Research progress on natural ß-glucan in intestinal diseases.

ß-Glucan, an essential natural polysaccharide widely distributed in cereals and microorganisms, exhibits extensive biological activities, including immunoregulation, anti-inflammatory, antioxidant, antitumor properties, and flora regulation. Recently, increasing evidence has shown that ß-glucan has activities that may be useful for treating intestinal diseases, such as inflammatory bowel disease (IBD), and colorectal cancer. The advantages of ß-glucan, which include its multiple roles, safety, abundant sources, good encapsulation capacity, economic development costs, and clinical evidence, indicate that ß-glucan is a promising polysaccharide that could be developed as a health product or medicine for the treatment of intestinal disease. Unfortunately, few reports have summarized the progress of studies investigating natural ß-glucan in intestinal diseases. This review comprehensively summarizes the structure-activity relationship of ß-glucan, its pharmacological mechanism in IBD and colorectal cancer, its absorption and transportation mechanisms, and its application in food, medicine, and drug delivery, which will be beneficial to further understand the role of ß-glucan in intestinal diseases.

Polysaccharides from Lyophyllum decastes reduce obesity by altering gut microbiota and increasing energy expenditure.

Polysaccharides are known to confer protection against obesity via modulation of gut microbiota. To expand our knowledge of mushroom-derived prebiotics, we investigated the structural characteristics and anti-obesity effects of Lyophyllum decastes polysaccharides. Two heteroglycans were purified and characterized. The isolated polysaccharides effectively reduced obesity and the related disorders in the diet-induced obese (DIO) mice. An altered gut microbiota with enrichments of Bacteroides intestinalis and Lactobacillus johnsonii and an increase of secondary bile acids were detected in the polysaccharide-treated mice. Supplementation of B. intestinalis and L. johnsonii prevented the obesity and hyperlipidemia in DIO mice, demonstrating their causal linkage to the efficacy of polysaccharides. An enhancement of energy expenditure in the brown adipose tissues due to up-regulation of the secondary bile acids-activated TGR5 pathway was deduced to be one of the mechanisms underlying the effect of polysaccharides. These results confirmed Lyophyllum decastes-derived polysaccharides as new prebiotics for preventing and treating obesity.

Isolation, purification, structural characterization, and hypoglycemic activity assessment of polysaccharides from Hovenia dulcis (Guai Zao).

Hovenia dulcis polysaccharides (HDPs) have a variety of important biological activities associated with potential applications in food engineering, pharmacy science, and health care. Herein, we isolated and purified polysaccharides from H. dulcis. Chemical composition analysis revealed that the purified polysaccharides (HDPs-2A) were composed of different molar ratios of mannose, Rha, GalA, GlcA, Glc, Gal, and Ara and had a molecular weight of 372.91 kDa. The structure of HDPs-2A was assessed by FT-IR, periodate oxidation, Smith degradation, methylation analysis, and NMR, allowing us to determine that the backbone of HDPs-2A is composed primarily of →5)-α-L-Araf-(1→, →5)-α-L-Araf-(1→, →3,5)-α-L-Araf-(1→, →6)-ß-D-Galp-(1→, →3,6)-ß-D-Galp-(1→, T-ß-D-Galp, →3)-ß-D-Galp-(1→, and T-α-D-Glcp. The results of atomic force microscopy (AFM) showed that HDPs-2A present an irregular polymer particle morphology in water. X-ray diffraction (XRD) results showed that HDPs-2A have a single crystal structure. Finally, we demonstrated that HDPs-2A have a good therapeutic effect on a rat model of type 2 diabetes.

Therapeutic attributes and applied aspects of biological macromolecules (polypeptides, fucoxanthin, sterols, fatty acids, polysaccharides, and polyphenols) from diatoms - A review.

