Infective endocarditis and antithrombotic therapy.

Incidence of infective endocarditis (IE) is progressively raising because of the increasing number of cardiovascular invasive procedures, support treatment and devices, awareness in the medical community and improved diagnostic modalities. IE pathophysiology is a unique model of immunothrombosis and the clinical course is often complicated by either thromboembolic or hemorrhagic events. Managing antithrombotic treatment is challenging and the level of supporting evidence scant. Aim of this review was to discuss and present the thromboembolic and bleeding complication associated with IE and review the available evidence on anti-thrombotic treatment in patients with IE with and without a previous indication to anti-thrombotic drugs.

Is There a Burnout Epidemic among Medical Students? Results from a Systematic Review.

Background and Objectives: Medical students represent the ideal target group for promoting mental health and mental wellbeing, being exposed to specific risk factors, such as the content of medical training, the exposure to sickness and death, and a stressful academic routine. Medical students report high levels of cynicism and emotional exhaustion, which represent two of the essential features of burnout syndrome. In this systematic review, studies assessing the levels of burnout among medical students through validated tools worldwide were analyzed. Materials and Methods: A systematic review has been performed in order to identify studies: (1) focusing on samples of medical students; (2) evaluating burnout syndrome using validated tools; (3) providing prevalence data on burnout; and (4) written in English. Results: Out of the 5547 papers initially obtained, 64 were finally included in the analysis. The sample sizes ranged from 51 to 2682 participants. Almost all studies had a cross-sectional design; the Maslach Burnout Inventory and its related versions were the most frequently used assessment tools. The prevalence of burnout, which was stratified based on gender and academic stage, ranged from 5.6 to 88%. Burnout was mostly predicted by thoughts of stopping medical education, negative life events, lack of support, dissatisfaction, and poor motivation. Conclusions: The prevalence of burnout syndrome in medical students is quite heterogeneous, reaching a peak of 88% in some countries. However, several predictors have been identified, including negative life events or poor motivation. These findings highlight the need to develop preventive interventions targeting the future generation of medical doctors, in order to improve their coping strategies and resilience styles.

Effect of very long-term storage and multiple freeze and thaw cycles on 11-dehydro-thromboxane-B2 and 8-iso-prostaglandin F2α, levels in human urine samples by validated enzyme immunoassays.

Biological samples are often frozen and stored for years and/or thawed multiple times, thus assessing their stability on long-term storage and repeated freeze-thaw cycles is crucial. The study aims were to assess:-the long-term stability of two major enzymatic and non-enzymatic metabolites of arachidonic acid, i.e. urinary 11-dehydro-thromboxane-(Tx) B2, 8-iso-prostaglandin (PG)F2α, and creatinine in frozen urine samples;-the effect of multiple freeze-thaw cycles. Seven-hundred and three urine samples measured in previously-published studies, stored at -40 °C, and measured for a second time for 11-dehydro-TxB2 (n = 677) and/or 8-iso-PGF2α (n = 114) and/or creatinine (n = 610) were stable over 10 years and the 2 measurements were highly correlated (all rho = 0.99, P < 0.0001). Urine samples underwent 10 sequential freeze-thaw cycles, with and without the antioxidant 4-hydroxy-2,2,6,6-tetramethylpiperidin-1-oxyl (10 mM); urinary 11-dehydro-TxB2 and creatinine were stable across all cycles (11-dehydro-TxB2: 100.4 ± 21%; creatinine: 101 ± 7% of baseline at cycle ten; n = 17), while 8-iso-PGF2α significantly increased by cycle 6 (151 ± 22% of baseline at cycle ten, n = 17, P < 0.05) together with hydrogen peroxide only in the absence of antioxidant. Arachidonic acid metabolites and creatinine appear stable in human urines stored at -40 °C over 10 years. Multiple freeze-thaw cycles increase urinary 8-iso-PGF2α in urine samples without antioxidants. These data are relevant for studies using urine samples stored over long-term and/or undergoing multiple freezing-thawing.

New pharmacological agents and novel cardiovascular pharmacotherapy strategies in 2023.

