Routine treatment pathways in a cohort of patients with major depression and suicidality in Italy: the ARIANNA observational study.

BACKGROUND: Major Depressive Disorder (MDD) with suicidal ideation, intent, or behavior is a psychiatric emergency with controversial care management. Our study describes the comprehensive treatment pathways of this population in Italian routine clinical practice. METHODS: ARIANNA [NCT04463108] is an observational prospective and retrospective cohort study involving both primary data collection and secondary data extract. A total of 137 adult MDD patients with suicidality were enrolled from 24 Italian care sites and followed for 90 days. Other than the description of treatment patterns, the impact of treatment on depressive symptoms and suicidality, the burden on the patient's and caregiver's quality of life, healthcare resource utilization and costs were described. RESULTS: Of the 133 eligible patients, 68.4% were female, and the median age was 47. Approximately half of the study population had a current severe major depressive episode. Treatment strategies at the time of active suicidal ideation with intent definition/confirmation (t0) were heterogeneous, increasing in complexity during observation. According to the MADRS, patients with remission at t0+1 day were 2.6%, with the mean total score decreasing from 37.2 at t0 to 32.3. LIMITATIONS: The study sites were not randomly selected. CONCLUSIONS: To the best of our knowledge, this is the first cohort study that prospectively describes the characteristics of patients with MDD and suicide risk in Italy, and how they are treated in clinical practice. The study confirms this is a difficult-to-treat population. In addition, a lack of rapid, effective treatment for reducing depressive symptoms and suicidality is observed.

Nationwide consensus on the clinical management of treatment-resistant depression in Italy: a Delphi panel.

BACKGROUND: Treatment-resistant depression (TRD) is defined by the European Medicines Agency as a lack of clinically meaningful improvement after treatment, with at least two different antidepressants. Individual, familiar, and socio-economic burden of TRD is huge. Given the lack of clear guidelines, the large variability of TRD approaches across different countries and the availability of new medications to meet the need of effective and rapid acting therapeutic strategies, it is important to understand the consensus regarding the clinical characteristics and treatment pathways of patients with TRD in Italian routine clinical practice, particularly in view of the recent availability of esketamine nasal spray. METHODS: A Delphi questionnaire with 17 statements (with a 7 points Likert scale for agreement) was administered via a customized web-based platform to Italian psychiatrists with at least 5 years of experience and specific expertise in the field of depression. In the second-round physicians were asked to answer the same statements considering the interquartile range of each question as an index of their colleagues' responses. Stata 16.1 software was used for the analyses. RESULTS: Sixty panellists, representative of the Italian territory, answered the questionnaire at the first round. For 8/17 statements more than 75% of panellists reached agreement and a high consensus as they assigned similar scores; for 4 statements the panellists assigned similar scores but in the middle of the Likert scale showing a moderate agreement with the statement, while for 5 statements there was indecision in the agreement and low consensus with the statement. CONCLUSIONS: This Delphi Panel showed that there is a wide heterogeneity in Italy in the management of TRD patients, and a compelling need of standardised strategies and treatments specifically approved for TRD. A high level of consensus and agreement was obtained about the importance of adding lithium and/or antipsychotics as augmentation therapies and in the meantime about the need for long-term maintenance therapy. A high level of consensus and agreement was equally reached for the identification of esketamine nasal spray as the best option for TRD patients and for the possibility to administrate without difficulties esketamine in a community outpatient setting, highlighting the benefit of an appropriate educational support for patients.

Clinical Features and Outcomes of 124 Italian Patients With Treatment Resistant Depression: A Real-World, Prospective Study.

