Treatment decision-making among patients with metastatic prostate cancer: Impact of decision locus of control on functional outcomes and decision satisfaction.

BACKGROUND: Shared decision-making (SDM) for metastatic prostate cancer (mPC) engages patients in the decision-making process and may be associated with better outcomes relative to physician- or patient-directed decision-making. We assessed the association between decision locus of control (DLOC) and patient-reported quality of life (QOL), functional outcomes, and decision satisfaction among mPC patients. METHODS: After a clinic visit in which a treatment decision was made (baseline), mPC patients completed DLOC and QOL surveys. QOL was re-assessed at 2- and 4-months post-baseline. Mean scores for each QOL dimension (physical, emotional, cognitive, social, and role functioning) were compared by DLOC group using mixed effects models. Patient preferences for DLOC and provider communication techniques were similarly collected via survey. RESULTS: Median age of participants (N = 101) was 69 years (range: 49-92); most were White (80%) and married (82%). 62% reported using SDM. At baseline, there were no differences in QOL dimensions between DLOC groups. At 4 months, patient-directed (p = 0.01) and SDM (p = 0.03) were associated with better physical functioning than physician-directed decision-making, and there was an indication of potentially greater decision satisfaction among patients who reported patient-directed (p = 0.06) or SDM (p = 0.10). SDM was the most reported preferred DLOC. CONCLUSION: mPC patients reporting SDM had better physical functioning at 4 months than physician- or patient-directed decision-making, suggesting measurable benefit from patient involvement in decision-making. Future investigations of these associations in larger, more diverse populations can further clarify these previously unmeasured benefits of patient engagement in treatment decisions.

Treatment Decision-Making in Metastatic Prostate Cancer: Perceptions of Locus of Control Among Patient, Caregiver, and Physician Triads.

BACKGROUND: Multiple treatments for metastatic prostate cancer have similar efficacy, leaving patients with complicated treatment choices. Shared decision-making can facilitate difficult treatment decisions, but the extent to which this is used for metastatic prostate cancer is unknown. We assessed patient, caregiver, and physician perceptions of decision locus of control (shared decision-making vs physician- or patient-directed decisions) and the degree of agreement between groups. METHODS: Triads of patients, caregivers, and physicians completed surveys of decision-making practices after a clinic visit in which a decision occurred. To evaluate the degree of agreement for decision locus of control, we used the quadratic-weighted kappa coefficient (κ). We used relative frequencies to evaluate which knowledge learned and treatment factors were most strongly endorsed by patients as informing and influencing their treatment decision-making, respectively. RESULTS: Fifty triads participated, with median patient age of 72 years. A majority of patients, caregivers, and physicians reported shared decision-making (66%, 56%, and 52%, respectively). Patients and physicians demonstrated minimal agreement about decision locus of control (44%, κ=0.35 [SD = 0.52]), but caregiver reports were not statistically significantly associated with physician and patient reports (38%, κ=0.23, [SD = 0.28]), p=0.055; 44%, κ=0.34 [SD = 1.98], p=0.14). Treatment efficacy was the most common patient-reported factor influencing treatment decisions (44%). CONCLUSION: This study characterized metastatic prostate cancer patients', caregivers', and physicians' experiences and communication preferences for treatment decision-making. Patients and physicians had greater agreement in decision locus of control compared with caregivers, yet patient-physician agreement was minimal. Metastatic prostate cancer patients report being influenced by information about treatment efficacy and clear next steps, and a desire for patient-friendly language and an invitation to be as involved in decision making at their preferred level. Emphasizing these may increase agreement in decision locus of control between all participants in the decision-making process.

Identification and characterization of piperine synthase from black pepper, Piper nigrum L.

Black pepper (Piper nigrum L.) is the world's most popular spice and is also used as an ingredient in traditional medicine. Its pungent perception is due to the interaction of its major compound, piperine (1-piperoyl-piperidine) with the human TRPV-1 or vanilloid receptor. We now identify the hitherto concealed enzymatic formation of piperine from piperoyl coenzyme A and piperidine based on a differential RNA-Seq approach from developing black pepper fruits. This enzyme is described as piperine synthase (piperoyl-CoA:piperidine piperoyl transferase) and is a member of the BAHD-type of acyltransferases encoded by a gene that is preferentially expressed in immature fruits. A second BAHD-type enzyme, also highly expressed in immature black pepper fruits, has a rather promiscuous substrate specificity, combining diverse CoA-esters with aliphatic and aromatic amines with similar efficiencies, and was termed piperamide synthase. Recombinant piperine and piperamide synthases are members of a small gene family in black pepper. They can be used to facilitate the microbial production of a broad range of medicinally relevant aliphatic and aromatic piperamides based on a wide array of CoA-donors and amine-derived acceptors, offering widespread applications.

