Use of nebulized liposomal amphotericin B and posaconazole as antifungal prophylaxis in patients with severe SARS-CoV2 infection in intensive care unit.

PURPOSE: COVID-19 associated pulmonary aspergillosis (CAPA) is common and linked with high fatality rates. To assess the impact on the incidence and outcome of CAPA of an antifungal prophylaxis (AFP) we compared two cohorts of COVID-19 patients admitted to intensive care units (ICU) in Brescia, Italy, from January to August 2021. METHODS: The study cohort included all mechanically ventilated patients observed between April 2021 and August 2021 with SARS-CoV-2-pneumonia, who received AFP with oral posaconazole (200 mg every 6 h) and nebulized liposomal amphotericin B (50 mg every 2 weeks) from ICU admission to 7 days after discharge or, if applicable, until tracheostomy removal. The control cohort included COVID-19 patients admitted to the same ICU between January and March 2021 who did not receive any AFP. Subjects with CAPA at ICU admission were excluded. RESULTS: We included 270 patients, of whom 64 (23.7%) received AFP. In patients in the study group, CAPA-related mortality was significantly reduced (29% vs. 48% p = 0.04), as well as the incidence of CAPA (3.1% vs 12.1%, p = 0.03). Patients who developed CAPA were older (mean of 70-y-old vs 63-y-old, p < 0.001). One subject discontinued posaconazole due to an adverse reaction. Among the 46 patients who received it, only one patient reached an effective plasma concentration of posaconazole. CONCLUSION: AFP was associated with reduced incidence and mortality from CAPA and was well tolerated in patients with severe COVID-19. Posaconazole concentrations below the efficacy threshold in almost all patients may be attributable to drug interactions and prompt further studies to define its clinical significance.

Novel Pharmacotherapies for Recurrent Pericarditis: Current Options in 2020.

Recent advances have shown impressive results by anti-interleukin 1 (IL-1) agents in refractory idiopathic recurrent pericarditis. PURPOSE OF REVIEW: We critically discuss the current state of the art of therapy of relapsing pericarditis, with a focus on new pharmacological approaches and on specific clinical settings such as pregnancy, pediatric patients, and secondary forms of relapsing pericarditis. RECENT FINDINGS: Antagonism of the IL-1 is highly effective in idiopathic recurrent pericarditis with autoinflammatory features. Currently, available anti-IL-1 agents are anakinra and canakinumab. Rilonacept is another IL-1 antagonist, currently studied in the phase-3 clinical trial RHAPSODY. Available data suggest similar efficacy and safety profiles of these three agents, although only anakinra has been tested in randomized clinical trials. These agents have slightly different pharmacological properties, being canakinumab a specific IL-1ß antagonist while anakinra and rilonacept are unselective IL-1α and IL-1ß blockers. To date, there is no evidence that specificity against IL-1ß affects safety and efficacy in patients with relapsing pericarditis, although it has been proposed that unspecific blockage might be useful in severe disease. Anakinra is the first anti-IL-1 agent with well-documented efficacy and safety in adult and pediatric patients with idiopathic relapsing pericarditis. Other anti-IL-1 agents are currently under study. Future research should clarify the optimal duration of therapy and tapering schedule of treatment with these agents. Moreover, biomarkers would be required to understand which patients will benefit from early administration of IL-1 blockers due to refractoriness to conventional therapy and which others will suffer from recurrences during the tapering of these agents. Lastly, future studies should focus on the subjects with the autoimmune or the pauci-inflammatory phenotype of idiopathic refractory pericarditis.

First-episode psychosis and migration in Italy (PEP-Ita migration): a study in the Italian mental health services.

