Discussing edaravone with the ALS patient: an ethical framework from a U.S. perspective.

The recent approval of edaravone by the United States Food and Drug Administration has generated a mix of hope tempered by reality. The costs of the drug, both monetarily and with regard to intensity of treatment, are high. The benefits, while modest, will be viewed through a very different lens by individuals depending on their goals of care. By virtue of our training and experience, physicians are ideally suited to understand and explain new treatments to our patients. As healthcare providers with a fiduciary responsibility to our patients, we must make sure they are fully informed about both the costs and benefits of non-curative therapies such as edaravone, and be prepared to discuss these in the context of their goals of care and potential impact on quality of life. Respect for our patients' autonomy is critical when discussing these issues, but we should always be guided by the ethical principles of beneficence and non-maleficence.

Paracetamol toxicity: what would be the implications of a change in Australian treatment guidelines?

OBJECTIVES: The present study aims to study the implications for resource utilisation if Australia adopted recent revised UK treatment guidelines for paracetamol poisoning. METHODS: Retrospective database review of paracetamol toxicity presentations and calls from the Victorian Poisons Information Centre (VPIC) and Austin Hospital, Victoria, Australia, from 1 January 2010 to 31 December 2011. There were 200 presentations at the Austin Hospital, and the VPIC received 4272 calls regarding paracetamol toxicity. An analytical model was designed to estimate the cost of this additional treatment and referral to hospital. The main outcome measures were the potential increase in number of admissions requiring treatment with N-acetylcysteine (NAC), costs involved and increased number of referrals to hospitals by the VPIC. RESULTS: Twenty-five (12.5%, 95% confidence interval 8.4-17.6%, P < 0.01) patients in our study who did not qualify for NAC therapy based upon the current Australasian paracetamol treatment guideline would have received it if the revised UK guideline was followed. Eighteen (72%) of these presented with acute single ingestions of paracetamol. No patients re-presented to our hospital with acute liver injury or required admission to the liver transplant unit. CONCLUSIONS: Alignment of current Australian paracetamol treatment guidelines with those in the UK would result in an increase in ED attendances as directed by Poisons Information Centres and hospital admissions for antidotal treatment. This would be associated with increased health expenditure and inpatient bed utilisation. The present study does not support the clinical need for adoption of UK paracetamol treatment guidelines in Australia.

Antioxidant and anti-fatigue effects of anthocyanins of mulberry juice purification (MJP) and mulberry marc purification (MMP) from different varieties mulberry fruit in China.

Anthocyanins, copiously distributed in a variety of colored fruits and vegetables, are probably the most important group of visible plant pigments besides chlorophyll. And the mulberry fruit is one of the anthocyanins-rich fruits. Total flavonols, total phenolic acids and anthocyanins contents of ten varieties mulberry juice purification (MJP) and mulberry marc purification (MMP) were determined. The highest content was 965.63±4.90 mg RE/g, 690.83±7.38 mg GAE/g and 272.00±1.20 mg cyanidin-3-glucoside/g FW, respectively. Moreover, MJP and MMP exhibited high antioxidant activity, including total force reduction (TRP), Fe³âº reducing power (FRAP) and DPPH • radical scavenging capacity. In addition, the anti-fatigue activity of MJP and MMP was determined through mice-burden swimming experiments. Interestingly, the antioxidant and anti-fatigue capacities of MMP were much higher than those of MJP. The experimental results suggested that the generally discarded mulberry marc had greater value of development and utilization as food processing waste.

Cost-effectiveness analysis of the neuroprotective agent edaravone for noncardioembolic cerebral infarction.

