Informe diário de evidências COVID-19: busca referente aos dias 4, 5 e 6 de julho de 2020 / COVID-19 daily evidence report: search for July 4, 5 and 6, 2020

O Informe Diário de Evidências é uma produção do Ministério da Saúde que tem como objetivo acompanhar diariamente as publicações científicas sobre tratamento farmacológico e vacinas para a COVID-19. Dessa forma, são realizadas buscas estruturadas em bases de dados biomédicas, referente ao dia anterior desse informe. Não são incluídos estudos pré-clínicos (in vitro, in vivo, in silico). A frequência dos estudos é demonstrada de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, coortes, entre outros). Para cada estudo é apresentado um resumo com avaliação da qualidade metodológica. Essa avaliação tem por finalidade identificar o grau de certeza/confiança ou o risco de viés de cada estudo. Para tal, são utilizadas ferramentas já validadas e consagradas na literatura científica, na área de saúde baseada em evidências. Cabe ressaltar que o documento tem caráter informativo e não representa uma recomendação oficial do Ministério da Saúde sobre a temática. Foram encontrados 17 artigos.

Acrodermatitis enteropática ampollosa / Bullous Acrodermatitis Enteropathica

La acrodermatitis enteropática (AE) es una genodermatosis autosómica recesiva causada por la mutación del gen responsable de codificar a la proteína transportadora de Zinc (Zn) SLC39A4. A pesar de ser una rara enfermedad es de fácil manejo y gran relevancia clínica. Se caracteriza por la siguiente tríada: dermatitis acral y periorificial, diarrea y alopecia. Comunicamos un caso de presentación atípica en una lactante de 6 meses de edad con lesiones periorificiales y ampollas acrales que resolvió rápidamente con la terapia suplementaria con Zinc (AU)

Enteropathic acrodermatitis is an autosomal recessive genodermatosis caused by the mutation of the gene responsible for encoding the Zinc transporter protein SLC39A4. Despite being a rare disease, it is easy to manage and of great clinical relevance. It is characterized by the following triad: acral and periorificial dermatitis, diarrhea and alopecia. We report a case of atypical presentation in an almost 6-month-old infant with periorificial lesions and acral blisters that quickly resolved with supplemental Zinc therapy (AU)

Pustulosis aguda erosiva del cuero cabelludo / Erosive pustular dermatosis of the scalp

La Pustulosis Erosiva del cuero cabelludo fue descrita por primera vez por Pye, Peachy y Burton en 1979, en mujeres mayores¹. De etiología y patogenia no del todo clara, se relaciona con exposición a trauma local. Se presenta como lesiones erosivas, costrosas y pustulosas de carácter estéril. Su cuadro histológico no es específico, por lo que el diagnóstico es de exclusión. Se han reportado múltiples tratamientos, pero los que han demostrado mejor resultado se basan en el uso de corticoides tópicos de alta potencia y retinoides orales. Presentamos un caso de pustulosis erosiva del cuero cabelludo en un paciente varón y una revisión de los principales aspectos clínicos e histopatológicos de esta enfermedad.

In 1979 Pye, Peachy and Burton described the Erosive Pustular Dermatosis of the scalp in elder women. The etiology and pathogenesis is still unknown; nonetheless, it is most commonly associated with the exposure to local trauma. The disease is manifested as sterile erosive, crusty and pustular lesions on the scalp. Its histological profile is unspecific; therefore, it is a diagnosis of exclusion. Multiple treatments have been reported, high-potency topical corticosteroids and oral retinoids have shown favorable response. Herein we present a case of an erosive pustular dermatosis of the scalp on a male patient and a review of the clinical and histological characteristics of this disease.

Diseño de formulación de sulfato de cinc 10 mg Zn2+/5 mL solución oral para uso pediátrico / Design of formulation of Zinc sulphate 10 mg Zn2+/5 mL oral solution for pediatric use