BACKGROUND: It has been frequently reported a higher incidence of psychotic disorders in immigrants than in native populations. There is, however, a lack of knowledge about risk factors which may explain this phenomenon. A better understanding of the causes of psychosis among first-generation migrants is highly needed, particularly in Italy, a country with a recent massive migration. METHODS/DESIGN: The "Italian study on first-episode psychosis and migration (PEP-Ita)" is a prospective observational study over a two-year period (1 January 2012-31 December 2013) which will be carried out in 11 Italian mental health centres. All participating centres will collect data about all new cases of migrants with first-episode psychosis. The general purpose ("core") of the PEP-Ita study is to explore the socio-demographic and clinical characteristics, and the pathways to care of a population of first-episode psychosis migrants in Italy. Secondary aims of the study will be: 1) to understand risk and protective factors for the development of psychotic disorders in migrants; 2) to evaluate the correlations between psychopathology of psychotic disorders in migrants and socio-demographic characteristics, migration history, life experiences; 3) to evaluate the clinical and social outcomes of first-episode psychoses in migrants. DISCUSSION: The results of the PEP-Ita study will allow a better understanding of risk factors for psychosis in first-generation migrants in Italy. Moreover, our results will contribute to the development of prevention programmes for psychosis and to the improvement of early intervention treatments for the migrant population in Italy.

Visceral Leishmaniasis in Immunocompetent Hosts in Brescia: A Case Series and Analysis of Cytokine Cascade.

Visceral leishmaniasis (VL) is a parasitic zoonosis caused by Leishmania spp. that usually manifests itself in immunocompromised subjects. It is a rare and neglected disease, and it is not endemic in the province of Brescia (Italy). Three cases of human VL occurred in Brescia from October to December 2021 in immunocompetent patients. We evaluated the patients looking for signs of underlying immunodeficiencies and conducted further epidemiological evaluations in the province of Brescia without success. An analysis of the sera levels of the main cytokines involved in the immune response to VL was performed. All patients presented a significant augmentation of CXCL-10, CCL-4, and IL-6. The patients tested during the acute phase showed an elevation of IL-1α, IL-5, IL-10, and IL-12, while in the recovery phase, higher levels of TNF-α and IL-7 were detected. Altogether, a predominant activation of the T-helper-2 pathway emerged during the acute phase of the parasite infection, while the cytokines associated with the T-helper-1 pathway were less represented. This imbalanced immune response to the parasite infection might play a crucial role in the development of VL in immunocompetent patients.

Role of Cefiderocol in Multidrug-Resistant Gram-Negative Central Nervous System Infections: Real Life Experience and State-of-the-Art.

Cefiderocol is a new molecule effective against multidrug-resistant (MDR) Gram-negative pathogens. Currently, there is limited evidence regarding the use of cefiderocol in central nervous system (CNS) infections. Data on the cerebrospinal fluid penetration rate of cefiderocol are limited and heterogeneous, and there is no consensus on the dosing scheme of cefiderocol to penetrate the blood-brain barrier. We present a case series and a literature review of CNS infections caused by MDR pathogens that were treated with cefiderocol: some of these patients were treated with different dose schemes of cefiderocol and underwent therapeutic drug monitoring both on plasma and cerebrospinal fluid (CSF). The CSF penetration rates and the clinical outcomes were evaluated.

Dalbavancin in Bone and Joint Infections: A Systematic Review.