Diatoms are ubiquitous, biologically widespread, and have global significance due to their unique silica cell wall composition and noteworthy applied aspects. Diatoms are being extensively exploited for environmental monitoring, reconstruction, and stratigraphic correlation. However, considering all the rich elements of diatoms biology, the current literature lacks sufficient information on the therapeutic attributes and applied aspects of biological macromolecules from diatoms, hampering added advances in all aspects of diatom biology. Diatoms offer numerous high-value compounds, such as fatty acids, polysaccharides, polypeptides, pigments, and polyphenols. Diatoms with a high content of PUFA's are targets of transformation into high-value products through microalgal technologies due to their wide application and growing market as nutraceuticals and food supplements. Diatoms are renewable biomaterial, which can be used to develop drug delivery systems due to biocompatibility, surface area, cost-effective ratio, and ease in surface modifications. Innovative approaches are needed to envisage cost-effective ways for the isolation of bioactive compounds, enhance productivity, and elucidate the detailed mechanism of action. This review spotlights the notable applications of diatoms and their biologically active constituents, such as fucoxanthin and omega 3 fatty acids, among others with unique structural and functional entities.

Assessment of an Extended Interval Fondaparinux Dosing Regimen for Venous Thromboembolism Prophylaxis in Critically Ill Patients with Severe Renal Dysfunction Using Antifactor Xa Levels.

OBJECTIVE: Pharmacologic options for venous thromboembolism (VTE) prophylaxis are often limited in critically ill patients due to thrombocytopenia and multisystem organ dysfunction. Fondaparinux offers potential advantages in the critically ill; however, it is currently contraindicated in severe renal dysfunction (SRD). We evaluated anti-factor Xa levels in critically ill patients with SRD who were receiving an extended interval dosing regimen of fondaparinux for VTE prophylaxis. METHODS: A prospective, single-arm, interventional study was conducted at two academic hospitals of the Detroit Medical Center. Eligible patients were in the intensive care unit, had an estimated creatinine clearance of less than 30 ml/minute, and had either acute kidney injury or end-stage renal disease; several patients were taking renal replacement therapy. Fondaparinux was administered at an extended interval dosing regimen of 2.5 mg subcutaneously every 48 hours. Fondaparinux peak and trough anti-factor Xa levels were obtained. Lower extremity venous duplex studies were performed at baseline and study completion to assess for deep vein thrombosis (DVT), and patients were monitored for bleeding complications. RESULTS: Thirty-two patients were enrolled. Patients received a median of four doses (interquartile range two to five) of fondaparinux. Fondaparinux peak (n=98) and trough (n=86) anti-factor Xa levels were 0.36 ± 0.18 mg/L and 0.17 ± 0.11 mg/L (mean ± SD), respectively, and were similar to levels reported in patients with normal renal function receiving conventional once-daily dosing. No lower extremity DVTs or suspected VTE events occurred. Two (6%) patients had significant bleeding events. CONCLUSIONS: In critically ill patients with SRD, an extended interval fondaparinux dosing regimen of 2.5 mg every 48 hours for VTE prophylaxis achieved peak and trough anti-factor Xa levels similar to those reported in noncritically ill patients with normal renal function receiving once-daily fondaparinux. This regimen offers an alternative for patients with SRD when heparinoids must be avoided.

Anti-diarrhoeal therapeutic potential and safety assessment of sulphated polysaccharide fraction from Gracilaria intermedia seaweed in mice.

Sulphated polysaccharides extracted from algae have been extensively studied for their diverse biological activities. Thus, the purpose of this study was to evaluate the chemical composition, the anti-diarrhoeal effect and acute toxicity of a sulphated polysaccharide fraction obtained from Gracilaria intermedia (SP-Gi). Initially, the FT-IR of SP-Gi revealed to be an agaran with sulphation at C-6 of the l-galactosyl residues. The anti-diarrhoeal activity of SP-Gi was evaluated in a castor oil-induced diarrhoea model. The effects of SP-Gi on enteropooling, Na +-K +-ATPase activity, gastrointestinal transit, and gastric emptying were then examined. Subsequently, the effect of SP-Gi on diarrhoea induced by cholera toxin (CT) and Escherichia coli was examined. In addition, an acute toxicity test was conducted in accordance with OECD guideline 423. Pre-treatment with SP-Gi reduces the total faeces, total diarrhoeal faeces, and enteropooling. SP-Gi (30mg/kg p.o.) increased Na+/K+-ATPase activity and reduced gastrointestinal transit through anticholinergic mechanisms. ELISA demonstrated that SP-Gi can interact with GM1 receptors and CT. SP-Gi reduced diarrhoea induced by E. coli and prevented weight loss in the animals. Moreover, SP-Gi did not induce any toxicity signs. These results suggest that SP-Gi is a possible candidate for the treatment of diarrhoeal illnesses.

