Effect of Valproate and Antidepressant Drugs on Clozapine Metabolism in Patients With Psychotic Mood Disorders

BACKGROUND: The aim of the present study was to appraise retrospectively the influence of valproate (VPA) and antidepressants (ADs) on the steady-state plasma concentrations of clozapine (CLZ), the prototype of various second-generation antipsychotics, norclozapine (NCLZ, its main metabolite), and their ratio (NCLZ:CLZ). METHODS: Sixty-seven psychotic patients with a prevalent diagnosis of bipolar disorder were studied. We then analyzed data altogether and subdivided them into 4 groups, according to pharmacological treatments: #1 CLZ (n = 21), #2 CLZ plus ADs (n = 13), #3 CLZ plus VPA (n = 16), and #4 CLZ plus ADs plus VPA (n = 17). RESULTS: First, significant positive between CLZ and NCLZ plasma levels (in nanograms/milliliter) and the drug daily dosages (in milligrams/kilogram of body weight) (n = 67) were observed (Spearman: rCLZ = 0.49; rNCLZ = 0.61; P < 0.001). We then normalized by given doses CLZ and NCLZ plasma levels, natural log transformed them, and performed analysis of variance factor analyses followed by pairwise comparisons, performed on the 4 groups and the 3 CLZ parameters. We identified significant drug effects on (1) CLZ plasma levels, significantly higher in group #2 versus group #1, and (2) NCLZ:CLZ ratio, lower in group #2 versus groups #1 and #3. Significant drug × gender interactions were observed in group #3, showing higher NCLZ levels and NCLZ:CLZ ratios in men compared with women. CONCLUSIONS: Despite its inherent limitations, this observational study confirms the significant increase in plasma CLZ concentrations and reduction in NCLZ:CLZ ratio when this drug was coadministered with ADs (group #2), an effect apparently counteracted by VPA (group #4). The drug × gender interactions in patients taking both CLZ and VPA (group #3) warrant further prospective study

Mood symptoms and suicidality across the autism spectrum

Abstract Background Autism spectrum is a psychopathological dimension which encompasses a wide range of clinical presentations: from subthreshold forms and autistic traits (AT), that can be found in the general population, to full-blown autism spectrum disorder (ASD). Many studies reported high rates of comorbidity between both ASD and AT and mood disorders, as well as a high prevalence of suicidal ideation among patients with ASD/AT. The aim of this study was to investigate the presence of mood symptoms and suicidal ideation and behaviors in patients with full-blown ASD and in subjects with AT, as well in a healthy control (HC) group, with a specific focus on which of the autistic features may be predictive of suicidal ideation and behaviors. Methods We recruited 262 adult subjects: 34 with ASD without intellectual impairment or language disability (ASD group), 68 fulfilling only one symptom criterion for ASD according to DSM-5 but who do not meet criteria for a full-blown diagnosis of ASD (AT group), and 160 HC. All subjects were assessed with the Structured Clinical Interview for DSM-5 (SCID-5); in addition, they were asked to fill two questionnaires: The Mood Spectrum, Self-report (MOODS-SR) and the Adult Autism Subthreshold Spectrum (AdAS Spectrum). Results ASD subjects reported significantly higher AdAS Spectrum and MOODS-SR total scores, as well as higher MOODS-SR depressive component total scores, when compared with AT and HC subjects. AT subjects scored significantly higher than the HC group. No significant differences were reported between ASD and AT subjects for the suicidality score according to MOODS-SR, despite both groups scored significantly higher than the HC group. The strongest predictor of suicidality score were MOODS-SR depressive component score and AdAS Spectrum Restricted interests and rumination domain score. Conclusions Our results highlight a correlation between autism and mood spectrum, as well as between suicidality and both ASD and AT. Subthreshold forms of ASD should be accurately investigated due to their relationship with suicidal thoughts and behaviors

Adult Autism Subthreshold Spectrum (AdAS Spectrum): Validation of a questionnaire investigating subthreshold autism spectrum.

