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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.

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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.

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Ozone therapy (OT), a medical procedure, has been showing good results during the coronavirus disease (COVID-19). We aimed to build an evidence and gaps map (EGM) of OT in the COVID-19 ranking the articles found according to levels of evidence and outcomes. The EGM brings bubbles of different sizes and different colors according to the articles. The OT intervention used was major or minor autohemotherapy, rectal insufflation and ozonized saline solution. EGM was based on 13 clinical studies using OT for COVID-19 involving a total of 271 patients. We found 30 outcomes related to OT in COVID-19. Our EGM divided the outcomes into six groups: 1-clinical improvement; 2-hospitalization; 3-inflammatory, thromboembolic, infectious, or metabolic markers; 4-radiological aspects, 5-viral infection and 6-adverse events. Major autohemotherapy was present in 19 outcomes, followed by rectal insufflation. Improvement in clinical symptoms of COVID-19, improvement of respiratory function, improvement of oxygen saturation, reduction in hospital internment, decrease in C-reactive protein, decrease in ferritin, decrease in lactate dehydrogenase, decrease in interleukin 6, decrease in D-dimer, radiological improvement of lung lesions and absence of reported adverse events were related in the papers. The most commonly used concentrations of OT in major autohemotherapy and in rectal insufflation were 40 µg/mL and 35 µg/mL, respectively. Here, we bring the first EGM showing the efficacy and safety of OT in the treatment of COVID-19. OT can be used as integrative medical therapy in COVID-19 at a low cost and improve the health conditions of the patients.

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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.

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Post-traumatic stress disorder (PTSD) has been associated with persistent, low-degree inflammation, which could explain the increased prevalence of autoimmune conditions and accelerated aging among patients. The aim of the present study is to assess which inflammatory and oxidative stress markers are associated with PTSD. We carried out a meta-analytic and meta-regression analysis based on a systematic review of studies comparing inflammatory and oxidative stress markers between patients with PTSD and controls. We undertook meta-analyses whenever values of inflammatory and oxidative stress markers were available in two or more studies. Overall, 28,008 abstracts were identified, and 54 studies were included, with a total of 8394 participants. The Newcastle-Ottawa Quality Assessment Scale was used to evaluate the quality of the studies. Concentrations of C-reactive protein (SMD = 0.64; 95% CI: 0.21 to 1.06; p = 0.0031; k = 12), interleukin 6 (SMD = 0.94; 95% CI: 0.36 to 1.52; p = 0.0014; k = 32), and tumor necrosis factor-α (SMD = 0.89; 95% CI: 0.23 to 1.55; p = 0.0080; k = 24) were significantly increased in patients with PTSD in comparison with healthy controls. Interleukin 1ß levels almost reached the threshold for significance (SMD = 1.20; 95% CI: -0.04 to 2.44; p = 0.0569; k = 15). No oxidative stress marker was associated with PTSD. These findings may explain why PTSD is associated with accelerated aging and illnesses in which immune activation has a key role, such as cardiovascular diseases and diabetes. In addition, they pointed to the potential role of inflammatory markers as therapeutic targets.

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Este mapa de evidências apresenta uma síntese gráfica de estudos clínicos sobre a aplicação da Ozonioterapia em casos de COVID-19. A partir de uma ampla busca bibliográfica 11 estudos clínicos foram incluídos no mapa e categorizados por tipo de intervenção e por desfechos. Os estudos avaliaram o efeito de 4 tipos de intervenção com Ozonioterapia: auto-hemoterapia maior, auto-hemoterapia menor, insuflação retal e solução salina ozonizada; para 6 grupos de desfechos relacionados à COVID-19: Melhora clínica; Internação hospitalar; Marcadores inflamatórios, tromboembólicos, infecciosos ou metabólicos; Aspectos radiológicos; Infecção viral; e Eventos adversos. Os círculos localizados nas intersecções entre as intervenções e os desfechos representam os estudos identificados e a quantidade. A cor do círculo representa o desenho do estudo: Verde para os Ensaios Clínicos Randomizados (RCTs), Amarelo para os Ensaios Clínicos não Randomizados (Non RCTs) e Estudos Clínicos quasi-experimental, e Vermelho para os Relatos de Caso e Estudos de Casos e Controle.

