MRI-targeted biopsy for detecting prostate cancer: have the guidelines changed our practices and our prostate cancer detection rate?

International Urology and Nephrology - In our center, until 2018, MRI-targeted biopsy was underused. Since January 2018, we systematically performed MRI-targeted biopsy for suspicious...     

DROP-OUT FROM CHRONIC PAIN TREATMENT PROGRAMMES: IS RANDOMIZATION JUSTIFIED IN BIOPSYCHOSOCIAL APPROACHES?

ObjectiveTo identify profiles of patients who are at risk of dropping out from biopsychosocial approaches to chronic pain management.PatientsA total of 575 patients were included in the study. Of these, 203 were randomized into 4 treatment groups: self-hypnosis/self-care; music/self-care; self-care; and psychoeducation/cognitive behavioural therapy. The remaining 372 patients were not randomized, as they presented with the demand to learn self-hypnosis/self-care, and therefore were termed a “self-hypnosis/self-care demanders” group.MethodsSocio-demographics and behavioural data were included in the analyses. Univariates analyses, comparing early drop-outs (never attended treatment), late drop-outs (6/9 sessions’ treatment) and continuers were conducted in order to select variables to include in a multivariate logistic regression.ResultsUnivariate analyses yielded 8 variables, out of 18 potential predictors for drop-out, which were eligible for inclusion in the multivariate logistic regression. The model showed that having an intermediate or high educational level protects against dropping out early or late in the pain management process. Having to wait for more than 4 months before starting the treatment increases the risk of never starting it. Being randomized increases the risk of never starting the treatment.ConclusionIn a context in which randomization is considered a “gold standard” in evidence-based practice, these results indicate that this very principle could be deleterious to pain management in patients with chronic pain.LAY ABSTRACTThe aim of this study was to identify profiles of patients who are at risk of dropping out from biopsychosocial approaches to chronic pain management. A total of 575 patients were included in the study. Of these, 203 patients were randomized into 4 treatment groups: self-hypnosis/self-care; music/self-care; self-care; psychoeducation/cognitive behavioural therapy. The remaining 372 patients were not randomized, as they presented with the demand to learn self-hypnosis/self-care, and hence formed a “self-hypnosis/self-care demanders” group. Analyses of socio-demographics and behavioural data were conducted, comparing early drop-outs (never attended treatment), late drop-outs (6/9 sessions’ treatment) and continuers. Results showed that having an intermediate or high educational level protects against dropping out early or late in the management process. Having to wait for more than 4 months before starting the treatment, and being randomized, increases the risk of never starting it. Thus, in a context in which randomization is considered as a “gold standard” in evidence-based practice, these results indicate that this very principle could be deleterious to pain management in patients with chronic pain.Key words: chronic pain, non-pharmacological treatment, randomization, drop-out, loss to follow-up, attrition

Chronic pain is a complex disorder in which pain appears persistent and prolonged (> 3 months) and includes biological, psychological and socio-professional factors that undermine patients’ everyday life. Patients and healthcare providers are increasingly turning to non-pharmacological treatments, such as hypnosis and music therapy, combined with cognitive behavioural therapy (CBT) (1). The efficacy of these treatment in managing chronic pain has been demonstrated (2–4).A major problem in clinical research is drop-out, which ranges from 5% to 46%, in chronic pain management, depending on the study (5). The first issue concerns the definition of drop-out, since this varies between authors: some regard drop-out as patients ending therapy before the agreed-end-of-treatment (6), others consider it as not attending therapy sessions even though patients have agreed to attend (7). The second issue is that few clinical studies in the field of chronic pain take drop-out into account, thus generating a bias in the overall results of clinical trials investigating the efficacy of such treatments (8). The lack of studies and the disagreement regarding definitions lead to a range of results in the study of drop-out predictors in chronic pain. Some authors have highlighted that a low educational level increases the risk of dropping out from therapy (cohort study (9)), while others have shown the contrary (randomized trial (10)). The same controversy can be seen when considering age, sex and personality (systematic review (5); randomized trial (10); retrospective study (11); non-randomized trial (12)). Predictors outside of patient-related factors have mostly been studied in the mental health literature. As the management of chronic pain and mental health is relatively similar, consideration of these factors seems relevant. A meta-analysis showed that, in psychotherapy settings, the therapist expertise had an influence on drop-out. The results demonstrated that when trainees (pre-degree attainment) lead the group therapy, patients tended to be more likely to drop-out (13). Another meta-analysis showed that patients’ motivational level predicted drop-out from psychotherapy (14). A further barrier to completing treatments is the waiting period between initial contact and the effective start of the treatment (retrospective study (15)). Another retrospective study highlighted that the longer the patients in a substance abuse treatment programme had to wait until the onset of treatment (≥8 days), the more likely they were not to attend the first session of the programme (16).Given the lack of consensus, a better understanding of the profile of drop-outs and contextual risk factors, is essential in order to prevent this phenomenon, enhance treatment adherence and, consequently, ameliorate the study of treatment efficacy in chronic pain.The aim of this study was to retrospectively identify patient- and context-related factors to explain drop-out from randomized biopsychosocial-based treatment programmes.     

