Complicações de acessos vasculares totalmente implantáveis inseridos no Hospital do Servidor Público Municipal - SP / Complications of fully implantable vascular accesses inserted at Hospital do Servidor Público Municipal - SP

Introdução: Os ports são cada vez mais aceitos no meio médico e por pacientes. Por ser um dispositivo totalmente implantável, requer menores cuidados locais, diminuindo a possibilidade de infecção ou outras complicações inerentes aos acessos centrais de longa duração. Levando-se em conta o risco das complicações, faz-se necessário analisar a prevalência de complicações após inserção dos ports, a fim de avaliar a eficácia e segurança do procedimento e identificar possíveis falhas do processo. Objetivo: Avaliar a prevalência de complicações após inserção de acessos venosos centrais totalmente implantáveis pela equipe de cirurgia vascular. Método: O estudo foi realizado na enfermaria e ambulatório da cirurgia vascular do Hospital do Servidor Público Municipal ­ SP, e incluiu pacientes atendidos no período de agosto de 2022 a agosto de 2023. Resultados: A amostra deste estudo foi constituída por 62 pacientes oncológicos, sendo 17 do sexo masculino (27%) e 45 do sexo feminino (73%). A comorbidade mais prevalente foi a Hipertensão Arterial Sistêmica isolada ou associada a outras doenças (40,3%, 25 pacientes). A neoplasia mais frequente foi o adenocarcinoma de colo em 14 pacientes (22,6%). Quanto ao acesso, a veia jugular interna direita foi a mais utilizada (50 pacientes, totalizando 80,6%). Quanto às complicações, estas estiveram ausentes em 56 pacientes (90,3%). Desconexão de cateter foi observada em 1 paciente (1,6%), hematoma infectado em 1 (1,6%), hematoma local em 1 (1,6%), hematoma em pós-operatório imediato em 1 (1,6%), infecção em 1 (1,6%), e trombose de veia jugular interna direita em 1 (1,6%). Em 60 pacientes não houve dificuldade de manuseio (96,8%), e em 5 pacientes o dispositivo necessitou ser retirado (8,1%). No total ocorreram 10 óbitos (16,1%) enquanto 52 pacientes permaneceram vivos após a avaliação (83,9%). Conclusão: A prevalência de complicações relacionadas à inserção de cateter em nossa amostra foi bastante reduzida, tendo sido identificadas em apenas 6 pacientes (9,7% do total). Desconexão de cateter, hematoma infectado, hematoma local, hematoma em pós-operatório imediato, infecção e trombose de veia jugular direita foram identificadas cada uma em um único paciente. Palavras-chave: Cirurgia Vascular. Portocath. Cateter Venoso Central. Complicações.

Descentralización de la elaboración de los tratamientos antineoplásicos. Optimización de los recursos / Decentralisation of the preparation of antineoplastic treatments. Resources

Objetivos: La metodología “Six Sigma” se basa en el análisis de los flujos de trabajo e identificación de los puntos de mejoras con el fin de lograr una máxima eficiencia en los procesos, tanto industriales como sanitarios. El objetivo de este estudio es comparar la eficiencia entre un sistema “clásico” de elaboración de quimioterapia centralizado en el Servicio de Farmacia frente a un modelo descentralizado. Material y métodos: Estudio observacional en el que se analizó la eficiencia de los modelos de elaboración de preparaciones quimioterápicas: 1.- Modelo clásico (MC), a partir del cual se suministran las preparaciones al Hospital de Día de Hematología: las campanas de elaboración de tratamientos y el farmacéutico están presentes en el Servicio de Farmacia.2.- Modelo descentralizado (MD): el farmacéutico y las campanas de preparación de la medicación se encuentran en Hospital de Día de Oncología. La eficiencia de cada sistema se evaluó mediante el tiempo transcurrido desde la recepción de la orden médica hasta la administración de la quimioterapia (TAQ).Resultados: El TAQ siguiendo el MD fue inferior que para el MC: 13,7 [5-28] minutos versus 71,0 [42-96] minutos (p<0,001) con una diferencia media de 57,3 minutos/preparación. El tiempo potencialmente ahorrado con el modelo descentralizado fue de 40,3 horas/día. Conclusiones: Con el presente trabajo hemos querido cuantificar y comparar la eficiencia de los dos modelos de elaboración de mezclas citostáticas, siendo desfavorable para el sistema clásico de centralización para la preparación de la medicación en los Servicios de Farmacia. (AU)