INTRODUCCIÓN: el sulfato de cinc en forma de solución se administra por vía oral para uso pediátrico, en la profilaxis y tratamiento de estados carenciales de cinc, por escasos aportes o mala absorción, previa determinación de las concentraciones plasmáticas. En niños se emplea como coadyuvante en el tratamiento de bajo peso y talla. OBJETIVO: diseñar una formulación de sulfato de cinc solución oral 10 mg Zn2+/5 mL para uso pediátrico. MÉTODOS: se presentó el estudio en el tiempo de los parámetros químicos, físicos, microbiológicos y toxicológicos de la formulación seleccionada. Se elaboraron tres lotes pilotos y un lote industrial. La estabilidad química en condiciones aceleradas y de estante fue conducida aplicando un método de valoración complejométrica con EDTA desarrollado en el Centro de Investigación y Desarrollo de Medicamentos (CIDEM). RESULTADOS: se obtuvo una formulación líquida incolora y traslúcida libre de partículas extrañas, con sabor dulce. En el ensayo de tolerancia por vía oral en ratas, no se observó toxicidad significativa atribuible a la administración de la formulación a la dosis estudiada. El resto de los parámetros evaluados en el estudio de estabilidad químico-físico de vida de estante mostraron resultados satisfactorios. CONCLUSIONES: la solución resultó ser estable química, física y microbiológicamente, almacenada a temperatura de 32 ± 2 ºC en frascos de vidrio ámbar durante un período de 24 meses. Al comparar los resultados del lote industrial con los lotes pilotos se observa que son similares, lo que demuestra que la tecnología desarrollada es factible de escalar a nivel industrial(AU)

INTRODUCTION: the zinc sulphate solution is orally administered for pediatric purposes, in prophylaxis and treatment of zinc deficiency resulting from inadequate diet or malabsorption. It is also used in children to manage low weight and height. OBJECTIVE: design of a formulation of oral zinc sulphate solution at 10 mg Zn2+/5 mL for pediatric use. METHODS: results of the physical-chemical stability studies, microbiology evaluation and toxicological test were shown for selected formulation. Three pilot scale-up batches and one industrial batch were prepared. The chemical stability under accelerated conditions and shelf-life studies were conducted on the basis of a compleximetric titration with EDTA method developed in the Center of Research and Development of Drugs (CIDEM). RESULTS: a colorless, translucent and sweet liquid formulation, free of foreign matters, was obtained. In the orally administered tolerance test made in rats, no signs of significant toxicity attributable to the administration of the formulation at the study dose were observed. The other parameters evaluated in the physical-chemical stability of the shelf life study proved to be satisfactory. CONCLUSIONS: the solution was chemically, physically and microbiologically stable at a temperature of 32 ± 2 ºC for a 24 month period. When comparing the results of the pilot scale-up batch and those of the industrial batch, they were similar. This showed that the developed technology is feasible at industrial scale(AU)

Efecto del zinc aminoquelado y el sulfato de zinc en la incidencia de la infección respiratoria y la diarrea en niños preescolares de centros infantiles / Effect of zinc amino acid chelate and zinc sulfate in the incidence of respiratory infection and diarrhea among preschool children in child daycare centers

Introducción. El déficit de zinc es común en niños de poblaciones en desarrollo. La deficiencia de zinc altera el sistema inmunológico y la resistencia a las infecciones. Objetivo. Evaluar el efecto de dos compuestos de zinc en la prevención de la infección respiratoria y la diarrea agudas. Materiales y métodos. Se llevó a cabo un ensayo comunitario triple ciego en 301 niños entre dos y cinco años de edad de centros infantiles de Medellín. Fueron seis conglomerados distribuidos aleatoriamente en tres grupos de intervención que recibieron zinc aminoquelado, sulfato de zinc y placebo durante cinco días de la semana a lo largo de 16 semanas. Se evaluaron diariamente los síntomas de infección respiratoria, diarrea aguda y efectos secundarios. Resultados. La incidencia de la infección respiratoria fue menor con el zinc aminoquelado (1,42 por 1.000 días-niño) comparado con el sulfato de zinc (1,57 por 1.000 días-niño) (RR=0,90, IC 95% : 0,382 a 2,153 , p=0,999) y con el placebo (3,3 por 1.000 días-niño) ( RR=0,43, IC 95% : 0,196 a 0,950 , p=0,049). La incidencia de diarrea aguda con el zinc aminoquelado (0,15 por 1.000 días-niño) fue menor que con el sulfato de zinc (1,18 0,78 por 1.000 días-niño) (RR=0,20, IC 95% : 0,0043 a 1,662, p=0,361) y que la del grupo placebo (0,49 por 1.000 días-niño) (RR=0,32, IC 95% : 0,006 a 3,990 , p=0,346). Conclusiones. El zinc aminoquelado tuvo mejor efecto en la disminución de la incidencia de la infección respiratoria y la diarrea agudas en niños preescolares comparado con los otros grupos de estudio.