Mouth rinsing with a sweet solution increases energy expenditure and decreases appetite during 60 min of self-regulated walking exercise.

Carbohydrate mouth rinsing can improve endurance exercise performance and is most ergogenic when exercise is completed in the fasted state. This strategy may also be beneficial to increase exercise capacity and the energy deficit achieved during moderate-intensity exercise relevant to weight control when performed after an overnight fast. Eighteen healthy men (mean (SD); age, 23 (4) years; body mass index, 23.1 (2.4) kg·m-2) completed a familiarisation trial and 3 experimental trials. After an overnight fast, participants performed 60 min of treadmill walking at a speed that equated to a rating of perceived exertion of 13 ("fairly hard"). Participants manually adjusted the treadmill speed to maintain this exertion. Mouth rinses for the experimental trials contained either a 6.4% maltodextrin solution with sweetener (CHO), a taste-matched placebo (PLA), or water (WAT). Appetite ratings were collected using visual analogue scales and exercise energy expenditure and substrate oxidation were calculated from online gas analysis. Increased walking distance during CHO and PLA induced greater energy expenditure compared with WAT (mean difference (90% confidence interval); 79 (60) kJ, P = 0.035, d = 0.24; and 90 (63) kJ, P = 0.024, d = 0.27, respectively). Appetite area under the curve was lower in CHO and PLA than WAT (8 (6) mm, P = 0.042, d = 0.43; and 6 (8) mm, P = 0.201, d = 0.32, respectively). Carbohydrate oxidation was higher in CHO than PLA and WAT (7.3 (6.7) g, P = 0.078, d = 0.47; and 10.1 (6.5) g, P = 0.015, d = 0.81, respectively). This study provides novel evidence that mouth rinsing with a sweetened solution may promote a greater energy deficit during moderate-exertion walking exercise by increasing energy expenditure and decreasing appetite. A placebo effect may have contributed to these benefits.

Clinical Assessment of Postoperative Anemia Associated with Edoxaban in Patients Undergoing Total Knee Arthroplasty Compared to Fondaparinux.

Edoxaban, an oral direct factor Xa inhibitor, was developed and approved for anticoagulant thromboprophylaxis after total knee arthroplasty (TKA). We retrospectively investigated the postoperative anemia by oral administration of edoxaban 30 mg compared with fondaparinux 2.5 mg in TKA patients. Two hundred twenty nine patients who underwent TKA in National Hospital Organization Okayama Medical Center from July 2010 to June 2012 were divided into two groups; pre and post approval of edoxaban: fondaparinux-group (F-group) and edoxaban-group (E-group). As the primary endpoint, the frequency of postoperative anemia was evaluated. Blood coagulation values and relations between these parameters and postoperative anemia were also investigated. The frequency of postoperative anemia was significantly higher in E-group than F-group patients (52.7% vs. 37.8%; p<0.05). Hemoglobin (Hgb) levels were decreased with the peak at postoperative day (POD) 3 in both groups, and the change of Hgb values from POD1 (ΔHgb) was significantly increased in the E-group (p=0.04). At each POD, prothrombin time (PT) and international normalized ratio of PT (PT-INR) prolonged from the preoperative day in E-group were significantly higher than F-group. Additionally, PT and PT-INR in the E-group at POD3 were significantly prolonged in patients with postoperative anemia and the sensitivity of cut-off values to predict postoperative anemia was superior to the activated partial thromboplastin time (APTT). Thus, as the frequency of postoperative anemia tended to be higher in E-group, edoxaban 30 mg might require vigilance, and prolonged PT and PT-INR could potentially predict edoxaban-associated postoperative anemia after TKA.

