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)

Comparative study between oral zinc sulphate, amino acids chelated zinc and placebo in treatment of viral warts

Background: Warts are tumors or growths caused by infection with Human Papilloma virus [HPV]. More than 100 HPV subtypes are known. They are a common presenting disease in children and adolescents which spread by direct contact or autoinoculation

The aim of the Work: The aim of this work was to assess and compare the efficacy and safety of oral zinc sulphate and amino acids chelated zinc in treatment of viral warts

Patients and Methods: This cross sectional case control study included 60 patients with multiple viral warts who were collected from the Dermatology, STDs and Andrology outpatient clinic of Fayoum university hospital during the period from November 2014 to November 2015. The patients were 29 males and 31 females with ages ranging from 15 to 60 years

Results: There was statistically significant difference in degree of response in zinc and control groups as no patient in control group showed any response while in both zinc groups 27.5% of patients showed variable degrees of response. Also, there was no statistically significant difference in degree of response in both zinc groups

Conclusion: Oral zinc in its both forms used in our study is safe but needs time to act and the response is not high, so it is not fit to be used as a monotherapy, but rather to be combined with other wart treatment modalities

Recommendations: More studies are needed to assess the therapeutic effect of zinc and its efficacy in combinations in warts treatment with higher doses and longer duration of treatment

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.

Effect of Zinc Supplementation on Adenosine Deaminase Activity in Leprosy.

Serum Adenosine Deaminase (ADA) acts as marker of cellular immunity and its activity is found to be altered in various diseases in which there is a cell mediated immune response (CMI) including leprosy. The role of zinc is well established in the development and maintainence of immunocompetence and its supplementation activates the immune response in particular Tlymphocytes and monocytes in several ways. The aim of the study was planned to evaluate the effect of nutritional zinc supplementation on cell mediated immune response by investigating the pre and post intervention serum ADA levels after oral zinc sulphate supplementation in leprosy patients. A total of 49 cases, 30 Tuberculoid Leprosy (TT) and 19 Lepromatous Leprosy (LL) patients, within the age group of 25-60 years were enrolled in the study along with 30 age matched healthy controls. Serum ADA was estimated in all the subjects before and after (2 months and 4 months) oral zinc supplementation. Pre intervention serum ADA level was observed to be significantly increased in both the TT and LL (p<0.001) groups as compared to controls, revealing raised immunological activity in the patients. After oral zinc sulphate supplementation serum ADA re-evaluation was done in 38 cases. A highly significant (p < 0.001 ) rise in ADA level was registered in the post intervention period (4 months supplementation) in TT cases with a moderately significant (p< 0.05) increase in LL cases, indicating the ability of oral zinc therapy to affectively alter the cell mediated immune response in leprosy.

Effect of Zinc Salts on Acid Secretion and Peptic Ulceration in Albino Rats.

The present study was carried out to see the effect of two zinc salts i.e zinc sulphate and zinc chloride on gastric ulcers induced by stress, pylorus ligation and aspirin in albino rats. The rats were divided into two main groups (zinc sulphate 30, 60, 90 mg/kg i.p and zinc chloride 10 and 20mg/kg i.p). They were further sub-divided into three sub-groups dependant on ulcer model i.e stress, pylorus ligation and aspirin induced ulcers. It was found that zinc sulphate and zinc chloride had a dose dependant reduction in ulcer index in all three models of gastric ulceration. Also, both the salts had anti acid secretory effect, raised pH of gastric secretion and reduced total acidity significantly. Thus zinc salts prevent gastric ulceration. Probably this effect is mediated by anti acid secretory action.

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).

Therapeutic evaluation of zinc and copper supplementation in acute diarrhea in children: double blind randomized trial.

OBJECTIVE: To test the hypothesis that daily supplementation of zinc and copper mixed with the oral rehydration solution (ORS) reduces the duration and the severity of acute diarrhea in children. METHODS: In a randomized, double blind, placebo controlled trial children aged 6 months to 59 months in an urban hospital with acute diarrhea, were assigned to receive the intervention of once daily 40 mg of zinc sulfate and 5 mg of copper sulfate dissolved in a liter of standard ORS (n = 102) or placebo (50 mg of standard ORS powder) dissolved in a liter of ORS (n = 98). RESULT: The baseline characteristics in the two groups were similar. The mean survival time (days) (SE) with diarrhea was not significantly different in the treatment (4.34 (0.2)) as compared to the placebo group (4.48 (0.2)), nor was there any difference in the median time to cure. Cure was less likely with longer duration of diarrhea prior to enrollment (P < 0.001), if the time taken for rehydration was more (P = 0.001) and if intravenous fluids were used (P = 0.03) regardless of the micronutrient supplementation. The proportion of children with diarrhea > 4 days was 46% in the placebo group with an adjusted odds ratio (OR) (95% CI) of 1.19 (1.58, 0.9; P = 0.2) as compared to 39% in the supplemented group. The most important risk factor for diarrhea > 4 days was diarrheal duration prior to enrollment with OR = 6.25 (3.7, 11.1). The supplemented group however had less severity of diarrhea with a lower proportion of children requiring unscheduled intravenous fluids (OR = 0.4; 95% CI 0.05, 2.2), with weight loss (OR = 0.7; 95% CI; 0.4, 1.3), with complications (OR = 0.15; 0.01, 1.3) and had no deaths as compared to two in the placebo group. CONCLUSIONS: This study showed that the most important predictor for duration of diarrhea in children was the severity of the disease at enrollment, and, not the supplementation. There were clinical beneficial effects of supplementation on rate of any complications and mortality. A larger trial is warranted before supplementation of micronutrients mixed with ORS are recommended for management of acute diarrhea.

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.

Treatment of Behcet's disease

Behcet's disease is characterized with multifactorial etiopathogenesis and multiclinical pictures. The treatment of patients with Behcet's disease is based on the severity of illness, and the most appropriate management of Behcet's disease requires a multidisciplinary approach. Although various therapeutic modalities have been employed for Behcet's disease, treatment is far from satisfactory. Treatment of Behcet's disease includes local, systemic, or surgical therapies. Limited success has been found with colchicine, azathioprine, indomethacin, cyclophosphamide, chlorambucil, levamisole, transfer factor, fibrinolytic therapy, and systemic corticosteroid. New therapeutic approaches have been introduced for Behcet's disease using cyclosporine, thalidomide, interferon, acyclovir, high-dose corticosteroids or cyclophosphamide pulse therapy, and FK 506. We suggest that therapeutic agents should be selected after thorough evaluation of the immune state of each patient by using various tests and by determining any aggravating or provoking factors involved. In general, a combination-agent regimen is more effective than a single-agent regimen. Early diagnosis and proper treatment can inhibit or at lease slow the progress of the disease remarkably.