Introduction: Zinc deficiency is common in children among populations in developing areas. Zinc deficiency alters the immune system and the resistance to infections. Objective: To evaluate the effect of two zinc compounds in the prevention of acute respiratory infection and acute diarrhea. Materials and methods: Randomized triple-blind community trial with 301 children between 2-5 years of age from six child daycare centers in Medellin, Colombia. Children were distributed in three groups receiving zinc amino acid chelate, zinc sulfate and placebo five days a week for 16 weeks. Daily symptoms of respiratory infection, acute diarrhea and side effects were evaluated. Results: The incidence of respiratory infection was lower with zinc amino acid chelate (1.42 per 1,000 child-days) compared with placebo (3.3 per 1,000 child-days) (RR=0.43, 95% CI: 0.196 to 0.950, p=0.049) and with zinc sulfate (1.57 per 1,000 child-days) (RR=0.90, 95% CI 0.382 to 2.153, p=0.999). The incidence of acute diarrhea with zinc amino acid chelate (0.15 per 1,000 child-days) was lower than with placebo (0.49 per 1,000 child-days) (RR=0.32, 95% CI 0.006 to 3.990, p=0.346) and with zinc sulfate (0.78 per 1,000 child-days) (RR=0.20, 95% CI: 0.0043 to 1.662, p=0.361). Conclusions: Zinc amino acid chelate had a better effect in reducing the incidence of acute respiratory infection and acute diarrhea in preschool children when compared with the other groups.

Wilson's disease: an analysis of 28 Brazilian children

OBJECTIVES: Clinical-laboratory and evolutionary analysis of twenty-eight patients with Wilson's disease. METHODS: Twenty-eight children (twelve females and sixteen males) with Wilson's disease were evaluated retrospectively between 1987 and 2009, with a follow-up of 72 months (1 - 240 months). The clinical, laboratory, and histologic features at diagnosis were recorded at the end of the study. RESULTS: The median age at diagnosis was 11 years (2 - 18 years). Twelve patients were asymptomatic, seven had hepatitis symptoms, five had raised aminotransferase levels, three had hepatomegaly associated with neurological disorders, one had fulminant hepatitis with hemolytic anemia, and six patients presented with a Kayser-Fleischer ring. A histological analysis revealed that six children had chronic hepatitis, seven had cirrhosis, two had steatosis, one had portal fibrosis, and one had massive necrosis. The treatment consisted of D-penicillamine associated with pyridoxine for 26 patients. Adverse effects were observed in the other two patients: one presented with uncontrollable vomiting and the other demonstrated elastosis perforans serpiginosa. At the end of the study, all 26 treated patients were asymptomatic. Twenty-four of the patients were treated with D-penicillamine and pyridoxine, and two were treated with trientine and zinc sulfate. A liver transplant was performed in one patient with fulminant hepatitis, but the final patient died 48 hours after admission to the intensive care unit. CONCLUSIONS: Family screenings associated with early treatment are important in preventing Wilson's disease symptoms and potentially fatal disease progression. The study suggests that Wilson's disease must be ruled out in children older than two years presenting with abnormal levels of hepatic enzymes because of the heterogeneity of symptoms and the encouraging treatment results obtained so far.

Comparação entre a eficácia da cimetidina e do sulfato de zinco no tratamento de verrugas múltiplas e recalcitrantes / Efficacy comparison between cimetidine and zinc sulphate in the treatment of multiple and recalcitrant warts

FUNDAMENTOS: Verrugas são proliferações epiteliais na pele e mucosas causadas por diversos tipos de HPV. Elas podem involuir espontaneamente ou aumentar em número e tamanho de acordo com estado imunitário do paciente. A cimetidina e o sulfato de zinco têm importante efeito no sistema imune, sendo usados como imunomoduladores no tratamento de diversas doenças. OBJETIVO:Comparar a eficácia terapêutica de cimetidina e sulfato de zinco no tratamento de verrugas cutâneas de difícil tratamento. MÉTODOS: Estudo prospectivo duplo-cego randomizado. Dezoito pacientes com verrugas múltiplas foram divididos em dois grupos, um recebeu cimetidina 35mg/kg/dia (máximo 1.200mg/dia), e o outro, sulfato de zinco 10mg/kg/dia (máximo de 600mg/dia) por três meses. RESULTADOS: Dos 18 pacientes do estudo, nove receberam cimetidina, e nove, sulfato de zinco; apenas um do grupo do sulfato de zinco não completou o tratamento devido a náuseas e vômitos. Cura foi obtida em cinco pacientes tratados com sulfato de zinco, e apenas um não obteve alteração das lesões. Do grupo da cimetidina cinco não apresentaram modificação, e quatro apresentaram diminuição inferior a 30% das lesões iniciais. CONCLUSÕES: Sulfato de zinco na dose de 10mg/kg/dia parece ser mais efetivo que cimetidina para o tratamento de crianças e adultos com verrugas múltiplas e de difícil manejo. A pequena casuística deste trabalho não permite, entretanto, conclusão categórica.

