Two-Injection Start Regimen of Long-Acting Aripiprazole in 133 Patients With Schizophrenia.

PURPOSE/BACKGROUND: Based on a population-pharmacokinetic model, the European Medicines Agency has recently approved a simplified starting strategy of aripiprazole once a month (AOM), injectable and long-acting antipsychotic, with two 400 mg injections and a single oral 20 mg dose of aripiprazole, administered on the same day, instead of 1 injection and 14 daily administrations of concurrent oral aripiprazole. However, to our knowledge, no previous study has reported the safety and tolerability of this regimen in real-world patients. METHODS/PROCEDURES: We retrospectively reviewed medical records of 133 patients who received the newly approved 2-injection start regimen as part of their standard care in 10 Italian clinical centers. FINDINGS/RESULTS: Adverse effects were mild or moderate, with no clinically evident difference from the adverse effects observed in previous trials where AOM was started with a single injection followed by 14 days of orally administered aripiprazole. None of the patients who started AOM after the 2-injection start regimen experienced severe adverse effects or severe adverse effects. IMPLICATIONS/CONCLUSIONS: The coadministration of 2 injections of 400 mg aripiprazole and 20 mg oral aripiprazole was not associated with safety concerns beyond those reported after a single injection followed by 14 days of orally administered aripiprazole. Our results should be interpreted with caution, due to the limited sample size and to the retrospective design of the study.

A challenging case of SARS-CoV-2- AIDS and Nocardiosis coinfection from the SMatteo COvid19 REgistry (SMACORE).

The COVID-19 pandemic is posing an unprecedented threat worldwide. One issue that has faltered, though, concerns the underestimated risk to trade all for COVID-19, misdiagnosing other potentially life-threatening diseases. Further still, the presence of respiratory symptoms in AIDS patients should stimulate more vigilant efforts to uncover other or additional infections. This case report highlights the pitfalls of diagnosing a rare pulmonary infection during the COVID-19 pandemic.

Transcranial Direct Current Stimulation Reduces Craving in Substance Use Disorders: A Double-blind, Placebo-Controlled Study.

OBJECTIVES: The use of transcranial direct current stimulation (tDCS) in addiction disorders is still on its rise in comparison with pharmacological and psychotherapeutic strategies that still show low level of evidence. In this study, we aimed to evaluate the efficacy of the anodic tDCS for the short-term treatment of substance craving and other psychiatric symptoms. METHODS: In this randomized, double-blind, sham-controlled trial, inclusion criteria included the diagnosis of substance use disorder and/or gambling disorder. The protocol includes 5 consecutive days of active or sham tDCS session. Cathode was placed over the left dorsolateral prefrontal cortex. Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, Young Mania Rating Scale, Barratt Impulsiveness Scale, South Oaks Gambling Screen, and visual analog scale (VAS) 1 to 10 for craving were administered at the baseline (T0) and after 5 days of treatment (T1). RESULTS: Thirty-four treatment-seeking subjects were randomized to sham (n = 16) and active stimulation (n = 18) groups. A statistically significant reduction of values at T1 was found in all subjects considering VAS (P < 0.001), Hamilton Depression Rating Scale (P < 0.001), Hamilton Anxiety Rating Scale (P < 0.001), and Barratt Impulsiveness Scale 11 (P = 0.032). A significant reduction for VAS craving in favor of the active stimulation (P = 0.011) was found. CONCLUSIONS: Our findings reveal a statistically significant rapid reduction of craving in the active tDCS group on the right dorsolateral prefrontal cortex with respect to sham group, confirming the scientific literature trend. Large samples, with maintenance tDCS therapy and long-term follow-up, are required to establish the potential of this noninvasive and easily delivered brain stimulation strategy.

Novel psychoactive substance consumption is more represented in bipolar disorder than in psychotic disorders: A multicenter-observational study.

