Use of topical colistin in bacterial keratitis caused by extensively drug-resistant Pseudomonas Aeruginosa: a case report / Uso de colistina tópica em ceratite bacteriana causada por Pseudomonas Aeruginosa extensivamente resistente a medicamentos: relato de caso

ABSTRACT Bacterial keratitis caused by multidrug-resistant strains of Pseudomonas aeruginosa is a therapeutic challenge due to a limited number of active antimicrobials and rapid progression to corneal necrosis and perforation. To report the use of topical colistin and surgical tarsorrhaphy in a case of keratitis caused by extensively drug-resistant Pseudomonas aeruginosa in a patient with severe coronavirus disease-2019 (COVID-19) pneumonia. A 56-year-old male was admitted to the intensive care unit with clinical symptoms of severe COVID-19 pneumonia. During his stay in the unit, he developed rapidly progressive keratitis with Pseudomonas aeruginosa resistant to all drugs except for colistin on culture. Due to incomplete lid closure, a temporary tarsorrhaphy was performed, and a regimen of descending-dose topical colistin was initiated. After five weeks, keratitis resolved completely. Extensively drug-resistant Pseudomonas aeruginosa is an unusual cause of bacterial keratitis. We describe the safe and effective use of topical colistin in a case with severe corneal involvement.

RESUMO A ceratite bacteriana causada por cepas multirresistentes de Pseudomonas aeruginosa é um desafio terapêutico, devido à disponibilidade limitada de antimicrobianos e à rápida progressão para necrose e perfuração da córnea. O objetivo deste artigo é relatar o uso de colistina tópica e tarsorrafia cirúrgica em um caso de ceratite por Pseudomonas aeruginosa amplamente resistente a medicamentos em um paciente com pneumonia grave por COVID19. Um homem de 56 anos foi internado em uma unidade de terapia intensiva com sintomas clínicos de pneumonia grave por COVID19. Durante sua permanência na unidade de terapia intensiva, o paciente desenvolveu uma ceratite rapidamente progressiva, cuja cultura foi positiva para Pseudomonas aeruginosa resistente a todos os antimicrobianos, exceto colistina. Devido ao fechamento incompleto da pálpebra, foi realizada uma tarsorrafia temporária e foi instituído um esquema de colistina tópica em doses decrescentes. Após cinco semanas, a resolução completa da ceratite foi alcançada. Pseudomonas aeruginosa amplamente resistente a medicamentos é uma causa incomum de ceratite bacteriana. Este relato descreve o uso seguro e eficaz da colistina tópica em um caso com comprometimento corneano grave.

Creación e implementación del Sistema de Entrega de Medicamentos a Pacientes Crónicos SIENMECRO: estudio cualitativo

Introducción: Frente a pandemia producida por el SARS-CoV-2, el gobierno peruano implementó diversas medidas como el cierre temporal de los establecimientos del primer nivel de atención y el sistema sanitario implementó diversas políticas y estrategias; una de ellas, fue la creación e implementación del proyecto del Sistema de Entrega de Medicamentos a Pacientes Crónicos (SIENMECRO). Objetivo: Describir el proceso de creación e implementación del proyecto SIENMECRO. Métodos: Investigación cualitativa de tipo estudio de caso que implicó la revisión de la documentación existente como textos y videos y, realización de entrevistas en profundidad a funcionarios y colaboradores involucrados desde la elaboración de la propuesta del SIENMECRO. Resultados: El proyecto SIENMECRO surge como una iniciativa positiva con la aspiración de impulsar un sistema integrado de salud que aborde la realidad sanitaria desde los determinantes sociales de la salud, debido a las dificultades de los pacientes para acudir a sus controles y recibir su tratamiento. A pesar de que no se contó con un plan integral de implementación y control del proyecto, fue fundamental para cubrir la necesidad de atención sanitaria a un segmento vulnerable de la población, evitando su traslado y preservando la salud de las personas más susceptibles de padecer complicaciones por la infección por COVID-19. Conclusiones: Es una iniciativa donde el sistema sanitario toma un rol más proactivo en beneficio de la población, implementando el uso de las tecnologías de información y comunicación en la atención de salud, articulando con los diversos prestadores y acercando los servicios a los ciudadanos más vulnerables.

Introduction: Faced with the pandemic produced by SARS-CoV-2, the Peruvian government implemented several measures such as the temporary closure of primary care facilities and the health system implemented various policies and strategies; one of them was to create and implement the Drug Delivery System for Chronic Patients (SIENMECRO) project. Objective: To describe the creation and implementation process of SIENMECRO project. Methods: Qualitative case study that involved reviewing existing documentation such as texts and videos and conducting in-depth interviews with officials and collaborators involved since the preparation of SIENMECRO proposal. Results: SIENMECRO project emerges as a positive initiative with the aspiration of promoting an integrated health system that addresses the health reality from the social determinants of health, due to patients' difficulties to go to their controls and to receive their treatment. Although there was no comprehensive plan for the implementation and control of the project, it was essential to cover the need for health care for a vulnerable segment of the population, avoiding their transfer and preserving the health of the people most likely to suffer complications from COVID-19 infection. Conclusions: It is an initiative where the health system takes a more proactive role for the benefit of the population, implementing the use of technology of the information and communication in health care, articulating with the various providers and bringing services closer to the most vulnerable citizens.

