Terapia farmacologica e suicidio: l’esperienza del Gabapentin e della Quetiapina. Considerazioni medico-legali basate su una meta-analisi

Riassunto Il Gabapentin e la Quetiapina sono due farmaci appartenenti a due categorie farmaceutiche diverse e presentano diverse indicazioni terapeutiche. Essi condividono la negativa caratteristica di essere legati ad un possibile coinvolgimento in episodi di suicidio. Inoltre il recente uso off-label del Gabapentin per la terapia dei disturbi bipolari ha fatto sì che entrambi i farmaci possano essere impiegati per trattare la stessa patologia, aprendo la possibilità di una loro associazione nei pazienti refrattari alla monoterapia, con l’eventualità che i singoli effetti collaterali si sommino. Obiettivo di questo lavoro è stimare, attraverso l’analisi della letteratura scientifica disponibile, il legame esistente tra l’assunzione di Gabapentin e/o Quetiapina ed il rischio di ideazione e/o comportamenti suicidari, individuare un possibile meccanismo d’azione che possa spiegarlo e valutare il possibile utilizzo di questi farmaci come mezzo per porre in atto il suicidio. Il medico nel prescrivere Gabapentin o Quetiapina deve essere consapevole dei rischi che essi comportano e ne deve fornire al proprio paziente una completa informazione che gli consentano di prestare un consenso consapevole alla terapia. Inoltre, attraverso visite regolari, deve porre in atto un attento monitoraggio durante tutto l’arco del trattamento che gli consenta di rilevare segni di allarme e stabilire tutti gli accorgimenti, comportamentali e terapeutici, che permettano di ridurre o prevenire il rischio di comportamenti suicidari nei pazienti. Tutto ciò risulta ancor più importante alla luce della possibilità di una terapia di associazione con i due farmaci, sulla quale non esistono studi specifici. La gabapentine (Gabapentin) et la quétiapine (Quetiapina) sont deux médicaments appartenant à des catégories pharmaceutiques différentes ayant des indications thérapeutiques distinctes. Ils ont en commun la caractéristique négative d’être liés à une augmentation possible du risque de suicide. En outre, la prescription non conforme de médicaments (off-label use) comme la gabapentine, récemment choisie a fait que les deux médicaments peuvent être utilisés pour le traitement des troubles bipolaires, ouvrant la possibilité de faire prendre les deux aux patients jugés réfractaires à la monothérapie : le risque est que l’effet secondaire de l’un se somme à celui de l’autre. Grâce à l’analyse de la littérature scientifique, l’objectif de cette étude est : d’évaluer la relation entre l’assomption de la gabapentine et de la quétiapine et le risque d’idéation suicidaire et/ou de passage à l’acte ; d’identifier un mécanisme d’action pouvant expliquer ce risque ; évaluer l’usage de ces médicaments comme moyen de passage à l’acte dans la crise suicidaire. Le médecin qui prescrit la gabapentine (Gabapentin) ou la quétiapine (Quetiapina) doit être conscient de leurs risques et doit en informer le patient le plus complètement possible afin que ce dernier puisse donner, en toute conscience, un son consentement à la thérapie. En outre, par le biais de consultations régulières, le médecin doit effectuer un monitorage attentif du traitement pour détecter les signaux d’alarme et trouver les échappatoires, comportementales et thérapeutiques, pour réduire ou prévenir le risque suicidaire chez les patients. Tout cela est plus important encore, vu la possibilité de l’association de deux médicaments sur laquelle il n’existe aucune étude spécifique. Gabapentin and Quietiapina are two drugs belonging to two different pharmaceutical classes thus offering different therapeutic indications. They both share the negative feature of being related to a possible implication in suicidal events. Moreover, the latest off-label use of Gabapentin for the bipolar disorders therapy has allowed the use of both these drugs in the treatment of the same pathology, thus opening the possibility of their combination in treating those patients refractory to single-drug therapy. By doing in this way, there is the possibility of joining their separate side effects. The aim of this study is to assess, through the analysis of the available scientific literature, the tie between the administration of Gabapentin and/or Quietiapina and the risk of conceiving and/or practicing suicidal behaviours so that to recognize a possible action mechanism able to explain such behaviours. In this way researchers intend to estimate the possible use of these drugs as a means to commit suicide. When prescribing Gabapentin or Quietiapina, physicians must be aware of the risks of these drugs so that to accurately inform patients who have to give their conscious assent to the therapy. Moreover, through regular visits, caregivers have to implement an attentive monitoring throughout the whole therapy time in order to spot any signs alerting all possible therapeutic procedures necessary to prevent or reduce the risk of suicidal behaviours in patients. All these considerations appear to be more important in the light of the possibility of a therapy combining these two drugs, which has not yet been specifically studied

Modelling of the Complex Groundwater Level Dynamics during Episodic Rainfall Events of a Surficial Aquifer in Southern Italy

