No Más Fracturas - Implementación de la primera Unidad de Coordinación de Fracturas en Chile: experiencia al año de funcionamiento / Implementation of a fracture liaison service. Experience with 177 patients

BACKGROUND: Every year about 9 million fragility fractures (FF) occur worldwide and 80% of these are underdiagnosed or undertreated. Aiming to close the gap of diagnosis and treatment of osteoporosis, Fracture Liaison Services (FLS) were developed. AIM: To describe the implementation of the first FLS in Chile, its inclusion criteria, patient enrolment, treatment adherence and referrals during the first year. MATERIAL AND METHODS: A FLS was implemented at a health care network composed by two hospitals. The International Osteoporosis Foundation (IOF) guidelines were applied with a nurse practitioner as the coordinator. From May 2020 to April 2021 all patients diagnosed with a FF in the emergency rooms were invited to participate. Patients with pathological fractures and active cancer were excluded. Demographical data, fracture location, previous fractures, treatment and adherence, and mortality were recorded. RESULTS: From 443 patients with a diagnosis of FF, 177 patients (40%) accepted to participate. Their mean age was 74 ± 13 years and 84% (149) were female. Forty eight percent (84) had a lower extremity FF. Hip fractures were the most common (67). Ninety-five patients reported previous FF and 11,2% (20) had received anti-osteoporotic treatment. At four months of follow-up, 62% (50) had received vitamin D and calcium supplementation and 20% (16) of those patients with an indication of anti-osteoporotic drugs, had received them. CONCLUSIONS: The implementation of the FLS was successful with a 40% enrolment of patients, receiving certification by the IOF.

Histomorphometry of Bone Microarchitecture in Rats Treated with Vitamin D and Bisphosphonate in the Management of Osteoporosis / Histomorfometria da microarquitetura óssea em ratas tratadas com vitamina D e bisfosfonato no manejo da osteoporose

Abstract Objective To verify how the combined administration of alendronate (ALN) and vitamin D3 (VD) acts on the bone microarchitecture in rats with glucocorticoid-induced osteoporosis. Methods The experiment used 32 90-day-old female Wistar rats weighing between 300 and 400g. The induction of osteoporosis consisted of intramuscular administration of dexamethasone at a dose of 7.5 mg/kg of body weight once a week for 5 weeks, except for the animals in the control group. The animals were separated into the following groups: G1 (control group without osteoporosis), G2 (control group with osteoporosis without treatment), G3 (group with osteoporosis treated with ALN 0.2 mg/kg), G4 (group with osteoporosis treated with VD 10,000UI/500μL), and G5 (group with osteoporosis treated with ALN þ VD). The right femurs of the rats were fixed in 10% buffered formaldehyde, decalcified, and processed for inclusion in paraffin. Histological sections were stained with hematoxylin-eosin for histomorphometric analysis. Cortical thickness and medullary cavity were measured in cross-sections. Results There was a statistical difference (p< 0.05) between groups G3 and G5 compared with the positive control group (G2), both related to the measurement of cortical thickness and to the total diameter of the bone. In the evaluation of the spinal area, only the G3 group has shown to be statistically different from the G2 group. Conclusion Concomitant treatment with daily ALN and weekly VD is effective in preventing glucocorticoid-induced bone loss. However, there was no difference between the therapy tested and treatment with ALN alone.

Resumo Objetivo Verificar como a administração conjunta de alendronato de sódio (ALN) e vitamina D3 (VD) atua na microarquitetura óssea em ratas com osteoporose induzida por glicocorticoide. Métodos O experimento utilizou 32 ratas da linhagem Wistar, com peso médio de 300 a 400g, com 90 dias de vida. A indução da osteoporose consistiu na administração de dexametasona na dose de 7,5 mg/kg de peso corporal, por via intramuscular, 1 vez por semana durante 5 semanas, à exceção dos animais do grupo controle. Os animais foram distribuídos nos seguintes grupos: G1 (grupo controle sem osteoporose), G2 (grupo controle com osteoporose sem tratamento), G3 (grupo com osteoporose tratado com ALN 0,2 mg/kg), G4 (grupo com osteoporose tratado com VD 10.000UI/500μL) e G5 (grupo com osteoporose tratado com ALN þ VD). Os fêmures direitos das ratas foram fixados em formol a 10% tamponado, descalcificados e processados para inclusão em parafina. Os cortes histológicos foram corados com hematoxilina-eosina para análise histomorfométrica. A espessura cortical e a cavidade medular foram medidas em cortes transversais. Resultados Houve diferença estatística (p< 0,05) entre os grupos G3 e G5 em relação ao grupo controle positivo (G2), tanto em relação à medida da espessura cortical quanto em relação ao diâmetro total do osso. Na avaliação da área medular, apenas o grupo G3 se mostrou estatisticamente diferente do grupo G2. Conclusão O tratamento concomitante com ALN diário e VD semanal é eficaz para prevenir a perda óssea induzida por glicocorticoide. No entanto, não houve diferença entre esta terapia testada e o tratamento apenas com o ALN.