Aim Increasing literature has shown the usefulness of a dimensional approach to autism. The present study aimed to determine the psychometric properties of the Adult Autism Subthreshold Spectrum (AdAS Spectrum), a new questionnaire specifically tailored to assess subthreshold forms of autism spectrum disorder (ASD) in adulthood. Methods 102 adults endorsing at least one DSM-5 symptom criterion for ASD (ASDc), 143 adults diagnosed with a feeding and eating disorder (FED), and 160 subjects with no mental disorders (CTL), were recruited from 7 Italian University Departments of Psychiatry and administered the following: SCID-5, Autism-Spectrum Quotient (AQ), Ritvo Autism and Asperger Diagnostic Scale 14-item version (RAADS-14), and AdAS Spectrum. Results The AdAS Spectrum demonstrated excellent internal consistency for the total score (Kuder–Richardson's coefficient=.964) as well as for five out of seven domains (all coefficients>.80) and sound test–retest reliability (ICC=.976). The total and domain AdAS Spectrum scores showed a moderate to strong (>.50) positive correlation with one another and with the AQ and RAADS-14 total scores. ASDc subjects reported significantly higher AdAS Spectrum total scores than both FED (p<.001) and CTL (p<.001), and significantly higher scores on the Childhood/adolescence, Verbal communication, Empathy, Inflexibility and adherence to routine, and Restricted interests and rumination domains (all p<.001) than FED, while on all domains compared to CTL. CTL displayed significantly lower total and domain scores than FED (all p<.001). A significant effect of gender emerged for the Hyper– and hyporeactivity to sensory input domain, with women showing higher scores than men (p=.003). A Diagnosis Gender interaction was also found for the Verbal communication (p=.019) and Empathy (p=.023) domains. When splitting the ASDc in subjects with one symptom criterion (ASD1) and those with a ASD, and the FED in subjects with no ASD symptom criteria (FED0) and those with one ASD symptom criterion (FED1) a gradient of severity in AdAS Spectrum scores from CTL subjects to ASD patients, across FED0, ASD1, FED1 was shown. Conclusions The AdAS Spectrum showed excellent internal consistency and test–retest reliability and strong convergent validity with alternative dimensional measures of ASD. The questionnaire performed differently among the three diagnostic groups and enlightened some significant effects of gender in the expression of autistic traits

Ground deformation reveals the scale-invariant conduit dynamics driving explosive basaltic eruptions

The mild activity of basaltic volcanoes is punctuated by violent explosive eruptions that occur without obvious precursors. Modelling the source processes of these sudden blasts is challenging. Here, we use two decades of ground deformation (tilt) records from Stromboli volcano to shed light, with unprecedented detail, on the short-term (minute-scale) conduit processes that drive such violent volcanic eruptions. We find that explosive eruptions, with source parameters spanning seven orders of magnitude, all share a common pre-blast ground inflation trend. We explain this exponential inflation using a model in which pressure build-up is caused by the rapid expansion of volatile-rich magma rising from depth into a shallow (&lt;400m) resident magma conduit. We show that the duration and amplitude of this inflation trend scales with the eruption magnitude, indicating that the explosive dynamics obey the same (scale-invariant) conduit process. This scale-invariance of pre-explosion ground deformation may usher in a new era of short-term eruption forecasting

Ground deformation reveals the scale-invariant conduit dynamics driving explosive basaltic eruptions

The mild activity of basaltic volcanoes is punctuated by violent explosive eruptions that occur without obvious precursors. Modelling the source processes of these sudden blasts is challenging. Here, we use two decades of ground deformation (tilt) records from Stromboli volcano to shed light, with unprecedented detail, on the short-term (minute-scale) conduit processes that drive such violent volcanic eruptions. We find that explosive eruptions, with source parameters spanning seven orders of magnitude, all share a common pre-blast ground inflation trend. We explain this exponential inflation using a model in which pressure build-up is caused by the rapid expansion of volatile-rich magma rising from depth into a shallow (&lt;400 m) resident magma conduit. We show that the duration and amplitude of this inflation trend scales with the eruption magnitude, indicating that the explosive dynamics obey the same (scale-invariant) conduit process. This scale-invariance of pre-explosion ground deformation may usher in a new era of short-term eruption forecasting