This evidence map presents a graphical summary of clinical studies on the application of Ozone Therapy in cases of COVID-19. From a wide bibliographic search, 11 clinical studies were included in the map and categorized by type of intervention and outcomes. The studies evaluated the effect of 4 types of intervention with Ozone Therapy: Major Autohemotherapy, Minor Autohemotherapy, Rectal Insufflation and Ozonized Saline; for 29 outcomes related to COVID-19, which on the map are divided into 6 groups: 1- clinical improvement; 2-hospitalization; 3- inflammatory, thromboembolic, infectious or metabolic markers; 4- radiological aspects, 5- viral infection and 6- adverse events. Circles located at the intersections between interventions and outcomes represent the identified studies and quantity. The color of the circle represents the study design: Green for Randomized Clinical Trials (RCTs), Yellow for Non-Randomized Clinical Trials (Non RCTs) and Quasi-experimental Clinical Studies, and Red for Case Reports and Case-Control Studies.

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Introduction: The Brazil has one of the largest public health systems in the world and in the 1980's, Traditional, Complementary and Integrative Medicine were introduced. In 2018, the treatment with ozone became a complementary integrative practice showing several benefits. However, its effectiveness needs to be researched. The objective of this evidence gap map is to describe contributions of Integrative Medicines-Ozone treatment in different clinical conditions, to promote evidence-based practice. Methods: We applied the methodology developed by Latin American and Caribbean Center on Health Sciences Information based on the 3iE evidence gap map. The EMBASE, PubMed and Virtual Health Library databases, using the MeSH and DeCS terms for the treatment with Ozone were used. Results: 26 systematic reviews were characterized, distributed in a matrix containing 6 interventions (parenteral oxygen/ozone gas mixture; parenteral ozonated water; systemic routes; topical application ozonated water; topical oxygen/ozone gas mixture; and topical ozonated oil) and 55 outcomes (cancer, infection, inflammation, pain, quality of life, wound healing and adverse effects). 334 associations between intervention and outcome were observed, emphasizing the parenteral oxygen/ozone gas mixture intervention (192 associations, 57%). Conclusions: The evidence gap map presents an overview of contributions of Ozone treatment in controlling pain, infections, inflammation and wound healing, as well as increasing the quality of life, and it is directed to researchers and health professionals specialized in Ozone treatment. No serious adverse effects were related. Therefore, this treatment may be even more widely known as an integrative treatment, considering its low cost, efficiency and safety. Future studies should adopt economic impact assessments and the organization of health services.

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Acute or chronic inflammatory reactions aim to control lesions, resist to pathogens attack and repair damaged tissue. The therapeutic administration of ozone known as ozone therapy appears as a possible treatment for tissue repair, as it promotes the healing of wounds. It has bactericidal, antiviral and antifungal properties and has been used as a therapeutic resource to treat inflammation. The objective was to carry out an integrative review regarding the use of ozonated oil in acute and chronic inflammations. The keywords "ozone therapy," "inflammation" and "ozone" were used in the Portuguese, Spanish and English languages. The paper selection was based on inclusion and exclusion criteria. In total, 28 articles were selected. It has been seen that ozonated oil is effective in healing cutaneous wounds. The beneficial effects are due to the healing of wounds, due to the reduction of microbial infection, debridement effect, modulation of the inflammatory phase, stimulation to angiogenesis as well as biological and enzymatic reactions that favor the oxygen metabolism, improving the wound cicatrization. In addition to promoting healing, ozonated oil reduces symptoms related to skin burns, prevents post-lesion hyperpigmentation, and reduces the pain of aphthous ulcers. Therefore, ozonated oil represents an effective and inexpensive therapeutic alternative that must be implanted in the public health system.

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Purpose: We aimed to evaluate the effect of blueberry extract and microparticles (MP) on sunscreen performance of multifunctional cosmetics. Octocrylene (OCT), benzophenone-3 (BENZ-3) and Tinosorb® M (MBBT) were employed as UV filters. Methods: An in-silico modeling was used to determine the UV filters concentrations to obtain high values of sunscreen protection factor (SPF) and UVA protection factor (UVA-PF). MBBT and blueberry-loaded microparticles (MPMB+B) and MBBT-loaded microparticles (MPMBBT) were prepared by spray-drying. OCT and BENZ-3 were added in the oil phase of cosmetics. Cosmetics A and B contained MPMB+B and MPMBBT, respectively, and cosmetic C was prepared without MP. Characterization, physicochemical stability and in vitro SPF was performed. UV filters distribution in human stratum corneum (SC) for each cosmetic was performed. Anti-oxidant activity of blueberry extract was evaluated. Results: Sunscreen combination with the highest SPF was selected for formulations. Formulations A and B maintained their rheological behavior over time, unlike formulation C. In-vitro SPFs for formulations A, B and C were 51.0, 33.7 and 49.6, respectively. We also developed and validated a method for analysis of the UV filters by HPLC/ PDA suitable for the in-vivo assay. In Tape stripping test, MBBT showed SC distribution similar for all cosmetic formulations. OCT and BENZ-3 distribution to formulation A and C was also similar. Blueberry extract showed antioxidant capacity of 16.71 µg/mL equivalent to vitamin C. Conclusion: Cosmetics containing MPs presented better physical stability. Blueberry increased the photoprotective capacity of the formulations and added extra benefits due to its anti-oxidant and anti-aging properties.

