Combination of Neovestitol and Vestitol Modifies the Profile of Periodontitis-Related Subgingival Multispecies Biofilm.

The aim of this study was to evaluate the effect of the combination of neovestitol-vestitol (CNV) compounds obtained from Brazilian red propolis on the microbiological profile of a mature multispecies subgingival biofilm. The biofilm with 32 bacterial species associated with periodontitis was formed for seven days using a Calgary device. Treatment with CNV (1600, 800, 400, and 200 µg/mL), amoxicillin (54 µg/mL), and vehicle control was performed for 24 h on the last day of biofilm formation. Biofilm metabolic activity and DNA-DNA hybridization (checkerboard) assays were performed. The groups treated with CNV 1600 and amoxicillin reduced 25 and 13 species, respectively, compared to the control vehicle treatment (p ≤ 0.05); both reduced P. gingivalis, while only CNV reduced T. forsythia. When the data from the two treatments (CNV and AMOXI) were compared, a statistically significant difference was observed in 13 species, particularly members of Socransky's orange complex. Our results showed that CNV at 1600 µg/mL showed the best results regarding the metabolic activity of mature biofilms and obtained a reduction in species associated with the disease, such as T. forsythia, showing a better reduction than amoxicillin. Therefore, CNV seems to be a promising alternative to eradicate biofilms and reduce their pathogenicity.

Subcutaneous ketamine reduces suicide risk and improves functioning in depression: A proof-of-concept study.

This investigation explores the efficacy of subcutaneous ketamine for mitigating depressive symptoms and suicidal ideation, addressing a crucial need for rapid-onset treatments in severe depression cases. It introduces an innovative approach to administering an NMDA receptor antagonist, significantly advancing psychopharmacological methods for treating suicidal behaviors as distinct entities, even within depressive episodes. The study's objective is to assess the impact of subcutaneous ketamine on diminishing suicidal thoughts and mood symptoms during depressive episodes through a naturalistic, prospective observational design. Conducted at Hospital de Clínicas de Porto Alegre, Brazil, between 2021 and 2023, the study involved 26 patients undergoing a current depressive episode. Of these, 23 completed the acute phase of treatment, and 18 were followed up for 6 months. The treatment regimen commenced with a ketamine dose of 0.5 mg/kg, which was adjusted according to individual responses under psychiatric supervision. The findings revealed substantial decreases in Columbia Suicide Severity Rating Scale scores following multiple ketamine sessions, with most patients achieving remission after approximately eight sessions. A notable reduction in depressive symptoms was also observed. A clear dose-response relationship was established, indicating that higher doses of ketamine were associated with more significant improvements in depressive symptoms, suicidal ideation, and overall functionality. Follow-up assessments suggested that these improvements were sustained over time. The subcutaneous administration of ketamine was generally well-tolerated, with minor and short-lived side effects. The study posits that subcutaneous ketamine may present a promising solution for treating severe depression accompanied by suicidal tendencies, particularly considering its positive influence on patient functionality and well-being. This method could offer a cost-effective and accessible treatment alternative, especially relevant in settings with limited resources. Given its potential in reducing long-term disability and economic viability, the study advocates for its broader application and further validation through larger, controlled trials. Trial Registration: ClinicalTrials.gov NCT05249309.

Inflammatory markers in outpatients with schizophrenia diagnosis in regular use of clozapine: a cross-sectional study.

It is known that inflammation worsen the course of schizophrenia and induce high clozapine serum levels. However, no study evaluated this change in function of clozapine daily dose in schizophrenia. We assessed the correlation between inflammation and severity symptoms in patients with schizophrenia that take and do not take clozapine. We also assessed the correlation between clozapine daily dose and inflammatory markers to patients who take this drug. Patients were recruited from Schizophrenia Ambulatory and Psychosocial Care Center of Clinical Hospital of Porto Alegre and from an association of relatives of patients with schizophrenia. Exam results, and other important clinical exam were assessed in patients record or patients were asked to show their exam in the case of outpatients. We included 104 patients, 90 clozapine users and 14 non-clozapine users. We calculate the systemic inflammatory markers [neutrophil-lymphocyte ratio (NLR), systemic immune inflammation index (SII), and the psychopathology severity by the Brief Psychiatric Rating Scaled anchored (BPRS-a)]. These variables were compared between clozapine users and non-clozapine users. It was used mean/median test according to data distributing, with study factor (SII, MLR, and PLR), the clinical outcome: severity of symptomatology (BPRS score), and clozapine daily dose as adjustment factor. Clozapine users exhibited a significantly higher neutrophil count (mean ± SD: 5.03 ± 2.07) compared to non-clozapine users (mean ± SD: 3.48 ± 1.27; p = 0.031). After controlling for comorbidity, other parameters also showed significant differences. These findings are consistent with previous studies that have demonstrated an inflammatory response following the administration of clozapine.

