Machine learning methods to predict outcomes of pharmacological treatment in psychosis

In recent years, machine learning (ML) has been a promising approach in the research of treatment outcome prediction in psychosis. In this study, we reviewed ML studies using different neuroimaging, neurophysiological, genetic, and clinical features to predict antipsychotic treatment outcomes in patients at different stages of schizophrenia. Literature available on PubMed until March 2022 was reviewed. Overall, 28 studies were included, among them 23 using a single-modality approach and 5 combining data from multiple modalities. The majority of included studies considered structural and functional neuroimaging biomarkers as predictive features used in ML models. Specifically, functional magnetic resonance imaging (fMRI) features contributed to antipsychotic treatment response prediction of psychosis with good accuracies. Additionally, several studies found that ML models based on clinical features might present adequate predictive ability. Importantly, by examining the additive effects of combining features, the predictive value might be improved by applying multimodal ML approaches. However, most of the included studies presented several limitations, such as small sample sizes and a lack of replication tests. Moreover, considerable clinical and analytical heterogeneity among included studies posed a challenge in synthesizing findings and generating robust overall conclusions. Despite the complexity and heterogeneity of methodology, prognostic features, clinical presentation, and treatment approaches, studies included in this review suggest that ML tools may have the potential to predict treatment outcomes of psychosis accurately. Future studies need to focus on refining feature characterization, validating prediction models, and evaluate their translation in real-world clinical practice

The enhancement of excitonic emission crossing Saha equilibrium in trap passivated CH3NH3PbBr3 perovskite

Metal-halide semiconductor perovskites have received great attention for the development of stable and efficient light emitting diodes and lasers, since they combine high charge carrier mobility and light emission spectral-purity with low-cost fabrication methods. Nevertheless, the role of excitons, free carries and trap states in perovskite light emission properties is still unclear due to their interdependence. In this paper we selectively manage trapping and light emission mechanisms by a reversible laser-assisted trap-passivation process performed on a CH3NH3PbBr3 perovskite layer, coupled to the inner modes of a high-quality micro-cavity, which only affects the radiative recombination. We show that photoluminescence is dominated by exciton radiative decay process and that trap states passivation increases the exciton gemination rate by reducing coulombic scattering of free electrons due to the ionized impurities. This picture provides a more general description than the model based on trap states-free Saha thermodynamic equilibrium between photo-generated species. The interdependence of free carries, trap states and excitons in the light emission properties of CH3NH3PbBr3 perovskite thin films and their relationship to device performance is a subject of debate. Here, the authors investigate the role of non-radiative recombination and demonstrate that the photoluminescence is dominated by exciton radiative decay processes

Efeito da oxigenioterapia hiperbárica na regeneração de lesões experimentais de nervos

O oxigênio hiperbárico exerce efeitos comprovadamente benéficos no tratamento de lesões isquêmicas agudas de partes moles e em feridas de difícil cicatrização. Nas lesões neurais por esmagamento, os mecanismos fisiopatológicos assemelham-se aos efeitos dependentes da isquemia tissular. Portanto, a terapia com oxigênio hiperbárico teria participação nos processos de reparação neural, que constitui um dos pontos críticos para a recuperação funcional após as lesões por esmagamento de nervos periféricos. Neste estudo, foram realizadas lesões por esmagamento em nervo ciático de ratos, submetidos à terapia com oxigênio hiperbárico no pós-operatório. Os resultados foram quantificados através de avaliação funcional pelo método de "walking-track analysis". Os índices de recuperação funcional observados não diferiram dos observados no grupo controle. Portanto, verificou-se que a terapia com oxigênio hiperbárico, no esquema proposto, não teve influência na recuperação funcional após lesões neurais por esmagamento.Hyperbaric oxygen has been successfully used on treatment of acute ischemic injuries involving soft tissues and chronic injuries. In nerve crush injuries, the mechanisms involved are very similar to those found in ischemic injuries. Consequently, it is logical to hypothesize that hyperbaric oxygen should improve nerve repair, which is a critical step on functional recovery. In the present study, we created standard nerve crush injuries on sciatic nerves of rats, which underwent treatment with hyperbaric oxygen. Results were assessed by functional evaluation using walking-track analysis. The functional recovery indexes observed did not differ from control group. We concluded that hyperbaric oxygen therapy, in the schedule used, had no influence on functional recovery after nerve crush injuries

