A randomized phase II trial of mitoxantrone, estramustine and vinorelbine or bcl-2 modulation with 13-cis retinoic acid, interferon and paclitaxel in patients with metastatic castrate-resistant prostate cancer: ECOG 3899

<p>Abstract</p> <p>Background</p> <p>To test the hypothesis that modulation of Bcl-2 with 13-cis retinoic acid (CRA)/interferon-alpha2b (IFN) with paclitaxel (TAX), or mitoxantrone, estramustine and vinorelbine (MEV) will have clinical activity in men with metastatic castrate-resistant prostate cancer (CRPC).</p> <p>Methods</p> <p>70 patients were treated with either MEV (Arm A) in a 3-week cycle or CRA/IFN/TAX with an 8-week cycle (Arm B). Patients were assessed for response, toxicity, quality of life (QOL), and the effect of treatment on Bcl-2 levels in peripheral blood mononuclear cells (PBMC).</p> <p>Results</p> <p>The PSA response rates were 50% and 23%, measurable disease response rates (CR+PR) 14% and 15%, and median overall survival 19.4 months and 13.9 months on Arm A and Arm B respectively. Transient grade 4 neutropenia occurred in 18 and 2 patients, and grade 3 to 4 thrombosis in 7 patients and 1 patient in Arm A and Arm B respectively. Patients on Arm B reported a clinically significant decline in QOL between baseline and week 9/10 (.71 s.d.), and a significantly lower level of QOL than Arm A (p = 0.01). As hypothesized, Bcl-2 levels decreased with CRA/IFN therapy only in Arm B (p = 0.03).</p> <p>Conclusions</p> <p>Treatment with MEV was well tolerated and demonstrated clinical activity in patients with CRPC. Given the adverse effect of CRA/IFN/TAX on QOL, the study of other novel agents that target Bcl-2 family proteins is warranted. The feasibility of measuring Bcl-2 protein in a cooperative group setting is hypothesis generating and supports further study as a marker for Bcl-2 targeted therapy.</p> <p>Trial Registration</p> <p><b>Clinical Trials Registration number</b>: CDR0000067865</p

Acceptability of the Distress Thermometer and Problem List to community-based telephone cancer helpline operators, and to cancer patients and carers

Background Cancer can be a distressing experience for cancer patients and carers, impacting on psychological, social, physical and spiritual functioning. However, health professionals often fail to detect distress in their patients due to time constraints and a lack of experience. Also, with the focus on the patient, carer needs are often overlooked. This study investigated the acceptability of brief distress screening with the Distress Thermometer (DT) and Problem List (PL) to operators of a community-based telephone helpline, as well as to cancer patients and carers calling the service. Methods Operators (n = 18) monitored usage of the DT and PL with callers (cancer patients/carers, >18 years, and English-speaking) from September-December 2006 (n = 666). The DT is a single item, 11-point scale to rate level of distress. The associated PL identifies the cause of distress. Results The DT and PL were used on 90% of eligible callers, most providing valid responses. Benefits included having an objective, structured and consistent means for distress screening and triage to supportive care services. Reported challenges included apparent inappropriateness of the tools due to the nature of the call or level of caller distress, the DT numeric scale, and the level of operator training. Conclusions We observed positive outcomes to using the DT and PL, although operators reported some challenges. Overcoming these challenges may improve distress screening particularly by less experienced clinicians, and further development of the PL items and DT scale may assist with administration. The DT and PL allow clinicians to direct/prioritise interventions or referrals, although ongoing training and support is critical in distress screening

Integrating the Hierarchical Taxonomy of Psychopathology (HiTOP) Into Clinical Practice