Aims: The «Six Sigma» methodology is based on the analysis of workflows and the identification of areas for improvement in order to achieve maximum efficiency in industrial and healthcare processes. The aim of this study is to compare the efficiency of a «classic» chemotherapy preparation system centralised in the Pharmacy Service versus a decentralised model.Material and methods: Observational study in which the efficiency of the models for the preparation of chemotherapy treatments was analysed: 1.- Classical model (MC), which has the treatment preparation cabinets and a pharmacist located in the Pharmacy Service, and from which the preparations are supplied to the Haematology Day Hospital. 2.- Decentralised model (MD), where both the pharmacist and the medication preparation cabinets are located in the Oncology Day Hospital .For the evaluation of the efficiency of each system, the time elapsed from the receipt of the medical order to the administration of chemotherapy (TAQ) was compared. Results: The TAQ following MD was less than for MC: 13.7 [5-28] minutes versus 71.0 [42-96] minutes (p<0.001) with a mean difference of 57.3 minutes/prescription. The potential time saved with the decentralised model was 40.3 hours/day. Conclusions: The aim of this study was to quantify and compare the efficiency of the two models for the preparation of cytostatic mixtures, showing that the classical centralised system for the preparation of medication in pharmacy services is unfavourable. (AU)

O odontólogo frente aos cuidados paliativos na oncologia / The dental surgeon facing palliative care in oncology: a literature review / El odontólogo ante los cuidados paliativos en oncología

Cuidados paliativos são um conjunto de procedimentos ofertados ao paciente por uma equipe multidisciplinar com objetivo de garantir bem-estar, autonomia,conforto e alívio de sintomas decorrentes de doença ou tratamento quando a cura é impossibilitada. O câncer representa uma das doenças que possuem chances de evoluir o paciente ao estágio terminal, momento em que cuidados paliativos são indicados e necessários. Dentro da equipe responsável, o cirurgião-dentista atua na prevenção, diagnóstico e tratamento de lesões expressas no sistema estomatognático que se manifestam estimuladas pelo câncer ou pelos tratamentos utilizados. O objetivo desta pesquisa é destacar a função do odontólogo dentro da equipe multidisciplinar paliativista para pacientes oncológicos. Trata-se de uma revisão bibliográfica sistemáticada literatura. Foram feitas buscas nas plataformas Biblioteca Virtual em Saúde (BVS) e Scientific Electronic Library Online (SciELO) e após aplicação dos critérios de inclusão e exclusão foram selecionados 14 artigos. A literatura evidencia que alterações orais estão relacionadas com o curso da neoplasia ou seu tratamento; as lesões mais descritas foram: mucosite, xerostomia, candidíase, cárie, periodontite e osteorradionecrose. Isso faz com que o paciente sofra limitações em realizar atividades básicas, alterando negativamente a sua qualidade de vida. A complexidade da manifestação oral pode interromper o tratamento antineoplásico. As medidas de enfrentamento mais empregadas para a saúde bucal do paciente oncológico são a laserterapia, bochechos com clorexidina 0,12%, instrução de higiene oral, uso de anti-inflamatórios, analgésicos e antifúngicos. A atuação do odontólogo na equipe multidisciplinar oncológica paliativista é indispensável para o controle das manifestações orais.

Palliative care comprises a set of procedures offered by a multidisciplinary team to patients who cannot be cured, aiming to restore and ensure well-being, autonomy, independence, comfort and relief from symptoms resulting from illness or treatments. Cancer commonly leads the patient to the terminal stage, and at this stage palliative care is indicated and necessary. Composing the multidisciplinary team, the dentist works in the prevention, diagnosis and treatment of injuries that arise in the stomatognathic system, which manifest themselves due to cancer or its treatments. The objective of this research was to highlight the work of the dentist in the multidisciplinary team of palliative care for cancer patients. This is a systematic bibliographic review of the literature, with an integrative character. Study searches were performed in the Virtual Health Library (VHL) and Scientific Electronic Library Online (SciELO). After applying the inclusion and exclusion criteria, 14 articles were selected. Results showed that oral alterations are completely related to the development of the neoplasm or its treatment; the most described lesions were: mucositis, xerostomia, candidiasis, osteoradionecrosis, radiation caries and periodontitis. These injuries make the patient suffer limitations to perform basic activities, such as eating or communicating, negatively altering their quality of life. The complexity of the oral manifestation can determine the interruption of the anticancer treatment. The most used coping measures for the oral healthof cancer patients are: low- potency laser therapy, mouthwash with 0.12% chlorhexidine, instructionin oral hygiene and use of anti-inflammatory, analgesic and antifungal drugs. The role of dentists in the multidisciplinary palliative oncology team is essential for the control of oral lesions.