Assessment of a Flavone-Polysaccharide Based Prescription for Treating Duck Virus Hepatitis.

Because polysaccharide and flavone ingredients display good antiviral activity, we developed a flavone/polysaccharide-containing prescription that would be effective against duck viral hepatitis (DVH) and investigated its hepatoprotective effects. Flavones were derived from Hypericum japonicum (HJF) (entire herb of Hypericum japonicum Thunb) and Salvia plebeia (SPF) (entire herb of Salvia plebeia R. Br.), and polysaccharides were derived from Radix Rehmanniae Recens (RRRP) (dried root of Rehmannia glutinosa Libosch). This prescription combination was based on the theory of syndrome differentiation and treatment in traditional Chinese veterinary medicine. In vitro and in vivo experiments were conducted using the three single ingredients compared to the combined HRS prescription to determine their anti-duck hepatitis A viral (anti-DHAV) activity. The results showed that all experimental conditions displayed anti-DHAV activity, but the HRS prescription presented the best effect. To further investigate the hepatoprotective effect of the HRS prescription on DHAV-induced hepatic injury, we tested the mortality rate, the hepatic pathological severity score, plasma biochemical indexes of hepatic function, blood DHAV gene expression levels and peroxidation damage evaluation indexes and then analyzed correlations among these indexes. The results demonstrated that the HRS prescription significantly decreased the mortality rate, reduced the severity of hepatic injury, decreased the hepatic pathological severity score, depressed blood DHAV gene expression levels, and returned the indexes of hepatic function and peroxidation almost to a normal level. These results indicate that the HRS prescription confers an outstanding hepatoprotective effect, and we expect that it will be developed into a new candidate anti-DHAV drug.

Cost-effectiveness of fondaparinux versus enoxaparin in non-ST-elevation acute coronary syndrome in Canada (OASIS-5).

BACKGROUND: Acute coronary syndrome (ACS) refers to a spectrum of life-threatening cardiac diseases usually due to coronary artery plaque rupture, subsequent thrombin generation plaque activation and thrombus formation. To date, no economic analyses have been published about the use of fondaparinux in NSTE-ACS patients in Canada. The purpose of our study is to estimate the lifetime cost-effectiveness of fondaparinux compared to enoxaparin for non-ST-elevation acute coronary syndrome (NSTE-ACS) patients in a Canadian hospital setting. METHODS: As an extension of a previous published economic analysis for US patients, an event-based decision analytic model was constructed using clinical and resource use data from OASIS-5, a randomized trial of 20,078 patients from 41 countries. A public payer perspective in the hospital setting was adopted. Resource use data from the trial were valued using Canadian costs. A cost regression model was developed to estimate the mean cost of managing the clinical events over the 180 day period. Annual costs of long-term care for ACS patients were added after 180 days until death. Long-term survival was incorporated using Canadian life tables with further adjustment for additional risks associated with NSTE-ACS. Quality-of-life (utility) decrements from published sources were applied to clinical events. Lifetime costs (2009 CAD$) and quality-adjusted life-years (QALYs), discounted annually at 5 %, were estimated for the typical patient in OASIS-5 (i.e., at mean covariate values). RESULTS: The trial data showed that fondaparinux is protective against all clinical events observed in the trial. The model showed that: over 180 days, fondaparinux dominates enoxaparin, producing similar estimates of QALYs gained and saving $439; over a patient's lifetime, fondaparinux yields an ICER of $4293/QALY. Based on PSA, the probabilities that fondaparinux dominates enoxaparin (less costly and more effective) and that is cost-effective at a $50,000 threshold were 42 % and 96 %, respectively. CONCLUSIONS: In the Canadian hospital setting, fondaparinux is cost-effective when compared to enoxaparin for the treatment of NSTE-ACS. This result holds both in the immediate post-event period and over the lifetimes of patients.

[Prevention of venous thromboembolic events by fondaparinux 2.5mg in patients hospitalized for an acute medical illness. ArchiMed Study]. / Prévention des évènements thromboemboliques veineux par fondaparinux 2,5mg chez des patients hospitalisés pour une affection médicale aiguë. Étude ArchiMed. ArchiMed hôpital - étude observationnelle d'usage du fondaparinux 2,5mg en vie réelle ; 718 patients inclus par 107 pharmaciens hospitaliers.

