Association between age of cannabis initiation and gray matter covariance networks in recent onset psychosis

Cannabis use during adolescence is associated with an increased risk of developing psychosis. According to a current hypothesis, this results from detrimental effects of early cannabis use on brain maturation during this vulnerable period. However, studies investigating the interaction between early cannabis use and brain structural alterations hitherto reported inconclusive findings. We investigated effects of age of cannabis initiation on psychosis using data from the multicentric Personalized Prognostic Tools for Early Psychosis Management (PRONIA) and the Cannabis Induced Psychosis (CIP) studies, yielding a total sample of 102 clinically-relevant cannabis users with recent onset psychosis. GM covariance underlies shared maturational processes. Therefore, we performed source-based morphometry analysis with spatial constraints on structural brain networks showing significant alterations in schizophrenia in a previous multisite study, thus testing associations of these networks with the age of cannabis initiation and with confounding factors. Earlier cannabis initiation was associated with more severe positive symptoms in our cohort. Greater gray matter volume (GMV) in the previously identified cerebellar schizophrenia-related network had a significant association with early cannabis use, independent of several possibly confounding factors. Moreover, GMV in the cerebellar network was associated with lower volume in another network previously associated with schizophrenia, comprising the insula, superior temporal, and inferior frontal gyrus. These findings are in line with previous investigations in healthy cannabis users, and suggest that early initiation of cannabis perturbs the developmental trajectory of certain structural brain networks in a manner imparting risk for psychosis later in life

Risk of hospitalization for heart failure in patients with type 2 diabetes newly treated with DPP-4 inhibitors or other oral glucose-lowering medications: A retrospective registry study on 127,555 patients from the Nationwide OsMed Health-DB Database

Aims Oral glucose-lowering medications are associated with excess risk of heart failure (HF). Given the absence of comparative data among drug classes, we performed a retrospective study in 32 Health Services of 16 Italian regions accounting for a population of 18 million individuals, to assess the association between HF risk and use of sulphonylureas, DPP-4i, and glitazones. Methods and results We extracted data on patients with type 2 diabetes who initiated treatment with DPP-4i, thiazolidinediones, or sulphonylureas alone or in combination with metformin during an accrual time of 2 years. The endpoint was hospitalization for HF (HHF) occurring after the first 6 months of therapy, and the observation was extended for up to 4 years. A total of 127 555 patients were included, of whom 14.3% were on DPP-4i, 72.5% on sulphonylurea, 13.2% on thiazolidinediones, with average 70.7% being on metformin as combination therapy. Patients in the three groups differed significantly for baseline characteristics: age, sex, Charlson index, concurrent medications, and previous cardiovascular events. During an average 2.6-year follow-up, after adjusting for measured confounders, use of DPP-4i was associated with a reduced risk of HHF compared with sulphonylureas [hazard ratio (HR) 0.78; 95% confidence interval (CI) 0.62-0.97; P = 0.026]. After propensity matching, the analysis was restricted to 39 465 patients, and the use of DPP-4i was still associated with a lower risk of HHF (HR 0.70; 95% CI 0.52-0.94; P = 0.018). Conclusion In a very large observational study, the use of DPP-4i was associated with a reduced risk of HHF when compared with sulphonylureas

Penile-scrotal flap vaginoplasty versus inverted penile skin flap expanded with spatulated urethra: A multidisciplinary single-centre analysis

This study is aimed to compare outcomes of penile-scrotal flap vaginoplasty to inverted penile skin flap expanded with spatulated urethra as a single-centre experience. Data regarding vaginoplasty performed between May 2003 and January 2014 were reviewed. Subjects were divided into two groups according to the surgical technique performed: perineal-scrotal flap vaginoplasty (Group A), and inverted penile skin flap expanded with spatulated urethra vaginoplasty (Group B). All patients underwent to psychological analysis before surgery. Functional follow-up was based on a modified validated Female Sexual Function Index. Overall, 67 patients with a mean (SD) age of 34 (\ub19.38) years underwent to surgery. 41 patients were included into the Group A and 26 into the Group B. Mean operative time among Groups A and B was 316 (\ub1101.65) and 594 (\ub189.06) minutes, respectively (p<0.0001). Longer postoperative hospitalization was shown in Group B (14 days \ub1 4,51) than in Group A (10 days \ub1 2,49); (p<0.0001). Group B patients showed a higher anemization rate requiring blood transfusion (p=0.00014) as well as compressive neuropathy (p=0.038). In addition to this, necrosis of the skin flap was reported in 8 patients of Group B (p<0.0001). Comprehensive functional follow-up data was included; spontaneous vaginal lubrication was not reported in 82.4% of Group A vs 12.5% cases of Group B (p=0.0085). When compared to penile-scrotal flap vaginoplasty, inverted penile skin flap expanded with spatulated urethra technique shows an increased risk of complications with comparable satisfaction rates whereas a higher spontaneous vaginal lubrication is reported. Sexological support is of utmost importance in this setting