C-N linked donor type porphyrin derivatives: unrevealed hole-transporting materials for efficient hybrid perovskite solar cells.

A new series of Zn(II) and Cu(II)-based porphyrin complexes 5a and 5b doubly functionalised with carbazole units were developed to be used as hole-transporting materials (HTMs) in perovskite solar cells (PSCs). These complexes were obtained via a nucleophilic substitution reaction mediated by PhI(OAc)2/NaAuCl4·2H2O, or using C-N transition metal-assisted coupling. The hole extraction capability of 5a and 5b was assessed using cyclic voltammetry; this study confirmed the better alignment of the Zn(II) complex 5a with the perovskite valence band level, compared to the Cu(II) complex 5b. The optimised geometry and molecular orbitals of both complexes also corroborate the higher potential of 5a as a HTM. Photoluminescence characterisation showed that the presence of 5a and 5b as HTMs on the perovskite surface resulted in the quenching of the emission, matching the hole transfer phenomenon. The photovoltaic performance was evaluated and compared with those of reference cells made with the standard HTM spiro-OMeTAD. The optimised 5-based devices showed improvements in all photovoltaic characteristics; their open circuit voltage (Voc) reached close to 1 V and short-circuit current density (Jsc) values were 13.79 and 9.14 mA cm-2 for 5a and 5b, respectively, disclosing the effect of the metallic centre. A maximum power conversion efficiency (PCE) of 10.01% was attained for 5a, which is 65% of the PCE generated by using the spiro-OMeTAD reference. This study demonstrates that C-N linked donor-type porphyrin derivatives are promising novel HTMs for developing efficient and reproducible PSCs.

Reduced Chitosan as a Strategy for Removing Copper Ions from Water.

Toxic heavy metals are priority pollutants in wastewater, commonly present in dangerous concentrations in many places across the globe. Although in trace quantities copper is a heavy metal essential to human life, in excess it causes various diseases, whereby its removal from wastewater is a necessity. Among several reported materials, chitosan is a highly abundant, non-toxic, low-cost, biodegradable polymer, comprising free hydroxyl and amino groups, that has been directly applied as an adsorbent or chemically modified to increase its performance. Taking this into account, reduced chitosan derivatives (RCDs 1-4) were synthesised by chitosan modification with salicylaldehyde, followed by imine reduction, characterised by RMN, FTIR-ATR, TGA and SEM, and used to adsorb Cu(II) from water. A reduced chitosan (RCD3), with a moderate modification percentage (43%) and a high imine reduction percentage (98%), proved to be more efficient than the remainder RCDs and even chitosan, especially at low concentrations under the best adsorption conditions (pH 4, RS/L = 2.5 mg mL-1). RCD3 adsorption data were better described by the Langmuir-Freundlich isotherm and the pseudo-second-order kinetic models. The interaction mechanism was assessed by molecular dynamics simulations, showing that RCDs favour Cu(II) capture from water compared to chitosan, due to a greater Cu(II) interaction with the oxygen of the glucosamine ring and the neighbouring hydroxyl groups.

A controlled open clinical trial of the positive effect of a physical intervention on quality of life in schizophrenia.

