Anxiety disorders are one of the most common mental illnesses, and a consistent increase was observed after the COVID-19 pandemic. Mindfulness refers to a process that leads to a mental state characterized by nonjudgmental awareness of the present experience. Mindfulness can be considered both a skill and a practice. The stronger is the ability to adopt a mindful state, the less suffering one will experience. While Mindfulness-based Psychotherapies have shown efficacy in their treatment, they have not yet been thoroughly studied in Italian public mental health services. In Detached Mindfulness, negative thoughts are acknowledged and avoided by turning them into actions using a standardized, time-limited, metacognitive intervention.

The purpose of this study is to examine the efficacy and cost-effectiveness of Detachment Mindfulness for twelve patients with Generalized Anxiety Disorder (GAD) not being treated pharmacologically.

We enrolled 12 patients diagnosed with GAD according to DSM-V in an 8-session program of Detached Mindfulness Psychotherapy (once a week). The Generalized Anxiety Disorder - 7 Scale (GAD-7) and the Kellner Symptom Questionnaire (SQ) were used to assess anxiety symptoms at baseline (T0), after 4 sessions (T1), and at the end of treatment (T2). The Client Satisfaction Questionnaire (CSQ-8) was used to assess treatment satisfaction.

The GAD-7 score showed consistent reductions in generalized anxiety symptoms after Detached Mindfulness treatment (mean decrease of -42% at the end of the program). As measured by SQ, patients also reported improvement in physical well-being, relaxation, and somatic symptoms significantly respect to baseline. As for treatment satisfaction, ten out of twelve patients rated their treatment as satisfactory. As reported by patients, mindfulness can become a powerful and effective means to relate to one’s own internal experiences such as anxiety or fear, learning to recognize them, staying with them and avoiding their consequences.

These results showed that detached mindfulness was an effective and cost-effective intervention for GAD, given the short amount of time it requires and the ease with which it can be implemented. For its extensive use in the public mental health system to be further supported, studies on larger populations are needed.

None Declared

Cholestasis characterised by conjugated hyperbilirubinemia is a marker of hepatobiliary dysfunction following neonatal cardiac surgery. We aimed to characterise the incidence of conjugated hyperbilirubinemia following neonatal heart surgery and examine the effect of conjugated hyperbilirubinemia on post-operative morbidity and mortality.

This was a retrospective study of all neonates who underwent surgery for congenital heart disease (CHD) at our institution between 1/1/2010 and 12/31/2020. Patient- and surgery-specific data were abstracted from local registry data and review of the medical record. Conjugated hyperbilirubinemia was defined as perioperative maximum conjugated bilirubin level > 1 mg/dL. The primary outcome was in-hospital mortality. Survival analysis was conducted using the Kaplan–Meier survival function.

Conjugated hyperbilirubinemia occurred in 8.5% of patients during the study period. Neonates with conjugated hyperbilirubinemia were more likely to be of younger gestational age, lower birth weight, and non-Caucasian race (all p < 0.001). Patients with conjugated hyperbilirubinemia were more likely to have chromosomal and non-cardiac anomalies and require ECMO pre-operatively. In-hospital mortality among patients with conjugated hyperbilirubinemia was increased compared to those without (odds ratio 5.4). Post-operative complications including mechanical circulatory support, reoperation, prolonged ventilator dependence, and multi-system organ failure were more common with conjugated hyperbilirubinemia (all p < 0.04). Patients with higher levels of conjugated bilirubin had worst intermediate-term survival, with patients in the highest conjugated bilirubin group (>10 mg/dL) having a 1-year survival of only 6%.

Conjugated hyperbilirubinemia is associated with post-operative complications and worse survival following neonatal heart surgery. Cholestasis is more common in patients with chromosomal abnormalities and non-cardiac anomalies, but the underlying mechanisms have not been delineated.