OBJECTIVE: To evaluate the average duration of in-hospital treatment with fondaparinux 2.5mg prescribed for venous thromboprophylaxis in acutely ill medical patients and to describe the treatment population. METHODS: Prospective, observational, national, multicentre, epidemiological study, performed in France at the request of the Transparency Commission of the French National Health Authority (Haute Autorité de Santé). This is part of a larger study program that also included a study with similar design in the general practice setting. The hospital practice part of the study was conducted by hospital pharmacists who were asked to include the first 15 adult subjects hospitalized in a non-surgical ward for whom fondaparinux 2.5mg was initiated for prophylaxis. RESULTS: Fifty-three pharmacists (49.5%) included a total of 718 patients. The average age was 71 ± 16 years (47%<75 years old); 54% were women. For 41% of patients, duration of fondaparinux 2.5mg administration ranged from 6 to 14 days. Eighty-five percent of patients had at least one acute illness related to the prescription of fondaparinux 2.5mg for thromboprophylaxis. Ten percent of the population had at least one risk factor listed on the Case Report Form. Characteristics of patients from the hospital practice study differ from those included in the general practice part of the ArchiMed Study program. CONCLUSION: The hospital practice part of the ArchiMed Study, which is similar to "audits of practices", shows that the real-life conditions of prescription of fondaparinux 2.5mg in patients hospitalized are generally in line with guidelines with respect to indication for thromboprophylaxis in acute medical illness.

Current management of venous thromboembolism in Japan: Current epidemiology and advances in anticoagulant therapy.

Venous thromboembolism (VTE), manifesting as either deep vein thrombosis or pulmonary embolism, is common worldwide including in Japan. The number of patients clinically diagnosed with VTE is increasing with the majority of cases occurring out-of-hospital and of milder severity. Cancer is the largest risk factor for VTE and VTE in cancer patients confers an increased 1-year mortality rate. However, the majority of VTE cases are considered "idiopathic" or "unprovoked." The limited efficacies of unfractionated heparin and warfarin have stimulated the development of new anticoagulant therapies. Recently, parenteral and oral administration of the Xa inhibitors fondaparinux and edoxaban, respectively, was approved in Japan. These agents have the potential to provide safer and more efficacious treatment options for VTE. Although further randomized studies are required to validate the utility of these agents, they are expected to substantially improve quality of life in VTE patients. This review summarizes the current status of VTE management in Japan focusing on current epidemiology and recent advances in anticoagulant therapy.

Marine-derived polysaccharides for regulation of allergic responses.

Polysaccharides are macromolecules made up of many monosaccharides joined together by glycosidic bonds. Polysaccharides from marine sources are widely distributed as the principle component in cell wall structures of seaweeds or exoskeletons of crustaceans. So far, marine polysaccharides have been used in many fields of biomaterials, food, cosmetic, and pharmacology. Especially, numerous pharmaceutical properties of marine polysaccharides have been revealed such as antioxidant, anti-inflammatory, antiallergic, antitumor, antiobesity, antidiabetes, anticoagulant, antiviral, immunomodulatory, cardioprotective, antihepatopathy, antiuropathy, and antirenalpathy activities. Recently, several marine polysaccharides such alginate, porphyran, fucoidan, and chitin and its derivatives have been found as modulators of allergic responses due to enhancing innate immune system, altering Th1/Th2 balance, inhibiting IgE production, and suppressing mast cell degranulation. This contribution, therefore, focuses specially on the immunomodulatory effect of marine polysaccharides and emphasizes their potential application as candidates of pharmaceuticals as well as nutraceuticals to prevent allergic disorders.

MDG-1, a polysaccharide from Ophiopogon japonicus, prevents high fat diet-induced obesity and increases energy expenditure in mice.