What Do Men with Metastatic Prostate Cancer Consider When Making Treatment Decisions? A Mixed-methods Study.

OBJECTIVE: Metastatic prostate cancer (mPCa) patients often make complicated treatment decisions, yet decision aids to facilitate shared decision-making for mPCa are uncommon. To inform the development of patient-centered mPCa decision aids, we examined what mPCa survivors considered most important when making treatment decisions. METHODS: Using an exploratory sequential approach, we conducted three focus groups with 14 advanced prostate cancer survivors (n=5, n=3, n=6 in each group) to identify considerations for making treatment decisions. Focus groups were audio-recorded and transcribed, and we identified qualitative themes. We then developed a quantitative survey to assess the importance of each theme and administered the survey to mPCa survivors (N=100). We used relative frequencies to determine the most strongly endorsed items and chi-squared and Fisher's exact tests to assess associations with participant characteristics. RESULTS: Focus groups yielded 11 themes, and the resulting survey included 20 items. The most strongly endorsed mPCa treatment considerations were: relying on physician's treatment recommendations (79% strongly agree); wanting to feel well enough to spend quality time with loved ones (72% strongly agree); the importance of dying in a manner consistent with one's wishes (70% strongly agree); hoping to eliminate cancer completely (68% strongly agree); and optimizing treatment efficacy (65% strongly agree). Age, race, marital status, employment status, and self-reported health were related to how strongly men endorsed various considerations for mPCa treatment decision-making. CONCLUSION: We identified multiple considerations that mPCa survivors appraised when making treatment decisions. These data may inform the development of patient-centered decision aids for mPCa.

A piperic acid CoA ligase produces a putative precursor of piperine, the pungent principle from black pepper fruits.

Black pepper (Piper nigrum L.) is known for its high content of piperine, a cinnamoyl amide derivative regarded as largely responsible for the pungent taste of this widely used spice. Despite its long history and worldwide use, the biosynthesis of piperine and related amides has been enigmatic up to now. In this report we describe a specific piperic acid CoA ligase from immature green fruits of P. nigrum. The corresponding enzyme was cloned and functionally expressed in E. coli. The recombinant enzyme displays a high specificity for piperic acid and does not accept the structurally related feruperic acid characterized by a similar C-2 extension of the general C6-C3 phenylpropanoid structure. The enzyme is also inactive with the standard set of hydroxycinnamic acids tested including caffeic acid, 4-coumaric acid, ferulic acid, and sinapic acid. Substrate specificity is corroborated by in silico modelling that suggests a perfect fit for the substrate piperic acid to the active site of the piperic acid CoA ligase. The CoA ligase gene shows its highest expression levels in immature green fruits, is also expressed in leaves and flowers, but not in roots. Virus-induced gene silencing provided some preliminary indications that the production of piperoyl-CoA is required for the biosynthesis of piperine in black pepper fruits.

Beyond thermodynamics: drug binding kinetics could influence epidermal growth factor signaling.

We modeled the kinetics of drug binding to protein kinases in the EGF signaling pathway relevant to non-small-cell lung cancer and found that binding kinetics could influence therapeutic potential, that fast binding kinetics was advantageous for most targets with a couple of exceptions, that targeting some protein kinases could enhance rather than attenuate the pathway, and that IC(50) could be sensitive to the kinetic parameters of drug binding.

Preparative separation of mixtures by mass spectrometry.

A specially designed mass spectrometer which allows for preparative separation of mixtures is described. This mass spectrometer allows for large ion currents, on the order of nanoamperes, to be produced by electrospray and transmitted into a high vacuum. Accumulation of nanomole quantities of collected and recovered material in several hours is demonstrated. The use of high-velocity ions reduces space charge effects at high ion currents. Separation of mass occurs simultaneously for all ions, providing a 100% duty cycle. The use of a linear dispersion magnet avoids compression at higher m/z ratios. A deceleration lens slows the ions to allow for soft landing at low kinetic energy. The ions are neutralized by ion pairing on an oxidized metal surface. Retractable landing plates allow for easy removal of the separated components.