OBJECTIVE: Comorbidities between psychiatric diseases and use of traditional substances of abuse are common. Nevertheless, there are few data regarding the use of novel psychoactive substances (NPS) among psychiatric patients. Aim of this multicentre survey is to investigate the consumption of a number of psychoactive substances in a young psychiatric sample. METHODS: Between December 2013 and September 2015, a questionnaire was administered in 10 Italian psychiatric care facilities to a sample of 671 patients, aged 18-26 (mean age 22.24; SD 2.87). RESULTS: About 8.2% of the sample declared to have used NPS at least once, and 2.2% had consumed NPS in the previous 3 months. The three psychiatric diagnoses most frequently associated with NPS use were bipolar disorder (23.1%), personality disorders (11.8%), and schizophrenia and related disorders (11.6%). In univariate regression analysis, bipolar disorder was positively associated with NPS consumption, an association that did not reach statistical significance in the multivariate analysis. CONCLUSIONS: The use of NPS in a young psychiatric population appears to be frequent, and probably still underestimated. Bipolar disorder shows an association with NPS use. Careful and constant monitoring and an accurate evaluation of possible clinical effects related to NPS use are necessary.

Transcranial Direct Current Stimulation in Substance Use Disorders: A Systematic Review of Scientific Literature.

INTRODUCTION: New treatment options such as noninvasive brain stimulation have been recently explored in the field of substance use disorders (SUDs), including transcranial direct current stimulation (tDCS). OBJECTIVES: In light of this, we have performed a review of the scientific literature to assess efficacy and technical and methodological issues resulting from applying tDCS to the field of SUDs. METHODS: Our analysis highlighted the following selection criteria: clinical studies on tDCS and SUDs (alcohol, caffeine, cannabis, cocaine, heroin, methamphetamine, and nicotine). Study selection, data analysis, and reporting were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Exclusion criteria were as follows: clinical studies about tDCS among behavioral addiction; review and didactic articles; physiopathological studies; and case reports. RESULTS: Eighteen scientific papers were selected out of 48 articles. Among these, 16 studied the efficacy of tDCS applied to the dorsolateral prefrontal cortex, and 8 suggested the efficacy of tDCS in reducing substance craving. CONCLUSIONS: In light of these data, it is premature to conclude that tDCS over the dorsolateral prefrontal cortex is a very efficient technique in reducing craving. Small sample size, different stimulation protocols, and study duration were the main limitations. However, the efficacy of tDCS in treating SUDs requires further investigation.

Drunkorexia: an emerging trend in young adults.

OBJECTIVE: Several studies demonstrated an association between alcohol consumption and unhealthy food habits. Particularly, in young adults it has been observed the tendency to use extreme forms of weight control as a way to compensate planned binge drinking. METHOD: A questionnaire was administered to a sample of 4275 healthy subjects (43.9% males; 56.1% females), aged between 18 and 26 (mean age 22.04). The survey investigated socio-economic characteristics, drinking habits with a specific focus on binge consumption, abnormal eating behaviours and psychoactive substance use. RESULTS: 34.1% of the overall sample reported to limit their calorie intake before drinking, with no significant gender difference. A significant correlation was found between drunkorexic attitudes and, respectively, binge drinking behaviours (p < .01), use of cocaine (p < .01), and use of Novel Psychoactive Substances (p < .01). DISCUSSION: Our data identified drunkorexia as a common behaviour among Italian young adults. Raising awareness on drunkorexia may help health care providers to timely address and approach its possible short- and long-term consequences. LEVEL OF EVIDENCE: Level V (descriptive study).

Novel psychoactive substances: use and knowledge among adolescents and young adults in urban and rural areas.