MDG-1, a water-soluble polysaccharide extracted from Ophiopogon japonicus, has potent hypoglycemic and weight control effects. We investigated the impact of MDG-1 on body weight, indirect calorimetry, body composition, plasma biochemical indices and obesity-related mitochondrial activity in diet-induced obese mice. Obese C57BL/6 mice induced by a high fat diet were given either vehicle or vehicle plus MDG-1 at 300 mg per body weight for 16-weeks. MDG-1 could evoked weight loss and reduce adipose tissue mass (by up to ∼ 50%) in the obese animals by increasing oxygen consumption and energy expenditure without inhibiting appetite or increasing physical activity. In addition, MDG-1 could ameliorate plasma lipid profiles, decrease leptin secretion, attenuate hepatic lipid accumulation and increased the expressions of genes related to lipid and energy metabolism in the liver. MDG-1 is a promising candidate drug to treat obesity-related metabolic diseases.

Selective pharmacological prophylaxis based on individual risk assessment using plasma levels of soluble fibrin and plasminogen-activator inhibitor-1 following total hip arthroplasty.

OBJECTIVES: The purpose of this prospective study was to evaluate the utility of preferential application of pharmacoprophylaxis based on the quantitative evaluation by soluble fibrin (SF) and plasminogen activator inhibitor-1 (PAI-1) analysis on the day after total hip arthroplasty (THA). METHODS: A hundred and sixteen patients were enrolled. High-risk patients were defined as those with elevated levels of SF or PAI-1, beyond their cut-off values, on the day after THA. For high-risk patients, fondaparinux was administered for 10 days postoperatively. When both plasma levels of SF and PAI-1 were less than their cutoff levels, the patients were regarded to be at low risk. For low-risk patients, only mechanical prophylaxis was applied. RESULTS: Sixty patients (52%) were considered to be at high risk. Among them, venous thromboembolism (VTE) was detected in five patients (8%) by CT angiography. In addition, there were four patients (3%) who developed bleeding complications. Fifty-six patients (48%) were considered to be at low risk, and only one patient (2%) developed VTE. CONCLUSION: The measurement of SF and PAI-1 levels on the day after surgery may be helpful to identify the individual risk for postoperative VTE. According to this evaluation, a half of patients might not need to administer anticoagulant agents following surgery.

Epidemiology, diagnosis, treatment and management of superficial-vein thrombosis of the legs.

Recent data on lower-limb superficial-vein thrombosis (SVT) may substantially impact its clinical management. Particularly, the clear confirmation that SVT is closely linked to deep-vein thrombosis (DVT) or pulmonary embolism (PE) highlights the potential severity of the disease. DVT or PE is diagnosed in 20-30% of SVT patients. Moreover, clinically relevant symptomatic thromboembolic events complicate isolated SVT (without concomitant DVT or PE at diagnosis) in 4-8% of patients. For the first time, an anticoagulant treatment, once-daily 2.5 mg fondaparinux for 45 days, was demonstrated to be effective and safe for preventing these symptomatic thromboembolic events in patients with lower-limb isolated SVT in the randomized, placebo-controlled CALISTO study. More recent data from another randomized trial support these findings. New recommendations on the management of SVT patients, including complete ultrasonography examination of the legs and, in patients with isolated SVT, prescription of once-daily 2.5 mg fondaparinux subcutaneously for 45 days on top of symptomatic treatments, may be proposed, wherever the cost of fondaparinux is acceptable. Superficial-vein thrombosis (SVT) of the lower limbs has long been regarded as a benign, self-limiting disease, expected to resolve spontaneously and rapidly, and requiring only symptomatic treatments [1,2]. However, the perception of this disease is now changing with the recent publication of data indicating its potential severity [3] and showing for the first time the benefit of a therapeutic strategy based on the administration of an anticoagulant treatment [4]. The overall management of this frequent disease therefore needs to be reconsidered.