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Midazolam (MDZ) is the first choice in palliative sedation, and commonly used in sleep induction in anesthesia, with rapid onset of action. However, monitoring of the level of sedation in patients is not accurate. We developed and validated a bioanalytical method to detect MDZ in plasma using high-performance liquid chromatography (HPLC) coupled to a photodiode array detector (PDA) for future monitoring of sedation. MDZ was extracted by solid-phase extraction (SPE). Analyses were performed on a C18 column, using 0.05% triethylamine and acetonitrile as mobile phase, analyzing at 220 nm. Recovery was evaluated by comparing extracted and nonextracted solutions. Precision, accuracy, linearity, limits of detection (LD) and quantification (LQ), specificity and selectivity were determined. The mean recovery obtained by SPE was 101.03%. The method was linear in the range 1.0-50.0 µg/mL. The LD and LQ were, respectively, 0.43 and 1.43 µg/mL. The specificity of the MDZ peak was adequate. The method was able to detect MDZ among other drugs. Plasma anticoagulants showed no interference with the drug detection. The bioanalytical method using HPLC-PDA and SPE was successfully validated and showed linearity, precision, accuracy, specificity and high sensitivity for detection of MDZ in human plasma.

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Este mapa apresenta uma visão geral das evidências e lacunas existentes sobre os efeitos da Ozonioterapia Médica para diversas condições clinicas e de saúde das pessoas. A partir de uma ampla busca bibliográfica de estudos publicados e não publicados entre 2000 e meados de 2019, foram incluídas no mapa 14 revisões sistemáticas. Todos os estudos foram avaliados, caracterizados e categorizados pela Sociedade Brasileira de Ozonioterapia Médica (SOBOM) e contou com o apoio da World Federation of Ozone Therapy (WFOT).

Este mapa presenta una visión general de la evidencia y las lagunas existentes sobre los efectos de la Ozonoterapia Médica para diversas condiciones clínicas y de salud de las personas. A partir de una amplia búsqueda bibliográfica de estudios publicados y no publicados entre 2000 y mediados de 2019, se incluyeron 14 revisiones sistemáticas en el mapa.Todos los estudios fueron evaluados, caracterizados y categorizados por la Sociedad Brasileña de Ozonioterapia Médica (SOBOM) y tuve el apoyo de la World Federation of Ozone Therapy (WFOT).

This map provides an overview of the evidence and gaps that exist on the effects of Medical Ozone Therapy for various clinical and health conditions of people. From a broad bibliographic search of published and unpublished studies between 2000 and mid-2019, 14 systematic reviews were included in the map. All studies were evaluated, characterized and categorized by the Brazilian Society of Medical Ozone Therapy (SOBOM) with support from the World Federation of Ozone Therapy (WFOT).

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ABSTRACT BACKGROUND AND OBJECTIVES: Osteoarthrosis affects 85% of the population over 75 years of age. It is divided into primary and secondary, however despite the knowledge at the molecular level the treatments are not yet fully effective. However, ozone therapy emerges as an alternative therapy, which is low cost and seems effective in the treatment of chronic pain. The objective of this study was to evaluate the current evidence to support or to refute the use of ozone therapy in the treatment of patients with osteoarthritis. CONTENTS: Systematic review using the keywords "ozone therapy", "ozone", "osteoarthritis", "arthritis", "randomized", "controlled" and "meta-analysis". The selection of publications was based on inclusion and exclusion criteria. In total, 9 articles were used. Among the 9 articles found regarding ozone therapy in osteoarthritis, 7 of them clearly show the benefits of ozone. The concentrations of ozone used in the studies ranged from 20µg/mL to 15g/mL. The route of administration was intra-articular and rectal insufflation. The frequency of use was, on average, 1 to 3 times a week and the treatment time was between 3 to 4 months in most of the studies. CONCLUSION: The use of ozone produces clinically relevant benefits in patients with osteoarthrosis. Therefore, ozone therapy in osteoarthrosis represents a low-cost, efficient therapeutic alternative that should be implemented in the country's Public Health, considering the prevalence of the disease.

