Effectiveness of lithium in subjects with treatment-resistant depression and suicide risk: results and lessons of an underpowered randomised clinical trial

BACKGROUND: As lithium treatment might be effective in reducing the risk of deliberate self-harm (DSH) in adult patients with unipolar affective disorders, we designed a pragmatic randomised trial to assess its efficacy in more than 200 patients with treatment-resistant depression. However, we randomised 56 patients only. The aim of this report is therefore twofold: first, to disseminate the results of this underpowered study which may be incorporated into future meta-analytical reviews; second, to analyse some critical aspects of the study which might explain failure to reach the target sample size.METHODS: We carried out a randomised, parallel group, assessor-blinded superiority clinical trial. Adults with a diagnosis of major depression, an episode of DSH in the previous 12 months and inadequate response to at least two antidepressants given sequentially at an adequate dose for an adequate time for the current depressive episode were allocated to add lithium to usual care (intervention arm) versus usual care alone (control arm). Suicide completion and acts of DSH during the 12 months of follow-up constituted the composite primary outcome.RESULTS: Of 58 patients screened for inclusion, 29 were allocated to lithium plus usual care and 27 were assigned to usual care without lithium. Six patients in the lithium plus usual care group and seven in the usual care group committed acts of DSH during the follow-up phase. The survival probability did not differ between the two treatment arms (Chi2 = 0.17, p =0.676). With regard to changes in the severity of depressive symptomatology from baseline to endpoint, no significant differences were detected.CONCLUSIONS: The present study failed to achieve the minimum sample size needed to detect a clinically meaningful difference between the two treatment arms. Consequently, the finding that lithium, in addition to usual care, did not exert a positive effect in terms of reduction of DSH after 12 months of follow-up is likely due to the lack of sufficient statistical power to detect a difference, if a difference existed. The dissemination of the results of this underpowered study will inform future meta-analytical reviews on lithium and suicide-related outcomes.TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00927550

Un forum su Giuseppe Dematteis e Geografia come immaginazione. Tra piacere della scoperta e ricerca di futuri possibili (2021)

In occasione della pubblicazione del volume di Giuseppe Dematteis La geografia come immaginazione. Tra piacere della scoperta e ricerca di futuri possibili (Donzelli, 2021), la Rivista ha deciso di ospitare un forum di approfondimento invitando studiose e studiosi di diversa estrazione a riflettere sui contenuti del libro e sull’itinerario personale dell’autore. Il volume raccoglie alcuni articoli di Dematteis, pubblicati tra il 1986 e il 2009, sull’ambiguità della geografia come sguardo in parte scientifico e in parte poetico, conoscenza di ciò che è e immaginazione di ciò che potrebbe essere, disciplina al tempo stesso moderna, pre-moderna e post-moderna, invitando a leggere la terra come un insieme di relazioni. Queste riflessioni interrogano la natura stessa del sapere geografico e chiamano in causa questioni relative al posizionamento e alla ‘utilità’ della disciplina nel dibattito scientifico e pubblico. L’occasione è stata inoltre ritenuta utile per riflettere su come è cambiata la geografia italiana in questi anni, dal punto di vista del percorso di ricerca di uno dei suoi massimi esponenti, il quale ha dedicato a questi temi pagine straordinarie sulle quali si sono formate generazioni di studiosi, geografi e non. Partire, quindi, da ciò che la geografia è, per provare a immaginare quello che potrebbe, dovrebbe o vorrebbe essere

Preliminary evaluation of a new Schistosoma Immunochromatographic Test

Over 90% of schistosomiasis infections occur in sub-Saharan Africa. A rapid ICT test would be a cheap and easy tool that could be used also in the field. We preliminarily evaluated the performance of a new Schistosoma black-latex based IgG-IgM ICT (Black-ICT) on serum samples. The results indicate a high sensitivity (98.0%) but the specificity depends on the application of a cut-off value that can discriminate between positive and negative samples. Considering a possible direct application of this test on blood from finger prick, the results are promising, providied that a signal intensity scale is developed, guiding the result interpretation

Effect of sulfhydryl and non-sulfhydryl angiotensin-converting enzyme inhibitors on endothelial function in essential hypertensive patients.