BACKGROUND: Approved for acute bacterial skin and skin structure infections, dalbavancin (DBV) has gradually acquired over the years a role as an off-label treatment for several infections caused by Gram-positive bacteria even in other anatomical sites. Osteoarticular (OA) infections are one of the most difficult-to-treat infections and, since the absence of recommendations, clinicians use different and heterogenic DBV dosing schedule regimens for the off-label treatment of osteomyelitis, spondylodiscitis, and septic arthritis. Our aim is to systematically review the current literature to describe DBV administration schedules and their outcome in OA infections. METHODS: According to the 2020 updated PRISMA guidelines, all peer-reviewed articles regarding the use of DBV in OA infections were included. We conducted a literature search on PubMed and Cochrane Controlled Trials. RESULTS: A total of 23 studies and 450 patients were included, prevalently male (144/195, 73.8%) and diabetic (53/163, 32.5%). Overall, 280 (280/388, 72.2%) osteomyelitis, 79 (79/388, 20.4%) spondylodiscitis, and 29 (29/388, 7.5%) septic arthritis were considered. Staphylococcus aureus (164/243, 67.5%) was the most common pathogen isolated. A previous treatment failure (45/96, 46.9%) was the main reason for a switch to a long-acting antibiotic. Most patients were successfully cured with DBV (318/401, 79.3%). A source control was performed in most patients with a favourable outcome (80.4%), while MRSA was prevalently isolated in people with an unfavourable outcome (57%). While a higher percentage of success was found in people who received three doses of DBV 1 week apart (92.3%), a higher rate of treatment failure was recorded in cases of when the DBV cycle was composed of less than two or more than four doses (27.8%). CONCLUSIONS: DBV has shown to be effective as a treatment for OA infections. The most favourable outcome was found in patients receiving three doses of DBV and with an adequate surgical management prior to antibiotic treatment. Although a rigorous administration schedule does not exist, DBV is a viable treatment option in the management of OA infections.

Trichosporon asahii Infective Endocarditis of Prosthetic Valve: A Case Report and Literature Review.

Trichosporon spp. endocarditis is a severe and hard-to-treat infection. Immunosuppressed subjects and carriers of prosthetic valves or intracardiac devices are at risk. This article presents the case of an immunocompetent 74-year-old man affected by endocarditis of the prosthetic aortic valve. After Bentall surgery, cultures of the removed valve demonstrated Trichosporon ashaii as the etiological agent. The patient was treated with amphotericin B at first and subsequently with fluconazole. Given the fragility of the patient and the aggressiveness of the pathogen, life-long prophylactic therapy with fluconazole was prescribed. After 5 years follow-up, no drug-related toxicities were reported and the patient never showed any signs of recurrence. The review of the literature illustrates that Trichosporon spp. endocarditis may present even many years after heart surgery, and it is often associated with massive valve vegetations, severe embolic complications, and unfavorable outcome. Due to the absence of international guidelines, there is no unanimous therapeutic approach, but amphotericin B and azoles are usually prescribed. Additionally, a prompt surgical intervention seems to be of paramount importance. When dealing with a life-threatening disease, such as mycotic endocarditis of prosthetic valves, it is essential to consider and treat even rare etiological agents such as Trichosporon spp.

The family in Italy: cultural changes and implications for treatment.

In Italy family is characterized by strong ties and is based on mutual aid of all its members. In the last 20 years, the structure of families has been significantly influenced by demographic, economic and professional changes, determining a transition from a patriarchal to a nuclear family model, with a higher number of single-parent families, single-person households, childless couples, same-sex couples. However, this transition has been slower than that occurring in other countries, probably as an ongoing impact of prevalent Catholic ideology. Major demographic changes in Italian families include, 1) a decrease in the number of marriages, delays in getting married and an high number of civil ceremonies, 2) a reduced birth rate; Italy is becoming one of the European countries with lowest growth rate, and with an increasing number of births out of wedlock, 3) an increased marital instability, with a constantly growing number of legal separations. Like many countries, relatives in Italy are highly involved in the care of patients with physical and mental disorders. There are a number of psychosocial interventions used in Italy including the 'Milan Systemic Approach' and family psycho-educational interventions. However, there are difficulties in implementing these interventions which are highlighted in this paper. We recommend research strategies to identify the best options to involve families in the care of mentally ill patients and to adequately support them.

Gram-Negative Endogenous Endophthalmitis: A Systematic Review.