Objective: Diagnosis is a cornerstone of clinical practice for mental health care providers, yet traditional diagnostic systems have well-known shortcomings, including inadequate reliability, high comorbidity, and marked within-diagnosis heterogeneity. The Hierarchical Taxonomy of Psychopathology (HiTOP) is a data-driven, hierarchically based alternative to traditional classifications that conceptualizes psychopathology as a set of dimensions organized into increasingly broad, transdiagnostic spectra. Prior work has shown that using a dimensional approach improves reliability and validity, but translating a model like HiTOP into a workable system that is useful for health care providers remains a major challenge. / Method: The present work outlines the HiTOP model and describes the core principles to guide its integration into clinical practice. Results: Potential advantages and limitations of the HiTOP model for clinical utility are reviewed, including with respect to case conceptualization and treatment planning. A HiTOP approach to practice is illustrated and contrasted with an approach based on traditional nosology. Common barriers to using HiTOP in real-world health care settings and solutions to these barriers are discussed. / Conclusions: HiTOP represents a viable alternative to classifying mental illness that can be integrated into practice today, although research is needed to further establish its utility

Feasibility of brief psychological distress screening by a community-based telephone helpline for cancer patients and carers

Background Up to one-third of people affected by cancer experience ongoing psychological distress and would benefit from screening followed by an appropriate level of psychological intervention. This rarely occurs in routine clinical practice due to barriers such as lack of time and experience. This study investigated the feasibility of community-based telephone helpline operators screening callers affected by cancer for their level of distress using a brief screening tool (Distress Thermometer), and triaging to the appropriate level of care using a tiered model. Methods Consecutive cancer patients and carers who contacted the helpline from September-December 2006 (n = 341) were invited to participate. Routine screening and triage was conducted by helpline operators at this time. Additional socio-demographic and psychosocial adjustment data were collected by telephone interview by research staff following the initial call. Results The Distress Thermometer had good overall accuracy in detecting general psychosocial morbidity (Hospital Anxiety and Depression Scale cut-off score ≥ 15) for cancer patients (AUC = 0.73) and carers (AUC = 0.70). We found 73% of participants met the Distress Thermometer cut-off for distress caseness according to the Hospital Anxiety and Depression Scale (a score ≥ 4), and optimal sensitivity (83%, 77%) and specificity (51%, 48%) were obtained with cut-offs of ≥ 4 and ≥ 6 in the patient and carer groups respectively. Distress was significantly associated with the Hospital Anxiety and Depression Scale scores (total, as well as anxiety and depression subscales) and level of care in cancer patients, as well as with the Hospital Anxiety and Depression Scale anxiety subscale for carers. There was a trend for more highly distressed callers to be triaged to more intensive care, with patients with distress scores ≥ 4 more likely to receive extended or specialist care. Conclusions Our data suggest that it was feasible for community-based cancer helpline operators to screen callers for distress using a brief screening tool, the Distress Thermometer, and to triage callers to an appropriate level of care using a tiered model. The Distress Thermometer is a rapid and non-invasive alternative to longer psychometric instruments, and may provide part of the solution in ensuring distressed patients and carers affected by cancer are identified and supported appropriately

What "best practice" could be in Palliative Care: an analysis of statements on practice and ethics expressed by the main Health Organizations

<p>Abstract</p> <p>Background</p> <p>In palliative care it would be necessary to refer to a model. Nevertheless it seems that there are no official statements which state and describe that model. We carried out an analysis of the statements on practice and ethics of palliative care expressed by the main health organizations to show which dimensions of end-of-life care are taken into consideration.</p> <p>Methods</p> <p>The official documents by the most representative health organisations committed to the definition of policies and guidelines for palliative and end-of-life care had been considered. The documents were analysed through a framework of the components of end-of-life care derived from literature, which was composed of 4 main "areas" and of 12 "sub-areas".</p> <p>Results</p> <p>Overall, 34 organizations were identified, 7 international organisations, and 27 organisations operating on the national level in four different countries (Australia, Canada, UK and United States). Up to 56 documents were selected and analysed. Most of them (38) are position statements. Relevant quotations from the documents were presented by "areas" and "sub-areas". In general, the "sub-areas" of symptoms control as well as those referring to relational and social issues are more widely covered by the documents than the "sub-areas" related to "preparation" and to "existential condition". Indeed, the consistency of end-of-life choices with the patient's wishes, as well as completion and meaningfulness at the end of life is given only a minor relevance.</p> <p>Conclusions</p> <p>An integrated model of the best palliative care practice is generally lacking in the documents. It might be argued that the lack of a fixed and coherent model is due to the relevance of unavoidable context issues in palliative care, such as specific cultural settings, patient-centred variables, and family specificity. The implication is that palliative care staff have continuously to adapt their model of caring to the specific needs and values of each patient, more than applying a fixed, although maybe comprehensive, care model.</p