We analyzed the complex dynamics that are involved the groundwater level variations due to the episodic rainfall supply in the Ionian coastal plain surficial aquifer located in Southern Italy. In this aquifer, as a consequence of the particular hydrogeological framework, both direct and lateral recharge mechanisms coexist. Hence, the dynamics of groundwater level variations are quite complex and strongly non-linear. Our focus was essentially on the short-term behavior of groundwater levels, with a specific analysis on episodic rainfall events. To model these dynamics, due to the presence of the preferential pathways in the infiltration processes, a kinematic dispersion wave model was used. Specifically, a one-dimensional and non-linear particle-based numerical model was developed. It uses ideal particles with constant water volume travel, according to celerity and hydraulic dispersion, to simulate the infiltration rate wave through the vadose zone. The infiltration rate that reaches the water table represents the input function to evaluate the aquifer groundwater level fluctuations. As a consequence of the special lithological and storage capacity characteristics of the surficial layers, groundwater flow conditions change from unconfined to confined. The developed model analyzes the direct groundwater supply under natural conditions, including episodic rainfall, and it has been validated using a high-resolution time series of rainfall data and groundwater level obtained from the monitoring station Terra Montonata

Dangerous liaisons? The role of inflammation and comorbidities in HIV and SARS-CoV-2 infection

In people living with HIV (PLWH), immune activation and inflammation levels are high even when viral suppression is maintained, potentially contributing to several comorbidities, and hampering the immune response to infections such as the recent SARS-CoV-2 disease 2019 (COVID-19)

The Efficacy of Selected Sodium Hypochlorite Heating Methods for Increasing and Maintaining Its Intracanal Temperature—An Ex Vivo Study

Background: Enhancement of the temperature of sodium hypochlorite (NaOCl) solution would increase its cleaning potential and decontamination of the root canal system. Therefore, the aim of the present in vitro investigation was to compare the efficacy of different methods of NaOCl heating by evaluating the temperature profiles developed at different levels of the root canal system. Methods: Five thermocouples were applied at different levels of the root canal system of extracted human premolars. NaOCl solution was heated according to two methods: extraoral heating (50 °C, 60 °C, and 70 °C) using a magnetic hotplate heater and intracanal heating by F-06, XF-30/04, and ML-12 pluggers at 100 °C, 150 °C, and 180 °C. Results: The extraoral heating method was ineffective to produce a significant temperature increase at the root apex. Comparable results were obtained using the intracanal heating method through the ML-12 plugger that showed slightly better results only when set at 180 °C. On the other hand, negligible differences were observed in terms of temperature maintenance at several levels of the root between the F-06 and XF-30/04 pluggers, even though the time intervals were higher in case of XF-30/04. Conclusions: The intracanal heating method provided a better temperature persistence in the middle third of the root canal system. Conversely, extraoral heating was ineffective to produce a significant temperature increase at the apex of the root. Comparable results were obtained even using the ML-12 plugger

Extraction of astaxanthin from microalga Haematococcus pluvialis in red phase by using generally recognized as safe solvents and accelerated extraction

Abstract Solvent Extraction was tested to extract astaxanthin from Haematococcus pluvialis in red phase (HPR), by investigating effects of solvents, extraction pressure and temperature. Astaxanthin isomers were identified and quantified in the extract. The performances of acetone and ethanol, Generally Recognized As Safe (GRAS) solvents, were explored. Negligible effect of pressure was found, while with increasing extraction temperature astaxanthin recovery increased till a maximum value, beyond which thermal degradation seemed to be greater than the positive effect of temperature on extraction. Furthermore, to maximize the extraction yield of astaxanthin, mechanical pre-treatment of HPR biomass was carried out and several extraction runs were consecutively performed. Experimental results showed that after the mechanical pre-treatment the astaxanthin recovery strongly increased while a single extraction run of 20 min was sufficient to extract more than 99% of total astaxanthin extracted. After pre-treatment, maximum recovery of about 87% was found for acetone (pressure = 100 bar; temperature = 40 °C; total time = 60 min)

Ionic dialysance allows an adequate estimate of urea distribution volume in hemodialysis patients

Ionic dialysance allows an adequate estimate of urea distribution volume in hemodialysis patients.BackgroundAn adequate estimation of urea distribution volume (V) in hemodialysis patients is useful to monitor protein nutrition. Direct dialysis quantification (DDQ) is the gold standard for determining V, but it is impractical for routine use because it requires equilibrated postdialysis plasma water urea concentration. The single pool variable volume urea kinetic model (SPVV-UKM), recommended as a standard by Kidney Disease Outcomes Quality Initiative (K/DOQI), does not need a delayed postdialysis blood sample but it requires a correct estimate of dialyser urea clearance.MethodsIonic dialysance (ID) may accurately estimate dialyzer urea clearance corrected for total recirculation. Using ID as input to SPVV-UKM, correct V values are expected when end-dialysis plasma water urea concentrations are determined in the end-of-session blood sample taken with the blood pump speed reduced to 50 mL/min for two minutes (Upwt2′). The aim of this study was to determine whether the V values determined by means of SPVV-UKM, ID, and Upwt2′ (VID) are similar to those determined by the “gold standard” DDQ method (VDDQ). Eighty-two anuric hemodialysis patients were studied.ResultsVDDQ was 26.3 ± 5.2 L; VID was 26.5 ± 4.8 L. The (VID–VDDQ) difference was 0.2 ± 1.6 L, which is not statistically significant (P = 0.242). Anthropometric volume (VA) calculated using Watson equations was 33.6 ± 6.0 L. The (VA–VDDQ) difference was 7.3 ± 3.3 L, which is statistically significant (P < 0.001).ConclusionAnthropometric-based V values overestimate urea distribution volume calculated by DDQ and SPVV-UKM. ID allows adequate V values to be determined, and circumvents the problem of delayed postdialysis blood samples