Los cuidados paliativos son un conjunto de procedimientos ofrecidos al paciente por un equipo multidisciplinar con el objetivo de garantizar el bienestar, la autonomía, el confort y el alivio de los síntomas derivados de la enfermedad o del tratamiento cuando la curación es imposible. El cáncer representa una de las enfermedades que tienen posibilidades de evolucionar al paciente hasta la fase terminal, momento en el que los cuidados paliativos son indicados y necesarios. Dentro del equipo responsable, el cirujano dentista actúa en la prevención, diagnóstico y tratamiento de las lesiones expresadas en el sistema estomatognático que se manifiestan estimuladas por el cáncer o por los tratamientos utilizados. El objetivo de esta investigación es destacar la función del odontólogo dentro del equipo paliativo multidisciplinar para pacientes oncológicos. Se trata de una revisión bibliográfica sistemática. Se realizaron búsquedas en las plataformas Virtual Health Library (BVS) y Scientific Electronic Library Online (SciELO) y tras aplicar los criterios de inclusión y exclusión, se seleccionaron 14 artículos. La literatura muestra que las alteraciones orales están relacionadas con el curso del cáncer o su tratamiento; las lesiones más comúnmente descritas fueron: mucositis, xerostomía, candidiasis, caries, periodontitis y osteorradionecrosis. Esto hace que el paciente sufra limitaciones para realizar actividades básicas, alterando negativamente su calidad de vida. La complejidad de la manifestación oral puede interrumpir el tratamiento antineoplásico. Las medidas de afrontamiento más utilizadas para la salud bucodental de los pacientes con cáncer son la terapia láser, los enjuagues bucales con clorhexidina al 0,12%, las instrucciones de higiene bucodental y el uso de fármacos antiinflamatorios, analgésicos y antifúngicos. La actuación del odontólogo en el equipo multidisciplinar de oncología paliativa es fundamental para el control de las manifestaciones orales.

Pharmacotherapy used for alcohol and cocaine use disorders in a CAPS-AD of Minas Gerais

Abstract Substance use disorder is one of the major social and public health problems in the world. The present study analyzed the pharmacoepidemiological profile of patients treated at the Psychosocial Treatment Center for Alcohol and Substance Use Disorders (CAPS-AD) for treatment of alcohol use disorders (AUD), cocaine use disorders (CUD) and concomitant alcohol and cocaine use disorders (A-CUD) in the city of Betim-MG. The study used quantitative and descriptive data and was based on the evaluation of medical records of patients attended from January to December 2016. After analyzing 295 medical records, the majority of study participants were male (83.7 %) with an average age of 46.26 for AUD, 28.88 for CUD and 34.29 for A-CUD. The most prescribed drugs for AUD were diazepam (54.1 %), thiamine (37 %), complex B vitamins (29.5 %), and disulfiram (2.7 %); for CUD, diazepam (26.9 %) and haloperidol (23.1 %). It should be noticed that although contraindicated by the guidelines, chlorpromazine (42.3 %, 25.3 %, 20.3 %) was prescribed for CUD, AUD, and A-CUD respectively. Knowing the pharmacoepidemiological profile of CAPS-AD patients is extremely important for making decisions regarding which medicines to make available to the population.

An overview of preparation and characterization of solid binary system and its application on transdermal film with variation of plasticizers

Chemotherapy induced nausea and vomiting (CINV) and post-operative nausea and vomiting (PONV) is a problem, often occurs in patient. Inspite of high bioavailability, the demerits such as: hepatic first pass metabolism and invasive nature of oral and parenteral dosage forms can be avoided with anti-emetic therapy of transdermal device. The major objective of the present study is to modify the hydrochloride (HCl) form of Ondansetron (OND) to the base form followed by improvement of solubility and permeability of OND by employing solid dispersion (SD) loaded patches. Preformulation study, as observed, begins with an approach to enthuse solubility of OND by SD technique choosing different carriers. The choice of carriers was rationalized by phase solubility study. Several combinations of transdermal films were prepared with pure drug, carriers and SDs with plasticizer Ka values of OND-HPßCD binary system were found lower (54.43 to 187.57 M-1) than that of OND-PVP K-30 binary system (1156.77 to 12203.6 M-1). The drug content of SDs and patches were found satisfactory. Better permeation rate (236.48±3.66 µg/3.935 cm2) with promising flux enhancement (8.30 fold) was found with DBP loaded SD patch (P6*). Hence, enhancement of solubility and permeability of P6* ensures that it can successfully enhance the bioavailability

Anti-proliferative effects of paroxetine alone or in combination with sorafenib in HepG2 cells

Abstract Hepatocellular carcinoma (HCC) is a common cause of cancer-related death. Sorafenib is the first approved drug for the treatment of advanced HCC. Depression is frequent in cancer patients. Moreover, sorafenib might exert depression as an adverse drug reaction and paroxetine, a selective serotonin reuptake inhibitor, is a recommended pharmacotherapy. This study aimed to investigate the potential synergistic effects of paroxetine and sorafenib on HepG2 cell proliferation and death. Paroxetine and sorafenib were administered to HepG2 cells as single-agents or in combination. Cell viability was determined with XTT cell viability assay. Cellular apoptosis and DNA content were assessed by flow cytometry. The expression of anti-apoptotic Bcl-2 was examined by immunofluorescence confocal microscopy. A lower dose of sorafenib was found to be required to inhibit cell proliferation when in combination with paroxetine. Similarly, the coadministration enhanced cellular apoptosis and resulted in cell cycle arrest. Confocal imaging revealed a remarkably lower cell density and increased expression of Bcl-2 following combined treatment of paroxetine with sorafenib. To our knowledge, this is the first study demonstrating the synergistic effect of paroxetine and sorafenib in HCC and might provide a potentially promising therapeutic strategy.