Analysis of management efficacy in patients with heavy menstrual bleeding associated with antithrombotic therapy / 中华妇产科杂志

Objective: To evaluate different methods' efficacy of controlling acute bleeding and managing long-term menstruation in patients with heavy menstrual bleeding (HMB) associated with antithrombotic therapy. Methods: The clinical data of 22 cases with HMB associated with antithrombotic therapy admitted to Peking University People's Hospital from January 2010 to August 2022 were analyzed, aged 39 years old (26-46 years). Changes in menstrual volume, hemoglobin (Hb), and quality of life were collected after control of acute bleeding and long-term menstrual management. Menstrual volume was assessed by pictorial blood assessment chart (PBAC), and quality of life was assessed by menorrhagia multi-attribute scale (MMAS). Results: (1) Treatment of acute bleeding: of the 22 cases with HMB associated with antithrombotic therapy, 16 cases were treated in our hospital and 6 in other hospital for emergency bleeding; of the 16 cases treated in our hospital, 3 underwent emergency intrauterine Foley catheter balloon compression due to severe bleeding (Hb decreased by 20 to 40 g/L within 12 hours). Of the 22 cases with antithrombotic therapy-related HMB, 15 (including 2 cases with severe bleeding) underwent emergency aspiration or endometrial resection, and intraoperative placement of levonorgestrel-releasing intrauterine system (LNG-IUS) followed by a significant reduction in bleeding volume; 3 cases had controlled acute bleeding after rivaroxaban dose reduction and continued observation; 2 cases were given gonadotropin-releasing hormone agonists to control acute bleeding in other hospital, of which 1 case was temporarily treated with periodic blood transfusion, and the other one patient underwent total hysterectomy; and 2 cases had temporary amenorrhea with oral mifepristone after intrauterine balloon compression or oral norethindrone. (2) Long-term menstrual management: of the 22 cases with antithrombotic therapy-related HMB, 15 had LNG-IUS placement and 12 had LNG-IUS placement for 6 months, and menstrual volume was significantly reduced [PBAC scores were 365.0 (272.5-460.0) vs 25.0 (12.5-37.5), respectively; Z=4.593, P<0.001], Hb was significantly increased [91.5 g/L (71.8-108.2 g/L) vs 128.5 g/L (121.2-142.5 g/L); Z=4.695, P<0.001], and quality of life was significantly improved [MMAS scores were 415.0 (327.5-472.5) vs 580.0 (570.0-580.0), respectively; Z=-3.062, P=0.002] before placement compared with 6 months after placement. Three rivaroxaban dose reduction patients' PBAC scores decreased by 20 to 35 but remained >100, and perceived quality of life did not change significantly. Two cases with temporary amenorrhea treated with oral mifepristone felt significantly improved quality of life, and the MMAS scores increased by 220 and 180, respectively. Conclusion: Intrauterine Foley catheter balloon compression, aspiration or endometrial ablation could be used to control acute bleeding in patients with antithrombotic therapy-related HMB, and LNG-IUS for long-term management could reduce menstrual volume, increase hemoglobin, and improve the quality of life of patients.

Adverse effects of hydroxyurea used for the treatment of myeloproliferative neoplasms

Hydroxyurea is administered to control elevated blood counts in patients with myeloproliferative neoplasms (MPNs) to reduce the risk of thrombosis and mortality. We reviewed the side effects of hydroxyurea, development of secondary malignancies, and drug resistance observed in some patients.Current Concepts: The low incidences of malformed births, intrauterine deaths, and spontaneous abortions associated with hydroxyurea therapy suggest that adverse pregnancy and fetal effects are unlikely. However, animal studies have reported malformations; therefore, the use of hydroxyurea during pregnancy is not recommended. Low-grade adverse events associated with hydroxyurea therapy include gastrointestinal symptoms such as nausea, upper gastrointestinal discomfort, and diarrhea. These symptoms are usually resolved by dose adjustment or temporary discontinuation. Approximately 10% of patients with MPNs are resistant to hydroxyurea, and another 10% are unable to tolerate it owing to side effects. Drug intolerance and resistance are the most common causes of inadequate cytoreductive control in patients with MPNs. Second-line cytoreductive agents should be considered to overcome the high risk of thrombosis and poor survival. The evolution to secondary hematologic cancers is related to the duration of the disease, not hydroxyurea administration.Discussion and Conclusion: In pregnant patients accidentally exposed to hydroxyurea, the risk should be discussed with the patient to determine whether to continue the pregnancy. Hydroxyurea administration increases the risk of skin cancer but does not affect the incidence of other secondary hematologic or solid cancers. Ropeginterferon or Janus kinase (JAK) inhibitors, including ruxolitinib, are recommended as alternative treatments if the patient is intolerant or resistant to hydroxyurea, as this is associated with poorer survival.

Application practice of drug clinical comprehensive evaluation thinking in management of temporary drug purchase in hospital / 中国药房

OBJECTIVE To explore the construction of a new scientific management model for temporary drug purchase，and to provide a reference for hospitals to improve the level of rational drug use. METHODS Guided by clinical diagnosis and treatment needs and patient medication safety， our hospital carried out the whole process management practice of temporarily purchased drugs by optimizing the review process， creating a review team， formulating pre-audit and post follow-up evaluation standards based on comprehensive drug evaluation， and evaluated the practice effect through the number of temporary purchase applications， implementation rate， drug structure optimization and other indicators. RESULTS Since January 2021， our hospital had implemented a new mode of temporary drug purchase management. By December 2022， clinical pharmacists had reviewed 111 temporary drug procurement applications， effectively intercepted 13 irrational drug use applications （11.71%）， reduced the overall implementation rate of temporary drug procurement by 8.36%，and proposed five batches of drug structure optimization suggestions； 24 drugs were successively introduced such as camrelizumab，sorafenib，busulfan. After optimizing the management mode，the number of temporary drug procurement applications decreased by more than half from 133 in 2019 and 138 in 2020 to 66 in 2021 and 45 in 2022. CONCLUSIONS The model is helpful to optimize the hospital drug catalog， strengthen rational drug use，ensure the safety of patients’ drug use， and fully reflects the professional value of clinical pharmacists in hospital pharmacy management and rational drug use.

