Patient preferences for treatment of castration-resistant prostate cancer in Japan: a discrete-choice experiment.

BACKGROUND: Up to a fifth of patients diagnosed with prostate cancer (PC) will develop castration-resistant prostate cancer (CRPC), which has been associated with a poor prognosis. The aim of this study was to consider the patient perspective as part of the overall treatment decision-making process for CRPC, given that an alignment between patient preference and prescribing has been shown to benefit patient outcomes. This study examines preferences of patients with CRPC in Japan for treatment features associated with treatments like RA-223, abiraterone, and docetaxel and to examine the extent to which treatment preferences may vary between symptomatic and asymptomatic patients. METHODS: A two-phase research approach was implemented. In Phase 1, N = 8 patients with CRPC were recruited from a single hospital to complete a qualitative interview to provide feedback on the draft survey. In Phase 2, N = 134 patients with CRPC were recruited from five hospitals to complete a paper survey. The survey included 6 treatment choice questions, each asking patients to choose between two hypothetical treatments for their CRPC. Each treatment alternative was defined by the following attributes: length of overall survival (OS), time to a symptomatic skeletal event (SSE), method of administration, reduction in the risk of bone pain, treatment-associated risk of fatigue and lost work days. A hierarchical Bayesian logistic regression was used to estimate relative preference weights for each attribute level and mean relative importance. RESULTS: A total of N = 133 patients with CRPC completed the survey and were included in the final analysis. Patients had a mean age of 75.4 years (SD = 7.4) and had been diagnosed with PC a mean of 6.5 years prior (SD = 4.4). Over the attribute levels shown, fatigue (relative importance [RI] = 24.9 %, 95 % CI: 24.7 %, 25.1 %) was the most important attribute, followed by reduction in the risk of bone pain (RI = 23.2 %, 95 % CI: 23.0 %, 23.5 %), and OS (RI = 19.2 %, 95 % CI: 19.0 %, 19.4 %). Although symptomatic patients placed significantly more importance on delaying an SSE (p < .05), no other preference differences were observed. CONCLUSIONS: CRPC patients were more concerned about reduced quality of life from side effects of treatment rather than extension of survival, which may have implications for shared decision-making between patients and physicians.

Heat-induced changes in the properties of modified skim milks with different casein to whey protein ratios.

The heat-induced changes in pH, Ca activity and viscosity after heating at 90 °C for 10 min of five modified skim milks were studied as a function of the initial pH of the milks at 25 °C. The milks had (i) different ratios of casein : whey protein (0.03, 1.74, 3.97, 5.27 and 7.25), (ii) the same total solids concentration (9% w/w) and (iii) prior to the adjustment of the pH, similar values of pH (6.67-6.74), concentration of serum calcium, and calcium activity, suggesting that the sera have similar mineral composition. The total protein concentrations of the milks differ (2.8-4.0%, w/w). The pH decrease in situ upon heating from 25-90 °C was similar for all the modified skim milks with the same starting pH, suggesting that the pH changes to milk on heating were primarily mediated by the initial mineral composition of the serum and were unaffected by the casein : whey protein ratio or the total protein content of the milk. The heat-induced changes in pH and calcium activity were largely reversible on cooling. The two milks with the lowest ratios of casein to whey protein gelled on heating to 90 °C for 10 min and cooling to 25 °C when the pH was adjusted to pH = 6.2 prior to heating. The viscosities of all other milks with casein to whey protein ratio of 3.97, 5.27 and 7.25 and/or pH ≥6.7 prior to heating did not change significantly. The effect of casein : whey protein ratio and the pH are the dominant factors in controlling the susceptibility to thickening of the milks on heating in this study.

Artificial Intelligence, Heuristic Biases, and the Optimization of Health Outcomes: Cautionary Optimism.

The use of artificial intelligence (AI) and machine learning (ML) in clinical care offers great promise to improve patient health outcomes and reduce health inequity across patient populations. However, inherent biases in these applications, and the subsequent potential risk of harm can limit current use. Multi-modal workflows designed to minimize these limitations in the development, implementation, and evaluation of ML systems in real-world settings are needed to improve efficacy while reducing bias and the risk of potential harms. Comprehensive consideration of rapidly evolving AI technologies and the inherent risks of bias, the expanding volume and nature of data sources, and the evolving regulatory landscapes, can contribute meaningfully to the development of AI-enhanced clinical decision making and the reduction in health inequity.

The influence of milk composition on pH and calcium activity measured in situ during heat treatment of reconstituted skim milk.

The pH and calcium activity of reconstituted skim milk solutions (9-21% w/w milk solids non-fat) on heating and after cooling were studied as a function of milk pH prior to heating (pH 6.2-7.2 at 25 degrees C) and added calcium complexing agents (phosphate or EDTA). The pH decreased as the temperature was raised from 25 to 90 degrees C and the magnitude of the pH decrease was greater with increase in initial pH at 25 degrees C before heating or milk concentration. The pH decrease on heating from 25 to 90 degrees C in skim milk solutions with added calcium complexing agents was lower than that of milk without the addition of these salts. The calcium activity decreased on heating from 25 to 60 degrees C. The magnitude of the change decreased with increase in initial pH at 25 degrees C before heating and milk concentration. The decrease in calcium activity on heating from 25 to 60 degrees C for skim milk solutions with added calcium complexing agents was lower than that of milk solutions without the addition of calcium complexing agents. The changes in pH and calcium activity on heating milk were largely reversible after cooling the milk. The results suggested that the pH and calcium activity at high temperatures are a function of the milk composition. Knowledge of the initial pH prior to heating alone is not sufficient for predicting the changes that occur during heating.