Small cell lung cancer: an overview of the targets

Abstract Lung cancer is the leading cause of cancer deaths worldwide. Small cell lung cancer (SCLC) accounts for approximately 15% of all lung cancer cases. Despite a frequently good response to first-line treatment with chemotherapy and/or radiotherapy, early relapse occurs in the majority of patients and 5-year survival is only about 5%. This histological subtype of lung cancer is strongly associated with tobacco smoking. The behavior of SCLC is unique within solid tumors. Initially, it positively responds to chemotherapy or radiotherapy. However, at relapse, which occurs early in the majority of cases, the tumor is resistant to available therapy and eventually will cause the death of the patient. These results in an overall 5-year survival of approximately 5% for the entire population of patients diagnosed with SCLC. This dismal prognosis has not significantly changed in past years. There is an urgent need for discovery targets to select patients more prone to having a proper response to the treatment, avoiding to reduce their resistance and resulting the increase of overall and progression-free survivals.

Desenvolvimento de inibidores duais de histona desacetilase 6 (HDAC6) e tirosina quinase (TQ) com vistas ao tratamento do câncer / Design of histone deacetylase 6 (HDAC6) and tyrosine kinase (TK) dual inhibitors for cancer treatment

Câncer é a denominação atribuída a um conjunto de doenças que são responsáveis pela segunda maior causa de morte no Brasil e no mundo. A quimioterapia figura entre uma das estratégias utilizadas para o tratamento e cura do câncer, sendo amplamente empregada em estratégias terapêuticas isoladas, ou em associação à radioterapia e cirurgia. A enzima histona desacetilase 6 (HDAC6) é responsável por desacetilar a cadeia lateral de N-acetillisinas em -tubulinas, desempanhando papel crítico na dinâmica do citoesqueleto celular, estando superexpressa em uma série de neoplasias. Neste sentido, na última década os receptores tirosina quinase (TQ) foram os principais alvos de fármacos aprovados para o tratamento do câncer e de doenças autoimunes e continuam atraindo a atenção de grupos de pesquisa dada a exorbitante diversidade do quinoma humano. É sabido que a monoterapia seja com inibidores de HDAC, seja com inibidores TQ, apresenta problemas de toxicidade, reações adversas, ineficácia, resistência e/ou recidiva. Diversos estudos relatam o desenvolvimento de inibidores duais de HDAC-TQ, almejando tanto a simplificação do tratamento, quanto sinergismo terapêutico e redução de efeitos adversos. Assim, o presente trabalho apresenta o planejamento, síntese e avaliação da citotoxicidade de inibidores duais, potencialmente seletivos para HDAC6 e receptores TQ. No total, 23 compostos foram sintetizados entre 2 a 4 etapas. Todos os compostos finais foram caracterizados por RMN (1H e 13C) e espectrometria de massas de alta resolução (HRMS). A citotoxicidade foi determinada pelo ensaio de MTT, em linhagens derivadas de tumores sólidos (HCT116 e MCF-7) e hematológicos (Jurkat e Namalwa). Os compostos apresentaram citotoxicidade em concentrações micro e nanomolares em todas as linhagens testadas, sendo que a linhagem MCF-7 foi a mais resistente à ação dos compostos, e as linhagens hematológicas foram as mais sensíveis. Os inibidores 4d-f foram os mais ativos na triagem por MTT, com IC50 iguais a 20, 30 e 50 nM, respectivamente, em células Jurkat. Estudos mecanísticos do efeito citotóxico indicaram que os compostos 4d-f exercem atividade de forma tempo-dependente, e majoritariamente por ação antiproliferativa, embora estímulos apoptóticos também tenham sido observados nos estudos. Simulações de ancoramento molecular (docking) e de relação entre as estruturas químicas dos compostos e suas respectivas atividades biológicas (REA) permitiram identificar padrões moleculares, propriedades físico-químicas e eletrônicas que potencialmente possuem relação com a atividade biológica dos compostos, permitindo futuras otimizações do arcabouço molecular desta série de compostos. Tomados em conjunto, os resultados deste trabalho revelam o potencial terapêutico de inibidores duais de HDAC6-TQ. Notadamente, os compostos apresentados aqui podem ser os primeiros potenciais inibidores duais de HDAC6-TQ a serem reportados na literatura