Research on the supply guarantee system of orphan drugs in South Korea from the perspective of accessibility and its enlightenment / 中国药房

OBJECTIVE To systematically introduce the supply guarantee system of orphan drugs in South Korea， and to provide reference for improving the accessibility of orphan drugs in China. METHODS The basic characteristics and practical experience of supply guarantee system of orphan drugs in South Korea were summarized by studying the marketing incentive mechanism， reserve supply mechanism and emergency use mechanism. Then， based on the research on the current situation and existing problems of orphan drug supply in China， specific suggestions were put forward to improve the accessibility of orphan drugs in China. RESULTS & CONCLUSIONS South Korea has effectively improved the accessibility of orphan drugs through orphan drug identification channels and supporting incentive policies， relying on the reserve supply mechanism and the import route for emergency use. Therefore， it is suggested that China should guarantee the normal supply of orphan drugs from three aspects： improving the recognition and incentive policy of orphan drugs， building a full-time management department of orphan drugs， and optimizing the temporary import path.

Exploration of pharmaceutical service model in multidisciplinary diagnosis and treatment of rare diseases in children / 中国药房

OBJECTIVE To explore the pharmaceutical service model in multidisciplinary diagnosis and treatment （MDT） of rare diseases in children. METHODS Clinical pharmacists of West China Second University Hospital （hereinafter referred to as “our hospital”） participated in the process of MDT of children’s rare diseases. Clinical pharmacists took part in the entire diagnosis and treatment process of children and established the MDT pharmaceutical service model of children’s rare diseases by formulating drug treatment plans based on evidence-based practice， improving the accessibility of drugs， pharmaceutical monitoring and drug treatment management. RESULTS From January 2021 to April 2022， clinical pharmacists of our hospital had participated in a total of 39 cases of rare diseases MDT in children， including 21 hospitalized children with rare diseases and 18 outpatient com children with rare diseases， involving a total of 23 rare diseases. Clinical pharmacists completed 45 pharmaceutical zhanglingli@scu.edu.cn rounds and 26 pharmaceutical consultations for rare diseases inpatients， 25 outpatients’ MDT and 5 pharmaceutical outpatient service for outpatients with rare diseases， 38 medication educations for inpatients and outpatients with rare diseases and 25 follow-up services for out-of-hospital patients. There were 24 cases （61.54%） of off-label drug use， involving 13 rare diseases and 16 therapeutic drugs， among which off-label drug use registration of 11 drugs had been completed or was in progress. The temporary purchase evaluations of 3 drugs had been completed； 268 cases of medical insurance drug and high-value drug prescription had been reviewed. CONCLUSIONS Our hospital have primarily established a loop pharmaceutical service model of MDT for children with rare diseases， which covers inpatients and outpatients. The model improves the availability and standardization of clinical application of therapeutic drugs， and diagnosis and treatment level for children with rare diseases in our hospital.

Uso de membrana amniótica como cobertura temporal en pacientes pediátricos con quemaduras / Use of amniotic membrane as temporary coverage in pediatric patients with burn

Introducción: Los niños con quemaduras tienen un manejo complejo por lo cual el uso de la membrana amniótica como una cobertura temporal es un método válido para su implementación. Objetivos: Demostrar el uso de la membrana amniótica como cobertura temporal en pacientes pediátricos con quemaduras de segundo grado superficiales y profundas internados en el Centro Nacional de Quemaduras y Cirugías Reconstructivas (CENQUER), en julio y diciembre del 2021. Materiales y métodos: Estudio descriptivo de tipo retrospectivo mediante la revisión de casos clínicos-quirúrgicos de los pacientes pediátricos que ingresaron por diagnóstico de quemadura de segundo grado superficial y profundo en el CENQUER, durante el período comprendido entre julio y diciembre del 2021, donde se aplicó́ membrana amniótica humana. Resultados: Población de 14 pacientes, 11 provenían del departamento central y 3 del interior del país, con un promedio de 13% (R: 3%-25,5%) de superficie corporal quemada (SCQ) todos con quemaduras en promedio 7% tipo AB y 6% tipo ABB, 7 ingresaron con una gravedad moderada, 4 graves y 3 leves; 7 del sexo masculino y 7 del femenino , con un rango de edades entre 8 meses y 11 años cuya media fue de 4 años y una mediana de 7 años, con respecto al peso un promedio de 18 kg al ingreso % (R: 9-35 kg), las causas de las lesiones fueron 12 por escaldadura por agua caliente (85 %) y 2 por escaldadura con comida; 10 pacientes presentaron internación en sala y en la Unidad de terapia intensiva Pediátrica (UTIP) 4 pacientes, el promedio de tiempo transcurrido desde la quemadura a la consulta fueron de 7 hs (R: 1-48 hs), las regiones anatómicas que se cubrieron fueron: 4 pacientes en miembros superiores y tórax anterior (28 %), 2 exclusivamente en tórax anterior (16 %), 4 solo en miembros superiores (28 %), 4 en miembros inferiores (28 %), a los que se les colocó amnios por única ocasión en 10 pacientes a las 24 hs de la internación y en 4 pacientes a las 48 hs de internación, se utilizó antobioticoterapia parenteral en 3 pacientes y 11 pacientes no necesitaron antibioticoterapia parenteral, no se presentaron complicaciones en ninguno de los pacientes y tuvieron un promedio de internación de 8 días (R: 3- 16 días). Conclusión: El uso de membrana amniótica humana en pacientes quemados son favorables para los pacientes pediátricos; como demuestra en el estudio el menor uso de antibioticoterapia parenteral por la cobertura rápida de las heridas causadas por las quemaduras y el menor número de días de internación.

