travail conjoint entre le Comité de l'évolution des pratiques en oncologie (CEPO) de la Direction québécoise du cancer du ministère de la Santé et des Services sociaux (MSSS) et le nouveau Comité scientifique permanent de l'évaluation des médicaments aux fins d'inscription (CSEMI) de l'INESSS, auquel siègent notamment des membres citoyens et des éthiciens. Une première étape a permis d'associer étroitement ces acteurs dans la détermination de la valeur thérapeutique des médicaments étudiés grâce à une approche qui favorise l'émergence de consensus. Le plan d'action prévoit également la poursuite des travaux pour continuer à améliorer le cadre d'analyse pharmacoéconomique et le cadre d'analyse éthique et sociétal afin de mieux tenir compte notamment du contexte vécu par les patients. Il prévoit également des travaux afin de mieux encadrer l'introduction de l'innovation dans le système de santé et de services sociaux. Rappelons par ailleurs que la fonction d'évaluation des médicaments aux fins d'inscription à l'INESSS exige un cadre strict et des règles précises afin de soutenir une démarche d'évaluation rigoureuse. Ce cadre d'évaluation des médicaments est composé des éléments suivants : -des critères d'évaluation, fixés par la Loi sur l'INESSS; -une compréhension commune à tous les partenaires concernés quant à la teneur et à la portée de chaque critère; -des modalités d'application précises. En se basant sur les réflexions réalisées à ce jour par le groupe de travail mis en place pour soutenir ces travaux, de nouvelles pistes d'analyse pour apprécier les quatre dossiers oncologiques étudiés ont ainsi pu être dégagées. Il faut noter que les travaux ont été faits sur une base pilote pour ces quatre médicaments et qu'il ne s'agit pas d'une réévaluation de ceux-ci, mais bien d'un réexamen effectué à la lumière des travaux réalisés par le groupe de travail mis sur pied par l'INESSS, de ses principales réflexions et des recommandations de son CSEMI. CONCLUSIONS: Les recommandations de l'INESSS présentées dans ce rapport sont faites à la lumière des réflexions en cours. En ce qui a trait au cadre d'évaluation, les réflexions se poursuivant sur les dimensions économiques, éthiques et sociétales pourraient amener, par exemple, à développer de nouveaux mécanismes de discussion visant à mieux apprécier la valeur perçue des médicaments concernés et à parfaire des outils de participation citoyenne. Par ailleurs, pour ce qui est des pratiques novatrices pour faciliter et encadrer l'accès aux nouveaux médicaments, de nouvelles avenues seront explorées afin de trouver des solutions adaptées à la situation des médicaments anticancéreux et à la réalité québécoise. Ces avenues pourraient prendre différentes formes, comme une inscription avec développement de la preuve, une inscription conditionnelle ou réservée à des centres spécialisés en cancer ou une poursuite de traitement conditionnelle à l'atteinte d'objectifs thérapeutiques à court terme, qui peuvent toutes être liées selon la circonstance à des ententes de partenariat novatrices afin de partager le risque financier lié à un accès élargi. Considérant les nombreux enjeux en place, ces analyses devront être réalisées en profondeur, en fonction de tous les aspects, soit clinique, économique, éthique et juridique. L'objectif de l'INESSS est de poursuivre ces réflexions en concertation avec ses partenaires, et ce, d'ici juin 2012 afin de produire un rapport qui présentera une série d'orientations à la portée du système de santé et de services sociaux québécois.

Cost-effectiveness of aspirin, celecoxib, and calcium chemoprevention for colorectal cancer.