Cancer is the name of a series of diseases that are the second main cause of death in Brazil and worldwide. Chemotherapy is one of the main strategies to treat and cure cancer, and has been widely applied as a single therapeutic agent, and in association with radiotherapy and surgery. Histone deacetylase 6 (HDAC6) deacetylates N-acetyllysine side chains of tubulin, playing crucial role on cytoskeletal dynamics, and could be overexpressed in several cancers. Tyrosine kinase receptors (TK) have been the main targets of FDA-approved drugs through the last decade for both cancer and autoimmune diseases, and have been attracting special attention of research groups due to the exorbitant diversity of the human kinome. It is known that either HDAC or TK single therapy have toxicity issues, adverse effects, inefficacy, resistance and/or recidive. Therefore, many studies report the design of HDAC-TK dual inhibitors aiming simpler treatments, synergism of action and side effects reduction. Herein, the design, synthesis and cytotoxic evaluation of dual and selective HDAC6-TK inhibitors are presented. A total of 23 compounds were designed and synthesized through 2 to 4 steps. All final compounds were characterized by 1H/13C NMR and high-resolution mass spectrometry (HRMS). The cytotoxicity of compounds was determined by MTT assay for both solid (HCT116 and MCF-7 cells) and hematological cancers (Jurkat and Namalwa cells). Compounds exhibited micro and nanomolar ranges of cytotoxicity for all cell lines tested. MCF-7 cells were the most resistant against the treatment, and hematological cells were more susceptible to the cytotoxic effect of the compounds. Compounds 4d-f were the most actives in the MTT screening against Jurkat cells (IC50 = 20, 30 and 50 nM, respectively). Mechanistic studies regarding the cytotoxic effects of 4d-f indicated that the compounds induced cell death in a time-dependent manner mainly via cytostatic activity even though apoptotic stimuli were observed also. Molecular docking and structure-activity relationships (SARs) allowed the identification of molecular patterns, and physicochemical and electronic properties that potentially modulate the biological activity of these compounds, allowing further optimizations of the molecular scaffold for these series of compounds. Taken together, the results of this study reveal the therapeutic potential of HDAC6-TK dual inhibitors. Noteworthy, the compounds reported herein could be the first HDAC6-TK dual inhibitors ever reported in literature

Safety and feasibility of 3-month interval access and flushing for maintenance of totally implantable central venous port system in colorectal cancer patients after completion of curative intended treatments.

ABSTRACT: Patients with colorectal cancer (CRC) treated with curative intent surgery undergo continuous fluorouracil (5-FU) infusion-based chemotherapy using totally implantable central venous port system (TICVPS) in cases with high risk of recurrence. Approximately 30% of patients relapse after therapy completion, especially within 2 years. Hence, many patients with high risk CRC keep the TICVPS for 6 to 24 months after treatment with regular intervals of TICVPS flushing. However, little is known about the proper interval duration of the port. The aim of this study is to investigate whether a 3 months extended interval is safe and if port maintenance is feasible.A retrospective cohort was compiled of patients with CRC who underwent curative intent surgery and perioperative chemotherapy using TICVPS between 2010 and 2017. The primary end point was TICVPS maintenance rate, including maintenance of TICVPS for at least 6 months, planned TICVPS removal after 6 months, and regaining the use of TICVPS at the time of recurrence.A total of 214 patients with CRC underwent curative intent treatments during the study period. Among them, 60 patients were excluded, including 6 patients for early recurrence within 3 months and 54 patients with violation of flushing interval. Finally, 154 patients were analyzed. Mean flushing interval was 98.4 days (95% confidence interval [CI], 96.2-100.6; range, 60-120). In December 2018, 35 patients kept the TICVPS, 92 patients had planned removal, 25 patients reused the TICVPS, and 2 patients had to unexpectedly remove the TICVPS due to site infection and pain. Thus, the functional TICVPS maintenance rate was 98.8% (152/154). Thirty-eight patients relapsed, and 30 patients were treated with intravenous chemotherapy. Among them, 25 patients (83.3%) reused the maintained TICVPS without a reinsertion procedures.Our study demonstrated that 3-month interval access and flushing is safe and feasible for maintaining TICVPS during surveillance of patients with CRC. An extended interval up to 3 months can be considered because it is compatible with CRC surveillance visit schedules.

Antimicrobial photodynamic inactivation mediated by methylene blue: Analysis of inactivation kinetics and biochemical mechanisms / Inativação fotodinâmica antimicrobiana mediada por azul de metileno: Análises de cinética de inativação e mecanismos bioquímicos

The widespread use of antimicrobial chemotherapy in medicine and livestock production imposed an evolutive selection of drug-resistant strains worldwide. As a result, the effectiveness of our current antimicrobial armamentarium is constantly being reduced to alarming levels. Therefore, novel antimicrobial therapeutic strategies are urgently needed. Antimicrobial photodynamic therapy (APDT) comes to this scenario as a powerful tool to counteract the emergence of microbial drug-resistance. Its mechanisms of action are based on simultaneous oxidative damage of multiple targets and, therefore, it is much less likely to allow any type of microbial resistance. Therefore, the objectives of this study were focused into establishing 1) a mathematical tool to allow precise analysis of microbial photoinactivation; 2) a broad analysis of APDT effectiveness against global priority drug-resistant pathogens; 3) inhibition of ßlactamase enzymes; and 4) how the biochemical mechanisms of APDT avoid emergence of resistance. The main results obtained through the investigation led by this thesis were divided into 4 scientific articles regarding each of the above-mentioned objectives. In summary, we discovered that 1) a power-law function can precisely fit all microbial inactivation kinetics data and provide insightful information of tolerance factors and lethal doses; 2) there is no correlation between drug-resistance and APDT sensitivity, i.e., extensively drug resistant microorganisms are killed in the same kinetics as drug-sensitive controls; 3) ß-lactamases are very sensitive to photodynamic inhibition; 4) biochemical mechanisms of APDT promote oxidative damages to external cell membranes, DNA and proteins whereas the main cause of microbial death seems to be directly associated with protein degradation. Thus, we conclude that APDT is effective against a broad-spectrum of pathogens and has minimum chances of promoting resistance mechanisms