BACKGROUND: The free radical scavenger edaravone has been reported useful for improvement in activities of daily living and for prevention of recurrent stroke in the edaravone versus sodium ozagrel in acute noncardioembolic ischemic stroke (EDO) trial. The aim of this report was to evaluate the cost-effectiveness of edaravone compared to the intravenous antiplatelet drug ozagrel sodium (ozagrel) for noncardioembolic stroke (non-CES) based on the EDO trial data. METHODS: A cost-effectiveness analysis was performed using the Markov model, which also incorporated the long-term course after the acute stage of non-CES. From the perspective of a health care payer, direct medical costs and nursing care costs were taken into account in the cost analysis. The quality-adjusted life year (QALY) served as an indicator of effectiveness. Simulation at 5 and 10 years after the onset of non-CES was carried out. The study involved 68-year-old patients with non-CES, selected against the EDO trial subject selection criteria. A 14-day treatment with edaravone 60 mg/day or ozagrel 160 mg/day was assumed as acute treatment for non-CES. RESULTS: The use of edaravone was associated with a reduction in total costs (0.51 million yen [$6,374] at 5 years and 0.64 million yen [$8,039]) at 10 years after the onset of non-CES) and improvement in QALYs (0.23 at 5 years and 0.38 at 10 years). Compared to ozagrel therapy, edaravone therapy was a cost-saving strategy for treating non-CES. CONCLUSIONS: Compared to ozagrel therapy, edaravone therapy for non-CES is not only useful from a clinical viewpoint, but also valuable from a socioeconomic perspective.

Paracetamol toxicity: What would be the implications of a change in UK treatment guidelines?

BACKGROUND: Treatment of single-time-point ingestion acute paracetamol (acetaminophen) poisoning with N-acetylcysteine (NAC) is guided by plotting a timed plasma paracetamol concentration on established nomograms. Guidelines in the UK differ from those in the U.S. and Australasia by having two treatment lines on the nomogram. Patients deemed to be at 'normal' risk of hepatotoxicity are treated using the treatment line starting at 200 mg/L at 4 h post-ingestion; those at higher risk are treated using the 'high risk' treatment line starting at 100 mg/L at 4 h post-ingestion. AIM: To examine the effect on treatment numbers if UK guidelines were to adopt a single treatment line nomogram or lower, risk-stratified treatment lines. METHODS: We undertook a retrospective analysis of a series of acute single-time-point paracetamol poisonings presenting to our inner city emergency department. Treatment numbers and effect on treatment costs were modelled for three alternative scenarios: a 150 line-a combined single treatment line starting at a 4 h concentration of 150 mg/L, a 100 line-a combined single treatment line starting at a 4 h concentration of 100 mg/L, and a 150/75 line-a double treatment line at the lower concentrations of 150 mg/L for normal risk and 75 mg/L for high risk patients. RESULTS: A total of 1,214 cases were identified. Under current UK guidance, 133 (11.0%) high risk cases and 98 (8.1%) normal risk cases needed treatment (total 231, 19.0%). A 150 line would result in 87 (7.2%) high risk cases and 155 (12.8%) normal risk cases needing treatment (total 242, 19.9%). A 100 line would result in 133 (11.0%) high risk and 251 (20.7%) normal risk cases needing treatment (total 384, 31.6%). A 150/75 line would result in 153 (12.6%) high risk and 155 (12.8%) normal risk cases needing treatment (total 308, 25.4%). CONCLUSIONS: Both a 100 line and a 150/75 line would result in a large increase in the number of patients being treated and an associated increase in the costs of treatment. A single 150 mg/L treatment line would simplify treatment algorithms and lead to a similar number of patients being treated with NAC overall. A potential concern however is whether any of the high risk cases that would no longer be treated might develop significant hepatotoxicity. After consideration of the evidence for dual treatment lines, we feel that these risks are small and that it is worth reconsidering a change of treatment recommendations to a single 150 line.

Phytochemicals and antioxidant capacities in rice brans of different color.