BACKGROUND: Studies have indicated that aspirin chemoprevention may be effective in preventing colorectal cancer within the general population, and aspirin, celecoxib, and calcium may be effective in preventing adenomas within those people who have previously undergone polypectomy. OBJECTIVE: To assess the cost-effectiveness of aspirin, celecoxib, and calcium chemoprevention in the context of the fecal occult blood test screening program. METHODS: An existing state transition model developed to assess colorectal cancer screening options was modified to incorporate the costs and outcomes associated with chemoprevention. Relative risks of disease progression were incorporated based on the effectiveness of the chemopreventive agents. Additional benefits and harms associated with chemoprevention were included. Sensitivity analyses were undertaken. RESULTS: Aspirin chemoprevention plus screening within the general population aged 50 to 60 years is estimated to cost £23,000 per quality-adjusted life year (QALY) gained compared with screening alone (based on 2008 prices). For individuals who have undergone polypectomy, calcium is estimated to cost between £8000 and £30,000 per QALY gained depending on the starting and stopping age of the chemoprevention policy. Based on current evidence, calcium has a higher probability than aspirin of providing value for money within this population, although the long-term benefits and harms are subject to considerable uncertainty. Celecoxib chemoprevention is unlikely to be considered to be cost-effective. CONCLUSION: Calcium chemoprevention is likely to be a cost-effective option for individuals who have undergone polypectomy. Further research is required to assess the long-term benefits and harms of calcium compared with aspirin chemoprevention. Chemoprevention appears less economically attractive within the general population.

Budget impact analysis of chemoprevention of breast cancer with tamoxifen and raloxifene among high-risk women in Japan.

'Cost saving' was suggested in our recent economic evaluation of chemoprevention of breast cancer targeting women at high risk in Japan. However, this budget impact analysis reveals that the introduction of chemoprevention appears to be not budget saving for approximately 20 years, whereas the level of budget impact seems affordable.

Chemoprevention: drug pricing and mortality: the case of tamoxifen.

BACKGROUND: Tamoxifen is a prototypic cancer chemopreventive agent, yet clinical trials have not evaluated its effect on mortality or the impact of drug pricing on its cost-effectiveness. METHODS: A state-transition Markov model for a hypothetical cohort of women age 50 years was used to evaluate the effects of tamoxifen on mortality and tamoxifen price on cost-effectiveness. Incidence and mortality rates for breast and endometrial cancers were derived from Surveillance, Epidemiology and End Results statistics, and noncancer outcomes were obtained from published studies. Relative risks of outcomes were derived from the National Surgical Adjuvant Breast and Bowel Project P-1 trial. Costs were based on Medicare reimbursements. RESULTS: Projected overall mortality for women at 1.67% 5-year breast cancer risk showed little difference with or without tamoxifen, resulting in a cost-effectiveness ratio of $1,335,690 per life-year saved as a result of tamoxifen use. Adjusting for the differential impact of estrogen receptor-negative cancers, tamoxifen increased mortality for women with a uterus until the 5-year breast cancer risk reached > or =2.1%. Assigning the Canadian price for tamoxifen dramatically reduced the incremental cost (to $123,780 per life-year saved). At that price, the use of tamoxifen was less costly and more effective for women with 5-year breast cancer risks >4%. CONCLUSIONS: Tamoxifen may increase mortality in women at the lower end of the "high-risk" range for breast cancer. If prices in the U.S. approximated Canadian prices, then tamoxifen use for breast cancer risk reduction in women with a 5-year risk >3% could be a reasonable strategy to reduce the incidence of breast cancer. Because they are used by many unaffected individuals, the price of chemopreventive agents has a major influence on their cost-effectiveness.

Cost effectiveness of extended adjuvant letrozole in postmenopausal women after adjuvant tamoxifen therapy: the UK perspective.

BACKGROUND: MA17 was a randomised placebo-controlled trial of letrozole 2.5 mg/day in 5187 estrogen receptor-positive, 50% node-negative, postmenopausal women (median age 62 years at enrollment) with early breast cancer, post-5 years' adjuvant tamoxifen therapy. The objective of this evaluation was to extrapolate the findings from the MA17 trial to estimate the lifetime cost effectiveness of letrozole in this setting. METHODS: A Markov model was used to estimate the incremental cost per QALY gained with extended adjuvant letrozole versus no therapy. Probabilities of disease progression and death were estimated using data from the MA17 study and other secondary sources. Costs of breast cancer care (letrozole therapy, surveillance, recurrences, terminal care) and treatment of osteoporosis and utilities were derived from literature. A full probabilistic sensitivity analysis was undertaken. The analysis was conducted from the perspective of the UK National Health Service (NHS) and cost estimates reflect 2004 values. All costs and outcomes were discounted at 3.5%. RESULTS: Extended adjuvant letrozole resulted in a gain of 0.36 QALYs per patient (13.66 vs 13.30 with no therapy). These benefits were obtained at an additional expected lifetime cost of 3732 pounds per patient (10,833 pounds letrozole vs 7101 pounds with no therapy). Cost effectiveness was estimated at 10,338 pounds per QALY gained (95% CI 5276, 43,828). The results were robust to sensitivity analyses. CONCLUSION: Five years of letrozole therapy appears to be cost effective from the NHS perspective and should be considered in women with early breast cancer, following tamoxifen adjuvant therapy.