O amplo uso da quimioterapia antimicrobiana impôs uma seleção evolutiva de cepas resistentes a medicamentos. Como resultado, a eficácia dos fármacos antimicrobianos tem sido reduzida a níveis alarmantes. Portanto, novas estratégias terapêuticas antimicrobianas são urgentemente necessárias. A terapia fotodinâmica antimicrobiana (TFDA) entra neste cenário como uma ferramenta poderosa para combater a resistência microbiana. Seus mecanismos de ação são baseados no dano oxidativo sobre múltiplos alvos e, portanto, é muito menos provável que permita o surgimento de qualquer tipo de resistência. Os objetivos deste estudo foram focados ao estabelecimento de 1) modelo matemático para análise precisa da fotoinativação microbiana; 2) ampla análise da eficácia da TFDA contra patógenos resistentes a fármacos antimicrobianos de prioridade global; 3) inibição de ß-lactamases por TFDA; e 4) como os mecanismos bioquímicos da TFDA evitam o surgimento de resistência. Os principais resultados obtidos através da investigação conduzida por esta tese foram divididos em 4 artigos científicos. Em resumo, descobrimos que 1) uma função de lei de potência pode ajustar com precisão todos os dados de cinética de inativação microbiana e fornecer informações detalhadas sobre fatores de tolerância e doses letais; 2) não há correlação entre resistência à quimioterapia antimicrobiana e sensibilidade à TFDA, isto é, cepas extensivamente resistentes aos antimicrobianos são inativadas sob a mesma cinética que controles sensíveis aos antimicrobianos; 3) ß-lactamases são altamente sensíveis à inibição fotodinâmica; 4) os mecanismos bioquímicos da TFDA promovem danos oxidativos às membranas celulares e DNA, porém, a principal causa de morte microbiana é diretamente associada à degradação das proteínas. Assim, concluímos que a TFDA é eficaz contra um amplo espectro de patógenos e tem chances mínimas de promover mecanismos de resistência

Cancer Cell Membrane Camouflaged Semi-Yolk@Spiky-Shell Nanomotor for Enhanced Cell Adhesion and Synergistic Therapy.

Cell adhesion of nanosystems is significant for efficient cellular uptake and drug delivery in cancer therapy. Herein, a near-infrared (NIR) light-driven biomimetic nanomotor is reported to achieve the improved cell adhesion and cellular uptake for synergistic photothermal and chemotherapy of breast cancer. The nanomotor is composed of carbon@silica (C@SiO2 ) with semi-yolk@spiky-shell structure, loaded with the anticancer drug doxorubicin (DOX) and camouflaged with MCF-7 breast cancer cell membrane (i.e., mC@SiO2 @DOX). Such biomimetic mC@SiO2 @DOX nanomotors display efficient self-thermophoretic propulsion due to a thermal gradient generated by asymmetrically spatial distribution. Moreover, the MCF-7 cancer cell membrane coating can remarkably reduce the bioadhesion of nanomotors in biological medium and exhibit highly specific self-recognition of the source cell line. The combination of effective propulsion and homologous targeting dramatically improves cell adhesion and the resultant cellular uptake efficiency in vitro from 26.2% to 67.5%. Therefore, the biomimetic mC@SiO2 @DOX displays excellent synergistic photothermal and chemotherapy with over 91% MCF-7 cell growth inhibition rate. Such smart design of the fuel-free, NIR light-powered biomimetic nanomotor may pave the way for the application of self-propelled nanomotors in biomedicine.

Structure activity relationship (SAR) maps: A student-friendly tool to teach medicinal chemistry in integrated pharmacotherapy courses.

BACKGROUND AND PURPOSE: Courses that integrate pharmacology, medicinal chemistry, and pharmacotherapy are widely implemented in pharmacy curriculums. The integration of medicinal chemistry is often challenging given the difficulty of material and time constraints. The objective of this pedagogical approach is to utilize structure activity relationship (SAR) maps as visual aids to teach students medicinal chemistry in an integrated course. EDUCATIONAL SETTING: SAR maps were designed and implemented within an integrated course focusing on cardiopulmonary diseases. Specific SAR maps used in lecture and class activities included phenylethylamines (adrenergic agonists (i.e. bronchodilators)) and aryloxypropanolamines (beta blockers). Students were assessed in class activities (formative) and exams (high stakes) for specific information surrounding drug structure and the SAR map. Drug properties assessed included essential pharmacophores, pharmacodynamics, physiochemical properties, metabolism, duration of action, and decision-making. FINDINGS: Results from assessment item analysis reveal that students performed well on medicinal chemistry questions related to the SAR maps (~90% correct on first exam). Students revealed in a survey that the SAR maps enhanced their understanding of medicinal chemistry concepts. SUMMARY: SAR maps are effective tools that visually teach students key concepts in medicinal chemistry. This millennial student-friendly tool is time-effective and promotes learning as opposed to drug structure memorization. The SAR map can be easily implemented in other integrated courses focused on various disease states.