BACKGROUND: Oxidative inactivation of nitric oxide (NO) is regarded as an important cause of reduced endothelium-dependent vasodilation in essential hypertension. Because zofenopril, an angiotensin-converting enzyme (ACE) inhibitor with a sulfhydryl (SH) group, has demonstrated antioxidant properties and to reduce adhesion molecule expression in vitro, in this study we evaluated the effect of this drug in comparison with the carboxylic ACE inhibitor ramipril and the beta-adrenoreceptor blocker atenolol on (1) circulating adhesion molecules and some oxidative stress parameters and (2) endothelium-dependent vasodilation in essential mildly hypertensive patients. METHODS: A total of 45 healthy subjects and 45 matched hypertensive patients participated in the study. Hypertensive patients were randomly treated with zofenopril (15 to 30 mg/d), ramipril (2.5 to 5 mg/d), and atenolol (50 to 100 mg/d). At baseline and after an 8-week therapy we evaluated blood pressure (BP) values, plasma and LDL hydroperoxides, plasma 8-isoprostanes, circulating levels of oxidized-(ox)LDL and of adhesion molecules (intercellular cell adhesion molecule-1 [ICAM-1], and vascular cell adhesion molecule-1 [VCAM-1], and E-selectin). Furthermore, all patients underwent ultrasound detection of brachial artery reactivity and endothelium-dependent dilation (flow-mediated dilation, FMD) was evaluated. RESULTS: All the treatments determined similar significant (P < .001) reduction of both systolic and diastolic BP values. Plasma (P < .01) and LDL hydroperoxides (P < .01), plasma 8-isoprostanes (P < .05), circulating oxLDL (P < .05), and adhesion molecules (P < .05) were significantly reduced only in patients receiving zofenopril. Similarly FMD was significantly increased (P < .001) in the zofenopril-treated group. CONCLUSIONS: Our results suggest that in mildly hypertensive patients without organ damage zofenopril, beyond its BP-lowering effects and through its sustained antioxidant activity, offers important advantages in reducing endothelial activation

Positive Touch Deprivation during the COVID-19 Pandemic: Effects on Anxiety, Stress, and Depression among Italian General Population

Physical distancing due to the COVID-19 Pandemic has limited the opportunities for family members, friends, and significant others to show physical affection (i.e., hugs, kisses, caresses, holding hands) during social interactions. The present study investigated the effects of positive touch and psychological distress in 991 Italian participants (Mage = 34.43, SD = 14.27). Results showed the frequency of hugs with the cohabiting partner significantly decreased the symptoms of depression (β = −1.187, p = 0.018, eβ = 0.30, 95% CI = 0.11–0.82), whereas the frequency of caresses with cohabiting relatives predicted the symptoms of anxiety (β = 0.575, p = 0.034, eβ = 1.78, 95% CI = 1.04–3.03). The frequency of hugs (β = −0.609, p = 0.049, eβ = 0.54, 95% CI = 0.30–1.00), and kisses (β = 0.663, p = 0.045, eβ = 1.94, 95% CI = 1.01–3.71) with non-cohabiting relatives predicted the symptoms of anxiety (χ2 = 1.35, df = 5, p = 0.93). These results suggest the importance of positive touch on psychological well-being in the social context

Effectiveness of lithium in subjects with treatment-resistant depression and suicide risk: a protocol for a randomised, independent, pragmatic, multicentre, parallel-group, superiority clinical trial.