Background: Gram-negative bacteria are causative agents of endogenous endophthalmitis (EBE). We aim to systematically review the current literature to assess the aetiologies, risk factors, and early ocular lesions in cases of Gram-negative EBE. Methods: All peer-reviewed articles between January 2002 and August 2022 regarding Gram-negative EBE were included. We conducted a literature search on PubMed and Cochrane Controlled Trials. Results: A total of 115 studies and 591 patients were included, prevalently Asian (98; 81.7%) and male (302; 62.9%). The most common comorbidity was diabetes (231; 55%). The main aetiologies were Klebsiella pneumoniae (510; 66.1%), Pseudomonas aeruginosa (111; 14.4%), and Escherichia coli (60; 7.8%). Liver abscesses (266; 54.5%) were the predominant source of infection. The most frequent ocular lesions were vitreal opacity (134; 49.6%) and hypopyon (95; 35.2%). Ceftriaxone (76; 30.9%), fluoroquinolones (14; 14.4%), and ceftazidime (213; 78.0%) were the most widely used as systemic, topical, and intravitreal anti-Gram-negative agents, respectively. The most reported surgical approaches were vitrectomy (130; 24.1%) and evisceration/exenteration (60; 11.1%). Frequently, visual acuity at discharge was no light perception (301; 55.2%). Conclusions: Gram-negative EBEs are associated with poor outcomes. Our systematic review is mainly based on case reports and case series with significant heterogeneity. The main strength is the large sample spanning over 20 years. Our findings underscore the importance of considering ocular involvement in Gram-negative infections.

Convalescent Plasma for Hospitalized COVID-19 Patients: A Single-Center Experience.

In Winter 2020, Italy, and in particular the Lombardy region, was the first country in the Western hemisphere to be hit by the COVID-19 pandemic. Plasma from individuals recovered from COVID-19 (COVID-19 convalescent plasma, CCP) was the first therapeutic tool adopted to counteract the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). In this retrospective cohort study, we report the experience of the city hospital of Mantua, Lombardy region, on the compassionate use of CCP in patients hospitalized for severe COVID-19. Between April 2020 and April 2021, 405 consecutive COVID-19 patients received 657 CCP units with a median anti-SARS-CoV-2 neutralizing antibody (nAb) titer of 160 (interquartile range (IQR), 80−320). Their median age was 68 years (IQR, 56−78 years), and 62% were males. At enrollment, 55% of patients had an increased body mass index (BMI), and 25.6% had at least three comorbidities. The 28-day crude mortality rate was 12.6% (51/405). Young age (<68 years), mild disease (admission to low-intensity departments) and early treatment (<7 days from symptoms onset) with high nAb titer (≥320) CCP were found as independently associated with a favorable response to CCP treatment. No safety concerns were recorded, with a rate of CCP-related adverse reactions (all of mild intensity) of 1.3%. In our real-life experience, the first in the western world, early administration of high-titer CCP was a safe and effective treatment for hospitalized COVID-19 patients.

Eating disorders on the web: risks and resources.

Our work is aimed at exploring the recent literature data on web sites, forums, and blogs, which promote eating disorders as normal life styles and their implication in the changes of the psychopatology of such disorders. We also want to understand whether new technologies have an impact in the course of the disorders or, on the other hand, whether they can also represent an instrument for searching help or information about them. The search strategy included a search of PsycINFO, Medline, and Ovid databases to identify research reports about pro-ana sites and their implication on the course of anorexia using the following key words: pro-ana, thinspiration, anorexia-web, online help eating disorders, anorexia nation.

Treated Incidence of Psychotic Disorders in the Multinational EU-GEI Study.

