Interaction between serotonin transporter gene variants and life events predicts response to antidepressants in the GENDEP project.

There is substantial inter-individual variation in response to antidepressants, and genetic variation may, in part, explain these differences. For example, there is evidence to suggest that variation in the serotonin transporter gene (SLC6A4) predicts response to selective serotonin reuptake inhibitors (SSRIs). Environmental factors such as the occurrence of stressful life events before treatment may also be important. One prior report suggests that both factors interact in predicting response to antidepressants. GENDEP, a prospective part-randomized pharmacogenomics trial, collected longitudinal data on the outcome of 811 patients with major depression undergoing treatment with either an SSRI (escitalopram) or a tricyclic antidepressant (nortriptyline). Life events experienced over 6 months preceding treatment were measured using a List of Threatening Experiences Questionnaire, and several polymorphisms in the serotonin transporter gene (SLC6A4) have been genotyped including the serotonin transporter-linked polymorphic region (5-HTTLPR). Stressful life events were shown to predict a significantly better response to escitalopram but had no effect on response to nortriptyline. Variation in the 5-HTTLPR and another polymorphism in the gene, STin4, significantly modified these effects. Gene-environment interactions including life events may therefore be important not only in the aetiology of depression, but also in predicting response to antidepressant medication.

Venous thromboembolism in critically ill patients affected by ARDS related to COVID-19 in Northern-West Italy.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that was first reported in Wuhan, China, and has subsequently spread worldwide. An association between increased venous thromboembolism in patients with pneumonia-related to COVID-19 has not yet been well described. PATIENTS AND METHODS: We aimed to illustrate cases of pulmonary thromboembolism in patients with acute respiratory distress syndrome related to COVID-19 treated in our intensive care unit. The medical records of patients affected by COVID-19 with acute respiratory distress syndrome in our institute from 1/3/2020 to 31/3/2020 were retrospectively reviewed. RESULTS: Our center registered a high prevalence of thromboembolic events among 62 patients affected by acute respiratory distress syndrome related to COVID-19 despite a regular antithrombotic prophylaxis. Out of these, 32 patients were transferred to other hospitals, and 30 were treated in our center. Venous thromboembolism was registered in 12 (19.3%) cases. In particular, 11 diagnoses of pulmonary embolism and 1 diagnosis of deep vein thrombosis were formulated. We described a case series of venous thromboembolism in nine patients treated in our Intensive Care Unit (ICU). Main pulmonary arteries were always involved in these patients. None of them died. CONCLUSIONS: In conclusion, critically ill patients with ARDS related to COVID-19 may have an increased risk of VTE that could be a leading cause of mortality. These patients require a high index of clinical suspicion and an accurate diagnostic approach, in order to immediately start an appropriate anticoagulant treatment.

Structural and functional macrophages alterations by ceramics of different composition.

Biomaterials may initiate several and complex biological reactions in host tissues, and the cell-biomaterial interactions can determine the release of mediators including monocytes and lymphocytes chemotactic factors. The present work was aimed to investigate in vitro the macrophage biological reactions of a natural apatite obtained by heat treatment at 400 degrees C of bovine bone, compared to other ceramics usually used for dental and orthopedic applications, using synthetic apatite and three types of alumina as controls. Particles chemotactic activity and powders oxidative burst evidenced no monocyte macrophages sensitivity reaction for natural and synthetic hydroxyapatite powders at great granulometry (> 50 microm); data were confirmed by ultrastructural observations; electron microscopy analysis showed macrophages with the features of healthy cells in the presence of both natural and synthetic apatites while macrophages grown in the presence of alumina seemed to be negatively affected. In conclusion, among all ceramics tested, natural apatite displayed a good compatibility with living cells, being better tolerated than synthetic hydroxyapatite which in turn is better tolerated than alumina.

[Epidemiologic study on the performance of a smoking prevention program in an adolescent population]. / Studio epidemiologico per la realizzazione di un programma di prevenzione del tabagismo in una popolazione di adolescenti.

In the last few years, the relative number of adolescent smokers has increased, which indicates the need to boost the adoption of new preventive strategies aimed at this part of the population. In order to be effective, preventive actions should be put in the local setting thoroughly knowing the target population and any specific-predictive factors of the insurgence of smoking addiction. To this purpose, we conducted a study aimed at describing the prevalence of smoking addiction in a population of 2472 adolescents and at identifying any predisposing factors. From the analysis of the results, both predisposing and protective factors emerged, together with many formative requests from the adolescents. On the basis of such results, we were able to create ad hoc preventive interventions. The proposed strategy seems to be potentially valid; however, we will be able to express a more precise judgment only at the end of the implementation phase.

Measuring depression: comparison and integration of three scales in the GENDEP study.

BACKGROUND: A number of scales are used to estimate the severity of depression. However, differences between self-report and clinician rating, multi-dimensionality and different weighting of individual symptoms in summed scores may affect the validity of measurement. In this study we examined and integrated the psychometric properties of three commonly used rating scales. METHOD: The 17-item Hamilton Depression Rating Scale (HAMD-17), the Montgomery-Asberg Depression Rating Scale (MADRS) and the Beck Depression Inventory (BDI) were administered to 660 adult patients with unipolar depression in a multi-centre pharmacogenetic study. Item response theory (IRT) and factor analysis were used to evaluate their psychometric properties and estimate true depression severity, as well as to group items and derive factor scores. RESULTS: The MADRS and the BDI provide internally consistent but mutually distinct estimates of depression severity. The HAMD-17 is not internally consistent and contains several items less suitable for out-patients. Factor analyses indicated a dominant depression factor. A model comprising three dimensions, namely 'observed mood and anxiety', 'cognitive' and 'neurovegetative', provided a more detailed description of depression severity. CONCLUSIONS: The MADRS and the BDI can be recommended as complementary measures of depression severity. The three factor scores are proposed for external validation.

[Autopsy today: an obsolete practice or an instrument for improving the quality of health care?]. / L'autopsia oggi: una pratica superata o uno strumento per migliorare la qualità delle prestazioni sanitarie?

INTRODUCTION: Autopsies are a fundamental moment of clinical audit that have been progressively decaying. MATERIALS AND METHODS: The autoptic rates of 6 hospitals of Piedmont Region (1639 autopsies, years 1995-97) were calculated. The Positive Predictive Value and Sensitivity (indicators of concordance between clinical and autoptic diagnosis) were calculated for each diagnosis; all discrepancies were classified as type I (adverse impact on patient's survival) and type II (uncertain impact) clinical errors. The diagnostic performance of medical, surgical and emergency staffs were compared with one another. RESULTS: Autopsies are rarely performed on the patients who died in hospital (7.13%). Independently from the diagnosis, the global concordance expresses a Positive Predictive Value of 37.22% and a Sensitivity of 47.71%. 401 type I errors and 307 type II errors were found. The best performance is reached by emergency staff. AIM: To evaluate the use and the meaning of autopsies in today's Italian healthcare organisations.