Justification: Schizophrenia is a severe mental disorder associated with important physical (obesity and low motor functional capacity) and metabolic (diabetes and cardiovascular diseases) changes that contribute to a more sedentary lifestyle and a low quality of life. Objective: The study aimed to measure the effect of two different protocols of physical exercise [aerobic intervention (AI) versus functional intervention ([FI)] on lifestyle in schizophrenia compared with healthy sedentary subjects. Methodology: A controlled clinical trial involving patients diagnosed with schizophrenia from two different locations [Hospital de Clinicas de Porto Alegre (HCPA) and Centro de Atenção Psicosocial (CAPS) in the city of Camaquã] was carried out. The patients undertook two different exercise protocols (IA: 5-min warm-up of comfortable intensity; 45 min of aerobic exercise of increasing intensity using any of the three modalities-a stationary bicycle, a treadmill, or an elliptical trainer; and 10 min of global stretching of large muscle groups; and FI: a 5 min warm-up with a stationary walk; 15 min of muscle and joint mobility exercises; 25 min of global muscle resistance exercises; and 15 min of breathing body awareness work) twice a week for 12 weeks and were compared with physically inactive healthy controls. Clinical symptoms (BPRS), life quality (SF-36), and physical activity levels (SIMPAQ) were evaluated. The significance level was p ≤ 0.05. Results: The trial involved 38 individuals, of which 24 from each group performed the AI, and 14 from each group underwent the FI. This division of interventions was not randomized but was instead decided upon for convenience. The cases showed significant improvements in quality of life and lifestyle, but these differences were greater in the healthy controls. Both interventions were very beneficial, with the functional intervention tending to be more effective in the cases and the aerobic intervention more effective in the controls. Conclusion: Supervised physical activity improved life quality and reduced sedentary lifestyle in adults with schizophrenia.

Ketamine study: Protocol for naturalistic prospective multicenter study on subcutaneous ketamine infusion in depressed patients with active suicidal ideation.

Background: Psychiatric disorders are associated with more than 90% of reported suicide attempts worldwide, but few treatments have demonstrated a direct effect in reducing suicide risk. Ketamine, originally an anesthetic, has been shown anti-suicide effects in clinical trials designed to treat depression. However, changes at the biochemical level were assessed only in protocols of ketamine with very limited sample sizes, particularly when the subcutaneous route was considered. In addition, the inflammatory changes associated with ketamine effects and their correlation with response to treatment, dose-effect, and suicide risk warrant further investigation. Therefore, we aimed to assess whether ketamine results in better control of suicidal ideation and/or behavior in patients with depressive episodes and whether ketamine affects psychopathology and inflammatory biomarkers. Materials and methods: We report here the design of a naturalistic prospective multicenter study protocol of ketamine in depressive episodes carried out at Hospital de Clínicas de Porto Alegre (HCPA) and Hospital Moinhos de Vento (HMV). The study was planned to recruit adult patients with Major depressive disorder (MDD) or Bipolar disorder (BD) types 1 or 2, who are currently in a depressive episode and show symptoms of suicidal ideation and/or behavior according to the Columbia-Suicide Severity Rating Scale (C-SSRS) and have been prescribed ketamine by their assistant psychiatrist. Patients receive ketamine subcutaneously (SC) twice a week for 1 month, but the frequency can be changed or the dose decreased according to the assistant physician's decision. After the last ketamine session, patients are followed-up via telephone once a month for up to 6 months. The data will be analyzed using repeated measures statistics to evaluate the reduction in suicide risk as a primary outcome, as per C-SSRS. Discussion: We discuss the need for studies with longer follow-ups designed to measure a direct impact on suicide risk and that additional information about the safety and tolerability of ketamine in particular subset of patients such as those with depression and ideation suicide. In line, the mechanism behind the immunomodulatory effects of ketamine is still poorly understood. Trial registration: https://clinicaltrials.gov/, identifier NCT05249309.

Application of 1H HR-MAS NMR-Based Metabolite Fingerprinting of Marine Microalgae.

Natural products from the marine environment as well as microalgae, have been known for the complexity of the metabolites they produce due to their adaptability to different environmental conditions, which has been an inexhaustible source of several bioactive properties, such as antioxidant, anti-tumor, and antimicrobial. This study aims to characterize the main metabolites of three species of microalgae (Nannochloropsis oceanica, Chaetoceros muelleri, and Conticribra weissflogii), which have important applications in the biofuel and nutrition industries, by 1H High-resolution magic angle spinning nuclear magnetic resonance (1H HR-MAS NMR), a method which is non-destructive, is highly reproducible, and requires minimal sample preparation. Even though the three species were found in the same ecosystem and a superior production of lipid compounds was observed, important differences were identified in relation to the production of specialized metabolites. These distinct properties favor the use of these compounds as leaders in the development of new bioactive compounds, especially against environmental, human, and animal pathogens (One Health), and demonstrate their potential in the development of alternatives for aquaculture.

Aerobic and Postural Strength Exercise Benefits in People with Schizophrenia.