Although cardiovascular diseases are the leading cause of death worldwide, their pharmacotherapy remains suboptimal. Thus, there is a clear unmet need to develop more effective and safer pharmacological strategies. In this review, we summarize the most relevant advances in cardiovascular pharmacology in 2023, including the approval of first-in-class drugs that open new avenues for the treatment of atherosclerotic cardiovascular disease and heart failure. The new indications of drugs already marketed (repurposing) for the treatment of obstructive hypertrophic cardiomyopathy, hypercholesterolemia, type 2 diabetes, obesity and heart failure, the impact of polypharmacy on guideline-directed drug use is highlighted as well as results from negative clinical trials. Finally, we end with a summary of the most important phase 2 and 3 clinical trials assessing the efficacy and safety of cardiovascular drugs under development for the prevention and treatment of cardiovascular diseases.

Thromboxane biosynthesis and future events in diabetes: the ASCEND trial.

BACKGROUND AND AIMS: Thromboxane (TX) A2, released by activated platelets, plays an important role in atherothrombosis. Urinary 11-dehydro-TXB2 (U-TXM), a stable metabolite reflecting the whole-body TXA2 biosynthesis, is reduced by ∼70% by daily low-dose aspirin. The U-TXM represents a non-invasive biomarker of in vivo platelet activation and is enhanced in patients with diabetes. This study assessed whether U-TXM is associated with the risk of future serious vascular events or revascularizations (SVE-R), major bleeding, or cancer in patients with diabetes. METHODS: The U-TXM was measured pre-randomization to aspirin or placebo in 5948 people with type 1 or 2 diabetes and no cardiovascular disease, in the ASCEND trial. Associations between log U-TXM and SVE-R (n = 618), major bleed (n = 206), and cancer (n = 700) during 6.6 years of follow-up were investigated by Cox regression; comparisons of these associations with the effects of randomization to aspirin were made. RESULTS: Higher U-TXM was associated with older age, female sex, current smoking, type 2 diabetes, higher body size, urinary albumin/creatinine ratio of ≥3 mg/mmol, and higher estimated glomerular filtration rate. After adjustment for these, U-TXM was marginally statistically significantly associated with SVE-R and major bleed but not cancer [hazard ratios per 1 SD higher log U-TXM (95% confidence interval): 1.09 (1.00-1.18), 1.16 (1.01-1.34), and 1.06 (0.98-1.14)]. The hazard ratio was similar to that implied by the clinical effects of randomization to aspirin for SVE-R but not for major bleed. CONCLUSIONS: The U-TXM was log-linearly independently associated with SVE-R in diabetes. This is consistent with the involvement of platelet TXA2 in diabetic atherothrombosis.

Oral Anticoagulants Beyond Warfarin.

Direct oral anticoagulants (DOACs) have largely replaced vitamin K antagonists, mostly warfarin, for the main indications for oral anticoagulation, prevention and treatment of venous thromboembolism, and prevention of embolic stroke in atrial fibrillation. While DOACs offer practical, fixed-dose anticoagulation in many patients, specific restrictions or contraindications may apply. DOACs are not sufficiently effective in high-thrombotic risk conditions such as antiphospholipid syndrome and mechanical heart valves. Patients with cancer-associated thrombosis may benefit from DOACs, but the bleeding risk, particularly in those with gastrointestinal or urogenital tumors, must be carefully weighed. In patients with frailty, excess body weight, and/or moderate-to-severe chronic kidney disease, DOACs must be cautiously administered and may require laboratory monitoring. Reversal agents have been developed and approved for life-threatening bleeding. In addition, the clinical testing of potentially safer anticoagulants such as factor XI(a) inhibitors is important to further optimize anticoagulant therapy in an increasingly elderly and frail population worldwide.

New trends in personalized treatment of depression.

PURPOSE OF REVIEW: Major depressive disorder (MDD) is a common and burdensome severe mental disorder, which is expected to become the leading cause of disease burden worldwide. Most patients with MDD remain untreated/undertreated. For many decades "a trial and error" approach has been adopted for selecting the best treatment plan for each individual patient, but more recently a personalized treatment approach has been proposed, by taking into account several individual and clinical factors (e.g., clinical stage, comorbidity, duration of illness). Therefore, the aim of this study is to address the most relevant innovations in the personalized treatment plan for patients with MDD. RECENT FINDINGS: In recent years, several pharmacological and nonpharmacological innovations have been introduced in the treatment of patients with MDD. As regards pharmacological treatments, the newly developed drugs have an innovative mechanism of action, targeting the glutamatergic systems. These drugs are highly effective in improving depressive symptoms, with a good level of safety and tolerability. As regards nonpharmacological interventions, innovations include both new strategies targeting different domains (e.g., lifestyle interventions aiming to improve the physical symptoms of depression or virtual reality) and classical interventions provided through innovative mechanisms (e.g., web-based psychotherapies and use of digital approaches). Patients globally report a good level of acceptability of these interventions. SUMMARY: Depression is a heterogeneous, complex and multidimensional disorder, representing one of the leading causes of disability worldwide. The final aim of the management of patients is functional recovery, which can be achieved by using personalized, integrated and recovery-oriented interventions. Several innovative pharmacological and nonpharmacological treatments are now available; interventions should be selected on the basis of the patient's needs and preferences in order to tailor the treatment, according to a shared decision-making approach.

