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This study aimed to characterize the population pharmacokinetics of sertraline in Mexican patients with psychiatric and substance use disorders. Fifty-nine patients (13 to 76 years old) treated with doses of sertraline between 12.5 and 100 mg/day were included. Plasma sertraline concentrations were determined in blood samples and five of the main substances of abuse were determined by rapid tests in urine samples. Demographic, clinical, and pharmacogenetic factors were also evaluated. Population pharmacokinetic analysis was performed using NONMEM software with first-order conditional estimation method. A one-compartment model with proportional residual error adequately described the sertraline concentrations versus time. CYP2D6*2 polymorphism and CYP2C19 phenotypes significantly influenced sertraline clearance, which had a population mean value of 66 L/h in the final model. The absorption constant and volume of distribution were fixed at 0.855 1/h and 20.2 L/kg, respectively. The model explained 11.3% of the interindividual variability in sertraline clearance. The presence of the CYP2D6*2 polymorphism caused a 23.1% decrease in sertraline clearance, whereas patients with intermediate and poor phenotype of CYP2C19 showed 19.06% and 48.26% decreases in sertraline clearance, respectively. The model was internally validated by bootstrap and visual predictive check. Finally, stochastic simulations were performed to propose dosing regimens to achieve therapeutic levels that contribute to improving treatment response.

BACKGROUND: The co-occurrence of substance use disorder with at least one other mental disorder is called dual pathology, which in turn is characterised by heterogeneous symptoms that are difficult to diagnose and have a poor response to treatment. For this reason, the identification and validation of biomarkers is necessary. Within this group, possible electroencephalographic biomarkers have been reported to be useful in diagnosis, treatment and follow-up, both in neuropsychiatric conditions and in substance use disorders. This article aims to review the existing literature on electroencephalographic biomarkers in dual pathology.
METHODS: A narrative review of the literature. A bibliographic search was performed on the PubMed, Science Direct, OVID, BIREME and Scielo databases, with the keywords: electrophysiological biomarker and substance use disorder, electrophysiological biomarker and mental disorders, biomarker and dual pathology, biomarker and substance use disorder, electroencephalography, and substance use disorder or comorbid mental disorder.
RESULTS: Given the greater amount of literature found in relation to electroencephalography as a biomarker of mental illness and substance use disorders, and the few articles found on dual pathology, the evidence is organised as a biomarker in psychiatry for the diagnosis and prediction of risk and as a biomarker for dual pathology.
CONCLUSIONS: Although the evidence is not conclusive, it suggests the existence of a subset of sites and mechanisms where the effects of psychoactive substances and the neurobiology of some mental disorders could overlap or interact.

OBJECTIVE: Maternal mental health and substance use, referred to as dual pathology, represent significant concerns associated with adverse pregnancy and birth outcomes, a prevalence higher than commonly anticipated. Nonetheless, a notable dearth exists ofevidence-based treatment protocols tailored for pregnant women with dual pathology.
METHODS: A systematic review, adhering to the PRISMA methodology, was conducted.
RESULTS: Out of the 57 identified papers deemed potentially relevant, only 2were ultimately included. Given the limited number of studies assessing the efficacy of psychological interventions utilizing randomized controlled trials (RCTs) for both mental health and substance misuse, and considering the diverse objectives and measures employed, definitive conclusions regarding the effectiveness of psychological interventions in this domain prove challenging.
CONCLUSIONS: Maternal mental health appears to be the proverbial \"elephant in the room\". The development of specialized and integrated interventions stands as an imperative to effectively address this pressing issue. As elucidated in the present review, these interventions ought to be grounded in empirical evidence. Furthermore, it is essential that such interventions undergo rigorous evaluation through RCTs to ascertain their efficacy levels. Ultimately, the provision of these interventions by psychology/psychiatric professionals, both within clinical practice and the RCTs themselves, is recommended to facilitate the generalizability of the results to specialized settings.

OBJECTIVE: To investigate the application value of multimodal MRI combined with PET metabolic parameters in detecting temporal lobe epilepsy (TLE) with dual pathology (DP) and the prediction effect of post-surgical outcomes in these patients.
METHODS: We retrospectively reviewed 50 patients with TLE-DP who underwent surgery at our hospital between January 2016 and December 2021 and collected the demographics, clinical characteristics, video-electroencephalography (v-EEG), neuroimaging, and surgical data. Seizure outcome data were collected during a regular follow-up of at least 12 months and were graded using Engel scores. Fisher\'s exact test was used to compare the differences in DP detection rates of various diagnostic modalities. Univariate and multivariate analyses were performed to explore the prognostic factors for predicting seizure outcomes post-surgery.
RESULTS: Of the 50 patients, 20 were males. The median age was 30, the median age at first seizure was 14, and the median duration was ten years. Voxel-based morphometry-PET statistical parametric mapping-PET/MRI (VBM-PSPM-PET/MRI) had the highest detection rate, followed by PET/MRI, VBM analysis, and PET-SPM. Regardless of follow-up duration, v-EEG, PET, image post-processing methods, and VBM-PSPM-PET/MRI statistically correlated with seizure outcomes using the log-rank test in the Kaplan-Meier analysis. Multivariate analysis showed that VBM-PSPM-PET/MRI was an independent predictor of TLE-DP (hazard ratio (HR) = 15.674, 95 % CI = 0.002-0.122, P < 0.00 1).
CONCLUSIONS: Our study illustrates that VBM-PSPM-PET/MRI has the highest detection value in patients with TLE-DP and can provide independent prognostic information for patients who undergo surgery. This approach has the most substantial potential for the selection of candidates for patients who undergo surgical treatment and for prognostic stratification.