BACKGROUND: Data on therapeutic interventions following deliberate self harm (DSH) in patients with treatment-resistant depression (TRD) are very scant and there is no unanimous consensus on the best pharmacological option for these patients. There is some evidence that lithium treatment might be effective in reducing the risk of completed suicide in adult patients with unipolar affective disorders, however no clear cut results have been found so far. The primary aim of the present study is to assess whether adding lithium to standard therapy is an effective treatment strategy to reduce the risk of suicidal behaviour in long term treatment of people with TRD and previous history of DSH. METHODS/DESIGN: We will carry out a randomised, parallel group, assessor-blinded superiority clinical trial. Adults with a diagnosis of major depression, an episode of DSH in the previous 12 months and inadequate response to at least two antidepressants given sequentially at an adequate dose for an adequate time for the current depressive episode will be allocated to add lithium to current therapy (intervention arm) or not (control arm). Following randomisation, treatment is to be taken daily for 1 year unless some clear reason to stop develops. Suicide completion and acts of DSH during the 12 months of follow-up will constitute the composite primary outcome. To preserve outcome assessor blindness, an independent adjudicating committee, blind to treatment allocation, will anonymously review all outcome events. DISCUSSION: The results of this study should indicate whether lithium treatment is associated with lower risk of completed suicide and DSH in adult patients with treatment resistant unipolar depression, who recently attempted suicide. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00927550

Overview of the RFX-mod fusion science activity

This paper reports the main recent results of the RFX-mod fusion science activity. The RFX-mod device is characterized by a unique exibility in terms of accessible magnetic con gurations. Axisymmetric and helically shaped reversed- eld pinch equilibria have been studied, along with tokamak plasmas in a wide range of q(a) regimes (spanning from 4 down to 1.2 values). The full range of magnetic con gurations in between the two, the so-called ultra-low q ones, has been explored, with the aim of studying speci c physical issues common to all equilibria, such as, for example, the density limit phenomenon. The powerful RFX-mod feedback control system has been exploited for MHD control, which allowed us to extend the range of experimental parameters, as well as to induce speci c magnetic perturbations for the study of 3D effects. In particular, transport, edge and isotope effects in 3D equilibria have been investigated, along with runaway mitigations through induced magnetic perturbations. The rst transitions to an improved con nement scenario in circular and D-shaped tokamak plasmas have been obtained thanks to an active modi cation of the edge electric eld through a polarized electrode. The experiments are supported by intense modeling with 3D MHD, gyrokinetic, guiding center and transport codes. Proposed modi cations to the RFX-mod device, which will enable further contributions to the solution of key issues in the roadmap to ITER and DEMO, are also brie y presented

Overview of the RFX Fusion Science Program

With a program well-balanced among the goal of exploring the fusion potential of the reversed field pinch (RFP) and that of contributing to the solution of key science and technology prob- lems in the roadmap to ITER, the European RFX-mod device has produced a set of high-quality results since the last 2010 Fusion Energy Conference. RFX-mod is a 2 MA RFP, which can also be operated as a tokamak and where advanced confinement states have 3D features studied with stellarator tools. Self-organized equilibria with a single helical axis and improved confinement (SHAx) have been deeply investigated and a more profound understanding of their physics has been achieved. First wall conditioning with Lithium provides a tool to operate RFX at higher density than before, and application of helical magnetic boundary conditions favour stationary SHAx states. The correlation between the quality of helical states and the reduction of magnetic field errors acting as seed of magnetic chaos has been robustly proven. Helical states provide a unique test-bed for numerical codes conceived to deal with 3D effects in all magnetic configura- tions. In particular the stellarator equilibrium codes VMEC and V3FIT have been successfully adapted to reconstruct RFX-mod equilibria with diagnostic input. The border of knowledge has been significantly expanded also in the area of feedback control of MHD stability. Non-linear dynamics of tearing modes and their control has been modelled, allowing for optimization of feedback models. An integrated dynamic model of the RWM control system has been developed integrating the plasma response to multiple RWMs with active and passive conducting structures (CarMa model) and with a complete representation of the control system. RFX has been oper- ated as a tokamak with safety factor kept below 2, with complete active stabilization of the p2, 1q Resistive Wall Mode (RWM). This opens the exploration of a broad and interesting operational range otherwise excluded to standard tokamaks. Control experiments and modelling led to the design of a significant upgrade of the RFX-mod feedback control system to dramatically enhance computing power and reduce system latency. The possibility of producing D-shaped plasmas is being explore