Clinical trajectories of individuals with severe mental illness continuing and discontinuing long-acting antipsychotics: a one-year mirror-image analysis from the STAR Network Depot study

Evidence on long-acting antipsychotics (LAIs) in unselected populations with severe mental illness is scant. In this mirror-image study, we compared multiple clinical outcomes 1 year before and after a first LAI prescription in adults with severe mental illness, describing clinical trajectories of LAI continuers and discontinuers. We compared LAI continuers and discontinuers through Mann–Whitney U test, Kaplan–Meier survival curves, regression for interval-censored data, and a maximum-likelihood mixed-model with individual random-effect and time as predictor. Of the 261 participants analyzed, 71.3% had schizophrenia-spectrum disorders, and 29.5% discontinued the LAI before 1 year. At baseline, LAI discontinuers had a shorter illness duration, lower attitude and adherence scores. The mirror-image analysis showed reduced hospital admissions only for LAI continuers. Over time, continuers spent less days hospitalized, but had more adverse events and more antipsychotics prescribed, with higher overall doses. In conclusion, this study shows that LAIs might be beneficial in unselected patient populations, provided that adherence is maintained. LAI continuers spent less time hospitalized, but received more antipsychotics and suffered from more cumulative adverse events over time. Therefore, the choice of initiating and maintaining a LAI should be carefully weighed on a case-by-case basis

Clinical trajectories of individuals with severe mental illness continuing and discontinuing long-acting antipsychotics: a one-year mirror-image analysis from the STAR Network Depot study

Evidence on long-acting antipsychotics (LAIs) in unselected populations with severe mental illness is scant. In this mirror-image study, we compared multiple clinical outcomes 1 year before and after a first LAI prescription in adults with severe mental illness, describing clinical trajectories of LAI continuers and discontinuers. We compared LAI continuers and discontinuers through Mann-Whitney U test, Kaplan-Meier survival curves, regression for interval-censored data, and a maximum-likelihood mixed-model with individual random-effect and time as predictor. Of the 261 participants analyzed, 71.3% had schizophrenia-spectrum disorders, and 29.5% discontinued the LAI before 1 year. At baseline, LAI discontinuers had a shorter illness duration, lower attitude and adherence scores. The mirror-image analysis showed reduced hospital admissions only for LAI continuers. Over time, continuers spent less days hospitalized, but had more adverse events and more antipsychotics prescribed, with higher overall doses. In conclusion, this study shows that LAIs might be beneficial in unselected patient populations, provided that adherence is maintained. LAI continuers spent less time hospitalized, but received more antipsychotics and suffered from more cumulative adverse events over time. Therefore, the choice of initiating and maintaining a LAI should be carefully weighed on a case-by-case basis

Off-label long acting injectable antipsychotics in real-world clinical practice: a cross-sectional analysis of prescriptive patterns from the STAR Network DEPOT study

Introduction: Information on the off-label use of Long-Acting Injectable (LAI) antipsychotics in the real world is lacking. In this study, we aimed to identify the sociodemographic and clinical features of patients treated with on- vs off-label LAIs and predictors of off-label First- or Second-Generation Antipsychotic (FGA vs. SGA) LAI choice in everyday clinical practice. Method: In a naturalistic national cohort of 449 patients who initiated LAI treatment in the STAR Network Depot Study, two groups were identified based on off- or on-label prescriptions. A multivariate logistic regression analysis was used to test several clinically relevant variables and identify those associated with the choice of FGA vs SGA prescription in the off-label group. Results: SGA LAIs were more commonly prescribed in everyday practice, without significant differences in their on- and off-label use. Approximately 1 in 4 patients received an off-label prescription. In the off-label group, the most frequent diagnoses were bipolar disorder (67.5%) or any personality disorder (23.7%). FGA vs SGA LAI choice was significantly associated with BPRS thought disorder (OR = 1.22, CI95% 1.04 to 1.43, p = 0.015) and hostility/suspiciousness (OR = 0.83, CI95% 0.71 to 0.97, p = 0.017) dimensions. The likelihood of receiving an SGA LAI grew steadily with the increase of the BPRS thought disturbance score. Conversely, a preference towards prescribing an FGA was observed with higher scores at the BPRS hostility/suspiciousness subscale. Conclusion: Our study is the first to identify predictors of FGA vs SGA choice in patients treated with off-label LAI antipsychotics. Demographic characteristics, i.e. age, sex, and substance/alcohol use co-morbidities did not appear to influence the choice towards FGAs or SGAs. Despite a lack of evidence, clinicians tend to favour FGA over SGA LAIs in bipolar or personality disorder patients with relevant hostility. Further research is needed to evaluate treatment adherence and clinical effectiveness of these prescriptive patterns