BACKGROUND: This study aimed to evaluate the effect of two different types of physical intervention on sedentary behavior and clinical changes in people with schizophrenia. METHOD: This is a clinical trial including people with schizophrenia in regular outpatient care who realized a 3-month exercise protocol and were separated into two groups: aerobic physical intervention (API) and postural physical intervention (PPI). All participants performed an assessment of (a) functional capacity through a 6 min walk test (6MWT), (b) flexibility using Well's bench, (c) disease severity using the Brief Psychiatric Rating Scale (BPRS), (d) quality of life using the SF-36 Questionnaire and (e) physical activity using the Simple Physical Activity Questionnaire (SIMPAQ). RESULTS: Thirty-eight patients with schizophrenia completed the intervention (24 patients in API and 14 patients in PPI). Regarding sedentary behavior, there was an improvement in the API group in the time exercising and in the PPI group concerning time in bed, time walking and exercising. Regarding quality of life, there was an improvement in the API group (functional capacity) and in the PPI group, there was an improvement in physical limitation, pain and emotional limitations. In the API group, there was an improvement in BMI (body mass index), diastolic blood pressure and systolic blood pressure. Functional capacity was improved only in the PPI group. There was no change in flexibility and disease severity. CONCLUSIONS: The study demonstrated a change response in the physical and mental aspects in people with schizophrenia after a change in sedentary behavior.

The impact of FDI on host countries' social welfare: a panel data analysis of 146 countries over the period 2002-2019.

Foreign direct investment (FDI) is an important driver of the increasing globalization of the word economy, and despite being a widely studied phenomenon, studies on the effects of FDI on host countries' social welfare are scarce. So, this work aims to analyze the impact of FDI on welfare measured through the human development index and its three dimensions (education, life expectancy, and income). Based on a sample of 146 countries for the period 2002-2019, the results obtained by two-staged least squares-instrumental variable estimation suggest that FDI impact on social welfare depends on the countries' human capital which reflects countries' absorptive capacity. Results also highlight the role of government expenses in consumption, political stability, and quality of technological infrastructures. Therefore, the results suggest that, in order to improve social welfare, countries should focus and gear their policies towards fostering the improvement of their human resources, political stability, and technological infrastructures.

Sites e aplicativos móveis como estratégias de comunicação durante a pandemia de Covid-19 no Brasil / Websites and mobile applications as communication strategies during the Covid-19 pandemic in Brazil / Sitios web y aplicaciones móviles como estrategias de comunicación durante la pandemia de Covid-19 en Brasil

Objetivo: identificar as métricas disponíveis para as ferramentas digitais que propagam a informação sobre a covid-19 na população brasileira. Metodologia: É um estudo documental, realizado em diferentes plataformas a fim de encontrar sites e aplicativos móveis responsáveis em passar as informações sobre a covid-19 e o estado de pandemia no Brasil. Posteriormente, foram estabelecidas métricas, utilizando a ferramenta SimilarWeb, que auxiliassem a determinar a frequência de uso e aceitação dessas ferramentas pela população. Resultados: No que diz respeito aos sites brasileiros, em primeiro lugar, com o maior número de acessos, encontra-se a página do Ministério da Saúde, do Governo Federal, com uma média de 68 milhões de acessos por mês. O SimularWeb ainda afirma que essa é a 3ª página mais procurada no Brasil. No que diz respeito aos aplicativos, os baixados na Play Store são: CoronavírusSUS e o aplicativo Dados do Bem. Os dispositivos também auxiliam para que as informações sejam passadas rapidamente, utilizando linguagem acessível e elementos atrativos. Conclusão: Nesse contexto, as ferramentas digitais tornaram-se o aliado ideal para a aquisição de novas informações, e assim promover a prevenção, o autocuidado, como a autotriagem e autoavaliação, e o controle do vírus, trazendo diversos benefícios a saúde.