The role of device-assisted therapies in the management of non-muscle invasive bladder cancer: A systematic review.

OBJECTIVE: Despite optimal treatment, patients affected by non-muscle invasive bladder cancer (NMIBC) suffer from high risk of recurrence and progression. Intravescical device assisted therapies such as radiofrequency induced thermochemotherapeutic effect (RITE) and electromotive drug administration (EMDA) have shown promising effect in enhancing the effect of intravescical chemotherapies. The aim of the study was to assess clinical outcomes of these two devices in non-muscle invasive bladder cancer. METHODS: A systematic literature review was performed in December 2019 using the Medline, Embase, and Web of Science databases. Only articles published in the last 10 years were considered (2009-2019). The articles were selected using the following keywords association: "bladder cancer" AND "EMDA' AND "synergo" AND "hyperchemotherapy" AND "electromotive drug administration", AND "radiofrequency induced thermochemotherapeutic" AND "RITE". RESULTS: We found 16 studies published in the last ten years regarding the efficacy of RITE (12 studies) and EMDA (4 studies) in the treatment of NMIBC. Both RITE and EMDA showed promising results in the treatment of intermediate and high risk NMIBC as well as in patients affected by recurrent BCa after BCG failure. In high-risk BCG naïve NMIBC patients treated with EMDA recurrence and progression rates were 68% and 95%, respectively. Considering RITE, recurrence and progression range rates were 43%-88% and 62%-97%, respectively. Discordance results were reported regarding its effect on patients with carcinoma in situ. However, only few studies could be compared since differences exist regarding inclusion criteria with high patients' heterogeneity. Considering recurrence after BCG, recurrence and progression range rates were 29%-29.2% and 62%-83% for RITE and 25% and 75% for EMDA, respectively. CONCLUSION: Delivery of intravescical hyperthermia seems to enhance the normal effect of intravescical chemotherapy instillation. Although prospective trials supported its effect on both BCG naïve and BCG failure patients, data are urgently required to validate these findings and to understand its effect on patients with carcinoma in situ. LEVEL OF PROOF: 3.

Evaluation of prevalence of different types of cancer and its chemotherapy in various ethnic groups of Pakistan: A retrospective study

The objective of the study was to evaluate different types of cancer and its chemotherapy in various ethnic groups of Pakistan. Ethnic groups includes, Pukhtoons, Punjabis, Sindhis, Muhajirs, Siraikis, Memoons, Hazaras, Hindkos, Baltis, Gilgitis, Kashmiris, and Afghanis. The data was collected from well reputed hospitals located in the different provinces of Pakistan. The collected data was taken from 15 hospitals where around 8500 patients visited during 2010 to 2017. From the visited patients, 8356 were analyzed for their ethnicity, age and sex while, 144 patients (male 77 and female 67) were excluded from analysis due to incomplete information or loss of follow-up. Among 8356 patients, 3762 were male (45%) whereas, 4594 were female (55%). The chemotherapy was carried out as per National Comprehensive Cancer Network guidelines (NCCN- guidelines). The most common five prevalent cancer among these ethnic groups were Head and Neck, Blood, Respiratory, Genito-urinary and Breast cancer. The most common cancer in female was breast cancer while, head and neck cancer was more prevalent in male. It can be concluded that the prevalence of cancer in Pakistan is very alarming, which may be due to lack of awareness, illiteracy, lack of national cancer control programs, and economics issues.

Inexpensive automated medication dispenser for persons with neurodegenerative illnesses in low resource settings.

Neurodegenerative illnesses due to diseases or old age are typical examples of clinical conditions that may affect the proper observation of prescribed medication usage with negative consequence on dose potency. Commercially available medicine dispenser for these populations are expensive, complex to operate and/or beyond the reach of those living in low resource settings due to lack of social protection. This study presents the design and construction of an inexpensive ($49.6) medication dispenser suitable for point of care applications in low resource settings. The dispenser was constructed using a simple control mechanism based on Arduino® IDE that controlled three different micro servo motors to accommodate different shapes of medication. Sequel to the laboratory trials by abled individuals, we were able to demonstrate between 58% and 100% accuracy of the device when the three servo motors were simultaneously used to dispense medication of three different sizes. Following rigorous clinical trials in the target population, we intend to deploy this device for wider and independent usage by users in order to prevent unnecessary hospital admission meant to enforce compliance with appropriate medication usage for the users.

Assessment of the aerosol distribution pattern of a single-port device for intraperitoneal administration of therapeutic substances.