INTRODUCTION: Novel psychoactive substances (NPS) are new psychotropic drugs, not scheduled under the International Conventions on Psychotropic Substances, but which may pose a relevant public health threat. In this study, we investigated knowledge and use of NPS in a sample of Italian youth in urban and rural areas. METHODS: Between December 2012 and October 2013, we administered a questionnaire to a sample of 3011 healthy subjects (44.7% men; 55.3% women), aged between 16 and 24 years and recruited in urban, intermediate and rural areas of Italy. RESULTS: Of the global sample, 53.3% declared to have some knowledge on NPS, with a higher knowledge in urban areas. Mephedrone (26%), desomorphine (22.6%) and methamphetamine (21.7%) were the most commonly known drugs. NPS use was reported by 4.7% of the sample, without significant differences between urban and rural areas; mephedrone (3.3%), synthetic cannabinoids (1.2%) and Salvia divinorum (0.3%) consumption has been identified. NPS use was also predictive of binge-drinking behaviours (χ(2) (4) = 929.58, p < .001). DISCUSSION: Urban areas may represent a focal point for preventive strategies, given the presence of higher levels of NPS knowledge. Moreover, the association between binge-drinking habits and NPS use was really strong. This issue should not be underestimated because of its medical, psychopathological and social consequences.

The WEST Study: A Retrospective and Multicentric Study on the Impact of Steroid Therapy in West Nile Encephalitis.

Background: The use of steroid therapy in potentially life-threatening neuroinvasive forms of West Nile infection (WNND) is controversial. The aim of this study is to assess the efficacy of steroid therapy in reducing intrahospital mortality, length of stay, and neurological sequelae at discharge. Methods: This was a multicenter, retrospective, observational study conducted in 5 hospitals in Northern Italy, headed by the Fondazione IRCSS Policlinico San Matteo (Pavia). We extracted all patient data with WNND diagnoses, comparing patients who received steroid treatment with patients who did not receive steroid treatment between January 2014 and January 2022. Comparisons between the 2 groups were performed using chi-square tests for categorical variables and Mann-Whitney tests for non-normal continuous data, and a generalized linear model for the binomial family was carried out. Results: Data from 65 WNND patients were extracted. Among these patients, 33 (50.7%) received steroid therapy at any point during their hospitalization. Receiving steroid therapy did not significantly reduce intrahospital mortality (odds ratio [OR], 1.70; 95% CI, 0.3-13.8; P = .89) or neurological sequelae at discharge (OR, 0.53; 95% CI, 0.16-1.76; P = .47). Conclusions: Steroid treatment is currently used on a single-case basis in severe WNND. More prospective data are needed to demonstrate a protective effect on mortality and neurological sequelae.

What is the impact of SARS-CoV-2 pandemic on antimicrobial stewardship programs (ASPs)? The results of a survey among a regional network of infectious disease centres.

Discontinuation of antimicrobial stewardship programs (ASPs) and increased antibiotic use were described during SARS-CoV-2 pandemic. In order to measure COVID-19 impact on ASPs in a setting of high multidrug resistance organisms (MDRO) prevalence, a qualitative survey was designed. In July 2021, eighteen ID Units were asked to answer a questionnaire about their hospital characteristics, ASPs implementation status before the pandemic and impact of SARS-CoV-2 pandemic on ASPs after the 1st and 2nd pandemic waves in Italy. Nine ID centres (50%) reported a reduction of ASPs and in 7 cases (38.9%) these were suspended. After the early pandemic waves, the proportion of centres that restarted their ASPs was higher among the ID centres where antimicrobial stewardship was formally identified as a priority objective (9/11, 82%, vs 2/7, 28%). SARS-CoV-2 pandemic had a severe impact in ASPs in a region highly affected by COVID-19 and antimicrobial resistance but weaknesses related to the pre-existent ASPs might have played a role.

Competing-risk analysis of coronavirus disease 2019 in-hospital mortality in a Northern Italian centre from SMAtteo COvid19 REgistry (SMACORE).