Objective: to identify the metrics available for digital tools that disseminate information about covid19 in the Brazilian population. Methodology: A survey was carried out on different platforms in order to find websites and mobile applications responsible for passing on information about covid-19 and the state of the pandemic in Brazil. Subsequently, metrics were established using the SimilarWeb tool, which would help determine the frequency of use and acceptance of these tools by the population. Results: With regard to Brazilian websites, in first place, with the highest number of accesses, is the page of the Ministry of Health, of the Federal Government, with an average of 68 million accesses per month. SimularWeb also claims that this is the 3rd most searched page in Brazil. With regard to apps, the ones downloaded from the Play Store are: CoronavirusSUS and the Data do Good app. The devices also help to transmit information quickly, using accessible language and attractive elements. Conclusion: In this context, digital tools have become the ideal ally for acquiring new information, and thus promoting prevention, self-care, such as self-screening and self-assessment, and virus control, bringing many health benefits

Objetivo: identificar las métricas disponibles para herramientas digitales que difunden información sobre covid-19 en la población brasileña. Metodología: se realizó una encuesta en diferentes plataformas para encontrar sitios web y aplicaciones móviles responsables de transmitir información sobre covid-19 y el estado de la pandemia en Brasil. Posteriormente se establecieron métricas utilizando la herramienta SimilarWeb, las cuales ayudarían a determinar la frecuencia de uso y aceptación de estas herramientas por parte de la población. Resultados: Con respecto a los sitios web brasileños, en primer lugar, con el mayor número de accesos, está la página del Ministerio de Salud, del Gobierno Federal, con un promedio de 68 millones de accesos por mes. SimularWeb también afirma que esta es la tercera página más buscada en Brasil. En cuanto a las aplicaciones, las que se descargan de la Play Store son: CoronavirusSUS y la aplicación Data do Good. Los dispositivos también ayudan a transmitir información de forma rápida, utilizando un lenguaje accesible y elementos atractivos. Conclusión: En este contexto, las herramientas digitales se han convertido en el aliado ideal para adquirir nueva información y así promover la prevención, el autocuidado, como la autoevaluación y la autoevaluación, y el control de virus, trayendo muchos beneficios para la salud.

Clozapine prescription trends in Brazil in the last decade

Objective: Clozapine is a second-generation antipsychotic indicated for treatment-resistant schizophrenia. Studies in several countries have shown a low rate of clozapine use despite the fact that approximately 30% of schizophrenia cases are treatment-resistant. In Brazil, few studies have addressed the frequency and variety of antipsychotic use in individuals diagnosed with schizophrenia (ICD F20). The objective of this study was to measure the rates of clozapine use in this population in the last decade using Brazilian Ministry of Health data. Methods: Prescriptions made between 2010 and 2020 in all 26 states and the Federal District registered at the Outpatient Information System Database from the Brazilian Health System (SIASUS) were evaluated. Results: A total of 25,143,524 prescriptions were recorded in this period, with clozapine representing 8.86% of all antipsychotics. The most frequently prescribed antipsychotic for patients with schizophrenia was olanzapine (35.8%), followed by quetiapine (27.5%). From 2010 to 2020, the rate of clozapine prescriptions in Brazil increased from 7.2% to 10.9%. Conclusions: Despite a slight increase in prescriptions in the last decade, clozapine is still underutilized in Brazil.

Clozapine prescription trends in Brazil in the last decade.

OBJECTIVE: Clozapine is a second-generation antipsychotic indicated for treatment-resistant schizophrenia. Studies in several countries have shown a low rate of clozapine use despite the fact that approximately 30% of schizophrenia cases are treatment-resistant. In Brazil, few studies have addressed the frequency and variety of antipsychotic use in individuals diagnosed with schizophrenia (ICD F20). The objective of this study was to measure the rates of clozapine use in this population in the last decade using Brazilian Ministry of Health data. METHODS: Prescriptions made between 2010 and 2020 in all 26 states and the Federal District registered at the Outpatient Information System Database from the Brazilian Health System (SIASUS) were evaluated. RESULTS: A total of 25,143,524 prescriptions were recorded in this period, with clozapine representing 8.86% of all antipsychotics. The most frequently prescribed antipsychotic for patients with schizophrenia was olanzapine (35.8%), followed by quetiapine (27.5%). From 2010 to 2020, the rate of clozapine prescriptions in Brazil increased from 7.2% to 10.9%. CONCLUSIONS: Despite a slight increase in prescriptions in the last decade, clozapine is still underutilized in Brazil.

Reaction of Corroles with Sarcosine and Paraformaldehyde: A New Facet of Corrole Chemistry.