Promoting mental health and preventing mental health problems in child and adolescent refugees and asylum seekers: A systematic review on psychosocial interventions.

BACKGROUND: According to the United Nations Commissioner for Refugees (UNHCR), children and adolescents represent 41% of all forcibly displaced individuals. They have to deal with conflicts, violence, and the many difficulties of flight and resettlement during a critical stage of their emotional, social, cognitive, and physical development. They are more likely to experience mental health problems during migration. Despite the several known risk factors, it is frequently challenging for refugees and asylum seekers to get mental health care. In this paper we review available studies on interventions aimed at promoting mental health and at preventing common mental disorders in immigrant adolescents and children. METHODS: The relevant PubMed, Scopus, PsychINFO and Web of Science databases were searched for papers published until March 21, 2023, using ("immigrants" OR "migration" OR "asylum seekers" OR "refugees") AND ("promotion" OR "prevention") AND ("mental health" OR "mental disorders" OR "psych*") AND ("children" OR "adolescents" OR "young adults") as search string. Fourteen articles qualified for the detailed review. RESULTS AND CONCLUSIONS: The majority of available interventions, although highly heterogeneous in format and content, showed significant improvement in several psychopathological dimensions, including trauma-related symptoms, psychological stress, anxiety, depressive and cognitive symptoms. Available studies on interventions for the prevention of mental disorders and the promotion of mental health in refugees and asylum seekers children and adolescents indicate that provided interventions were associated with a global improvement for participants. Implementation strategies to improve their scalability are highly needed.

Biological correlates of treatment resistant depression: a review of peripheral biomarkers.

Introduction: Many patients fail to respond to multiple antidepressant interventions, being defined as "treatment-resistant depression" (TRD) patients. TRD is usually associated with increased severity and chronicity of symptoms, increased risk of comorbidity, and higher suicide rates, which make the clinical management challenging. Efforts to distinguish between TRD patients and those who will respond to treatment have been unfruitful so far. Several studies have tried to identify the biological, psychopathological, and psychosocial correlates of depression, with particular attention to the inflammatory system. In this paper we aim to review available studies assessing the full range of biomarkers in TRD patients in order to reshape TRD definition and improve its diagnosis, treatment, and prognosis. Methods: We searched the most relevant medical databases and included studies reporting original data on possible biomarkers of TRD. The keywords "treatment resistant depression" or "TRD" matched with "biomarker," "inflammation," "hormone," "cytokine" or "biological marker" were entered in PubMed, ISI Web of Knowledge and SCOPUS databases. Articles were included if they included a comparison with healthy controls (HC). Results: Of the 1878 papers identified, 35 were included in the present study. Higher plasma levels of IL-6 and TNF-α were detected in TRD patients compared to HC. While only a few studies on cortisol have been found, four papers showed elevated levels of C-reactive protein among these patients and four articles focused on immunological cells. Altered kynurenine metabolism in TRD patients was reported in two studies, while contrasting results were found with regard to BDNF. Conclusion: Only a few biological alterations correlate with TRD. TNF-α seems to be the most relevant biomarker to discriminate TRD patients from both HC and treatment-responsive MDD patients. Moreover, several discrepancies among studies have been found, due to methodological differences and the lack of a standardized diagnostic definition of TRD.

A Systematic Review on the Effectiveness of Antipsychotic Drugs on the Quality of Life of Patients with Schizophrenia.