An accurate prediction of the clinical outcomes of European patients requiring hospitalisation for Coronavirus Disease 2019 (COVID-19) is lacking. The aim of the study is to identify predictors of in-hospital mortality and discharge in a cohort of Lombardy patients with COVID-19. All consecutive hospitalised patients from February 21st to March 30th, 2020, with confirmed COVID-19 from the IRCCS Policlinico San Matteo, Pavia, Lombardy, Italy, were included. In-hospital mortality and discharge were evaluated by competing risk analysis. The Fine and Gray model was fitted in order to estimate the effect of covariates on the cumulative incidence functions (CIFs) for in-hospital mortality and discharge. 426 adult patients [median age 68 (IQR 56 to 77 years)] were admitted with confirmed COVID-19 over a 5-week period; 292 (69%) were male. By 21 April 2020, 141 (33%) of these patients had died, 239 (56%) patients had been discharged and 46 (11%) were still hospitalised. Among these 46 patients, updated as of 30 May, 2020, 5 (10.9%) had died, 8 (17.4%) were still in ICU, 12 (26.1%) were transferred to lower intensity care units and 21 (45.7%) were discharged. Regression on the CIFs for in-hospital mortality showed that older age, male sex, number of comorbidities and hospital admission after March 4th were independent risk factors associated with in-hospital mortality. Older age, male sex and number of comorbidities definitively predicted in-hospital mortality in hospitalised patients with COVID-19.

Neotectonics of the Sea of Galilee (northeast Israel): implication for geodynamics and seismicity along the Dead Sea Fault system.

The Sea of Galilee in northeast Israel is a freshwater lake filling a morphological depression along the Dead Sea Fault. It is located in a tectonically complex area, where a N-S main fault system intersects secondary fault patterns non-univocally interpreted by previous reconstructions. A set of multiscale geophysical, geochemical and seismological data, reprocessed or newly collected, was analysed to unravel the interplay between shallow tectonic deformations and geodynamic processes. The result is a neotectonic map highlighting major seismogenic faults in a key region at the boundary between the Africa/Sinai and Arabian plates. Most active seismogenic displacement occurs along NNW-SSE oriented transtensional faults. This results in a left-lateral bifurcation of the Dead Sea Fault forming a rhomb-shaped depression we named the Capharnaum Trough, located off-track relative to the alleged principal deformation zone. Low-magnitude (ML = 3-4) epicentres accurately located during a recent seismic sequence are aligned along this feature, whose activity, depth and regional importance is supported by geophysical and geochemical evidence. This case study, involving a multiscale/multidisciplinary approach, may serve as a reference for similar geodynamic settings in the world, where unravelling geometric and kinematic complexities is challenging but fundamental for reliable earthquake hazard assessments.

Gambling disorder and bilateral transcranial direct current stimulation: A case report.

INTRODUCTION: Gambling disorder (GD) is a major public health concern with currently no validated and efficacious treatments approved. In this single case study, we report the short- and long-term effect of bilateral transcranial direct current stimulation (tDCS) of dorsolateral prefrontal cortex (DLPFC) on craving and impulse control in a subject with GD. METHODS: The patient is a 26-year-old Caucasian male with an 8-year history of GD as well as alcohol and cocaine misuse. Treatment consisted of twice-a-day stimulation for 10 days. According to the literature, both the left (to control craving) and the right (to control emotional impulses) DLPFC were stimulated. Patients subsequently received tDCS once a week for 3 months and then once every 2 weeks for another 3 months. RESULTS: After 10 days of treatment, the subject reported improved psychiatric symptoms (depression, anxiety, and impulsivity), as well as reduced gambling craving symptom severity. After 3 and 6 months of treatment, the clinical picture further improved. DISCUSSION: This is the first report of tDCS effectiveness in a single case study of GD. Therapeutic effects, both on the addictive behavior and on psychiatric comorbid symptomatology, were lasting and continued over 6 months of tDCS maintenance treatment. Future case-control studies are required to test the efficacy of this tool in patients with GD.

Psychotropic drugs and ventricular repolarisation: The effects on QT interval, T-peak to T-end interval and QT dispersion.