Cost-effectiveness of aspirin chemoprevention for Barrett's esophagus.

BACKGROUND: Recent data suggest that nonsteroidal anti-inflammatory drugs, including aspirin, may prevent the progression of Barrett's esophagus to adenocarcinoma. However, use of aspirin is associated with numerous potential complications, including gastrointestinal bleeding and hemorrhagic strokes. We used a modeling approach to determine and compare the effectiveness and cost-effectiveness of aspirin with and without endoscopic surveillance to prevent esophageal adenocarcinoma. METHODS: A Markov Monte Carlo decision model was constructed to compare four strategies for management of Barrett's esophagus: aspirin therapy, endoscopic surveillance with biopsies, both, or neither. Patients who took a daily enteric-coated aspirin were modeled to have a 50% reduction in the incidence of esophageal adenocarcinoma but could have complications related to therapy, at which point the aspirin was discontinued. Potential cardiac benefits of aspirin and its role in the chemoprevention of other cancers were not included in the analysis. The analysis was from a societal perspective from age 55 years until death. Sensitivity analyses were performed to investigate the effects of changes in model parameters on estimated costs and effectiveness outcomes across a wide range of assumptions. RESULTS: Aspirin therapy was more effective and less costly than no therapy, resulting in 0.19 more quality-adjusted life years (QALYs). The combination of aspirin and endoscopic surveillance produced 0.27 more QALYs than no therapy at a cost of 13,400 U.S. dollars more, for an associated incremental cost-effectiveness ratio of 49,600 U.S. dollars/QALY. Aspirin use in combination with endoscopic surveillance dominated endoscopic surveillance alone, resulting in 0.06 more QALYs and 11,400 U.S. dollars less cost. The model's results were sensitive to increasing age and to decreased benefit or delay in aspirin's chemopreventive efficacy. CONCLUSION: Using published values of parameters, regardless of whether a patient undergoes endoscopic surveillance, aspirin use in the management of Barrett's esophagus appears to be a cost-effective strategy to prevent esophageal adenocarcinoma.

Tamoxifen plus chemotherapy versus tamoxifen alone as adjuvant therapies for node-positive postmenopausal women with early breast cancer: a stochastic economic evaluation.

BACKGROUND: There remains uncertainty around the appropriate choice of adjuvant therapies to offer postmenopausal women with node-positive early breast cancer. OBJECTIVE AND STUDY DESIGN: To present the results derived from a discrete event simulation (DES) model that compared tamoxifen plus chemotherapy versus tamoxifen alone in node-positive postmenopausal women diagnosed with early breast cancer. METHODS: The data populating the model were mainly derived from the existing literature, which was analysed to specify probability distributions describing the uncertainty around the true value of each input parameter. The specified probability distributions facilitated the stochastic analysis of the decision model, whereby distributions of the model's outputs [aggregate costs and quality-adjusted life years (QALYs)] were estimated. RESULTS: The baseline results show that the addition of chemotherapy to tamoxifen in this patient group is relatively cost effective (under pound 4000 per additional QALY), but the distribution of the incremental cost-effectiveness ratio shows a wide range, including 10% of observations in which tamoxifen dominates tamoxifen plus chemotherapy. CONCLUSIONS: The results demonstrate the intuitive nature of stochastic evaluations of healthcare technologies, which may ease decision-makers' interpretation of cost-effectiveness results.