Introduction: Children with burns have a complex management for which the use of the amniotic membrane as a temporary cover is a valid method for its implementation. Objectives: Demonstrate the use of the amniotic membrane as temporary coverage in pediatric patients with superficial and deep second-degree burns admitted to the National Center for Burns and Reconstructive Surgery (CENQUER), in July and December 2021. Materials and methods: Descriptive retrospective study through the review of clinical-surgical cases of pediatric patients who were admitted due to a diagnosis of superficial and deep second-degree burns in the CENQUER, during the period between July and December 2021, where human amniotic membrane was applied. Results: Population of 14 patients, 11 came from the central department and 3 from the interior of the country, with an average of 13% (R: 3%-25.5%) of burned body surface area (SCQ), all with average 7% AB type burns. and 6% type ABB, 7 admitted with moderate severity, 4 severe and 3 mild; 7 males and 7 females, with an age range between 8 months and 11 years, whose average was 4 years and a median of 7 years, with respect to weight an average of 18 kg at admission % (R: 9- 35 kg), the causes of the injuries were 12 due to scalding due to hot water (85%) and 2 due to scalding with food; 10 patients were hospitalized in the ward and in the Pediatric Intensive Care Unit (PICU) 4 patients, the average time elapsed from the burn to the consultation was 7 hours (R: 1-48 hours), the anatomical regions that were covered were: 4 patients in the upper limbs and anterior thorax (28%), 2 exclusively in the anterior thorax (16%), 4 only in the upper limbs (28%), 4 in the lower limbs (28%), who received amnios for a single occasion in 10 patients at 24 hours of hospitalization and in 4 patients at 48 hours of hospitalization, parenteral antibiotic therapy was used in 3 patients and 11 patients did not need parenteral antibiotic therapy, there were no complications in any of the patients and they had an average hospital stay of 8 days (R: 3-16 days). Conclusion: The use of human amniotic membrane in burn patients is favorable for pediatric patients; As shown in the study, the lower use of parenteral antibiotic therapy due to the rapid coverage of wounds caused by burns and the lower number of days of hospitalization.

Potencial remineralizante del fluoruro diamino de plata al 38% en dentina de dientes temporales afectada por caries / Remineralizing potential of 38% silver diamine fluoride in dentin affected by dental caries

Introducción: la caries es una enfermedad compleja que afecta a cualquier edad. La prevalencia es mayor en la primera dentición, sobre todo en población con baja percepción económica. El fluoruro diamino de plata (FDP) al 38% ha sido utilizado como una alter- nativa de tratamiento para esta enfermedad. Funciona como una solución remineralizante y cariostática. Objetivo: evaluar el efecto remineralizante del FDP al 38% en dentina afectada por lesiones de caries en molares temporales. Material y métodos: estudio clínico, epidemiológico, descriptivo, longitudinal y experimental. Se llevó a cabo en molares de primera dentición de niños de tres a cinco años de edad. Los niños seleccionados tenían molares con lesiones cariosas dentinarias, Pitts las denomina D3. No se incluyeron niños con dientes que presentaron patologías pulpares irreversibles. La aplicación del FDP al 38% la efectuó un operador entrenado para esta finalidad. Se utilizaron los criterios de Nyvad para determinar el grado de dureza de la dentina y con ello deducir su remineraliza- ción. Se observó la permanencia de la remineralización efectuada por un periodo de cinco meses. Resultado y conclusión: el FDP es un compuesto eficaz en 91% de los casos en un periodo de cinco meses o más (AU)

Introduction: dental caries is a complex disease that affects any age. The prevalence is higher in primary dentition, especially in a population with low economic perception. 38% silver diamine fluoride (FDP) has been used as an alternative treatment for this disease. It works as a remineralizing and cariostatic solution. Objective: to evaluate the remineralizing effect of 38% FDP on dentin affected by dental caries, in temporary molars. Material and methods: clinical, epidemiological, descriptive, longitudinal and experimental study. It was carried out in temporary molars of children between three and five years of age. The selected children presented molars with dental carious lesions, Pitts calls them D3. Children with teeth that presented irreversible pulp pathologies were not included. The application of the FDP to 38% was carried out by an operator trained for this purpose. The Nyvad criteria were used to determine the degree of hardness of the dentin and thereby deduce its remineralization. The permanence of the remineralization carried out was observed for a period of five months. Result and conclusion: the FDP is an effective compound in 91% of the cases, in a period of five months or more (AU)

Intra-articular Infiltration of Platelet-Rich Plasma versus Hyaluronic Acid in Patients with Primary Knee Osteoarthritis: Preliminary Results from a Randomized Clinical Trial / Infiltração intraarticular de plasma rico em plaquetas versus ácido hialurônico em pacientes com osteoartrose primária do joelho: Ensaio clínico randomizado com resultados preliminares

Abstract Objective The present study aimed to compare the effects of intraarticular infiltration of platelet-rich plasma with those of hyaluronic acid infiltration in the treatment of patients with primary knee osteoarthritis. Methods A randomized clinical trial was conducted with 29 patients who received an intraarticular infiltration with hyaluronic acid (control group) or platelet-rich plasma. Clinical outcomes were assessed using the visual analog scale for pain and the Western Ontario and McMaster Universities Arthritis Index (WOMAC) questionnaire before and after the intervention. In addition, the posttreatment adverse effects were recorded. Categorical variables were analyzed using the chi-square and Fisher exact tests, whereas continuous variables were analyzed using the Student t test, analysis of variance, and the Wilcoxon test; all calculations were performed with the Stats package of the R software. Results An independent analysis of each group revealed a statistical difference within the first months, with improvement in the pain and function scores, but worsening on the 6th month after the procedure. There was no difference in the outcomes between the groups receiving hyaluronic acid or platelet-rich plasma. There was no serious adverse effect or allergic reaction during the entire follow-up period. Conclusion Intraarticular infiltration with hyaluronic acid or platelet-rich plasma in patients with primary knee gonarthrosis resulted in temporary improvement of functional symptoms and pain. There was no difference between interventions.

Resumo Objetivo Comparar o efeito da infiltração intraarticular do plasma rico em plaqueta com a do ácido hialurônico no tratamento de pacientes com osteoartrose primária de joelho. Métodos Realizou-se um ensaio clínico randomizado com 29 pacientes, sendo um grupo submetido à infiltração com ácido hialurônico (controle) e o outro com plasma rico em plaquetas. Os desfechos clínicos avaliados foram a escala visual analógica da dor; o questionário Western Ontario and McMaster Universities Arthritis Index (WOMAC), antes e depois da intervenção; e os efeitos adversos após as aplicações. Utilizou-se os testes do qui-quadrado e exato de Fisher para as variáveis categóricas, e o teste t de Student, análise de variância, e Wilcoxon para as variáveis contínuas, através do software R. Resultados A análise independente de cada grupo revelou uma diferença estatística nos meses iniciais, com melhora dos escores de dor e função; porém, com piora no 6° mês após o procedimento. Não houve diferença dos desfechos avaliados entre os grupos que foram submetidos à infiltração com ácido hialurônico ou com plasma rico em plaquetas. Não houve efeito adverso grave ou reação alérgica durante todo o seguimento. Conclusão A infiltração intraarticular com ácido hialurônico ou plasma rico em plaquetas nos joelhos dos pacientes com gonartrose primária apresentou melhora temporária dos sintomas de função e dor. Não houve diferença entre as duas intervenções.