Details on the unexpected formation of two new (dimethylamino)methyl corrole isomers from the reaction of 5,10,15-tris(pentafluorophenyl)corrolatogallium(III) with sarcosine and paraformaldehyde are presented. Semi-empirical calculations on possible mechanism pathways seem to indicate that the new compounds are probably formed through a Mannich-type reaction. The extension of the protocol to the free-base 5,10,15-tris(pentafluorophenyl)corrole afforded an unexpected new seven-membered ring corrole derivative, confirming the peculiar behavior of corroles towards known reactions when compared to the well-behaved porphyrin counterparts.

UV-C irradiation-based inactivation of SARS-CoV-2 in contaminated porous and non-porous surfaces.

The SARS-CoV-2 pandemic emphasized effective cleaning and disinfection of common spaces as an essential tool to mitigate viral transmission. To address this problem, decontamination technologies based on UV-C light are being used. Our aim was to generate coherent and translational datasets of effective UV-C-based SARS-CoV-2 inactivation protocols for the application on surfaces with different compositions. Virus infectivity after UV-C exposure of several porous (bed linen, various types of upholstery, synthetic leather, clothing) and non-porous (types of plastic, stainless steel, glass, ceramics, wood, vinyl) materials was assessed through plaque assay using a SARS-CoV-2 clinical isolate. Studies were conducted under controlled environmental conditions with a 254-nm UV-C lamp and irradiance values quantified using a 254 nm-calibrated sensor. From each material type (porous/non-porous), a product was selected as a reference to assess the decrease of infectious virus particles as a function of UV-C dose, before testing the remaining surfaces with selected critical doses. Our data show that UV-C irradiation is effectively inactivating SARS-CoV-2 on both material types. However, an efficient reduction in the number of infectious viral particles was achieved much faster and at lower doses on non-porous surfaces. The treatment effectiveness on porous surfaces was demonstrated to be highly variable and composition-dependent. Our findings will support the optimization of UV-C-based technologies, enabling the adoption of effective customizable protocols that will help to ensure higher antiviral efficiencies.

Allergic reaction induced by subcutaneous administration of ketamine: a case report.

Ketamine can be used for depression and suicidal ideation due to its effectiveness and low complication rates; moreover, allergic reactions are rare. Immediately after subcutaneous (SC) ketamine administration, a 22-year-old man rapidly developed hives on the trunk and face without oxygen desaturation. Symptoms disappeared after treatment with prednisolone. This case presents an allergic reaction to ketamine compatible with mast cell activation and release of preformed mediators, without being able to prove whether the event was mediated by immunoglobulin E. This is the only case reported to date of an allergic reaction to SC ketamine for psychiatric treatment.

Chemical Profile and Antimicrobial Activity of the Marine Diatom Chaetoceros muelleri.

Microalgae, due to its rapid growth, low nutritional requirements, and versatility of adaptation to different environmental conditions, has aroused the biotechnological interest, synthesizing novel molecules with antioxidant, anticoagulant, anti-inflammatory, antitumor, and antimicrobial activities. In this sense, we carried out the bioprospection of Chaetoceros muelleri, a marine diatom employed in aquaculture, as a candidate to the development of new drugs for the treatment of bacterial infections. The chemical profile of extracts in different solvents (hexane, chloroform, methylene chloride, ethyl acetate, methanol, and acetone) were analyzed by 1 H-NMR. The hexane extract was the most active against all bacteria species tested, including Mycobacterium tuberculosis, with a minimum inhibitory concentration of 100 µg/ml. Contrarily, the methanol extract was inactive against all tested microorganisms and, in addition, was the only one with IC50 >800 µg/mL, showing no cytotoxicity in VERO cell lines. All other extracts showed antibacterial potential and IC50 values varying between 267.58 and 142.47 µg/ml. The fact that C. muelleri is a microalga easily grown on bioreactors on a large scale may promote its biotechnological use, especially as scaffolds for the development of new compounds against bacterial species of clinical and public health interest.

Risk of neutropenia among clozapine users and non-users: results from 5,847 patients