OBJECTIVE: We aimed to investigate in a clinical setting, the effects of different classes of psychotropic drugs on cardiac electrophysiological measures linked with an increased risk of sudden cardiac death. METHODS: We conducted a cross-sectional study in a population of 1059 psychiatric inpatients studying the effects of various psychotropic drugs on the T-peak to T-end (TpTe) interval, QT dispersion and QT interval. RESULTS: Methadone use showed a strong association with TpTe prolongation (odds ratio (OR)=12.66 (95% confidence interval (CI), 3.9-41.1), p<0.001), an effect independent from action on QT interval. Mood stabilisers showed significant effects on ventricular repolarisation: lithium was associated with a TpTe prolongation (OR=2.12 (95% CI, 1.12-4), p=0.02), while valproic acid with a TpTe reduction (OR=0.6 (95% CI, 0.37-0.98), p=0.04). Among antipsychotics, clozapine increased TpTe (OR=9.5 (95% CI, 2.24-40.39), p=0.002) and piperazine phenothiazines increased QT dispersion (OR=2.73 (95% CI, 1.06-7.02), p=0.037). CONCLUSIONS: Treatment with psychotropic drugs influences TpTe and QT dispersion. These parameters might be considered to better estimate the sudden cardiac death risk related to specific medications. Beyond antipsychotics and antidepressants, mood stabilisers determine significant effects on ventricular repolarisation.

Alcohol drinking patterns in young people: A survey-based study.

Binge drinking represents a major clinical and public health concern. Here, we investigated the prevalence of binge drinking and its related consequences, in a population of young adults. A questionnaire was administered to a sample of 4275 healthy subjects. In the overall sample, the percentage of binge drinkers was 67.6 per cent; among regular alcohol users, 79.5 per cent reported episodes of binge drinking. Among binge drinkers, several serious consequences were identified (staggering and stuttering, amnesia, loss of control, aggressiveness, sexual disinhibition). Raising awareness about the seriousness of binge drinking may help health care providers to identify cases early on and provide appropriate treatments.

New drugs on the Internet: the case of Camfetamine.

INTRODUCTION: The number of new psychoactive substances (NPS) advertised for sale online is constantly increasing and it has become a phenomenon of global concern. Among NPS, Camfetamine has been rediscovered as recreational drug in 2011. Very little information is still available in the scientific literature on its nature and potential health risks. METHODS: Data in scientific literature were integrated with a multilingual qualitative assessment of a range of online resources over the period of 32 months (May 2011-January 2014). RESULTS: N-Methyl-3-phenyl-norbornan-2-amine (Camfetamine) may act as an indirect dopaminergic agonist in the central nervous system and may have mild-moderate opioid activity too. There are no current epidemiological data about recreational use of Camfetamine; our research shows that it is indeed used especially by individuals with a history of recreational polydrug misuse. It facilitates mental alertness, induces relaxation, and, unlike many other stimulants, seems not to be associated with severe physical effects. Valid causes for concern issued in our research may be Camfetamine intravenous or intramuscular administration as well as its use in conjunction with other psychoactive substances. CONCLUSIONS: It is here highlighted that more large-scale studies need to be carried out to confirm and better describe both the extent of Camfetamine misuse and possible psychotropic/adverse effects.

Pharmacological treatments in gambling disorder: a qualitative review.

Gambling disorder (GD) is a psychiatric condition associated with both social and family costs; DSM-5 currently includes GD among addictive disorders. Despite the high burden of this condition, to date there are no treatment guidelines approved by Food and Drug Administration (FDA). Purpose of this paper is to offer a qualitative overview about the different pharmacologic agents used for the treatment of GD. Our analysis, conducted on a final selection of 75 scientific papers, demonstrates that a variety of pharmaceutical classes have been utilised, with different results. Published data, although limited by brief duration of the studies and small number of enrolled subjects, shows mixed evidence for serotonergic antidepressants, opioid antagonists, and mood stabilizers. Other compounds, such as glutamatergic agents and psychostimulants, deserve further studies.