Treatment Resistant Depression (TRD) is a complex, heterogeneous and multifactorial clinical condition that affects patients’ quality of life, their psychosocial functioning as well as suicidal risk. Intranasal esketamine is a new add-on treatment specifically approved for TRD.

The aim of the study was to evaluate the efficacy and safety of intranasal esketamine treatment combined with intensive Cognitive Behavioral psychotherapy (CBT), together with treatment satisfaction, in two complex clinical cases of TRD with high suicidal risk in a 12 months follow-up.

Two male patients, 67 and 63 years old, with TRD, defined by at least two therapeutic failures with SSRI/SNRI and positive screening for high suicidal risk at the Columbia Suicide Severity Rating Scale, were selected for treatment with intranasal esketamine + CBT as an add-on to SSRI/SNRI antidepressant therapy. Psychopathological assessment were made by means of Hamilton Depression Rating Scale (HAM-D), Hamilton Anxiety Rating Scale (HAM-A), Columbia Suicide Severity Rating Scale (C-SSRS), Clinical Global Impression (CGI), Short Form Health Questionnaire (SF-36 items) at T0, every 7 days for the first 3 months, then every month. Treatment satisfaction was evaluated by means of the Client Satisfaction Questionnaire (CSQ-8), administered by trained nursing staff at 1, 3, 6 and 12 months. CBT specifically focused on depression was administered by a certified psychotherapist, weekly for the first 4 months, fortnightly for the next 3 months, monthly for the remaining 3 months.

After 2 administrations of esketamine the total HAM-D score was reduced by an average of 10 units and the suicidal risk was progressively reduced to zero according to C-SSRS. After 12 months one of the two patients reached and actually maintains clinical remission; the other one maintains a condition of mild depression; both without suicidal ideation and with a significant increase in perceived quality of life. Treatment was well tolerated, with mild and temporary adverse effects, self-limited to the administration sessions. CBT has contributed to increasing insight, cognitive resources, social interaction and self-esteem, and has made it possible to structure and carry on new life projects. The variation of the mean scores for CSQ-8 shows that esketamine + CBT treatment was considered as very satisfactory throughout the observation period.

Intranasal esketamine associated with intensive CBT sessions showed to be effective, safe and satisfactory in the real world clinical management of two complex cases of TRD with high suicidal risk, improving quality of life, social functioning and eliminating suicidal ideation within 12 months follow-up. Satisfaction with the treatment contributed to strengthening adherence and improving the operator-patient therapeutic relationship.

None Declared

Although clozapine is considered the most effective drug for Treatment Resistant Schizophrenia (TRS), only 40% of patients treated will meet clinical response. Literature reviews and meta-analytic data offer no definite conclusions about the most effective clozapine augmentation strategies. Nevertheless, it has been suggested that the lack of evidence should not discourage clinicians from trying out new strategies in individual patients. Brexpiprazole is a novel 5-HT and DA modulator antipsychotic that exhibits partial agonism to D2/D3 and 5HT1A receptors, antagonism to 5HT2A and α-1B/2C receptors and represents a promising new drug in the pharmacotherapy of schizophrenia for both acute and maintenance treatment. In current literature there is no evidence of experiences in brexpiprazole augmentation for clozapine resistant patients.

This case report describes a successful clinical experience of brexpiprazole augmentation in a complicated case of clozapine resistant paranoid schizophrenia with consistent negative symptoms, the clinical evolution and metabolic improvement consequent to this therapy combination.

In a 27 male TRS patient, sequentially treated with adequate doses of risperidone, cariprazine, aripiprazole and olanzapine monotherapy, prescribed for adequate time, clozapine treatment was started, with a gradual titration from 25 to 300 mg/day, without significant clinical response on both positive and negative symptoms. Successively was introduced fluoxetine, from 10 to 30 mg/day, with no relevant clinical improvement. After 2 months of pharmacological stabilization with clozapine and fluoxetine described dosages, brexpiprazole was introduced starting from 1 mg/day and rapidly increasing till 4 mg/day.