BACKGROUND: In the last 20 years, intraperitoneal chemotherapy (IPC) has been explored as a modality for the management of peritoneal metastases of gynecologic, gastrointestinal, and primary peritoneal tumors. Direct delivery of chemotherapeutic agents to the peritoneal cavity space has proved superior to systemic chemotherapy when evaluating characteristics such as drug concentration reached in the peritoneal space, penetration into peritoneal metastases, and chemotherapy-related toxicity. Traditionally, IPC is delivered by peritoneal lavage with a liquid solution. This form of delivery has limitations, including inhomogeneous intraperitoneal distribution and limited ability to penetrate tissues and metastatic nodules. An alternative mode of delivery is so-called pressurized intraperitoneal aerosol chemotherapy (PIPAC). Within this context, the present study sought to identify the pattern of spatial distribution of therapeutic solutions aerosolized into the peritoneal space using a single-port PIPAC device and ascertain whether the aerosolized method is superior to the traditional (liquid) mode of IPC delivery. METHODS: Analysis of the rate of intra-abdominal staining with aerosolized 2% silver nitrate in five porcine models. RESULTS: Assessment of differences in stain impregnation between the upper, middle, and lower abdomen did not reveal significant differences (p = 0.42). The median sum scores were 1 for the upper abdomen and 3 for the middle and lower abdomen. CONCLUSIONS: Aerosolization does not reach all regions of the abdomen homogeneously. However, adequate exposure of the upper abdomen, mid-abdomen, and lower abdomen to chemotherapeutic agents can be achieved with PIPAC.

Access and use of medicines by elderly individuals with dementia

The objective is to reveal the difficulties concerning the access and use of medicines by elderly individuals with dementia, reported by their caregivers. This qualitative study applied the participant observation method during pharmaceutical appointments performed in a specialized geriatrics service of the University Hospital of Brasília. Caregivers reported facing difficulties regarding the itinerary for medicines access in public pharmacies, as well as the high cost of these technologies in private establishments. Psychiatric symptoms, cognitive deficits, behavioral changes, apraxia, dysphagia, among other clinical manifestations of dementia syndromes, incapacitates the elderly for self-responsibility concerningthe use of drugs, which accentuates the complexity of medicines administration within the care process. In conclusion, it is fundamental to recognize caregivers' role in promoting the rational use of medicines, and so this theme should be highlighted within the pharmaceutical services context.

Predrawn prehospital medications are microbiologically safe for up to 48 hours.

BACKGROUND: Prehospital medical teams are commonly required to administer a range of medications for urgent stabilisation and treatment. The safe preparation of medications during resuscitation requires attention, time and resources, and can be a source of medication error. In our two road and HEMS (Helicopter Emergency Medical Service) prehospital services, medication errors are mitigated by predrawing commonly used medications to set concentrations daily (Hunter Retrieval Service, HRS) or second-daily (CareFlight Sydney, CFS). However, there are no published data confirming that such practice is microbiologically safe. METHODS: A convenience sample of 299 predrawn medication syringes with syringe dwell times up to 48 hours were collected at the end of their operational deployment. Predrawn medication syringes collected for culture were ketamine, midazolam, fentanyl, thiopentone, rocuronium, suxamethonium, metaraminol and normal saline. The samples were incubated and cultured at a tertiary hospital pathology laboratory using best-practice methodology for non-tissue samples. The samples were collected from June 2017 to February 2018. RESULTS: The mean dwell times ranged from 30.7 hours (fentanyl at HRS) to 48.5 hours (rocuronium at CFS). None of the 299 cultured samples yielded significant micro-organisms. One sample of suxamethonium with a syringe dwell time of 34 hours grew Bacillus cereus but was likely a contaminant introduced during sample collection. CONCLUSION: Predrawing of the eight studied medications for urgent prehospital procedures appears to be a microbiologically safe practice with syringe dwell times up to 48 hours.

Late complications of totally implantable venous access ports in patients with cancer: Risk factors and related nursing strategies.

The aim of this study was to assess the incidence rate and the risk factors for late complications associated with use of central totally implanted venous access devices (TIVAPs) in patients with cancer, and to devise nursing strategies to minimize late complications.This retrospective study included 500 patients with TIVAPs from 2012 to 2015. Multivariable logistic regression analysis was performed to assess the effect of sex, age, primary diagnosis, duration of surgery, and the length of hospital stay on the incidence of late complications of TIVAP.The cumulative maintenance period of TIVAP was 159,605 days. Late complications included catheter-related obstruction (n = 14; 2.8%), infection (n = 3; 0.6%), drug extravasation (n = 1; 0.2%), and catheter exposure (n = 1; 0.2%). Multivariate analyses revealed that age, breast cancer, lung cancer, and gastric cancer were risk factors for the late complications associated with TIVAP.There was a low incidence of late complications with TIVAP use. Catheter-related obstruction is the most frequent late complication of TIVAP. Risk factors for TIVAP-associated late complications include age and certain cancers, such as breast cancer, lung cancer, and gastric cancer.

Evaluaciones rápidas de la eficacia y la seguridad de los nuevos medicamentos / Rapid assessments of the efficacy and safety of new medicinal products

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