Risk Sharing Agreement: a pilot project in the Brazilian Unified Health System

Risk Sharing Agreement is defined as an agreement in which the State agrees to offer temporary access to a new drug, while the pharmaceutical industry accepts to receive the product according to the performance of the drug in real conditions of use. Risk sharing necessarily depends on the collection of additional evidence that may refer to the therapeutic benefits or the volume of patients, according to the assessment of its use in practice. The authors described the experience of the pilot project of a Risk Sharing Agreement in the Unified Health System.

Acordo de Compartilhamento de Risco: projeto-piloto no Sistema Único de Saúde / Risk Sharing Agreement: a pilot project in the Brazilian Unified Health System

O Acordo de Compartilhamento de Risco é definido como um acordo no qual o Estado concorda em oferecer acesso temporário a um novo medicamento, enquanto a indústria farmacêutica aceita receber pelo produto conforme o desempenho do medicamento em reais condições de uso. A partilha de risco depende, necessariamente, da coleta de evidências adicionais, que podem se referir aos benefícios terapêuticos ou ao volume de pacientes, conforme avaliação de seu uso na prática. Os autores descreveram a experiência do projeto-piloto de Acordo de Compartilhamento de Risco no Sistema Único de Saúde.

Risk Sharing Agreement is defined as an agreement in which the State agrees to offer temporary access to a new drug, while the pharmaceutical industry accepts to receive the product according to the performance of the drug in real conditions of use. Risk sharing necessarily depends on the collection of additional evidence that may refer to the therapeutic benefits or the volume of patients, according to the assessment of its use in practice. The authors described the experience of the pilot project of a Risk Sharing Agreement in the Unified Health System.

Crizotinib in the treatment of ALK gene mutation positive children with inflammatory myofibroblastic tumor: a report of 4 cases / 中华实用儿科临床杂志

Objective:To investigate the efficacy and safety of targeted therapy with Crizotinib for children with ALK gene mutation positive inflammatory myofibroblastic tumor (IMT). Methods:A retrospective analysis was performed on 4 children with ALK gene mutation positive IMT admitted to Shanghai Children′s Hospital from January 2019 to June 2021.Among them, 3 cases were given the targeted drug Crizotinib[280 mg/(m 2· time), q12h] orally, and 1 case was observed after complete tumor resection to analyze the efficacy and adverse drug reactions. Results:All 4 cases were male, aged from 2 years and 3 months to 11 years and 3 months.The tumors originated from the abdominal cavity in 2 cases, the right orbit in 1 case, and the right lung in 1 case.Pathological immunohistochemistry and fluorescence in situ hybridization were both positive for ALK gene mutation, and complete remission was achieved after comprehensive treatment.Among them, 3 patients were treated with oral Crizotinib, and 2 patients were tried to stop taking the drug for 1 year, relapsed 1 month later, and still achieved complete remission after the second treatment.The 4 cases were followed up for 8-30 months, and all survived.All the cases showed no abnormalities in blood image, liver and kidney function, myocardial enzyme profile, cardiac function, hearing and vision, and 2 cases showed prolonged Q-T interval in the course of Crizotinib treatment, which could be recovered by temporary withdrawal of drug, and no abnormality in electrocardiogram was found in continued drug use. Conclusions:Crizotinib was used to treat ALK mutation positive IMT, shrink tumor and consolidate postoperative treatment, which is a good choice for IMT in children with difficult surgical resection and refractory recurrence.

Manejo quirúrgico de biopolímeros en punta nasal: reporte de caso y revisión de la literatura / Surgical Management of Biopolymers in Nasal Tip: Case Report and Literature Review

Introducción: los rellenos faciales han sido ampliamente utilizados a nivel mundial. Existen rellenos temporales, semipermanentes y permanentes. En cuanto a los rellenos permanentes, la silicona es la más utilizada y está aprobada por la agencia gubernamental de los Estados Unidos, la Administración de Alimentos y Medicamentos (FDA), en dos presentaciones para el desprendimiento de la retina. En 1997 se autorizó el uso off-label de Adatosil y Silicon 100, ambas prescritas durante la relación médico-paciente. Se han descrito múltiples eventos adversos secundarios a la inyección de silicona como relleno facial, principalmente síntomas inflamatorios, reacción a cuerpo extraño, sepsis y migración del producto, que por lo general se presentan por una aplicación inapropiada por personal sin entrenamiento. Caso clínico: se presenta el caso de un paciente masculino en la quinta década de la vida, a quien le aplicaron silicona en aceite a nivel de la punta nasal; posteriormente, presenta dermatopatía secundaria sin respuesta al manejo médico, por lo cual requiere manejo quirúrgico para el retiro del material alogénico y reconstrucción nasal secundaria. Se dan recomendaciones para el manejo quirúrgico de estos pacientes.