After 6 weeks of treatment, PANSS positive and negative subscales showed a significant decrease, respectively from 28 to 17 and from 42 to 20, while general psychopathology subscale decreased from 66 to 34. Negative sub-items with major improvement were those regarding blunted affect, emotional withdrawal, poor rapport, and passive/apathetic social withdrawal. Brexpiprazole augmentation also allowed to slowly decrease (in 6 months) clozapine dose till actual 150 mg/day, with a significant improvement in general tolerability and a slow decline in metabolic parameters (BMI from 36.5 to 30.3; fasting glucose from 112 to 92 mg/dL; total cholesterol from 248 to 182 mg/dL; total triglycerides from 392 to 198 mg/dL).

In this case report brexpiprazole augmentation in a clozapine resistant young schizophrenic patient was an effective strategy with significant symptoms improvement, in particular in PANSS general psychopathology and PANSS negative subscales. The consequent clozapine dose reduction contribute to the slow decrease in metabolic parameters considered.

None Declared

Psychoses represent serious psychiatric disorders in which an individual perceptions, thoughts, mood and behavior are significantly altered. Each person who develops a psychosis lives a unique set of symptoms and experiences that may widely vary depending on life circumstances. Although cognitive behavioral psychotherapy (CBT) for psychosis is recommended by main international guidelines, its effectiveness in real-world is still a subject of controversy.

The aim of this study was to evaluate, in an Italian outpatient clinical setting, eventual improvements induced by a 6 months intensive CBT specific programme focused on metacognition and emotional regulation and its consequences on psychosocial functioning and subjective well-being in pharmacologically stabilized psychotic patients.

Eight patients with schizophrenia spectrum disorders (DSM-V), clinically and pharmacologically stabilized, were included in a 6-month program of weekly CBT sessions with focus on metacognition, emotional dysregulation, social functioning and subjective well-being. Patients were assessed with the Metacognitions Questionnaire-30, Difficulties in Emotion Regulation Scale, Heinrichs Quality of Life Scale, The Psychological General Well-Being Index, Brief Psychiatric Rating Scale, Hamilton Depression Rating Scale at baseline and at 3 and 6 months, to verify any improvement on these specific domains and, possibly, on general psychopathology.

In this study CBT showed to be effective on all domains evaluated, most notably for younger patients with a short history of disease (<5 years). Metacognitive capacity was the dimension with most evident improvements, followed by the ability to modulate emotions and the consequent improvement in psychosocial functioning and perceived subjective well-being. During the 6 months follow-up none of the enrolled patients experienced symptoms exacerbation or psychotic relapses.

In conclusion, the 6-month CBT treatment showed to be effective for stabilized psychotic patients, improving metacognitive functions, emotional regulation, psychosocial functioning, and subjective well-being. In addition, insight, adherence and the therapeutic alliance improved. The absence of psychotic relapses is not attributable with certainty to the effect of CBT since, for this purpose, longer duration studies on larger case series and with RCT methods are required. However, it is plausible that the improvement obtained in disease awareness and adherence may be a facilitating factor in relapse reduction.

None Declared

SARS-Co-V2 neuroinvasive ability might be the basis for the onset of delirium and neuropsychiatric outcomes.

We hypothesized that some infected patients with preexisting cognitive dysfunction may present delirium as unique manifestation of COVID-19 infection or as a prodrome of a new episode consistent with the psychiatric history.

We conducted a PubMed literature search to verify whether cognitive impairment might predispose to COVID-19. We included three patients with mild cognitive impairment and delirium at admission for SARS-Co-V2 suspected infection. Delirium was diagnosed according to DSM-5 criteria‚ Cognitive Assessment Method and Coma Glasgow Scale.