Measurement of the Forward-Backward Asymmetry in the B -> K(*) mu+ mu- Decay and First Observation of the Bs -> phi mu+ mu- Decay

We reconstruct the rare decays $B^+ \to K^+\mu^+\mu^-$, $B^0 \to K^{*}(892)^0\mu^+\mu^-$, and $B^0_s \to \phi(1020)\mu^+\mu^-$ in a data sample corresponding to $4.4 {\rm fb^{-1}}$ collected in $p\bar{p}$ collisions at $\sqrt{s}=1.96 {\rm TeV}$ by the CDF II detector at the Fermilab Tevatron Collider. Using $121 \pm 16$ $B^+ \to K^+\mu^+\mu^-$ and $101 \pm 12$ $B^0 \to K^{*0}\mu^+\mu^-$ decays we report the branching ratios. In addition, we report the measurement of the differential branching ratio and the muon forward-backward asymmetry in the $B^+$ and $B^0$ decay modes, and the $K^{*0}$ longitudinal polarization in the $B^0$ decay mode with respect to the squared dimuon mass. These are consistent with the theoretical prediction from the standard model, and most recent determinations from other experiments and of comparable accuracy. We also report the first observation of the $B^0_s \to \phi\mu^+\mu^- decay and measure its branching ratio${\mathcal{B}}(B^0_s \to \phi\mu^+\mu^-) = [1.44 \pm 0.33 \pm 0.46] \times 10^{-6}$using$27 \pm 6$signal events. This is currently the most rare$B^0_s$ decay observed.Comment: 7 pages, 2 figures, 3 tables. Submitted to Phys. Rev. Let

Measurements of the properties of Lambda_c(2595), Lambda_c(2625), Sigma_c(2455), and Sigma_c(2520) baryons

We report measurements of the resonance properties of Lambda_c(2595)+ and Lambda_c(2625)+ baryons in their decays to Lambda_c+ pi+ pi- as well as Sigma_c(2455)++,0 and Sigma_c(2520)++,0 baryons in their decays to Lambda_c+ pi+/- final states. These measurements are performed using data corresponding to 5.2/fb of integrated luminosity from ppbar collisions at sqrt(s) = 1.96 TeV, collected with the CDF II detector at the Fermilab Tevatron. Exploiting the largest available charmed baryon sample, we measure masses and decay widths with uncertainties comparable to the world averages for Sigma_c states, and significantly smaller uncertainties than the world averages for excited Lambda_c+ states.Comment: added one reference and one table, changed order of figures, 17 pages, 15 figure

Search for a New Heavy Gauge Boson Wprime with Electron + missing ET Event Signature in ppbar collisions at sqrt(s)=1.96 TeV

We present a search for a new heavy charged vector boson $W^\prime$ decaying to an electron-neutrino pair in $p\bar{p}$ collisions at a center-of-mass energy of 1.96\unit{TeV}. The data were collected with the CDF II detector and correspond to an integrated luminosity of 5.3\unit{fb}^{-1}. No significant excess above the standard model expectation is observed and we set upper limits on $\sigma\cdot{\cal B}(W^\prime\to e\nu)$. Assuming standard model couplings to fermions and the neutrino from the $W^\prime$ boson decay to be light, we exclude a $W^\prime$ boson with mass less than 1.12\unit{TeV/}c^2 at the 95\unit{%} confidence level.Comment: 7 pages, 2 figures Submitted to PR