The Clinical Impact of Methotrexate-Induced Stroke-Like Neurotoxicity in Paediatric Departments: An Italian Multi-Centre Case-Series

Introduction: Stroke-like syndrome (SLS) is a rare subacute neurological complication of intrathecal or high-dose (≥500 mg) Methotrexate (MTX) administration. Its clinical features, evoking acute cerebral ischaemia with fluctuating course symptoms and a possible spontaneous resolution, have elicited interest among the scientific community. However, many issues are still open on the underlying pathogenesis, clinical, and therapeutic management and long-term outcome. Materials and Methods: We retrospectively analyzed clinical, radiological and laboratory records of all patients diagnosed with SLS between 2011 and 2021 at 4 National referral centers for Pediatric Onco-Hematology. Patients with a latency period that was longer than 3 weeks between the last MTX administration of MTX and SLS onset were excluded from the analysis, as were those with unclear etiologies. We assessed symptom severity using a dedicated arbitrary scoring system. Eleven patients were included in the study. Results: The underlying disease was acute lymphoblastic leukemia type B in 10/11 patients, while fibroblastic osteosarcoma was present in a single subject. The median age at diagnosis was 11 years (range 4–34), and 64% of the patients were women. Symptoms occurred after a mean of 9.45 days (± 0.75) since the last MTX administration and lasted between 1 and 96 h. Clinical features included hemiplegia and/or cranial nerves palsy, paraesthesia, movement or speech disorders, and seizure. All patients underwent neuroimaging studies (CT and/or MRI) and EEG. The scoring system revealed an average of 4.9 points (± 2.3), with a median of 5 points (maximum 20 points). We detected a linear correlation between the severity of the disease and age in male patients. Conclusions: SLS is a rare, well-characterized complication of MTX administration. Despite the small sample, we have been able to confirm some of the previous findings in literature. We also identified a linear correlation between age and severity of the disease, which could improve the future clinical management

Psychopathological Impact in Patients with History of Rheumatic Fever with or without Sydenham’s Chorea: A Multicenter Prospective Study

Sydenham’s chorea (SC) is a post-streptococcal autoimmune disorder of the central nervous system, and it is a major criterium for the diagnosis of acute rheumatic fever (ARF). SC typically improves in 12–15 weeks, but patients can be affected for years by persistence and recurrencies of both neurological and neuropsychiatric symptoms. We enrolled 48 patients with a previous diagnosis of ARF, with or without SC, in a national multicenter prospective study, to evaluate the presence of neuropsychiatric symptoms several years after SC’s onset. Our population was divided in a SC group (n = 21), consisting of patients who had SC, and a nSC group (n = 27), consisting of patients who had ARF without SC. Both groups were evaluated by the administration of 8 different neuropsychiatric tests. The Work and Social Adjustment Scale (WSAS) showed significantly (p = 0.021) higher alterations in the SC group than in the nSC group. Furthermore, 60.4% (n = 29) of the overall population experienced neuropsychiatric symptoms other than choreic movements at diagnosis and this finding was significantly more common (p = 0.00) in SC patients (95.2%) than in nSC patients (33.3%). The other neuropsychiatric tests also produced significant results, indicating that SC can exert a strong psychopathological impact on patients even years after its onset

Thermal Remote Sensing for Global Volcano Monitoring: Experiences From the MIROVA System