Introduction: Injectable facial fillers have been widely used worldwide. There are temporary, semipermanent, and permanent fillers. Regarding permanent fillers silicone is the most widely used, approved by the Food and Drug Administration (FDA) in two presentations Adatosil and Silicon 100 for retinal detachment. In 1997 the FDA allows for the off-label use prescribed within the doctor-patient relationship. There have been reported multiple adverse events, mainly inflammatory symptoms, foreign body reactions, sepsis, and product migration generally occurring by inappropriate application by untrained personnel. Case report: We present the case of a male patient in the fifth decade of life who underwent the application of silicone oil at the level of the nasal tip, and later presented secondary dermatopathy without response to medical management, which requires surgical management to remove the allogeneic material and secondary nasal reconstruction

Educação em saúde mental no trabalho: protagonismo dos trabalhadores no contexto sindical / Mental health education at work: worker's protagonism within unions

Resumo Objetivo: relatar a experiência de uma atividade de extensão sobre saúde mental no trabalho, utilizando a estratégia de Educação em Saúde, desenvolvida por docentes de uma universidade pública federal, por demanda do Sindicato dos Metalúrgicos e trabalhadores de uma empresa do interior do Estado de São Paulo. Métodos: a atividade foi planejada conjuntamente por docentes e trabalhadores. Foram desenvolvidos cinco encontros com base em estratégias participativas de Educação em Saúde de forma a provocar a reflexão dos participantes a partir das experiências vivenciadas. Foram feitos ajustes ao longo do processo direcionados às demandas que surgiam nos encontros. Resultados: as discussões versaram sobre os tópicos: (a) temas emergentes em saúde mental; (b) depressão, ansiedade e uso de álcool/drogas; (c) Rede de Atenção Psicossocial municipal; (d) saúde mental no trabalho. Além disso, partindo das experiências prévias vivenciadas no cotidiano do trabalho, foram feitas reflexões sobre a importância da identificação precoce das situações de sofrimento, da rede de suporte entre trabalhadores e da organização do fluxo de cuidado na Rede de Atenção Psicossocial municipal. Conclusão: a parceria entre trabalhadores, sindicato e universidade se mostrou potente para ações de Educação em Saúde e fortalecimento do protagonismo do trabalhador no contexto do trabalho.

Abstract Objective: to report an extension activity on mental health at work, based on Health Education strategies, conducted by university professors-upon request by the Steelworkers Union-with participation of industrial workers, in São Paulo, Brazil. Methods: carried out by professors and workers, the planning resulted in five meetings based on Health Education participative strategies. Throughout the process, adjustments were made aimed at the demands that arose in the meetings. Results: the discussions included (a) emerging issues in mental health, (b) depression, anxiety and alcohol/drug use, (c) municipal Psychosocial Care Network, (d) mental health at work. Moreover, based on previous experiences in the daily work routine, the participant reflected on the importance of early identification of mental suffering, the need for a support network among workers, and the organization of the care flow within the municipal Psychosocial Care Network. Conclusion: the partnership between workers, the Union and university proved to be an important tool to develop Health Education actions and strengthen worker's protagonism.

Estratégias de mediação utilizadas por trabalhadores da área de drogas / Mediation strategies used by workers from the drug and alcohol field

As estratégias de mediação, para a psicodinâmica do trabalho, compreendem as estratégias de defesa e as de enfrentamento empregadas pelo trabalhador para mediar o sofrimento laboral. Este estudo visa compreender essas estratégias utilizadas por trabalhadores que executam as políticas públicas sobre drogas no eixo cuidado, em uma cidade do sul do Rio Grande do Sul. De abordagem qualitativa, este estudo é transversal e descritivo, e contou com duas etapas: entrevista individual e questionário sociodemográfico com 20 trabalhadores; e grupo focal com sete participantes no primeiro encontro e outros quatro no segundo. Utilizou-se a análise de conteúdo de Bardin. A priori, foram definidas as categorias estratégias de defesa e estratégias de enfrentamento. Na primeira, as subcategorias encontradas foram: racionalização; negação; desinvestimento afetivo e cognitivo; e isolamento. Na segunda, destacaram-se a transgressão, revoluções moleculares, busca por capacitação e busca por diálogo. Identificou-se a necessidade de espaços de trocas entre o coletivo de trabalhadores. Espera-se subsidiar discussões sobre o funcionamento dos serviços e seu impacto na vida dos trabalhadores, visando promover a saúde mental

Mediation strategies for the psychodynamics of work include not the defense strategies but also confrontation ones, which workers use to mediate labor suffering. This research aims to understand the strategies employed by workers who implement public drug policies on care services in a southern municipality in the state of Rio Grande do Sul. This cross-sectional and descriptive study adopted a qualitative approach in two stages: individual interviews and sociodemographic questionnaire with 20 workers; and focal group sessions with seven participants in our first meeting and four, in the second one. To analyze the data, we resorted to Bardin's analysis of content. We defined categories as a priori defense and confrontation strategies. In the first category, we found subcategories such as rationalization, nonacceptance, lack of emotional and cognitive investment, and isolation. In the second category, we highlight the following subcategories: transgression, molecular revolutions, search for training, and quest for dialogue. We also found the need for exchange spaces between workers. We expect to subside discussions about the functioning of services and their impact on workers' lives, aiming to promote mental health

Foot drop - an uncommon presentation of FOLFOX toxicity

A quimioterapia com FOLFOX (oxaliplatina, leucovorina e 5-fluorouracilo) é frequentemente utilizada em doentes com cancro colorretal. Os sais de platina são conhecidos por serem uma classe de quimioterápicos que comumente induzem neurotoxicidade periférica. Na toxicidade induzida pela oxaliplatina, os sintomas sensitivos são os mais frequentes. Neste artigo, apresentamos dois casos clínicos de pacientes com adenocarcinoma de cólon, ambos submetidos à quimioterapia com FOLFOX4, e que desenvolveram neurotoxicidade incomum, apresentando pé pendente após o terceiro ciclo de tratamento. Esta manifestação clínica pode ser explicada por dano axonal nos neurônios motores periféricos do nervo peroneal comum (fibular), que fornece inervação motora aos músculos do pé. A paralisia do nervo fibular causa fraqueza súbita nos músculos do pé, que parece ser temporária. Ambos os doentes recuperaram completamente do evento sem necessidade de ajustes no tratamento, nem introdução de medicamentos diferentes. A apresentação de pé pendente como toxicidade da quimioterapia ainda é pouco compreendida. Os casos relatados mostram o pé pendente como uma manifestação grave e incomum de neuropatia induzida por FOLFOX, que pode ser transitória, e não requer necessariamente intervenção específica.