Custo-efetividade de fondaparinux em pacientes com Síndrome Coronariana Aguda sem supradesnivelamento do ST / Cost-effectiveness of fondaparinux in patients with acute coronary syndrome without ST-segment Elevation

FUNDAMENTO: O uso combinado de agentes antitrombínicos, antiplaquetários e estratégias invasivas na síndrome coronariana aguda sem supradesnivelamento do ST (SCAsSST) reduz eventos cardiovasculares. O fondaparinux demonstrou equivalência à enoxaparina na redução de eventos cardiovasculares, porém com menor índice de sangramento nos pacientes que usaram fondaparinux. OBJETIVO: Avaliar o custo-efetividade de fondaparinux versus enoxaparina em pacientes com SCAsSST no Brasil a partir da perspectiva econômica do Sistema Único de Saúde (SUS). MÉTODOS: Um modelo de decisão analítico foi construído para calcular os custos e consequências resultantes dos tratamentos comparados. Os parâmetros do modelo foram obtidos do estudo OASIS-5 (N = 20.078 pacientes com SCAsSST randomizados para fondaparinux ou enoxaparina). O desfecho avaliado foi um composto de eventos cardiovasculares (isto é, morte, infarto agudo do miocárdio, isquemia refratária e sangramentos graves) nos dias 9, 30 e 180 pós-SCAsSST. Foram avaliados todos os custos diretos de tratamento e eventos relacionados à SCAsSST. O ano da análise foi 2010 e os custos foram descritos em reais (R$). RESULTADOS: No dia 9, o custo de tratamento por paciente foi R$ 2.768 para fondaparinux e R$ 2.852 para enoxaparina. Aproximadamente 80% do custo total foram associados a tratamentos invasivos. Os custos com medicamentos representaram 10% do custo total. As taxas combinadas de eventos cardiovasculares e de sangramentos maiores foram 7,3% e 9,0% para fondaparinux e enoxaparina, respectivamente. Análises de sensibilidade confirmaram os resultados iniciais do modelo. CONCLUSÃO: O fondaparinux para tratamento de pacientes com SCAsSST é superior à enoxaparina em termos de prevenção de novos eventos cardiovasculares com menor custo. (Arq Bras Cardiol. 2012; [online].ahead print, PP.0-0).

BACKGROUND: The combined use of antithrombotic agents, antiplatelet agents and invasive strategies in acute coronary syndrome without ST-segment elevation (ACSWSTE) reduces cardiovascular events. Fondaparinux has demonstrated equivalence to enoxaparin in reducing cardiovascular events, but with a lower rate of bleeding in patients using fondaparinux. OBJECTIVE: Evaluate the cost-effectiveness of fondaparinux versus enoxaparin in patients with ACSWSTE in Brazil from the economic perspective of the Brazilian Unified Health System (SUS). METHODS: A decision analytic model was constructed to calculate the costs and consequences of the compared treatments. The model parameters were obtained from the OASIS-5 study (N = 20,078 patients with ACSWSTE randomized to fondaparinux or enoxaparin). The target outcome consisted of cardiovascular events (i.e., death, myocardial infarction, refractory ischemia and major bleeding) on days 9, 30 and 180 after ACSWSTE. We evaluated all direct costs of treatment and ACSWSTE-related events. The year of the analysis was 2010 and the costs were described in reais (R$). RESULTS: On day 9, the cost of treatment per patient was R$ 2,768 for fondaparinux and R$ 2,852 for enoxaparin. Approximately 80% of total costs were associated with invasive treatments. The drug costs accounted for 10% of the total cost. The combined rates of cardiovascular events and major bleeding were 7.3% and 9.0% for fondaparinux and enoxaparin, respectively. Sensitivity analyses confirmed the initial results of the model. CONCLUSION: The use of fondaparinux for the treatment of patients with ACSWSTE is superior to that of enoxaparin in terms of prevention of further cardiovascular events at lower cost. (Arq Bras Cardiol. 2012; [online].ahead print, PP.0-0).

Cost-effectiveness of fondaparinux in patients with acute coronary syndrome without ST-segment elevation.