Importance: Psychotic disorders contribute significantly to the global disease burden, yet the latest international incidence study of psychotic disorders was conducted in the 1980s. Objectives: To estimate the incidence of psychotic disorders using comparable methods across 17 catchment areas in 6 countries and to examine the variance between catchment areas by putative environmental risk factors. Design, Setting, and Participants: An international multisite incidence study (the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions) was conducted from May 1, 2010, to April 1, 2015, among 2774 individuals from England (2 catchment areas), France (3 catchment areas), Italy (3 catchment areas), the Netherlands (2 catchment areas), Spain (6 catchment areas), and Brazil (1 catchment area) with a first episode of nonorganic psychotic disorders (International Statistical Classification of Diseases and Related Health Problems, Tenth Revision [ICD-10] codes F20-F33) confirmed by the Operational Criteria Checklist. Denominator populations were estimated using official national statistics. Exposures: Age, sex, and racial/ethnic minority status were treated as a priori confounders. Latitude, population density, percentage unemployment, owner-occupied housing, and single-person households were treated as catchment area-level exposures. Main Outcomes and Measures: Incidence of nonorganic psychotic disorders (ICD-10 codes F20-F33), nonaffective psychoses (ICD-10 codes F20-F29), and affective psychoses (ICD-10 codes F30-F33) confirmed by the Operational Criteria Checklist. Results: A total of 2774 patients (1196 women and 1578 men; median age, 30.5 years [interquartile range, 23.0-41.0 years]) with incident cases of psychotic disorders were identified during 12.9 million person-years at risk (crude incidence, 21.4 per 100 000 person-years; 95% CI, 19.4-23.4 per 100 000 person-years). A total of 2183 patients (78.7%) had nonaffective psychotic disorders. After direct standardization for age, sex, and racial/ethnic minority status, an 8-fold variation was seen in the incidence of all psychotic disorders, from 6.0 (95% CI, 3.5-8.6) per 100 000 person-years in Santiago, Spain, to 46.1 (95% CI, 37.3-55.0) per 100 000 person-years in Paris, France. Rates were elevated in racial/ethnic minority groups (incidence rate ratio, 1.6; 95% CI, 1.5-1.7), were highest for men 18 to 24 years of age, and were lower in catchment areas with more owner-occupied homes (incidence rate ratio, 0.8; 95% CI, 0.7-0.8). Similar patterns were observed for nonaffective psychoses; a lower incidence of affective psychoses was associated with higher area-level unemployment (incidence rate ratio, 0.3; 95% CI, 0.2-0.5). Conclusions and Relevance: This study confirmed marked heterogeneity in risk for psychotic disorders by person and place, including higher rates in younger men, racial/ethnic minorities, and areas characterized by a lower percentage of owner-occupied houses.

Pathways to mental health care in Italy: results from a multicenter study.

BACKGROUND AND AIMS: In Italy, the reform of the mental health system in 1978 should have drastically changed the provision of care and pathways of patients seeking to obtain it. The aim of this article is to examine the current pathways to psychiatric care in Italy. METHODS: We used a method developed in the World Health Organization international collaborative studies to investigate pathways to care in 15 Italian mental health centers. We recruited 420 patients with a psychiatric illness and explored the care pathways they took to reach to psychiatric services and the delays from the onset of illness to reaching psychiatric care. RESULTS: The majority of patients (33.8%) had direct access to mental health care, whereas the others arrived to a specialist in psychiatry through general hospitals (20.3%), general practitioners (33.0%) or private practitioners (9.8%). The main diagnosis for referral was neurotic disorder (36.6%), followed by affective disorder (35.4%) and psychotic disorder (11.5%). The delay from onset of illness to psychiatric care was greater for patients with psychotic disorders than for those with affective and neurotic disorders. The most frequently prescribed treatments were pharmacotherapy (56%), psychological support (8%), and psychotherapy (7.0%); 15% of the patients received no treatment. CONCLUSIONS: Our multicenter study shows that although general practitioners and hospital doctors are still the main referral point for mental health care, a greater proportion of patients are first seen in private settings or directly reach mental health centers, compared to previous surveys conducted in Italy. However, a stronger collaboration of psychiatrists with general practitioners and psychologists is still needed.

Prevalence of bullying victimisation amongst first-episode psychosis patients and unaffected controls.