Background: Warts are epithelial proliferations on the skin and mucous membrane caused by various types of HPV. They can decrease spontaneously or increase in number and size according to patient's immune status. Cimetidine and zinc sulphate have important effects on the immune system and are used as immunomodulators in the treatment of various diseases. Objective: To compare the efficacy of cimetidine and zinc sulphate in the treatment of multiple and recalcitrant warts. Methods: A random double-blind prospective study. Eighteen patients with multiple warts were divided into two groups: one took 35mg/Kg/day of cimetidine (maximum 1200 mg/day) and the other 10 mg/Kg/day of zinc sulphate (maximum 600 mg/day) for three months. Results: Among the 18 patients who participated in the study, nine took cimetidine and nine zinc sulphate. Just one patient in the zinc sulphate group did not complete treatment due to nausea and vomiting. Five patients who were treated with zinc sulphate were cured and only one did not show modifications in lesions. Among the group who was treated with cimetidine, five did not show modifications in lesions and four showed decrease from baseline below 30%. Conclusions: 10 mg/Kg/day zinc sulphate dose seems to be more effective than cimetidine for the treatment of children and adults with multiple and difficult-to-handle warts. However, the small number of patients did not enable any definitive conclusion.

Periapical tissue healing after post space preparation with or without use of a protection plug and root canal exposure to the oral environment: study in dogs

The purpose of this study was to evaluate the influence of coronal leakage on the healing of dogs' periapical tissues after root canal filling, post space preparation and protection or not with a temporary sealer plug. Forty root canals of dogs' teeth were instrumented and filled by the lateral condensation technique with gutta-percha points and Endomethasone or CRCS sealers. After post space preparation, the remaining filling material was protected or not with a plug of temporary Coltosol sealer and exposed to the oral environment for 90 days. Thereafter, the animals were sacrificed and the specimens were removed and prepared for histomorphological and histobacteriological analysis. The findings revealed 35 percent of microbial leakage in the groups without plugs and 15 percent of leakage in the groups with plugs. Statistical analysis showed that the use of a Coltosol plug improved significantly the histomorphological results regardless of the type of root canal sealer (p=0.05) and that CRCS and Endomethasone sealers showed similar results (p>0.05).

O propósito deste trabalho foi avaliar a influência da infiltração coronária no reparo dos tecidos periapicais após obturação dos canais radiculares, preparo para pino e proteção ou não de um "plug" de cimento temporário. Quarenta canais de dentes de cães foram instrumentados e obturados pela técnica da condensação lateral ativa com cones de guta-percha e os cimentos Endomethasone e CRCS. Após preparo para pino os remanescentes do material obturador foram protegidos ou não com um "plug" do cimento temporário Coltosol e expostos ao meio oral por 90 dias. Decorrido este período, os animais foram mortos e os espécimes foram removidos e preparados para análises histomorfológica e histobacteriológica. Foi observado 35 por cento de casos de infiltração bacteriana nos grupos sem "plug" e 15 por cento nos grupos com "plug". Concluiu-se estatisticamente que o "plug" de Coltosol foi eficiente no controle da infiltração coronária de microorganismos (p=0,05), e que os cimentos CRCS e Endomethasone apresentaram resultados semelhantes (p>0,05).

Zinc sulphate in the treatment of cutaneous leishmaniasis: in vitro and animal study

This study was designed to evaluate the effectiveness of zinc sulphate both in vitro and in an animal model against both strains of old world cutaneous leshmaniasis. The in vitro sensitivities of promastigotes and axenic amastigotes of both Leishmania major and L. tropica to zinc suphate was determined, the LD50 calculated and compared to the standard treatment for cutaneous leishmaniais pentavalent antimony compounds. The results show that the two forms of both strains were sensitive to zinc sulphate and their respective LD50 were lower compared to the pentavalent antinomy compound. Furthermore the sensitivities of the forms of both strains were tested using a simple slide method and compared to results of the standard method. To confirm this result, zinc sulphate was administered orally to mice infected with cutaneous leishmaniasis both therapeutically and prophylactically. Results showed that oral zinc sulphate was effective in both treatment and prophylaxis for cutaneous leishmaniasis. These results encourage the use of oral zinc sulphate in the treatment of cutaneous leishmaniasis clinically.