Diagnosis of chronic Q fever is often difficult for clinicians, particularly in the presence of a second pathology. In addition to the chronic constitutional symptoms, the most common manifestations of chronic Q fever include infective endocarditis and endovascular infection. We describe a case of prosthetic valve infective endocarditis caused by both Streptococcus sanguinis and Coxiella burnetti on a background of a previous aortic graft and bioprosthetic aortic valve replacement 2 years earlier. The diagnosis of chronic Q fever infective endocarditis was delayed because the significance of the abnormal valve histology from the patient\'s previous surgery was initially overlooked. It was only after the patient had relapsed on appropriate therapy for the S. sanguinis prosthetic valve endocarditis that a subsequent review of the operative valve histology, along with the patient\'s epidemiological risk factors, led to consideration of an additional culture-negative cause for infective endocarditis. Histological examination of the valve tissue had shown exophytic fibrin vegetations and acute inflammation. Further clinical assessment revealed previous exposure to Q fever and C. burnetti DNA was detected via polymerase chain reaction on the valve tissue. Q fever infective endocarditis must be considered if valves are inflamed or have vegetations with a subsequent negative culture. It should also still be considered in the presence of an alternative bacteraemia if the patient has risk factors for exposure.

BACKGROUND: Rasmussen\'s encephalitis (RE) is a rare, predominantly pediatric epilepsy disorder of unknown etiology. It classically affects one of the cerebral hemispheres and histologically shows cortical chronic inflammation, gliosis, and neuronal loss. The etiopathogenesis of RE remains unknown, with genetic, infectious, and autoimmune factors all speculated to play a role. Although the histologic findings in RE are well described, few studies have investigated a large cohort of cases looking for the coexistence of RE with focal cortical dysplasia (FCD).
METHODS: The study is a retrospective review of RE patients who underwent surgical resection of brain tissue between 1979 and 2021. Relevant patient history was retrieved, and available histologic slides were reviewed. The histologic severity of RE was described according to the Pardo criteria. In cases where FCD was present, the observed patterns of FCD (namely Ia, Ib, IIa, IIb, etc.) were described using the International League Against Epilepsy (ILAE) classification.
RESULTS: Thirty-eight resection specimens from 31 patients formed the study cohort. Seventeen patients (54.8 %) were male; average age at surgery was 8 years (range: 2-28 years). Twenty-seven resection specimens (71.1 %) from 23 patients (74 %) showed evidence of coexistent FCD. Most cases with FCD resembled the ILAE type Ib (n = 23) pattern. Cases of RE that did not show FCD were either Pardo stage 1 (n = 5) or 4 (n = 6), with all Pardo stage 2 and 3 cases demonstrating FCD.
CONCLUSIONS: FCD was found in most patients with RE (74 %). The most observed pattern of FCD was ILAE Ib.

The relevance of secondary epileptogenesis for human epilepsy remains a controversial subject decades after it was first described in animal models. Whether or not a previously normal brain region can become independently epileptogenic through a kindling-like process has not, and cannot, be definitely proven in humans. Rather than reliance on direct experimental evidence, attempts to answering this question must depend on observational data. In this review, observations based largely upon contemporary surgical series will advance the case for secondary epileptogenesis in humans. As will be argued, hypothalamic hamartoma-related epilepsy provides the strongest case for this process; all the stages of secondary epileptogenesis can be observed. Hippocampal sclerosis (HS) is another pathology where the question of secondary epileptogenesis frequently arises, and observations from bitemporal and dual pathology series are explored. The verdict here is far more difficult to reach, in large part because of the scarcity of longitudinal cohorts; moreover, recent experimental data have challenged the claim that HS is acquired consequent to recurrent seizures. Synaptic plasticity more than seizure-induced neuronal injury is the likely mechanism of secondary epileptogenesis. Postoperative running-down phenomenon provides the best evidence that a kindling-like process occurs in some patients, evidenced by its reversal. Finally, a network perspective of secondary epileptogenesis is considered, as well as the possible role for subcortical surgical interventions.

BACKGROUND: Health care provision during the COVID-19 pandemic and confinement has led to significant changes in the activity of addiction centers. These changes in healthcare activity may have had a greater impact on patients with dual pathology. The aim of this study is to compare the treatment indicators of patients with dual pathology in addiction centers during the pre-confinement, confinement, and post-confinement periods.
METHODS: A retrospective observational study was conducted for the period between 1 February 2019 and 30 June 2021. A total of 2785 patients treated in specialized addiction services were divided into three periods according to their time of admission: pre-confinement, confinement, and post-confinement.
RESULTS: During the pre-pandemic period, the addiction centers attended to an average of 121.3 (SD = 23.58) patients, decreasing to 53 patients during confinement (SD = 19.47), and 80.69 during the post-confinement period (SD = 15.33). The number of appointments scheduled monthly for each patient decreased during the confinement period, although this number increased after confinement. There was a reduction in the number of toxicological tests carried out both during and after confinement (except for alcohol).
CONCLUSIONS: The results show a reduction in the number of patients seen and the care activity delivered to dual diagnosis patients. These results, which were caused by the COVID-preventive measures, may affect the progress and recovery of dual patients. A greater investment is needed to bring the care activity up to the standards of the years prior to confinement.

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