Chemotherapy based on FOLFOX (oxaliplatin, leucovorin, and 5-fluorouracil) regimen is frequently used in colorectal cancer patients. Oxaliplatin and other platinum agents are known to be a class of chemotherapy drugs that commonly induce peripheral neurotoxicity. The most frequent oxaliplatin related neurotoxicity is sensitive symptoms. Here, we present two cases of patients with colon adenocarcinoma, both undergoing chemotherapy with FOLFOX4, who developed uncommon neurotoxicity, presenting with foot drop after the third treatment cycle. Foot drop may be explained by axonal damage of peripheral motor neurons of the common peroneal (fibular) nerve, which provides motor innervation to the foot muscles. Peroneal nerve palsy causes sudden weakness in the muscles of the foot that seems to be temporary. Both patients completely recovered from the event. There was no need for treatment adjustments, neither introduction of different drugs. Foot drop as chemotherapy toxicity is still poorly understood. The reported cases show foot drop as a severe and uncommon manifestation of FOLFOX-induced neuropathy, that might be transitory, and does not necessarily requires specific intervention.

Estudo de estabilidade de anfetaminas e produtos de biotransformação de cocaína e tetraidrocanabinol em amostras de urina seca em papel (dried urine spots) / Stability study of amphetamines, biotransformation products of cocaine and tetrahydrocannabinol in dried urine spots

O número de pessoas utilizando substâncias ilícitas de forma recreativa aumenta a cada ano, chamando a atenção de estudiosos de diversas áreas do conhecimento. Com isso, a demanda de exames toxicológicos exigida para trabalhadores, vítimas de crimes e esportistas também tem crescido. A amostra biológica mais utilizada para análises toxicológicas continua sendo a urina, visto que sua obtenção é menos invasiva, possibilita coletar grande volume de amostra e pode-se detectar substâncias até dias após ter ocorrido a exposição ou consumo. Entretanto, estas amostras necessitam de um grande volume físico para serem armazenadas e transportadas aos laboratórios, devendo ser mantidas em temperatura baixa e controlada para conservação. Outro ponto a se considerar é a quantidade de amostra insuficientemente coletada, ou extravasamento do conteúdo, contaminando outras amostras e muitas vezes, inviabilizando a análise. Uma alternativa recente para tais problemas é utilizar a técnica chamada de dried urine spots (DUS), onde poucos microlitros de urina são colocados em um papel absorvente e secos sob temperatura ambiente, preservando de agentes degradantes os componentes presentes na urina. Assim, o objetivo deste trabalho é avaliar a estabilidade das substâncias do presente estudo em alta temperatura, temperatura ambiente e em temperaturas de 4°C e -20°C. Para este fim, foi necessário desenvolver, validar e aplicar métodos de extração e determinação de anfetaminas e produtos de biotransformação de cocaína e tetraidrocanabinol carboxílico (THCCOOH) em amostras dried urine spot, utilizando cromatografia líquida acoplada à espectrometria de massas. Os picos foram identificados por UPLC-ESI-MS/MS, com tempo total de 5 mins utilizando fase A- água, formiato de amônio e 0,1% ácido fórmico, e B- metanol: acetonitrila (6:4) + 0,1% de ácido fórmico. A extração foi feita utilizando acetonitrila: metanol: acetona (1:1:1) +ácido fórmico 0,1%. Não foi possível iniciar a validação de THCCOOH, visto uma possível complexação do analito com o papel. Para as outras substâncias, o método cromatográfico desenvolvido se mostrou eficiente e seletivo, com LOD e LOQ de 10 ng/mL para todos os analitos, sendo linear até 1000 ng/mL, atendeu as especificações de precisão e exatidão e carryover. As amostras permaneceram estáveis ao longo de 32 dias nas temperaturas estudadas, demonstrando a segurança em se utilizar a técnica de DUS para armazenamento e transporte de amostras biológicas dentro da faixa de temperatura do estudo até 32 dias

The number of people using illegal substances in a recreational way increases each year, drawing the attention of scholars from different areas of knowledge. As a result, the demand for workplaces drug tests, toxicological tests for victims of crimes and dopping has also grown. The biological sample most used for toxicological tests remains urine, since obtaining it is less invasive, it is possible to collect a large volume of sample and it is possible to detect substances up to days after exposure or consumption has occurred. However, these samples require a large physical volume to be stored and transported to the laboratories, and must be kept at a low temperature for conservation. Another point to consider is the amount of sample insufficiently collected, or leakage of the content, causing contamination of other samples and often making the analysis unfeasible. A recent alternative to such problems is to use "dried urine spots" (DUS), where few microliters of urine are placed on absorbent paper and dried at room temperature, preserving the components present in the urine from degrading agents. Thus, the objective of this work is to evaluate the stability of the substances in this study at high temperature, room temperature and at temperatures of 4°C and -20°C. For this purpose, it was necessary to develop, validate and apply methods of extraction and determination of amphetamines and biotransformation products of cocaine and carboxylic tetrahydrocannabinol (THCCOOH) in dried urine spot samples, using liquid chromatography coupled to mass spectrometry (LC-MS). The peaks were identified liquid chromatography coupled to a mass spectrometer (UPLC-ESI-MS/MS), with a total time of 5 mins using phase A- water, ammonium formate and 0.1% formic acid, and B- methanol: acetonitrile (6:4) + 0.1% formic acid. Extraction was done using acetonitrile: methanol: acetone (1:1:1) + 0.1% formic acid. It was not possible to perform the validation of THCCOOH, given a possible complexation of the analyte with the paper. To the others substances, the chromatographic method developed proved to be efficient and selective, with LOD and LOQ of 10 ng/mL for all analytes, being linear up to 1000 ng/mL, meeting the specifications of precision and accuracy and carryover. The samples remained stable for 32 days at the temperatures studied, demonstrating the safety of using the DUS technique for storage and transport of biological samples until 32 days on temperature range studied