RESUMO JUSTIFICATIVA E OBJETIVOS: A osteoartrose atinge 85% da população com mais de 75 anos. A mesma é dividida em primária e secundária, porém apesar do conhecimento a nível molecular, os tratamentos ainda não são totalmente eficazes. Entretanto, a ozonioterapia, é de baixo custo e parece efetiva no tratamento da dor crônica. O objetivo deste trabalho foi avaliar as evidências atuais que apoiem ou refutem o uso da ozonioterapia no tratamento de pacientes com osteoartrose. CONTEÚDO: Revisão sistemática, utilizando as palavras-chave: "ozone therapy", "ozone", "osteoarthritis", "arthritis", "randomised", "controlled" e "meta-analysis". A seleção das publicações foi feita a partir de critérios de inclusão e exclusão. Ao total foram utilizados 9 artigos. Dentre os 9 artigos encontrados a respeito de ozonioterapia na osteoartrose, 7 deles mostraram claramente os benefícios do ozônio. As concentrações de ozônio utilizadas nos estudos variaram de 20µg/mL a 15g/mL. A via de administração utilizada foi a intra-articular e a insuflação retal. A frequência do uso foi, em média, de 1 a 3 vezes por semana e o tempo de tratamento foi entre 3 a 4 meses na maior parte dos estudos. CONCLUSÃO: O uso do ozônio produz benefícios clinicamente relevantes em pacientes com osteoartrose, portanto a ozonioterapia na osteoartrose representa uma alternativa terapêutica de baixo custo, e eficiente, que deve ser implantada na Saúde Pública do país, tendo em vista a prevalência da doença.

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Ozone helps decontamination environments due to its oxidative power, however present toxicity when it is in high concentrations, by long periods of exposition. This study aimed to assess the safety of ozone generator air purifier at concentrations of 0.05 ppm in rats exposed to 3 and 24 h/day for 14 and 28 days. No significant differences are observed between groups in clinical signs, feed and water intake, relative body weight gain and relative weight of organs, macroscopy and microscopy of lungs, and oxidative plasma assay. In this exposure regime, ozone does not cause genotoxicity and no significant changes in pulmonary histology indicative of toxicity. Ozone generated in low concentrations, even in exposure regimes above the recommended is safe, both acute and sub-acute exposition.

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Objetivo ­ As infecções relacionadas à assistência à saúde são um problema mundial. A contaminação de pacientes através de mãos e objetos constitui-se na principal causa de infecção. O objetivo deste foi avaliar a contaminação bacteriana de terminais de computadores utilizados em diferentes setores do Hospital da Cidade de Passo Fundo-RS (HCPF), analisando o possível papel dos mesmos como fômites de infecção hospitalar. Métodos ­ Ao todo foram coletadas amostras de 221 terminais de computadores situados em setores críticos, semicríticos e não críticos. A coleta foi realizada com swab umedecido em solução salina, por fricção, sendo o material semeado em placas de Petri contendo ágar sangue e ágar MacConkey. As placas foram incubadas a 35-37ºC por 24 horas e as colônias presentes nos meios de cultura foram identificadas por técnicas convencionais. Resultados ­ Em 87,5% das amostras houve crescimento de micro-organismos, sendo identificados 11 tipos de bactérias. Cocos Gram-positivos foram os mais frequentes, com predominância de Staphylococcus coagulase-negativos (44,3%). As bactérias Gram-negativas foram responsáveis por apenas 4,2% dos casos. Não houve diferença significativa entre os três setores, embora Staphylococcus aureus tenha ocorrido com maior frequência nos setores críticos. Conclusão ­ Elevados níveis de contaminação foram observados nos terminais de computadores dos três setores, reforçando a importância da higienização desses equipamentos para evitar a transmissão cruzada de micro-organismos para os pacientes.

Objective ­ Infections related to health care is a global problem. Contamination of patients through hands and objects constitutes the main cause of infection. The objective of this study was to evaluate the bacterial contamination on computer terminals of different sectors of the Hospital da Cidade de Passo Fundo-RS (HCPF), to determine their possible role as sources of hospital infections. Methods ­ Samples were collected from 221 computer terminals located in critical, semi-critical, and non-critical sectors. The collection was made by rubbing the terminals with saline solution moistened swabs, then applying to blood and MacConkey agars in Petri dishes. After incubation at 35ºC to 37ºC for 24 hours, any resulting colonies in the medium were identified by conventional methods. Results ­ There was micro-organism growth in 87.5% of the samples, identified as 11 types of bacteria. Gram-positive cocci were the most frequent, predominantly Staphylococcus coagulase-negative. Gram-negative bacteria accounted for only 4.2% of the cases. There was no significant difference among the three sectors, although critical sectors had a higher frequency of Staphylococcus aureus. Conclusion ­ High levels of contamination were observed on computer terminals of all three sectors, re-enforcing the importance of equipment sanitation to prevent micro-organism cross transmission to patients.