The role of attitudes toward medication and treatment adherence in the clinical response to LAIs: findings from the STAR Network Depot Study

Background: Long-acting injectable (LAI) antipsychotics are efficacious in managing psychotic symptoms in people affected by severe mental disorders, such as schizophrenia and bipolar disorder. The present study aimed to investigate whether attitude toward treatment and treatment adherence represent predictors of symptoms changes over time. Methods: The STAR Network "Depot Study" was a naturalistic, multicenter, observational, prospective study that enrolled people initiating a LAI without restrictions on diagnosis, clinical severity or setting. Participants from 32 Italian centers were assessed at three time points: baseline, 6-month, and 12-month follow-up. Psychopathological symptoms, attitude toward medication and treatment adherence were measured using the Brief Psychiatric Rating Scale (BPRS), the Drug Attitude Inventory (DAI-10) and the Kemp's 7-point scale, respectively. Linear mixed-effects models were used to evaluate whether attitude toward medication and treatment adherence independently predicted symptoms changes over time. Analyses were conducted on the overall sample and then stratified according to the baseline severity (BPRS < 41 or BPRS ≥ 41). Results: We included 461 participants of which 276 were males. The majority of participants had received a primary diagnosis of a schizophrenia spectrum disorder (71.80%) and initiated a treatment with a second-generation LAI (69.63%). BPRS, DAI-10, and Kemp's scale scores improved over time. Six linear regressions-conducted considering the outcome and predictors at baseline, 6-month, and 12-month follow-up independently-showed that both DAI-10 and Kemp's scale negatively associated with BPRS scores at the three considered time points. Linear mixed-effects models conducted on the overall sample did not show any significant association between attitude toward medication or treatment adherence and changes in psychiatric symptoms over time. However, after stratification according to baseline severity, we found that both DAI-10 and Kemp's scale negatively predicted changes in BPRS scores at 12-month follow-up regardless of baseline severity. The association at 6-month follow-up was confirmed only in the group with moderate or severe symptoms at baseline. Conclusion: Our findings corroborate the importance of improving the quality of relationship between clinicians and patients. Shared decision making and thorough discussions about benefits and side effects may improve the outcome in patients with severe mental disorders

CT Perfusion as a Predictor of the Final Infarct Volume in Patients with Tandem Occlusion

Background: CT perfusion (CTP) is used in patients with anterior circulation acute ischemic stroke (AIS) for predicting the final infarct volume (FIV). Tandem occlusion (TO), involving both intracranial large vessels and the ipsilateral cervical internal carotid artery could generate hemodynamic changes altering perfusion parameters. Our aim is to evaluate the accuracy of CTP in the prediction of the FIV in TOs. Methods: consecutive patients with AIS due to middle cerebral artery occlusion, referred to a tertiary stroke center between March 2019 and January 2021, with an automated CTP and successful recanalization (mTICI = 2b - 3) after endovascular treatment were retrospectively included in the tandem group (TG) or in the control group (CG). Patients with parenchymal hematoma type 2, according to ECASS II classification of hemorrhagic transformations, were excluded in a secondary analysis. Demographic, clinical, radiological, time intervals, safety, and outcome measures were collected. Results: among 319 patients analyzed, a comparison between the TG (N = 22) and CG (n = 37) revealed similar cerebral blood flow (CBF) > 30% (29.50 +/- 32.33 vs. 15.76 +/- 20.93 p = 0.18) and FIV (54.67 +/- 65.73 vs. 55.14 +/- 64.64 p = 0.875). Predicted ischemic core (PIC) and FIV correlated in both TG (tau = 0.761, p < 0.001) and CG (tau = 0.315, p = 0.029). The Bland-Altmann plot showed agreement between PIC and FIV for both groups, mainly in the secondary analysis. Conclusion: automated CTP could represent a good predictor of FIV in patients with AIS due to TO