Rice bran, a byproduct of the rice milling process, contains most of the phytochemicals. This study aimed at determining the concentrations of lipophilic, solvent-extractable (free), and cell wall-bound (bound) phytochemicals and their antioxidant capacities from brans of white, light brown, brown, purple, and red colors, and broccoli and blueberry for comparison. The concentrations of lipophilic antioxidants of vitamin E (tocopherol and tocotrienols) and γ-oryzanols were 319.67 to 443.73 and 3861.93 to 5911.12 µg/g bran dry weight (DW), respectively, and were not associated with bran color. The total phenolic, total flavonoid, and antioxidant capacities of ORAC (oxygen radical absorbance capacity), DPPH (2,2-diphenyl-1-picrylhydrazyl) radical scavenging, and iron-chelating in the free fraction were correlated with the intensity of bran color, while variations of these in the bound fraction were less than those in the free fraction among brans. Compounds in the bound fraction had higher antioxidant capacity of ORAC than DPPH, relative to those in the free fraction. The bound fraction of light-color brans contributed as much to its total ORAC as the free fraction. Total proanthocyanidin concentration was the highest in red rice bran, while total anthocyanin was highest in purple brans. The predominant anthocyanin was cyanidin-3-glucoside. Red and purple brans had several fold higher total phenolics and flavonoids as well as ORAC and DPPH, from both free and bound fractions, than freeze-dried blueberry and broccoli. These results indicate that rice brans are natural sources of hydrophilic and lipophilic phytochemicals for use in quality control of various food systems as well as for nutraceutical and functional food application.

Preparation of reactive oxygen scavenging peptides from tilapia (Oreochromis niloticus) skin gelatin: optimization using response surface methodology.

Gelatin extracted from tilapia skin was hydrolyzed with Properase E. Response surface methodology (RSM) was applied to optimize the hydrolysis condition (temperature [T], enzyme-to-substrate ratio [E/S], pH and reaction time [t]), to obtain the hydrolysate with the highest hydroxyl radical (•OH) scavenging activity. The optimum conditions obtained were T of 44.2 °C, E/S of 2.2%, pH of 9.2, and t of 3.4 h. The predicted •OH scavenging activity of the hydrolysate under the optimum conditions was 60.7%, and the actually experimental scavenging activity was 60.8%. The hydrolysate was fractionated by ultrafiltration, and 4 fractions were collected. The fraction TSGH4 (MW<2000 Da) showed the strongest •OH scavenging activity with the highest yield. Furthermore, reactive oxygen species (ROS) scavenging activities of TSGH4 with different concentrations were investigated in 5 model systems, including superoxide anion radical (•O2), •OH, hydrogen peroxide (H2O2), peroxynitrite (ONOO-), and nitric oxide (NO•), compared with reduced glutathione (GSH). The results showed that TSGH4 significantly scavenged these ROS, and could be used as a functional ingredient in medicine and food industries.

An efficient and economical MTT assay for determining the antioxidant activity of plant natural product extracts and pure compounds.

Antioxidants scavenge free radicals, singlet oxygen, and electrons in cellular redox reactions. The yellow MTT [3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide] is reduced to a purple formazan by mitochondrial enzymes. NADPH is the basis of established in vitro cell viability assays. An antioxidant assay has been developed utilizing the redox reaction between MTT and selected natural product extracts and purified compounds. This simple, fast, and inexpensive MTT antioxidant assay is comparable with the lipid peroxidation inhibitory assay and can be mechanized to achieve high throughput.

Evaluation, prevention and management of radiotherapy-induced xerostomia in head and neck cancer patients.

PURPOSE OF REVIEW: As part of the multidisciplinary approach to head and neck cancer patients, radiation therapy plays an essential role, improving locoregional control. Radiation therapy-induced xerostomia is a late side-effect that increases the risk for developing dental caries and compromises oral mucosal integrity, resulting in oral pain, loss of taste, difficulties with swallowing and chewing, sleep disorders and worse quality of life. This review focuses on evaluation, prevention and management of radiation therapy-induced xerostomia. RECENT FINDINGS: In terms of xerostomia prevention, some clinical trials evaluating amifostine and intensity-modulated radiation therapy have shown positive results. Pilocarpine is a useful agent as a treatment of radiation-induced xerostomia in head and neck cancer patients. SUMMARY: Despite some advances in radiation therapy-induced xerostomia prevention, its treatment is an area in which advances are urgently needed.

