TP53 outperforms other androgen receptor biomarkers to predict abiraterone or enzalutamide outcome in metastatic castration-resistant prostate cancer

Purpose: To infer the prognostic value of simultaneous androgen receptor (AR) and TP53 profiling in liquid biopsies from patients with metastatic castration-resistant prostate cancer (mCRPC) starting a new line of AR signaling inhibitors (ARSi). Experimental Design: Between March 2014 and April 2017, we recruited patients with mCRPC (n = 168) prior to ARSi in a cohort study encompassing 10 European centers. Blood samples were collected for comprehensive profiling of Cell Search-enriched circulating tumor cells (CTC) and circulating tumor DNA (ctDNA). Targeted CTC RNA sequencing (RNA-seq) allowed the detection of eight AR splice variants (ARV). Low-pass whole-genome and targeted gene-body sequencing of AR and TP53 was applied to identify amplifications, loss of heterozygosity, mutations, and structural rearrangements in ctDNA. Clinical or radiologic progression-free survival (PFS) was estimated by Kaplan-Meier analysis, and independent associations were determined using multivariable Cox regression models. Results: Overall, no single AR perturbation remained associated with adverse prognosis after multivariable analysis. Instead, tumor burden estimates (CTC counts, ctDNA fraction, and visceral metastases) were significantly associated with PFS. TP53 inactivation harbored independent prognostic value [HR 1.88; 95% confidence interval (CI), 1.18-3.00; P = 0.008], and outperformed ARV expression and detection of genomic AR alterations. Using Cox coefficient analysis of clinical parameters and TP53 status, we identified three prognostic groups with differing PFS estimates (median, 14.7 vs. 7.51 vs. 2.62 months; P < 0.0001), which was validated in an independent mCRPC cohort (n = 202) starting first-line ARSi (median, 14.3 vs. 6.39 vs. 2.23 months; P < 0.0001). Conclusions: In an all-comer cohort, tumor burden estimates and TP53 outperform any AR perturbation to infer prognosis. See related commentary by Rebello et al., p. 169

Interdisciplinary diabetes care teams operating on the interface between primary and specialty care are associated with improved outcomes of care: findings from the Leuven Diabetes Project

<p>Abstract</p> <p>Background</p> <p>Type 2 diabetes mellitus is a complex, progressive disease which requires a variety of quality improvement strategies. Limited information is available on the feasibility and effectiveness of interdisciplinary diabetes care teams (IDCT) operating on the interface between primary and specialty care. A first study hypothesis was that the implementation of an IDCT is feasible in a health care setting with limited tradition in shared care. A second hypothesis was that patients who make use of an IDCT would have significantly better outcomes compared to non-users of the IDCT after an 18-month intervention period. A third hypothesis was that patients who used the IDCT in an Advanced quality Improvement Program (AQIP) would have significantly better outcomes compared to users of a Usual Quality Improvement Program (UQIP).</p> <p>Methods</p> <p>This investigation comprised a two-arm cluster randomized trial conducted in a primary care setting in Belgium. Primary care physicians (PCPs, n = 120) and their patients with type 2 diabetes mellitus (n = 2495) were included and subjects were randomly assigned to the intervention arms. The IDCT acted as a cornerstone to both the intervention arms, but the number, type and intensity of IDCT related interventions varied depending upon the intervention arm.</p> <p>Results</p> <p>Final registration included 67 PCPs and 1577 patients in the AQIP and 53 PCPs and 918 patients in the UQIP. 84% of the PCPs made use of the IDCT. The expected participation rate in patients (30%) was not attained, with 12,5% of the patients using the IDCT. When comparing users and non-users of the IDCT (irrespective of the intervention arm) and after 18 months of intervention the use of the IDCT was significantly associated with improvements in HbA1c, LDL-cholesterol, an increase in statins and anti-platelet therapy as well as the number of targets that were reached. When comparing users of the IDCT in the two intervention arms no significant differences were noted, except for anti-platelet therapy.</p> <p>Conclusion</p> <p>IDCT's operating on the interface between primary and specialty care are associated with improved outcomes of care. More research is required on what team and program characteristics contribute to improvements in diabetes care.</p> <p>Trial registration</p> <p>NTR 1369.</p

Barriers and facilitators to evidence based care of type 2 diabetes patients: experiences of general practitioners participating to a quality improvement program