Efficacy and safety of the sofosbuvir/velpatasvir combination for the treatment of patients with early mild to moderate COVID-19

: SARS-CoV-2 is still a health problem worldwide despite the availability of vaccines. Therefore, there is a need for effective and safe antiviral. SARS-CoV-2 and HCV necessitate RNA-dependent RNA polymerase (RdRp) for replication; therefore, it has been hypothesized that RdRp inhibitors used to treat HCV may be effective treating SARS-CoV-2. Accordingly, we evaluated the effect of the sofosbuvir/velpatasvir (SOF/VEL) combination in early SARS-CoV-2 infection. A multicenter case-control study was conducted, enrolling 120 patients with mild or moderate COVID-19, of whom 30, HCV coinfected or not, received SOF/VEL tablets (400/100&nbsp;mg) once daily for 9&nbsp;days within a median of 6&nbsp;days from the beginning of infection and 90 controls were treated with standard care. The primary endpoint was the effect on viral clearance, and the secondary endpoint was the improvement of clinical outcomes. Nasal swabs for SARS-CoV-2 by PCR were performed every 5-7&nbsp;days. Between 5-14&nbsp;days after starting SOF/VEL treatment, SAS-CoV-2 clearance was observed in 83% of patients, while spontaneous clearance in the control was 13% (p &lt; 0.001). An earlier SARS-CoV-2 clearance was observed in the SOF/VEL group than in the control group (median 14 vs 22&nbsp;days, respectively, p &lt; 0.001) also when the first positivity was considered. None of the patients in the SOF/VEL group showed disease progression, while in the control group, 24% required more intensive treatment (high flow oxygen or noninvasive/invasive ventilation), and one patient died (p &lt; 0.01). No significant side effects were observed in the SOF/VEL group. Early SOF/VEL treatment in mild/moderate COVID-19 seems to be safe and effective for faster elimination of SARS-CoV-2 and to prevent disease progression

Laparoscopic and robotic ureteral stenosis repair: a multi-institutional experience with a long-term follow-up

The treatment of ureteral strictures represents a challenge due to the variability of aetiology, site and extension of the stricture; it ranges from an end-to-end anastomosis or reimplantation into the bladder with a Boari flap or Psoas Hitch. Traditionally, these procedures have been done using an open access, but minimally invasive approaches have gained acceptance. The aim of this study is to evaluate the safety and feasibility and perioperative results of minimally invasive surgery for the treatment of ureteral stenosis with a long-term follow-up. Data of 62 laparoscopic (n\uc2&nbsp;=\uc2&nbsp;36) and robotic (n\uc2&nbsp;=\uc2&nbsp;26) treatments for ureteral stenosis in 9 Italian centers were reviewed. Patients were followed according to the referring center\ue2\u80\u99s protocol. Laparoscopic and robotic approaches were compared. All the procedures were completed successfully without open conversion. Average estimated blood loss in the two groups was 91.2\uc2&nbsp;\uc2\ub1\uc2&nbsp;71.9\uc2&nbsp;cc for the laparoscopic and 47.2\uc2&nbsp;\uc2\ub1\uc2&nbsp;32.3\uc2&nbsp;cc for the robotic, respectively (p\uc2&nbsp;=\uc2&nbsp;0.004). Mean days of hospitalization were 5.9\uc2&nbsp;\uc2\ub1\uc2&nbsp;2.4 for the laparoscopic group and 7.6\uc2&nbsp;\uc2\ub1\uc2&nbsp;3.4 for the robotic group (p\uc2&nbsp;=\uc2&nbsp;0.006). No differences were found in terms of operative time and post-operative complications. After a median follow-up of 27\uc2&nbsp;months, the robotic group yielded 2 stenosis recurrence, instead the laparoscopic group shows no cases of recurrence (p\uc2&nbsp;=\uc2&nbsp;0.091). Minimally invasive approach for ureteral stenosis is safe and feasible. Both robotic and pure laparoscopic approaches may offer good results in terms of perioperative outcomes, low incidence of complications and recurrence

Could ischemic colitis be the first manifestation of COVID-19? A case report

We report on a case of SARS-CoV-2-infected patient with clinical and histologic features mimicking ischaemic colitis. This case provides evidence that SARS-CoV-2 may compromise the microvascular blood flow in the intestinal wall, with a parallel activation of the inflammatory cascade, either in the absence, or earlier of any pulmonary involvement