Methadone versus morphine as a first-line strong opioid for cancer pain: a randomized, double-blind study.

PURPOSE: To compare the effectiveness and side effects of methadone and morphine as first-line treatment with opioids for cancer pain. PATIENTS AND METHODS: Patients in international palliative care clinics with pain requiring initiation of strong opioids were randomly assigned to receive methadone (7.5 mg orally every 12 hours and 5 mg every 4 hours as needed) or morphine (15 mg sustained release every 12 hours and 5 mg every 4 hours as needed). The study duration was 4 weeks. RESULTS: A total of 103 patients were randomly assigned to treatment (49 in the methadone group and 54 in the morphine group). The groups had similar baseline scores for pain, sedation, nausea, confusion, and constipation. Patients receiving methadone had more opioid-related drop-outs (11 of 49; 22%) than those receiving morphine (three of 54; 6%; P =.019). The opioid escalation index at days 14 and 28 was similar between the two groups. More than three fourths of patients in each group reported a 20% or more reduction in pain intensity by day 8. The proportion of patients with a 20% or more improvement in pain at 4 weeks in the methadone group was 0.49 (95% CI, 0.34 to 0.64) and was similar in the morphine group (0.56; 95% CI, 0.41 to 0.70). The rates of patient-reported global benefit were nearly identical to the pain response rates and did not differ between the treatment groups. CONCLUSION: Methadone did not produce superior analgesic efficiency or overall tolerability at 4 weeks compared with morphine as a first-line strong opioid for the treatment of cancer pain.     

Urinary pharmacokinetics of betalains following consumption of red beet juice in healthy humans.

The aim of the present pilot study was to characterise the renal elimination of betalains after consumption of red beet juice (RBJ). Six healthy, non-smoking female volunteers were given a single oral dose of either 500 mL of a commercial RBJ containing 362.7 mg of betalains and 500 mL of tap water, respectively, in a sequential manner. Urine was collected in intervals up to 24 h post-dose. Renal excretion of betalains was determined spectrophotometrically and quantified as betanin-equivalents. In addition, the identity of individual compounds was confirmed by HPLC coupled with diode-array detection and positive ion electrospray mass spectrometry, respectively. The amount (mean+/-S.D.) of intact betalains (betanin and isobetanin) recovered in urine was 1001+/-273 microg corresponding to 0.28+/-0.08% of the administered dose. Maximum excretion rates were observed after a median tmax,R of 3.0 h (range 2.5-8.0 h) amounting to 91.7+/-30.1 microg/h. The terminal elimination rate constant (lambdaz) and the corresponding half-life were 0.097+/-0.021 h(-1) and 7.43+/-1.47 h, respectively. Using the lambdaz estimates obtained the expected total betalain amount excreted in urine was 1228+/-291 microg. Based on the results obtained it is assumed that either the bioavailability of the betalains is low or that renal clearance is a minor route of systemic elimination for these compounds. The urinary excretion rates of unmetabolised betalains were fast and appeared to be monoexponential suggesting a one-compartment model. In order to get a more complete picture of the pharmacokinetics and health-promoting properties of red beet betalains, quantitative data on betalain bioavailability should include measurements of unchanged compounds and their corresponding metabolites in plasma, urine and bile.     

Evolution and conservation of microsatellite markers for Leishmania tropica.

Sixteen polymorphic microsatellite markers were developed for phylogenetic analysis of Leishmania tropica. The phylogenetic tests done demonstrated that they do provide a powerful tool for epidemiological studies. They were also tested for their ability to differentiate strains of other species of Leishmania, confirming that microsatellite markers developed for one leishmanial species cannot generally be used for other leishmanial species. In addition to length variation, a high degree of allelic heterozygosity was seen among the strains investigated, suggestive of sexual recombination within the species L. tropica.     

Fabry disease and vascular risk factors: future strategies for patient-based studies and the knockout murine model

Fabry disease is secondary to deficiency of the lysosomal enzyme α-galactosidase A, leading to altered glycosphingolipid metabolism and accumulation that is often associated with endothelial dysfunction. Current evidence suggests that there is impairment of the vascular nitric oxide pathway, with abnormalities evident in the cerebral circulation and in the dermal vasculature of patients with Fabry disease. Some of these findings have been confirmed in a mouse model of Fabry disease. The murine model, however, allows investigation of Fabry disease at a non-clinical level and a near complete investigation of biological processes within an affected tissue. This is of particular utility in allowing gene expression analysis of clinically inaccessible tissues such as the aorta.
Conclusion: Future developments in array technology for proteins and DNA single nucleotide polymorphism analysis, together with gene expression microarray analysis, may open a new chapter in our understanding of the biology of lysosomal storage disorders.     

Integration of Oncology and Palliative Care: A Systematic Review

Background.

Both the American Society of Clinical Oncology and the European Society for Medical Oncology strongly endorse integrating oncology and palliative care (PC); however, a global consensus on what constitutes integration is currently lacking. To better understand what integration entails, we conducted a systematic review to identify articles addressing the clinical, educational, research, and administrative indicators of integration.

Materials and Methods.

We searched Ovid MEDLINE and Ovid EMBase between 1948 and 2013. Two researchers independently reviewed each citation for inclusion and extracted the indicators related to integration. The inter-rater agreement was high (κ = 0.96, p < .001).

Results.

Of the 431 publications in our initial search, 101 were included. A majority were review articles (58%) published in oncology journals (59%) and in or after 2010 (64%, p < .001). A total of 55 articles (54%), 33 articles (32%), 24 articles (24%), and 14 articles (14%) discussed the role of outpatient clinics, community-based care, PC units, and inpatient consultation teams in integration, respectively. Process indicators of integration include interdisciplinary PC teams (n = 72), simultaneous care approach (n = 71), routine symptom screening (n = 25), PC guidelines (n = 33), care pathways (n = 11), and combined tumor boards (n = 10). A total of 66 articles (65%) mentioned early involvement of PC, 18 (18%) provided a specific timing, and 28 (28%) discussed referral criteria. A total of 45 articles (45%), 20 articles (20%), and 66 articles (65%) discussed 8, 4, and 9 indicators related to the educational, research, and administrative aspects of integration, respectively.

Conclusion.

Integration was a heterogeneously defined concept. Our systematic review highlighted 38 clinical, educational, research, and administrative indicators. With further refinement, these indicators may facilitate assessment of the level of integration of oncology and PC.     

In Situ Nano-Indentation of a Gold Sub-Micrometric Particle Imaged by Multi-Wavelength Bragg Coherent X-ray Diffraction

The microstructure of a sub-micrometric gold crystal during nanoindentation is visualized by in situ multi-wavelength Bragg coherent X-ray diffraction imaging. The gold crystal is indented using a custom-built atomic force microscope. A band of deformation attributed to a shear band oriented along the (221) lattice plane is nucleated at the lower left corner of the crystal and propagates towards the crystal center with increasing applied mechanical load. After complete unloading, an almost strain-free and defect-free crystal is left behind, demonstrating a pseudo-elastic behavior that can only be studied by in situ imaging while it is invisible to ex situ examinations. The recovery is probably associated with reversible dislocations nucleation/annihilation at the side surface of the particle and at the particle-substrate interface, a behavior that has been predicted by atomistic simulations. The full recovery of the particle upon unloading sheds new light on extraordinary mechanical properties of metal nanoparticles obtained by solid-state dewetting.