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Plain Language Summary Title: What Psychiatrists Should Know About Prescribed Safer Opioid Supply., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: While early psychosis intervention (EPI) has proliferated in recent years amid evidence of its effectiveness, programmes often struggle to deliver consistent, recovery-based care. NAVIGATE is a manualised model of EPI with demonstrated effectiveness consisting of four components: individualised medication management, individual resiliency training, supported employment and education and family education. We aim to implement NAVIGATE in geographically diverse EPI programmes in Ontario, Canada, evaluating implementation and its effect on fidelity to the EPI model, as well as individual-level outcomes (patient/family member-reported and interviewer-rated), system-level outcomes (captured in provincial administrative databases) and engagement of participants with lived experience., Methods and Analysis: This is a multisite, non-randomised pragmatic hybrid effectiveness-implementation type III mixed methods study coordinated at the Centre for Addiction and Mental Health (CAMH) in Toronto. Implementation is supported by the Provincial System Support Program, a CAMH-based programme with provincial offices across Ontario, and Extension of Community Healthcare Outcomes Ontario Mental Health at CAMH and the University of Toronto. The primary outcome is fidelity to the EPI model as measured using the First Episode Psychosis Services-Fidelity Scale. Four hundred participants in the EPI programmes will be recruited and followed using both individual-level assessments and health administrative data for 2 years following NAVIGATE initiation. People with lived experience will be engaged in all aspects of the project, including through youth and family advisory committees., Ethics and Dissemination: Research ethics board approval has been obtained from CAMH and institutions overseeing the local EPI programmes. Study findings will be reported in scientific journal articles and shared with key stakeholders including youth, family members, programme staff and policymakers., Trial Registration Number: NCT03919760; Pre-results., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Adrenocortical carcinoma (ACC) may rarely be a component of inherited cancer syndromes such as Li-Fraumeni syndrome and Beckwith-Wiedemann syndrome. ACC caused by a BRCA2 mutation has never been reported., Methods: Nucleotide sequencing of BRCA2 in lymphocyte and tumoral DNA of a 50-year-old male who presented with an androgen-secreting ACC and a strong family history of breast, ovarian, and pancreatic cancers., Results: A germline BRCA2 2 bp heterozygous deletion at nucleotide 8765 (8765delAG) leading to a frameshift mutation (p.Glu2846GlyfsX23) was detected. Only the BRCA2 deleted allele was retained in the ACC tumoral DNA compared with the control DNA supporting a loss of heterozygosity in the tumor., Conclusion: This is the first reported case of a patient with ACC associated with a BRCA2 germline mutation. Loss of heterozygosity in ACC DNA suggests a causal link with the BRCA2 8765delAG mutation., Competing Interests: The authors have no conflicts of interest to disclose.

New information has been provided over the last years regarding treatment of prolactinomas and will be reviewed in this update. Medical treatment with a dopamine agonist (DA) remains the cornerstone of therapy and cabergoline is the first choice, due to its high efficacy and good tolerability profile. Prolonged remission after discontinuation of DA may be observed if treatment has been given for at least two years, normal prolactin has been obtained with a low dose and tumoral diameter has been reduced by at least 50%. Although the risk of restrictive cardiac valve disease is low at the standard doses of cabergoline used for the treatment of hyperprolactinaemia, long-term echocardiographic surveillance is however indicated, in particular in resistant patients who need higher doses of cabergoline (2.0 mg/week or more). Neurosurgical treatment of prolactinomas is less effective than medical therapy and recurrence of hyperprolactinaemia is frequent. Besides classical indications such as drug intolerance, resistance or acute complications, new indications have emerged such as young patients with a high likelihood of complete tumour resection and who do not wish to take prolonged medical treatment, or patients who require high doses of cabergoline, in whom surgical debulking may significantly improve postoperative hormonal control. Finally, recent data indicate that cabergoline is safe for the developing foetus and for the mother, and therefore should not be preventively withdrawn in a young woman wishing to become pregnant., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

The purpose of this study was to compare different methods to identify metabolically healthy but obese (MHO) individuals in a cohort of obese postmenopausal women. We examined the anthropometric and metabolic characteristics of 113 obese (age: 57.3 +/- 4.8 years; BMI: 34.2 +/- 2.7 kg/m(2)), sedentary postmenopausal women. The following methods were used to identify MHO subjects: the hyperinsulinemic-euglycemic clamp (MHO: upper quartile of glucose disposal rates); the Matsuda index (MHO: upper quartile of the Matsuda index); the homeostasis model assessment (HOMA) index (MHO: lower quartile of the HOMA index); having 0-1 cardiometabolic abnormalities (systolic/diastolic blood pressure > or =130/85 mm Hg, triglycerides (TG) > or =1.7 mmol/l, glucose > or =5.6 mmol/l, HOMA >5.13, high-sensitive C-reactive protein (hsCRP) >0.1 mg/l, high-density lipoprotein-cholesterol (HDL-C) <1.3 mmol/l); and meeting four out of five metabolic factors (HOMA < or =2.7, TG < or =1.7 mmol/l, HDL-C > or =1.3 mmol/l, low-density lipoprotein-cholesterol < or =2.6 mmol/l, hsCRP < or =3.0 mg/l). Thereafter, we measured insulin sensitivity, body composition (dual-energy X-ray absorptiometry), body fat distribution (computed tomography scan), energy expenditure, plasma lipids, inflammation markers, resting blood pressure, and cardiorespiratory fitness. We found significant differences in body composition (i.e., peripheral fat mass, central lean body mass (LBM)) and metabolic risk factors (i.e., HDL-C, hsCRP) between MHO and at risk individuals using the different methods to identify both groups. In addition, significant differences between MHO subjects using the different methods to identify MHO individuals were observed such as age, TG/HDL, hsCRP, and fasting insulin. However, independently of the methods used, we noted some recurrent characteristics that identify MHO subjects such as TG, apolipoprotein B, and ferritin. In conclusion, the present study shows variations in body composition and metabolic profile based on the methods studied to define the MHO phenotype. Therefore, an expert consensus may be needed to standardize the identification of MHO individuals.