Pharmacological antipsychotic drug interventions represent the cornerstone of the management of patients with schizophrenia and other psychotic spectrum disorders. The choice of the "best" treatment should be made on the basis of several clinical domains. However, despite available treatments, the quality of life reported by patients with schizophrenia taking antipsychotics is still very poor, and this outcome is rarely taken into account in trials assessing the efficacy and effectiveness of antipsychotic treatments. Therefore, we performed a systematic review in order to assess the impact of antipsychotic treatment on patients' quality of life. In particular, we aimed to identify any differences in the improvement in quality of life according to the (a) type of formulation of antipsychotic drugs (i.e., oral vs. depot vs. long-acting injectable); (b) type of the drug (first vs. second vs. third generation); and (c) patients' clinical characteristics. One hundred and eleven papers were included in the review. The main findings were as follows: (1) quality of life is usually considered a secondary outcome in trials on the efficacy and effectiveness of drugs; (2) second-generation antipsychotics have a more positive effect on quality of life; and (3) long-acting injectable antipsychotics are associated with a more stable improvement in quality of life and with a good safety and tolerability profile. Our systematic review confirms that quality of life represents a central element for selecting the appropriate treatment for people with schizophrenia. In particular, the availability of new treatments with a better tolerability profile, a proven effectiveness on patients' cognitive and social functioning, and with a more stable blood concentration might represent the appropriate strategy for improving the quality of life of people with schizophrenia.

Childhood maltreatment, alexithymia and eating disorder psychopathology: A mediation model.

BACKGROUND: The relationship between childhood maltreatment and eating disorder psychopathology has been under-investigated. OBJECTIVE: The purpose of this study was to investigate the role of alexithymia in mediating the relationship between childhood maltreatment experiences and eating disorder (ED) symptoms. PARTICIPANTS AND SETTING: One-hundred-forty-three women with anorexia nervosa, 110 women with bulimia nervosa and 108 healthy women filled in the Eating Disorder Inventory-2, the Childhood Trauma Questionnaire and the Toronto Alexithymia Scale-20 (TAS-20). METHODS: A mediator path model including childhood trauma types as predictors, the subscales of the TAS-20 as mediators and ED specific symptoms as dependent variables was conducted in individuals with EDs and in healthy women. RESULTS: In women with EDs emotional abuse was directly associated with body dissatisfaction and was associated to drive to thinness, bulimia and body dissatisfaction through the mediation of difficulties to identify emotions. In healthy women, physical neglect was directly associated to drive to thinness and bulimia, but no significant mediation effect through alexithymia emerged. CONCLUSION: Impaired emotion recognition mediates the association between childhood emotional abuse and ED symptoms. Individuals with early emotional abuse may experience ED symptoms to manage confused emotional perceptions. Improving emotional understanding and acceptance may be a treatment target in early maltreated individuals with EDs.

One-year efficacy of a lifestyle behavioural intervention on physical and mental health in people with severe mental disorders: results from a randomized controlled trial.

This multicentric randomized controlled trial (RCT), carried out in six Italian University mental health sites, aims to test the efficacy of a six-month psychosocial intervention (LYFESTYLE) on Body Mass Index (BMI), body weight, waist circumference, fasting glucose, triglycerides, cholesterol, Framingham and HOmeostasis Model Assessment of insulin resistance (HOMA-IR) indexes in patients with schizophrenia, bipolar disorder, and major depression. Moreover, the efficacy of the intervention has also been tested on several other physical and mental health domains. Patients were randomly allocated to receive the six-month experimental intervention (LIFESTYLE) or a behavioural control intervention. All enrolled patients were assessed at baseline and after one year. We recruited 401 patients (206 in the experimental and 195 in the control group) with a diagnosis of schizophrenia or other psychotic disorder (29.9%), bipolar disorder (43.3%), or major depression (26.9%). At one year, patients receiving the experimental intervention reported an improvement in body mass index, body weight, waist circumference, HOMA-IR index, anxiety and depressive symptoms and in quality of life. Our findings confirm the efficacy of the LIFESTYLE intervention in improving physical and mental health-related outcomes in patients with severe mental illnesses after one year.

The Efficacy of Psychoeducational Family Intervention for Major Depression: Study Protocol of a Randomized Controlled Trial.