Urgencias médicas durante la práctica estomatológica / Medical emergencies during dental practice

Introducción: Las urgencias médicas pueden ocurrir durante la práctica estomatológica. Objetivo: Abordar elementos actuales sobre la epidemiología, prevención, cuadro clínico y tratamiento de las urgencias médicas más frecuentes durante la atención estomatológica. Material y Métodos: Se realizó una revisión bibliográfica en septiembre de 2021. Se evaluaron revistas de impacto de Web of Science (19 revistas). Se consultaron bases de datos de MEDLINE, Google Académico, PubMed y SciELO con los descriptores: "medical emergency", "odontology treatment", "epidemiology". Se incluyeron artículos en idioma español e inglés, mayoritariamente de los últimos 5 años. Los que mejor cumplieron los criterios de revisión fueron 31 artículos y fueron incluidos como referencias en este artículo. Desarrollo: Las urgencias más frecuentes son las lipotimias y los síncopes vaso vágales. El diagnóstico basado en los antecedentes patológicos y hallazgos clínicos permite tomar conductas adecuadas. La terapéutica actual aboga por la protocolización de la atención y el uso justificado, sustentado por el conocimiento, de un botiquín de medicamentos de urgencia. Conclusiones: Las urgencias médicas pueden ocurrir durante la práctica estomatológica y poner en riesgo la vida de los pacientes. Su incidencia es variable, el riesgo para la vida no es frecuente y la sobrevida es elevada. Confeccionar una adecuada historia clínica y preparar al personal evitará complicaciones posteriores(AU)

Introduction: Medical emergencies can occur during dental practice. Objective: To address current issues in the epidemiology, prevention, clinical picture and treatment of the most frequent medical emergencies during dental treatment. Material and Methods: A literature review was conducted in September 2021. Web of science impact journals (19 journals) were evaluated. Medline, PubMed, Google Scholar, and SciELO databases were consulted using the following descriptors: "medical emergency", "odontology treatment", and "epidemiology". Articles in Spanish and English were included, preferably those published within the last 5 years. A total of 31 articles were obtained and included as references in this article. Development: Lipothymia and vasovagal syncope are the most frequent emergencies. The diagnosis based on pathological antecedents and clinical findings allows us to take appropriate behaviors. The current therapy advocates for the protocolization of care and justified use, supported by knowledge about a first-aid kit. Conclusions: Medical emergencies can occur during dental practice, putting patients´ lives at risk. The incidence is changeable and the survival rate is high. The development of an adequate clinical history and training of the staff will prevent further complications(AU)

Protocolo de desensibilización rápida en pacientes con reacción moderada a severa de hipersensibilidad a citostáticos / Rapid desensitization protocol in patients with moderate to severe hypersensitivity reaction to cytostatics

Introducción: La desensibilización rápida a medicamentos induce una tolerancia temporal a los quimioterapéuticos que provocan reacciones de hipersensibilidad. Objetivo: Evaluar el protocolo de desensibilización rápida en escenario ambulatorio en pacientes que presentaron reacciones de hipersensibilidad a fármacos citotóxicos. Métodos: Se realizó un estudio observacional, y retrospectivo, de 30 pacientes con cáncer que desarrollaron reacciones de hipersensibilidad entre los años 2016 y 2018, tratados en el Hospital de Día del Servicio de Oncología del Clínico Quirúrgico Hermanos Ameijeiras. Se clasificaron según su intensidad, y se analizaron variables demográficas, características clínicas, y síntomas presentados. Se utilizó un protocolo en doce etapas basado en tres diluciones del fármaco. Se administró premedicación en todos los casos. Se realizó estadística descriptiva, y para la asociación entre variables, se utilizó la prueba estadística Chi-cuadrado. Resultados: La mediana de edad fue 54 años (23;77). Predominaron las mujeres; los menores de 60 años; tumor primario de colon; antecedentes de alergia; el oxaliplatino como fármaco más implicado; las RHS durante la infusión; e intensidad moderada. Fueron más frecuentes los síntomas cutáneos y gastrointestinales. Con la aplicación del protocolo se completó la quimioterapia planificada a los 30 pacientes (145 ciclos adicionales). Solo se presentaron ocho desensibilizaciones con reacciones leves de tipo cutáneas. El 94,5 por ciento de las desensibilizaciones no presentaron reacción alguna. Conclusiones: Constituye el primer reporte nacional de la utilización exitosa de un protocolo de desensibilización rápida a citostáticos que demostró ser eficaz y seguro en el escenario ambulatorio, con un manejo multidisciplinario(AU)

Introduction: Rapid desensitization to drugs induces a temporary tolerance to chemotherapeutics causing hypersensitivity reactions. Objective: To evaluate the rapid desensitization protocol in an outpatient setting in patients who had hypersensitivity reactions to cytotoxic drugs. Methods: An observational and retrospective study was carried out in 30 cancer patients, who developed hypersensitivity reactions, from 2016 to 2018. They were treated in the outpatient Oncology service at Hermanos Ameijeiras Surgical Clinical Hospital. These subjects were classified according to intensity; demographic variables, clinical characteristics, and symptoms were analyzed. A twelve-step protocol based on three dilutions of the drug was used. Premedication was administered in all cases. Descriptive statistics and for the association between variables were performed. Chi-square statistical test was used. Results: The median age was 54 years (23; 77). Predominance was observed in women, those under 60 years of age, primary colon tumor, history of allergy, oxaliplatin as the drug most implicated, HRH during infusion, and moderate intensity. Skin and gastrointestinal symptoms were more frequent. The planned chemotherapy was completed with the application of the protocol, in all 30 patients (145 additional cycles). There were only eight desensitization with mild skin-type reactions. 94.5 percent of desensitizations did not show any reaction. Conclusions: It constitutes the first national report of successful use of a rapid desensitization protocol to cytostatics that proved to be effective and safe in the outpatient setting with multidisciplinary management(AU)