Literature analysis evidenced patients presenting delirium or delirium-like symptoms as clinical manifestation of COVID-19, plus a cognitive impairment‚ from mild to severe‚ which preexisted or was evidenced during the acute phase or after the infection. Most studies described delirium in patients with a past neurological/psychiatric history. Contrasting data emerged on the potential link between COVID-19 and delirium in patients with cognitive impairment and without a past neuropsychiatric history. Our patients had no history of other medical complications. Our first patient had no psychiatric history‚ the second reported only a depressive episode‚ and the third had story of bipolar disorder. Delirium resolved completely after 2 days in the first patient. The other patients required 4 and 14 days to resolve: delirium appeared as the prodrome of a new psychiatric episode in line with their past history.

Clinicians should acknowledge the possibility that COVID-19 infection may appear as delirium and acute psychiatric sequelae as unique manifestation.

No significant relationships.

TRD is a highly disabling condition, often responsible for chronic clinical course, high number of relapses and elevated suicide risk. Intranasal esketamine is currently the only available pharmacological therapy specifically indicated for TRD, as add-on therapy to antidepressant treatment with SSRI or SNRI.

The purpose of the study was to evaluate the safety and efficacy of intranasal esketamine associated with CBT in a complex clinical case of TRD, over a six-month follow-up.

A 67-year-old patient with TRD was selected for treatment with intranasal esketamine+CBT as add-on to antidepressant therapy. Before each treatment session the HAM-D rating scale was administered. The patient underwent weekly CBT sessions throughout the 6 months follow-up. The effect on physical well-being and social functioning was evaluated by means of Short-Form-Health-Survey-36.

After the first two administrations of intranasal esketamine the total score on HAM-D decreased by 10 units (from 26 to 16). After 6 weeks of treatment decreased from 26 to 12 with the disappearance of suicidal ideation present at T0. After 6 months the total HAM-D score decreased from 26 to 8. Treatment was well tolerated, with mild adverse effects, confined to the first two hours post-administration. In particular, mild sedation, dizziness, slight transient blood pressure rise were reported, never required medical intervention and resolved spontaneously during the observation period.

Intranasal esketamine add-on therapy + CBT was an effective and safe treatment allowing to achieve and maintain symptomatic remission in a complex case of TRD, improving quality of life, social functioning, and reducing suicidal ideation over a six-month follow-up.

No significant relationships.

DIALOG+ is a digital psychosocial intervention aimed at making routine meetings between patients and clinicians therapeutically effective. This study aimed to evaluate the cost-effectiveness of implementing DIALOG+ treatment for patients with psychotic disorders in five low- and middle-income countries in Southeast Europe alongside a cluster randomised trial.

Resource use and quality of life data were collected alongside the multi-country cluster randomised trial of 468 participants with psychotic disorders. Due to COVID-19 interruptions of the trial’s original 12-month intervention period, adjusted costs and quality-adjusted life years (QALYs) were estimated at the participant level using a mixed-effects model over the first 6 months only. We estimated the incremental cost-effectiveness ratio (ICER) with uncertainty presented using a cost-effectiveness plane and a cost-effectiveness acceptability curve. Seven sensitivity analyses were conducted to check the robustness of the findings.

The average cost of delivering DIALOG+ was €91.11 per participant. DIALOG+ was associated with an incremental health gain of 0.0032 QALYs (95% CI –0.0015, 0.0079), incremental costs of €84.17 (95% CI –8.18, 176.52), and an estimated ICER of €26,347.61. The probability of DIALOG+ being cost-effective against three times the weighted gross domestic product (GDP) per capita for the five participating countries was 18.9%.

Evidence from the cost-effectiveness analyses in this study suggested that DIALOG+ involved relatively low costs. However, it is not likely to be cost-effective in the five participating countries compared with standard care against a willingness-to-pay threshold of three times the weighted GDP per capita per QALY gained.

In Southeast Europe (SEE) standard treatment of patients with psychosis is largely based on pharmacotherapy with psychosocial interventions rarely available. DIALOG+ is a digital psychosocial intervention designed to make routine care therapeutically effective. This trial simultaneously examined effectiveness of DIALOG+ versus standard care on clinical and social outcomes (Aim 1) and explored intervention fidelity (Aim 2).