Objective To evaluate the barriers and facilitators to high-quality diabetes care as experienced by general practitioners (GPs) who participated in an 18-month quality improvement program (QIP). This QIP was implemented to promote compliance with international guidelines. Methods Twenty out of the 120 participating GPs in the QIP underwent semi-structured interviews that focused on three questions: 'Which changes did you implement or did you observe in the quality of diabetes care during your participation in the QIP?' 'According to your experience, what induced these changes?' and 'What difficulties did you experience in making the changes?' Results Most GPs reported that enhanced knowledge, improved motivation, and a greater sense of responsibility were the key factors that led to greater compliance with diabetes care guidelines and consequent improvements in diabetes care. Other factors were improved communication with patients and consulting specialists and reliance on diabetes nurse educators. Some GPs were reluctant to collaborate with specialists, and especially with diabetes educators and dieticians. Others blamed poor compliance with the guidelines on lack of time. Most interviewees reported that a considerable minority of patients were unwilling to change their lifestyles. Conclusion Qualitative research nested in an experimental trial may clarify the improvements that a QIP may bring about in a general practice, provide insight into GPs' approach to diabetes care and reveal the program's limits. Implementation of a QIP encounters an array of cognitive, motivational, and relational obstacles that are embedded in a patient-healthcare provider relationshipGeert Goderis, Liesbeth Borgermans, Chantal Mathieu, Carine Van Den Broeke, Karen Hannes, Jan Heyrman and Richard Gro

A cluster randomized trial to improve adherence to evidence-based guidelines on diabetes and reduce clinical inertia in primary care physicians in Belgium: study protocol [NTR 1369]

Contains fulltext : 70617.pdf (publisher's version ) (Open Access)ABSTRACT: BACKGROUND: Most quality improvement programs in diabetes care incorporate aspects of clinician education, performance feedback, patient education, care management, and diabetes care teams to support primary care physicians. Few studies have applied all of these dimensions to address clinical inertia. AIM: To evaluate interventions to improve adherence to evidence-based guidelines for diabetes and reduce clinical inertia in primary care physicians. DESIGN: Two-arm cluster randomized controlled trial. PARTICIPANTS: Primary care physicians in Belgium. INTERVENTIONS: Primary care physicians will be randomly allocated to 'Usual' (UQIP) or 'Advanced' (AQIP) Quality Improvement Programs. Physicians in the UQIP will receive interventions addressing the main physician, patient, and office system factors that contribute to clinical inertia. Physicians in the AQIP will receive additional interventions that focus on sustainable behavior changes in patients and providers. OUTCOMES: Primary endpoints are the proportions of patients within targets for three clinical outcomes: 1) glycosylated hemoglobin < 7%; 2) systolic blood pressure differences </=130 mmHg; and 3) low density lipoprotein/cholesterol < 100 mg/dl. Secondary endpoints are individual improvements in 12 validated parameters: glycosylated hemoglobin, low and high density lipoprotein/cholesterol, total cholesterol, systolic blood pressure, diastolic blood pressure, weight, physical exercise, healthy diet, smoking status, and statin and anti-platelet therapy. PRIMARY AND SECONDARY ANALYSIS: Statistical analyses will be performed using an intent-to-treat approach with a multilevel model. Linear and generalized linear mixed models will be used to account for the clustered nature of the data, i.e., patients clustered withinimary care physicians, and repeated assessments clustered within patients. To compare patient characteristics at baseline and between the intervention arms, the generalized estimating equations (GEE) approach will be used, taking the clustered nature of the data within physicians into account. We will also use the GEE approach to test for differences in evolution of the primary and secondary endpoints for all patients, and for patients in the two interventions arms, accounting for within-patient clustering. TRIAL REGISTRATION: number: NTR 1369

Innovatie in de zorg:een dringende noodzaak

Een editoriale overweging bij een artikel over een innovatief project in Geelstatus: publishe

Randvoorwaarden voor een betere samenwerking tussen huisartsen: wat is de mening van de beroepsgroep ?

De meeste huisartsen beseffen het nut en de voordelen van samenwerken. Maar welke randvoorwaarden zijn er nodig om van samenwrking een succes te maken ? In opdracht van het Ministerei van Volksgezondheid werd in 2001 een 200-tal huisartsen hiervoor bevraagd. Een forfaitairbetalingssysteem voor de niet-prestatiegebonden taken wordt door 63,6% van hen als essentieel geacht om goed te kunnen samenwerken. Ook logistieke ondersteuning, delgeijk infrastructuur, geregeld overleg, goede taakafspraken, gemeenschappelijke visie en doelstellingen rond huisartsengeneeskunde en praktijkvoering en ten slotte wederzijds respect en vertrouwen zijn belangrijke pijlers van een goede samenwerking.status: publishe

Names and roles for the generalist doctor in Africa

CITATION: Reid, S., et al. 2010. Names and roles for the generalist doctor in Africa. African Journal of Primary Health Care & Family Medicine, 2(1): 1-5, doi: 10.4102/phcfm.v2i1.242.The original publication is available at http://www.phcfm.orgThe following dialogue between six family physicians was used as one of several discussion papers at the Regional Africa WONCA Conference in 2009 and was designed to stimulate debate and dialogue on the nature of Family Medicine in Sub-Saharan Africa. This is an edited version of an actual email exchange between March and June 2009, edited by the conference convenor, and reproduced with the kind permission of the authors.http://www.phcfm.org/index.php/phcfm/article/view/242Publisher's versio