Objective: Clozapine is underprescribed due to neutropenia risk. Blood tests every 3 months in those on continuous treatment for > 1 year who have never had an absolute neutrophil count (ANC) < 2,000/µL has been proposed as a monitoring strategy; however, there are no South American data to support this recommendation. This study sought to investigate whether clozapine use and other variables could explain the occurrence of ANC < 1,000/µL in patients with severe mental disorders. Methods: A total of 5,847 subjects were included, 1,038 on clozapine. We performed a Cox regression considering the outcome as ANC < 1,000/µL at any time point. Predictors were sex, age, ethnicity, clozapine use, ANC > 2,000/µL during the first year of blood monitoring, and presence of a severe medical condition. Results: In the Cox regression model, ethnicity (white) (hazard ratio [HR] 0.53; 95%CI 0.29-0.99, p < 0.05) and ANC > 2,000/µL (HR 0.04; 95%CI 0.01-0.10, p < 0.001) were protective factors, while presence of a severe medical condition (HR 69.35; 95%CI 37.45-128.44, p < 0.001) was a risk factor for ANC < 1,000/µL. Other variables were not significant, including clozapine use (HR 1.33; 95%CI 0.74-2.39, p > 0.05). Conclusions: These findings suggest that clozapine does not increase the risk of neutropenia in subjects with ANC > 2,000/µL during the first year of use and in the absence of a severe medical condition. These results could help guide clinical and public-health decisions regarding clozapine blood monitoring guidelines.

Risk of neutropenia among clozapine users and non-users: results from 5,847 patients.

OBJECTIVE: Clozapine is underprescribed due to neutropenia risk. Blood tests every 3 months in those on continuous treatment for > 1 year who have never had an absolute neutrophil count (ANC) < 2,000/µL has been proposed as a monitoring strategy; however, there are no South American data to support this recommendation. This study sought to investigate whether clozapine use and other variables could explain the occurrence of ANC < 1,000/µL in patients with severe mental disorders. METHODS: A total of 5,847 subjects were included, 1,038 on clozapine. We performed a Cox regression considering the outcome as ANC < 1,000/µL at any time point. Predictors were sex, age, ethnicity, clozapine use, ANC > 2,000/µL during the first year of blood monitoring, and presence of a severe medical condition. RESULTS: In the Cox regression model, ethnicity (white) (hazard ratio [HR] 0.53; 95%CI 0.29-0.99, p < 0.05) and ANC > 2,000/µL (HR 0.04; 95%CI 0.01-0.10, p < 0.001) were protective factors, while presence of a severe medical condition (HR 69.35; 95%CI 37.45-128.44, p < 0.001) was a risk factor for ANC < 1,000/µL. Other variables were not significant, including clozapine use (HR 1.33; 95%CI 0.74-2.39, p > 0.05). CONCLUSIONS: These findings suggest that clozapine does not increase the risk of neutropenia in subjects with ANC > 2,000/µL during the first year of use and in the absence of a severe medical condition. These results could help guide clinical and public-health decisions regarding clozapine blood monitoring guidelines.

Differential Physical and Mental Benefits of Physiotherapy Program Among Patients With Schizophrenia and Healthy Controls Suggesting Different Physical Characteristics and Needs.

In contrast to several other severe illnesses marked by inflammation and autoimmunity that now have potent and efficient treatments and even cures, schizophrenia (SCZ) is a disease still associated with poor outcome, incapacity, and social burden. Even after decades of research on the brain and behavior, this illness is still associated with profound effects on both mental health and physical health, with recent studies showing that treatment is more efficient when associating drugs with psychological and physical treatments. Most of the studies measured the effects of physical intervention compared with usual care and demonstrated a positive effect as an add-on treatment. What remains unclear is the different effects of the same intervention in normal subjects in a sample of patients with the illness. The study aimed to evaluate the effects of physical intervention over motor functional capacity and mental health in patients with SCZ compared with healthy controls (HC). The outcomes were (a) functional capacity [by 6-min walk test (6MWT)], (b) body flexibility index (Wells' bench), (c) disease severity [by Brief Psychiatric Rating Scale (BPRS)], (d) quality of life [by 36-Item Short Form (SF-36) questionnaire], and (e) physical activity [Simple Physical Activity Questionnaire (SIMPAQ)]. The intervention was associated with significant decrease of body mass index (BMI), blood pressure, disease severity, and improvement in daily life activities. Unexpectedly, it was observed that schizophrenics, compared with matched HC, were at a lower level of performance in the beginning, remained below HC over the studied time despite similar physical intervention, and had different changes. The intervention had lower effects over physical capacity and better effects over quality of life and disease severity. The results confirm previous studies comparing patients receiving physical intervention but suggest that they may receive different types of intervention, suited for their different baseline fitness, motivation, and capacity to engage in physical effort over sustained time. Additionally, they point to extended time of intervention of multidisciplinary treatment (physical and psychological-cognitive techniques) to improve outcomes in SCZ.