BACKGROUND: Despite increasing evidence suggesting that childhood maltreatment is significantly associated with psychosis, the specific role of bullying in the onset of psychotic disorders is still unclear. This study aimed to examine whether bullying was more prevalent amongst individuals presenting to services for the first time with a psychotic disorder than in unaffected community controls. METHODS: Data on exposure to bullying, psychotic symptoms, cannabis use and history of conduct disorder were collected cross-sectionally from 222 first-presentation psychosis cases and 215 geographically-matched controls. Bullying victimisation was assessed retrospectively as part of the Brief Life Events schedule. Logistic regression was used to examine associations between exposure to bullying and case-control status, while controlling for potential confounders. RESULTS: Psychosis cases were approximately twice as likely to report bullying victimisation when compared to controls. No significant interactions between bullying and either gender or cannabis use were found. Controls reporting being a victim of bullying were approximately twice as likely to also report at least one psychosis-like symptom. CONCLUSIONS: Our results extend previous research by suggesting that bullying victimisation may contribute to vulnerability to develop a psychotic disorder in some individuals.

[Urban insecurity and fear of crime in people suffering from mental disorders: a study in 24 Mental Health Centers in Italy]. / Insicurezza percepita e paura del crimine in persone affette da disturbi mentali: uno studio in 24 Centri di Salute Mentale.

AIMS: To assess in a sample of people with mental disorders: 1) fear of crime and perceived insecurity; 2) the association between fear of crime and insecurity; 3) the incidence of crimes. METHODS: Twenty-four Italian mental health centres have been invited to participate in the study from the network of the Early Career Psychiatrists' Committee of the Italian Psychiatric Association. In each participating centre, the first 20 patients consecutively accessing the mental health centre between February and April 2011 have been recruited. All patients have been assessed using validated assessment tools. RESULTS: The final sample consists of 426 patients. They are mostly female (70.1%), with a mean age of 45 years (± 13.5), and with a good level of education. Fifty-two percent of patients have a diagnosis of mood disorders, and 37.8% on anxiety spectrum disorders. About half of the sample declares that the most prominent feeling toward life is uncertainty. Almost all patients report to have at least one big fear, with the most frequently report being: 1) loss or death of a loved one (41.2%); 2) financial constraint (28.4%); 3) physical or mental health problems (26.5%). DISCUSSION AND CONCLUSIONS: Our results show the presence of a common sense of uncertainty among patients, probably as a result of the historical moment we are facing. It is reasonable that this attitude toward life can have a detrimental impact on patients' psychological and physical wellbeing, contributing to high levels of distress. Further studies are needed in order to clarify the possible relationship between fears, uncertainty and mental disorders.

Do child abuse and maltreatment increase risk of schizophrenia?

INTRODUCTION: Although childhood abuse is a recognised risk factor for depression, post-traumatic stress disorder, and substance misuse, its role in the aetiology of psychotic disorder remained controversial. This is in part because the putative effect of childhood trauma on psychosis has been mostly evaluated by small, cross sectional, uncontrolled studies that raised methodological issues. METHODS: Papers concerning the association between childhood trauma and psychotic disorders (to November, 2011) were identified using a comprehensive search of PubMed, Psychinfo, and Scopus and analysing reference list of relevant papers. A narrative synthesis was used to summarise results. RESULTS: An association between childhood abuse and psychotic symptoms was consistently reported by large cross sectional surveys with an effect ranging from 1.7 to 15. However, we cannot conclude that the relationship is causal as lack of longitudinal studies prevent us from fully excluding alternative explanations such as reverse causality. Gender, cannabis use, and depressive and post-traumatic stress disorder symptoms appear to moderate the effect of childhood trauma on psychotic disorders. However, specificity of childhood abuse in psychotic disorders and, particularly, in schizophrenia has not been demonstrated. CONCLUSION: Although the association between childhood abuse and psychosis has been replicated, the etiological role of such early adversity has yet to be fully clarified. So far none of the studies reported support the hypothesis that childhood abuse is either sufficient or necessary to develop a psychotic disorder. It seems likely that any effect of childhood abuse on schizophrenia needs to be understood in terms of genetic susceptibility and interaction with other environmental risk factors.