Prehydration alone is sufficient to prevent contrast-induced nephropathy after day-only angiography procedures--a randomised controlled trial.

BACKGROUND: Contrast agents used in angiography procedures for patients with cardiovascular disease are known to cause contrast-induced nephropathy (CIN), which may be partially due to the production of nephrotoxic oxygen-free radicals. It is uncertain whether administration of intravenous (IV) anti-oxidant, N-acetylcysteine (NAC), can prevent reduction in renal function and whether this is a cost-effective approach. METHODS: Sixty-five day-only patients with renal impairment (mean serum creatinine concentration 0.16+/-0.03 mmol/l) due to undergo coronary or peripheral angiography and/or stenting were randomly assigned to IV NAC 300 or 600 mg immediately before and after the procedure or IV fluid alone. RESULTS: Of the 60 patients with complete data, none had acute CIN (increase in serum creatinine concentration > or = 0.044 mmol/l, 48 h after administration of contrast agent). Eight patients (13%) have demonstrated an increase in their serum creatinine concentration > or = 0.044 mmol/l 30 days after administration of contrast agent: 2/19 (11%) in the control group, 2/21 (10%) in the 600 mg NAC group and 4/20 (20%) the 300 mg NAC group (p = 0.66). The mean volumes of contrast agent used and prehydration given for each of the three groups did not differ significantly (p > 0.83). There was significant improvement in creatinine clearance within each group from baseline to 30 days (p < or = 0.03), but no significant difference between the groups at 48 h and 30 days (p > or = 0.43). Considering the cost of NAC and its administration, we estimate that this would translate to a saving of dollar 26,637 per annum. CONCLUSION: For day-stay patients with mild-to-moderate chronic renal impairment undergoing angiography and/or intervention, prehydration alone is less complicated and more cost-effective than a combination of IV NAC (at doses used) and hydration.

Cost effectiveness and cost utility of acetylcysteine versus dimethyl sulfoxide for reflex sympathetic dystrophy.

OBJECTIVE: To determine the cost effectiveness and cost utility of acetylcysteine versus dimethyl sulfoxide (DMSO) for patients with reflex sympathetic dystrophy (RSD), from a societal viewpoint. DESIGN: An economic evaluation was conducted alongside a double-dummy, double-blind, randomised, controlled trial. Patients were followed for 1 year. The primary outcome measure was the Impairment-level Sum Score (ISS). Utilities were determined by the EuroQOL instrument (EQ-5D). Both cost-effectiveness and cost-utility analyses were performed. Differences in mean direct, indirect and total costs were estimated. Corresponding 95% confidence intervals were calculated by bootstrapping techniques. RESULTS: Both groups (DMSO, n = 64; acetylcysteine, n = 67) showed relevant improvement; no differences in effects were found. Only the total direct costs were significantly lower in the DMSO group for the period of 0-52 weeks. The incremental cost-effectiveness ratios showed that, in general, DMSO generated fewer costs and more effects compared with acetylcysteine. Post-hoc subgroup analyses on cost effectiveness suggested that patients with warm RSD could be best treated with DMSO and patients with cold RSD with acetylcysteine. These results were based on small subsamples. CONCLUSION: In general, DMSO is the preferred treatment for patients with RSD.

Nutritional strategies in cardiovascular disease control: an update on vitamins and conditionally essential nutrients.

Several nutritional interventions for cardiovascular disease (CVD) prevention and therapy have recently appeared in the biomedical literature. These include appropriate use of several vitamins (E, C, B6, folate) and conditionally essential nutrients (CoQ10, L-arginine, propionyl L-carnitine). Possible undesirable consequences of long term nutritional supplementation with vitamin E and of adverse drug-nutrient interactions between the statins and CoQ10 are also considered. Although additional intervention studies are needed, current scientific evidence generally supports nutritional supplementation with these nutrients as an effective adjunctive strategy for CVD control.