The opening lectures in chemistry of the French pharmacists

The opening lectures, which formerly marked the beginning of a professor's duties in an academic institution, are important documents for science historians. Several opening lectures in chemistry (organic, inorganic, analytical, biological or medicinal chemistry), which were given by French pharmacists in the Ecole or the Faculté de pharmacie de Paris, in the Muséum national d'histoire naturelle in Paris, or in the Collège de France are analyzed. First, these lectures reveal formal aspects, such as the history of the chair or a eulogy of the works and personal qualities of the predecessor. Then, the educational aspects contained in the opening lectures provide information, as well as the opinions of the new professor about teaching and research, history of the subject and its interest for the pharmaceutical students. The final aspects cited concerned the education of the new professor, the birth of his vocation and the help provided by his mentors during his university studies, his periods of instruction and his first experimental works. The opening lecture reveals sociological aspects of how knowledge was built.     

Norepinephrine promotes tumor microenvironment reactivity through β3-adrenoreceptors during melanoma progression

Stress has an emerging role in cancer and targeting stress-related β-adrenergic receptors (AR) has been proposed as a potential therapeutic approach in melanoma. Here we report that β3-AR expression correlates with melanoma aggressiveness. In addition, we highlight that β3-AR expression is not only restricted to cancer cells, but it is also expressed in vivo in stromal, inflammatory and vascular cells of the melanoma microenvironment. Particularly, we demonstrated that β3-AR can (i) instruct melanoma cells to respond to environmental stimuli, (ii) enhance melanoma cells response to stromal fibroblasts and macrophages, (iii) increase melanoma cell motility and (iv) induce stem-like traits. Noteworthy, β3-AR activation in melanoma accessory cells drives stromal reactivity by inducing pro-inflammatory cytokines secretion and de novo angiogenesis, sustaining tumor growth and melanoma aggressiveness. β3-ARs also play a mandatory role in the recruitment to tumor sites of circulating stromal cells precursors, in the differentiation of these cells towards different lineages, further favoring tumor inflammation, angiogenesis and ultimately melanoma malignancy. Our findings validate selective β3-AR antagonists as potential promising anti-metastatic agents. These could be used to complement current therapeutic approaches for melanoma patients (e.g. propranolol) by targeting non-neoplastic stromal cells, hence reducing therapy resistance of melanoma.     

Müllerian inhibiting substance contributes to sex-linked biases in the brain and behavior

Many behavioral traits and most brain disorders are common to males and females but are more evident in one sex than the other. The control of these subtle sex-linked biases is largely unstudied and has been presumed to mirror that of the highly dimorphic reproductive nuclei. Sexual dimorphism in the reproductive tract is a product of Müllerian inhibiting substance (MIS), as well as the sex steroids. Males with a genetic deficiency in MIS signaling are sexually males, leading to the presumption that MIS is not a neural regulator. We challenge this presumption by reporting that most immature neurons in mice express the MIS-specific receptor (MISRII) and that male Mis^−/− and Misrii^−/− mice exhibit subtle feminization of their spinal motor neurons and of their exploratory behavior. Consequently, MIS may be a broad regulator of the subtle sex-linked biases in the nervous system.