Synthesis and Characterization of Graphene Oxide-Polystyrene Composite Capsules with Aqueous Cargo via a Water-Oil-Water Multiple Emulsion Templating Route.

Graphene oxide/polystyrene (GO/PS) nanocomposite capsules containing a two-compartment cargo have been successfully fabricated using a Pickering emulsion strategy. Highly purified GO sheets with typically micrometer-scale lateral dimensions and amphiphilic characteristics were prepared from the oxidation reaction of graphite with concomitant exfoliation of the graphite structure. These GO sheets were employed as a stabilizer for oil-in-water emulsions where the oil phase comprised toluene or olive oil. The stability and morphology of the emulsions were extensively studied as a function of different parameters including GO concentration, aqueous phase pH, ultrasonication time, effects of added electrolytes and stability to dilution. In selected conditions, the olive oil emulsions showed spontaneous formation of multiple w/o/w emulsions with high stability, whereas toluene formed simple o/w emulsions of lower overall stability. Olive oil emulsions were therefore used to prepare capsules templated from emulsion droplets by surrounding the oil phase with a GO/PS shell. The GO sheets, emulsions and composite capsules were characterized using a variety of physical and spectroscopic techniques in order to unravel the interactions responsible for capsule formation. The ability of the capsules to control the release of a model active agent in the form of a hydrophilic dye was explored, and release kinetics were monitored using UV-visible spectroscopy to obtain rate parameters. The composite capsules showed promising sustained release properties, with release rates 11× lower than the precursor GO-stabilized multiple emulsion droplets.

A low-cost light-scattering detector for the flow-injection nephelometric determination of sulfate.

A simple low-cost flow-through light-scattering detector was developed for determining the particle mass concentration in colloidal suspensions. Employing a laser pointer as a light source and a photodiode IC as a light sensor, the detector was shown to have good sensitivity, yet was small and battery operated. The detector was demonstrated to be effective for the flow-injection nephelometric determination of sulfate by precipitation as barium sulfate.

Calcium phosphates in Ca(2+)-fortified milk: phase identification and quantification by Raman spectroscopy.

Calcium phosphate nanoclusters (CPNs) are important for the structure, function, and nutrient density of many dairy products. Phosphorylated amino acids in caseins stabilize calcium phosphate as nanoclusters which are amorphous to X-ray diffraction and exist within casein micelles, and these CPNs play a key role in micelle stability. Addition of calcium to milk results in further calcium phosphate removal from the serum, and there is uncertainty about the nature of the material formed and its stability. In this work we investigate both the solution and colloidal phases in CaCl2 enriched bovine milk to identify, quantify, and determine the solubility of the calcium phosphate material formed in response to calcium addition to milk. The P-O stretching bands are quite distinct in the Raman spectra of the main synthetic calcium phosphate mineral phases, including the amorphous calcium phosphate phase. In response to adding between 5 and 40 mM CaCl2 to milk, the serum phosphate concentration decreased asymptotically from 7.5 ± 0.2 to 0.54 ± 0.05 mM. Using Raman spectroscopy with a combination of internal and external standards, it was possible to show that the calcium phosphate material formed after Ca(2+) addition to milk was the same as amorphous calcium phosphate nanoclusters present in the absence of added calcium. The use of an internal standard allowed a quantitative analysis of the spectra which demonstrated that the amorphous calcium phosphate formed accounted for all of the calcium and phosphate that was removed from solution in response to calcium addition.

The use of sedimentation field flow fractionation and photon correlation spectroscopy in the characterization of casein micelles.

Sedimentation Field Flow Fractionation (SdFFF) was combined with Photon Correlation Spectroscopy (PCS), to characterize changes in the structure of the colloidal particles of reconstituted skim milk of diameter >50 nm (aggregates of casein and calcium phosphate known as casein micelles) with the changes in partitioning (with the addition of salt) of calcium (Ca), inorganic phosphate (Pi) and casein between the serum and colloidal phases of the milk. The number weighted particle size distributions are determined. These are well represented by a log-normal distribution. Methods are presented for estimating the relative contributions of scattering and absorbance to the SdFFF detector signal and for taking both into account when analysing SdFFF data. The values found for the effective density of the casein micelles were in good agreement with the literature and ranged from (1.06-1.08 g cm(-3)) according to the composition of micelles. The changes in the scattering intensity as determined by PCS correlated with the changes in the particle composition. Although the concentrations of colloidal calcium phosphate (CCP) (1.1-3.5 g/kg milk) and micellar casein (18.1-27.2 g/kg milk) varied considerably only small changes in the size distribution of particles >50 nm diameter were observed except for milk to which 30 mmol Pi+10 mmol Ca/kg milk had been added where the particle size distribution shows a swelling of the particles consistent with a lower than expected value for the particle density. These observations suggest that the micelles have the ability to both lose (depleted micelles) and accommodate (enriched micelles) more casein, calcium and inorganic phosphate in their interior, thus confirming the model of the micelles which postulates an open structure allowing freedom of movement of casein and small ions.