Volcanic activity is always accompanied by the transfer of heat from the Earth's crust to the atmosphere. This heat can be measured from space and its measurement is a very useful tool for detecting volcanic activity on a global scale. MIROVA (Middle Infrared Observation of Volcanic Activity) is an automatic volcano hot spot detection system, based on the analysis of MODIS data (Moderate Resolution Imaging Spectroradiometer). The system is able to detect, locate and quantify thermal anomalies in near real-time, by providing, on a dedicated website (www.mirovaweb.it), infrared images and thermal flux time-series on over 200 volcanoes worldwide. Thanks to its simple interface and intuitive representation of the data, MIROVA is currently used by several volcano observatories for daily monitoring activities and reporting. In this paper, we present the architecture of the system and we provide a state of the art on satellite thermal data usage for operational volcano monitoring and research. In particular, we describe the contribution that the thermal data have provided in order to detect volcanic unrest, to forecast eruptions and to depict trends and patterns during eruptive crisis. The current limits and requirements to improve the quality of the data, their distribution and interpretation are also discussed, in the light of the experience gained in recent years within the volcanological community. The results presented clearly demonstrate how the open access of satellite thermal data and the sharing of derived products allow a better understanding of ongoing volcanic phenomena, and therefore constitute an essential requirement for the assessment of volcanic hazards. Peer reviewe

Parathyroidectomy and survival in a cohort of Italian dialysis patients: results of a multicenter, observational, prospective study

Background: Severe secondary hyperparathyroidism (SHPT)&nbsp;is associated with mortality in end stage kidney disease (ESKD). Parathyroidectomy (PTX) becomes necessary when medical therapy fails, thus highlighting the interest to compare biochemical and clinical outcomes of patients receiving either medical treatment or surgery. Methods: We aimed to compare overall survival and biochemical control of hemodialysis patients with severe hyperparathyroidism, treated by surgery or medical&nbsp;therapy&nbsp;followed-up for 36&nbsp;months.&nbsp;Inclusion criteria were age older than 18&nbsp;years, renal failure requiring dialysis treatment (hemodialysis or peritoneal dialysis) and ability to sign the consent form. A control group of&nbsp;418 patients treated in the same centers,&nbsp;who did not undergo parathyroidectomy was selected after matching&nbsp;for&nbsp;age, sex, and dialysis vintage. Results: From 82 Dialysis units in Italy, we prospectively collected data of 257 prevalent patients&nbsp;who underwent parathyroidectomy (age&nbsp;58.2 ± 12.8 years; M/F: 44%/56%, dialysis&nbsp;vintage: 15.5 ± 8.4 years) and of 418 control patients who did not undergo parathyroidectomy (age&nbsp;60.3 ± 14.4 years; M/F 44%/56%; dialysis vintage 11.2 ± 7.6 y). The survival rate was higher in the group&nbsp;that underwent&nbsp;parathyroidectomy (Kaplan–Meier log rank test = 0.002). Univariable analysis (HR 0.556, CI: 0.387–0.800, p = 0.002) and multivariable analysis (HR 0.671, CI:0.465–0.970, p = 0.034), identified parathyroidectomy as a&nbsp;protective factor of overall survival. The prevalence of patients at KDOQI targets for PTH was lower in patients&nbsp;who underwent parathyroidectomy&nbsp;compared to controls (PTX vs non-PTX: PTH &lt; 150&nbsp;pg/ml: 59% vs 21%, p = 0.001; PTH at target: 18% vs 37% p = 0.001; PTH &gt; 300&nbsp;pg/ml 23% vs 42% p = 0.001). The control group received more intensive medical treatment&nbsp;with higher prevalence of vitamin D (65% vs 41%, p = 0.0001), calcimimetics (34% vs 14%, p = 0.0001) and phosphate binders (77% vs 66%,&nbsp;p = 0.002). Conclusions: Our data suggest that parathyroidectomy is associated with survival rate&nbsp;at 36 months, independently of biochemical control. Lower exposure to high PTH levels could represent an advantage in the long term. Graphical abstract: [Figure not available: see fulltext.]