This study aims to assess the efficacy of a psychoeducational family intervention (PFI) to reduce the severity of depressive symptoms and to improve psychosocial functioning and to increase social contacts in a sample of patients with major depressive disorder (MDD). The degree to which PFI will reduce patients' relapses, hospitalizations, and self-stigmatization and will improve their quality of life will also be assessed. Other secondary outcomes include the improvement of relatives' coping strategies, family burden, expressed emotions and quality of life. This non-profit, unfunded, national, multicentric randomized controlled trial with blinded outcome assessments will be carried out in 24 Italian university outpatient units. Families will be assessed at baseline and at 6, 12, and 24 months post-randomization. Our working hypothesis is that the PFIs will reduce the patients' severity of depressive symptoms, their relapses, and their hospitalizations, and that they will improve their psychosocial functioning and quality of life. We expect these results to be maintained after 12 and 24 months, albeit with a reduction in magnitude. The sample will consist of 384 patients randomized at a 1:1 ratio and stratified according to center, age, gender, and educational level.

Can Brain-Derived Neurotrophic Factor Be Considered a Biomarker for Bipolar Disorder? An Analysis of the Current Evidence.

Brain-derived neurotrophic factor (BDNF) plays a key role in brain development, contributing to neuronal survival and neuroplasticity. Previous works have found that BDNF is involved in several neurological or psychiatric diseases. In this review, we aimed to collect all available data on BDNF and bipolar disorder (BD) and assess if BDNF could be considered a biomarker for BD. We searched the most relevant medical databases and included studies reporting original data on BDNF circulating levels or Val66Met polymorphism. Only articles including a direct comparison with healthy controls (HC) and patients diagnosed with BD according to international classification systems were included. Of the 2430 identified articles, 29 were included in the present review. Results of the present review show a reduction in BDNF circulating levels during acute phases of BD compared to HC, which increase after effective therapy of the disorders. The Val66Met polymorphism was related to features usually associated with worse outcomes. High heterogeneity has been observed regarding sample size, clinical differences of included patients, and data analysis approaches, reducing comparisons among studies. Although more studies are needed, BDNF seems to be a promising biomarker for BD.

The effect of social media and infodemic on mental health during the COVID-19 pandemic: results from the COMET multicentric trial.

On January 30, 2020, the World Health Organization (WHO) declared the status of pandemic due to the COVID-19 infection. The initial phases of the pandemic were characterized by uncertainty and public fears. In order to cope with such unexpected conditions, people adopted different coping strategies, including search for information, accessing Internet, and using social media. The present study based on the COMET collaborative research network aims to: (1) assess use of Internet and of social media among the Italian general population; (2) explore differences in web usage between people with pre-existing mental disorders and the general population; (3) identify changes over time in social media usage along the phase 1 of the pandemic; (4) identify the clinical, socio-demographic and contextual predictors of excessive use of social media. A significant increase in time spent on Internet, with an average time of 4.8 ± 0.02 h per day, was found in the global sample of 20,720 participants. Compared with the general population, Internet use was significantly higher in people with pre-existing mental disorders (5.2 ± 0.1 h vs. 4.9 ± 0.02; p < 0.005). According to the multivariate logistic regression model, the risk of excessive use of social media and Internet was significantly higher in people with moderate levels of depressive symptoms (OR: 1.26, CI 95%: 0.99 to 1.59, p < 0.0.005); while protective factors were being students (OR: 0.72, CI 95%: 0.53 to 0.96, p < 0.0029) and living in central Italy (OR: 0.46, CI 95%: 0.23 to 0.90, p < 0.002). The evaluation of social media and Internet use by the general population represents a first step for developing specific protective and supportive interventions for the general population, including practical suggestions on how to safely use Internet and social media.

Defining heparin resistance: communication from the ISTH SSC Subcommittee of Perioperative and Critical Care Thrombosis and Hemostasis.

The term heparin resistance (HR) is used by clinicians without specific criteria. We performed a literature search and surveyed our SSC membership to better define the term when applied to medical and intensive care unit patients. The most common heparin dosing strategy reported in the literature (53%) and by survey respondents (80.4%) was the use of weight-based dosing. Heparin monitoring results were similar based on the proportion of publications and respondents that reported the use of anti-Xa and activated partial thromboplastin time. The most common literature definition of HR was >35 000 U/d, but no consensus was reported among survey respondents regarding weight-based and the total dose of heparin when determining resistance. Respondent consensus on treating HR included antithrombin supplementation, direct thrombin inhibitors, or administering more heparin as the strategies available for treating HR. A range of definitions for HR exist. Given the common use of heparin weight-based dosing, future publications employing the term HR should include weight-based definitions, monitoring assay, and target level used. Further work is needed to develop a consensus for defining HR.