A hybrid type II effectiveness–implementation, cluster-randomized trial was conducted in five SEE countries: Bosnia and Herzegovina, Kosovo*, Montenegro, North Macedonia, and Serbia. The intervention was offered to patients six times across 12 months instead of routine care. The outcomes were subjective quality of life (primary), clinical symptoms, satisfaction with services, and economic costs. Intervention fidelity was operationalized as adherence to the protocol in terms of frequency, duration, content, and coverage. Data were analyzed using multilevel regression.

A total of 81 clinicians and 468 patients with psychosis were randomized to DIALOG+ or standard care. The intervention was delivered with high fidelity. The average number of delivered sessions was 5.5 (SD = 2.3) across 12 months. Patients in the intervention arm had better quality of life (MANSA) at 6 months (p = 0.03). No difference was found for other outcomes at 6 months. Due to disruptions caused by the COVID-19 pandemic, 12-month data were not interpretable.

DIALOG+ improved subjective quality of life of individuals with psychosis at 6 months (after four sessions), albeit with small effect size. The intervention has the potential to contribute to holistic care of patients with psychosis.

It is not known with certainty how different phenotypes are transmitted in groups of families divided into three generations.

Having meticulously searched for terms of psychopathogic lexicon that best translated the sterile categorical diagnosis, we obtained three dimensional groups for all six families in the three generations.

We calculated the frequencies and percentages of the three dimensional groups for the three generations of families based on sex.

The chi-square TEST attests a p-value = 0.049, statistically significant for the dimensional group “A”. (Tab. 3)

The genetics, and above all the epigenetics, of the phenotypes are periodically transmitted in group “A” and group “C” in the female and male sex. (Graphs 2.1.1 and 2.3.1) Different phenotypes indicate that the complexity of the interactions of the regulatory mechanisms of genes with the environment is extremely significant for the group with the most severe psychiatric pathology.

The knowledge about the association of physical activity (PA) and sedentary behaviours (SB) with the most considered healthy dairy products consumption, as milk and yogurt, in childhood is scared.

To assess the longitudinal relationship between specific lifestyle behaviours (PA and SB) and combined dairy consumption (milk + yogurt) in a sample of European children.

Two measurements, with 2 years’ interval (T0 and T1), were conducted in 1 688 (50.8% boys) childrenfrom the IDEFICS study. Dietary information was parental-registered by a 24-hour dietary recall. At both time points, sedentary behaviour and objective estimation of PA was obtained by accelerometers. Different groups were defined according to the international children's PA and SB behaviours recommendations over time. The cut-offs for the SB and PA recommendations were established on 2hour/day of SB and 2 hour/day of moderate to vigorous PA. Multilevel ordinal logistic regression models were used to assess the group's association with the combined dairy consumption (milk + yogurt), adjusted for potential confounders (sex, body mass index zscore, intervention versus control region, parental education level, dietary quality index, energy intake and the consumption by each dairy group at T0).

Nine groups of meeting or not both recommendations (SB and PA) were obtained. Those children who meeting both lifestyle recommendations at both measurement points, had higher probability to consume more milk and yogurt (p < 0.05), in comparison to the rest of combinations.Those children who did not meet any recommendations at both time points were less likely to consume milk + yogurt (OR: 0.47, 95%CI:0.26–0.83) than those who met both recommendations at both time points. Those children which improved one behaviours (PA or SB) between both measurement point were associated with low consumption of milk + yogurt (OR:0.41, 95%CI 0.22;0.74; OR:0.40, 95%CI 0.22,0.72), compared with those who meet both lifestyle recommendations at both periods (T0 and T1). Also, those which improved both behaviours (PA and SB) were less likely to consume milk + yogurt (OR:0.34, 95%CI 0.15–0.80) than those who were physically active and low sedentary at both time points.

These results suggest that European children with a healthy lifestyle regarding PA and SB over time, had the highest milk and yogurt consumption in comparison with other children.