BACKGROUND: The combined use of antithrombotic agents, antiplatelet agents and invasive strategies in acute coronary syndrome without ST-segment elevation (ACSWSTE) reduces cardiovascular events. Fondaparinux has demonstrated equivalence to enoxaparin in reducing cardiovascular events, but with a lower rate of bleeding in patients using fondaparinux. OBJECTIVE: Evaluate the cost-effectiveness of fondaparinux versus enoxaparin in patients with ACSWSTE in Brazil from the economic perspective of the Brazilian Unified Health System (SUS). METHODS: A decision analytic model was constructed to calculate the costs and consequences of the compared treatments. The model parameters were obtained from the OASIS-5 study (N = 20,078 patients with ACSWSTE randomized to fondaparinux or enoxaparin). The target outcome consisted of cardiovascular events (i.e., death, myocardial infarction, refractory ischemia and major bleeding) on days 9, 30 and 180 after ACSWSTE. We evaluated all direct costs of treatment and ACSWSTE-related events. The year of the analysis was 2010 and the costs were described in reais (R$). RESULTS: On day 9, the cost of treatment per patient was R$ 2,768 for fondaparinux and R$ 2,852 for enoxaparin. Approximately 80% of total costs were associated with invasive treatments. The drug costs accounted for 10% of the total cost. The combined rates of cardiovascular events and major bleeding were 7.3% and 9.0% for fondaparinux and enoxaparin, respectively. Sensitivity analyses confirmed the initial results of the model. CONCLUSION: The use of fondaparinux for the treatment of patients with ACSWSTE is superior to that of enoxaparin in terms of prevention of further cardiovascular events at lower cost.

[A retrospective study of UFT and oral leucovorin plus PSK combination adjuvant chemotherapy in patients with stage III colon cancer].

OBJECTIVE: To perform a retrospective analysis of UFT and oral leucovorin plus PSK combination adjuvant chemotherapy for stage III colon cancer in order to evaluate both treatment efficacy and toxicity. SUBJECTS: Between 2003 and 2009, 273 stage III colon cancer patients underwent surgery in our institute, and we studied 156 of them. RESULTS: Patients' median age was 72 years old; 87 men and 69 women. Of all patients, 119 had stage IIIa and 37 had stage IIIb. The 3-year disease, free survival rates for stage III, stage IIIa and stage IIIb patients were 73. 9%and 80. 6%and 51. 4%, respectively, and the 3-year overall survival rates for stage III was 97. 6%. With regard to toxicity, liver function disorder was observed in 9. 6%of the patients as the most frequent adverse event, but there was no grade 3 or 4 toxicity. CONCLUSION: UFT and oral leucovorin plus PSK combination adjuvant chemotherapy for stage III colon cancer showed a good response especially for stage III a.

Fondaparinux versus enoxaprin in the management of acute coronary syndromes in Switzerland: A cost comparison analysis.

QUESTION UNDER STUDY: Anticoagulation therapy is routinely used in cases of non ST-segment elevation acute coronary syndromes (NSTE-ACS). The most commonly used drug in such events is enoxaparin, a low molecular weight heparin. Fondaparinux, a synthetic pentasaccharide, is as effective as enoxaparin in terms of survival or residual angina pectoris and significantly reduces bleeding complications. The purpose of this study was to assess the magnitude of cost reductions if enoxaparin were replaced by fondaparinux in Switzerland. METHODS: Costs of hospital stay for NSTE-ACS with or without bleeding complications at the Geneva University Hospitals were determined for patients admitted between July 1st, 2007 and June 30th, 2008. These costs were applied to subjects recruited in the AMIS Plus registry, which gathers information on ACS in Swiss hospitals, using three scenarios. Firstly, using the baseline incidence of bleeding episodes observed in the AMIS plus registry. Secondly, using the baseline incidence of haemorrhagic episodes observed in the Geneva University Hospitals sample and thirdly, using the incidence of haemorrhagic episodes observed in the OASIS-5 study. These results and costs were then extrapolated to the national level. RESULTS: At the Swiss national level, replacement of enoxaparin by fondaparinux would generate annual savings ranging from 854,000 Swiss Francs (scenario 1) to 3,400,000 Swiss Francs (scenario 2) and 2,845,000 Swiss Francs (scenario 3). Estimated savings accounted for 55 to 63% of total hospital costs. CONCLUSIONS: Use of fondaparinux instead of enoxaparin in patients with NSTE-ACS could yield substantial savings at the local as well as the national level in Switzerland.