Introduction: Treatment-resistant depression (TRD) is a debilitating condition affecting 20-30% of patients with major depressive disorders (MDD). Currently, there is no established standard of care for TRD, and wide variation in the clinical approach for disease management has been documented. Real-world data could help describe TRD clinical features, disease burden, and treatment outcome and identify a potential unmet medical need. Methods: We analyzed the Italian data from a European, prospective, multicentric, observational cohort study of patients fulfilling TRD criteria by the European Medicine Agency, with moderate to severe major depressive episode, and starting a new antidepressant treatment according to routinary clinical practice. They were followed up for minimum 6 months. Treatments received throughout the study period, disease severity, health-related quality of life and functioning were prospectively recorded and analyzed. Results: The Italian subcohort included 124 TRD patients (30.2% of patients of the European cohort; mean age 53.2 [sd = 9.8], women: 82, 66.1%). At enrollement, the mean (SD) duration of MDD was 16 years (sd = 11.1) and the mean duration of the ongoing major depressive episode (MDE) was 97.5 weeks (sd = 143.5); low scores of quality of life and functioning were reported. The most frequently antidepressant classes started at baseline (data available for 98 subjects) were selective serotonin reuptake inhibitors (SSRI, 42 patients [42.9%]) and serotonin-norepinephrine reuptake inhibitors (SNRI, 32 patients [32.7%]). In terms of treatment strategies, 50 patients (51%) started augmentation therapies, 18 (18.4%) combination therapies and 24 (24.5%) monoterapies (6 patients [6%] started a non-antidepressant drug only). Fourteen patients (11.3%) were treated with a psychosocial approach, including psychotherapy. After 6 months of treatment, clinical assessments were collected for 89 patients: 64 (71.9%) showed no response, 9 (10.1%) response without remission and 16 (18.0%) were in remission; non-responder patients showed lower quality of life and higher disability scores than responder patients. Conclusions: In our sample of TRD patients, we documented substantial illness burden, low perceived quality of life and poor outcome, suggesting an unmet treatment need in TRD care in Italy. Registration Number: ClinicalTrials.gov, number: NCT03373253.

Lessons learned from the first 109 laparoscopic cholecystectomies performed in a single pediatric surgery center.

BACKGROUND: Laparoscopic cholecystectomy (LC) is a frequent operation in adults but is seldom performed in children. A retrospective review of 109 consecutive patients who underwent LC over an 11-year period was performed to see what lessons were learned from this experience. METHODS: From January 1996 to January 2007, a total of 109 patients were referred to our unit to undergo LC. Nine adult patients were excluded from the analysis. The remaining 100 pediatric patients form the basis of this report. Isolated cholecystectomies were performed using a four-trocar technique, with a fifth trocar added for cases in which splenectomy was required. One patient with main bile duct dilatation at preoperative echography underwent peroperative cholangiography. RESULTS: We recorded three anatomic anomalies (3%), two involving the bile duct and one the cystic artery. We recorded four minor problems during surgery: In one case there was failure of the tip of reusable scissors, and in three cases there was a small perforation of the gallbladder during the dissection step. We recorded four (4%) postoperative complications, which required redo surgery: one patient with bleeding from the cystic artery; one case of dislocation of clips positioned on the cystic duct; and two patients with lesions of the main bile duct that had not been detected during surgery. The treatment consisted in choledojejunostomy on postoperative day 7 in one case and suture of the choledocus on a stent positioned using endoscopic retrograde cholangiopancreatography on postoperative day 5 in the second case. Both biliary complications occurred in patients more than 14 years of age. We also recorded one umbilical granuloma. CONCLUSIONS: LC is an effective procedure in children. On the basis of our experience, it seems that major complications can occur even with experienced surgeons, and they are more frequent in teenagers. Biliary or vascular anomalies of the gallbladder are encountered in about 3% of patients.

One-trocar ileo-colic resection in a newborn infant with a cystic lymphangioma of the small-bowel mesentery.

We report a case of a newborn with a cystic lymphangioma of the small-bowel mesentery discovered antenatally at ultrasound and confirmed postnatally at computed tomography scan. The lesion together with the caecum and the last centimeters of ileum were resected by using only one trocar positioned lateroumbilically. In this paper, we describe the advantages of MIS to treat newborn with abdominal masses.

Single trocar transanal endoscopy in a child.

Single trocar transanal endoscopic surgery (STTE) is a well-known technique for evaluation and management of rectal lesions in adults. We used an 11mm balloon trocar with a 10mm operative optic, introduced into the anal canal to excise a rectal lesion along with multiple rectal biopsies in a child. Rectal visibility was good with an ease to maintain the rectum insufflated.

Chromosome-protein interactions in polyomavirus virions.

In this work, we sought to determine whether the components of the murine polyomavirus capsid establish specific interactions with the minichromosome encapsidated into the mature viral particles by using the cis-diamminedichloroplatinum(II) cross-linking reagent. Our data indicated that VP1, but not minor capsid proteins, interacts with the viral genome in vivo. In addition, semiquantitative PCR assays performed on cross-linked DNA complexes revealed that VP1 binds to all regions of the viral genome but significantly more to the regulatory region. The implications of such an interaction for viral infectivity are discussed.