Bupropion as an add-on therapy in depressed bipolar disorder type I patients with comorbid cocaine dependence.

OBJECTIVES: The treatment of bipolar disorder type I (BD-I) with a comorbid cocaine dependence disorder (CDD) is a challenge in current psychiatric practice. Drugs with proven efficacy in manic/mixed episodes, such as atypical antipsychotics and mood stabilizers, sometimes do not prevent depressive relapses; on the other hand, the use of antidepressants during acute depressive episodes may increase the risk of a manic switch. The aim of the present study was to investigate the short-term efficacy of bupropion augmentation in acutely depressed BD-I patients with co-occurring CDD. METHODS: Twelve depressed BD-I patients, with a comorbid CDD, treated with valproate 1000 to 1500 mg/d and aripiprazole 10 mg/d, were randomly assigned to receive bupropion 150 mg/d as an open-label add-on therapy (n = 5) or to continue their previous treatment (n = 7). RESULTS: After 4 weeks of observation, patients receiving add-on therapy with bupropion have improved in terms of Hamilton Depression Rating Scale scores and Drug Abuse Screening Test scores, with respect to those of the comparison group, whereas no significant increase of Young Mania Rating Scale scores over time was observed. CONCLUSIONS: Our preliminary findings suggest that combining bupropion with mood stabilizers and atypical antipsychotics may be a good therapeutic option in short-term treatment of depressed BD-I patients with comorbid CDD.

Substance use in the club scene of Rome: a pilot study.

OBJECTIVE: Over the last few years, a wide number of unregulated substances have been marketed on the Web and in smart and head shops; they are usually advertised as legal alternatives to commonly known drugs and are defined as "smart drugs," "legal highs," and "novel psychoactive substances" (NPS). Aim of our work is to describe use habits and distribution of NPS in a population of young adults in Rome club scene. METHODS: A self-administered questionnaire was proposed to subjects over 18 years of age at the entrance of 5 nightclubs in Rome. Socioeconomic characteristics and substance use were investigated. RESULTS: Preliminary results give evidence that 78% of respondents have a lifetime history of NPS use. In addition, 56% of the sample has consumed illicit drugs in the past and 39% has used psychoactive substances in the 12 hours preceding the questionnaire administration. CONCLUSIONS: A significant proportion of subjects report use of novel psychoactive substances; traditional illicit drugs consumption, particularly cocaine, appears to be very high as well in the club scene. These data highlight a serious public health challenge, since pharmacological, toxicological, and psychopathological effects linked to interactions among all these substances may be unpredictable and sometimes fatal in vulnerable individuals.

Novel psychoactive substances in young adults with and without psychiatric comorbidities.

OBJECTIVE: Comorbidities between psychiatric diseases and consumption of traditional substances of abuse (alcohol, cannabis, opioids, and cocaine) are common. Nevertheless, there is no data regarding the use of novel psychoactive substances (NPS) in the psychiatric population. The purpose of this multicentre survey is to investigate the consumption of a wide variety of psychoactive substances in a young psychiatric sample and in a paired sample of healthy subjects. METHODS: A questionnaire has been administered, in different Italian cities, to 206 psychiatric patients aged 18 to 26 years and to a sample of 2615 healthy subjects matched for sex, gender, and living status. RESULTS: Alcohol consumption was more frequent in the healthy young population compared to age-matched subjects suffering from mental illness (79.5% versus 70.7%; P < 0.003). Conversely, cocaine and NPS use was significantly more common in the psychiatric population (cocaine 8.7% versus 4.6%; P = 0.002) (NPS 9.8% versus 3%; P < 0.001). CONCLUSIONS: The use of novel psychoactive substances in a young psychiatric population appears to be a frequent phenomenon, probably still underestimated. Therefore, careful and constant monitoring and accurate evaluations of possible clinical effects related to their use are necessary.