El rol de los suplementos vitamínicos en pacientes con depresión / The role of vitamin supplements in patients with depression

La depresión es un trastorno del estado de ánimo que se caracteriza por la existencia de un sentimiento de tristeza lo suficientemente intenso como para interferir en el desarrollo de las actividades habituales. A partir de un caso clínico real, en el que una paciente con depresión solicita a su médico de cabecera sumar un suplemento de vitaminas a su plan terapéutico, revisamos la evidencia disponible sobre el uso de estos micronutrientes para el tratamiento de la depresión, y encontramos que no existen pruebas robustas que avalen la suplementación vitamínica en pacientes con este problema de salud. (AU)

Depression is a mood disorder characterised by the existence of a feeling of sadness intense enough to interfere with the performance of normal activities. Based on a real clinical case, in which a patient with depression asked her family doctor to add a vitamin supplement to her therapeutic plan, we reviewed the available evidence on the use of these micronutrients for the treatment of depression and found that there is no robust evidence to support vitamin supplementation in patients with this health problem. (AU)

Vitamin D supplementation in pregnant women or infants for preventing allergic diseases: a systematic review and meta-analysis of randomized controlled trials / 中华医学杂志(英文版)

BACKGROUND@#It is still unclear if and to what extent antenatal or infant or childhood vitamin D supplementation would affect the development of allergy diseases later in life. This study aimed to review the efficacy of vitamin D supplementation in pregnant women, infants, or children for the prevention of allergies.@*METHODS@#MEDLINE (PubMed), EMBASE (OVID), and the Cochrane Central Register of Controlled Trials were searched up to March 1, 2020. We included only randomized controlled trials (RCTs). We performed a systematic review and meta-analysis for vitamin D supplementation in primary allergy prevention. These trials were assessed for risk of bias using the Cochrane Collaboration domains and the consensus was reached via discussion with the full study group. We descriptively summarized and quantitatively synthesized original data to evaluate vitamin D supplementation in primary allergy prevention by using Review Manager software for meta-analysis.@*RESULTS@#The search yielded 1251 studies. Seven RCTs were included in this analysis. A meta-analysis revealed that vitamin D supplementation for pregnant women or infants may not decrease the risk of developing allergic diseases, such as asthma or wheezing (supplementation for pregnant women, risk ratio [RR]: 1.01, 95% confidence interval [CI]: 0.81-1.26, P = 0.90, I2 = 47%; supplementation for infants, RR: 1.00, 95% CI: 0.70-1.43, P = 0.99, I2 = 0%; supplementation for pregnant women and infants, RR: 0.35, 95% CI: 0.10-1.25, P = 0.11), eczema (supplementation for pregnant women, RR: 0.95, 95% CI: 0.80-1.13, P = 0.77, I2 = 0%; supplementation for infants, RR: 0.84, 95% CI: 0.64-1.11, P = 0.19, I2 = 42%), allergic rhinitis (supplementation for pregnant women, RR: 0.93, 95% CI: 0.78-1.11, P = 0.15, I2 = 47%), lower respiratory tract infection (LRTI) (supplementation for pregnant women, RR: 0.97, 95% CI: 0.85-1.11, P = 0.59, I2 = 0%), or food allergy.@*CONCLUSIONS@#Supplementation of vitamin D in pregnant women or infants does not have an effect on the primary prevention of allergic diseases.@*SYSTEMATIC REVIEW REGISTRATION@#PROSPERO (CRD42020167747).

Expression of Vitamin D Receptor and Vitamin D Receptor Gene Polymorphisms (BsmI, FokI, and TaqI) in Patients with Pterygium / Expressão do gene do receptor da vitamina D e de seus polimorfismos (BsmI, FokI e TaqI) em pacientes com pterígio

ABSTRACT Purpose: This study aimed to determine the role of vitamin D receptor in the pathogenesis of pterygium. The vitamin D receptor eexpression levels in pterygium tissue, blood vitamin D levels, and frequency of selected vitamin D receptor gene polymorphisms (BsmI, FokI, and TaqI) were compared between patients with pterygium and healthy participants. Methods: The study included patients with pterygiumeee (n=50) and healthy volunteers (n=50). The serum vitamin D levels were measured for both groups. Immunohistochemical staining for vitamin D receptor ewas performed on sections obtained from the pterygium and adjacent healthy conjunctival tissues of the same individuals. The genomic existence of vitamin D receptor epolymorphisms (BsmI, FokI, and TaqI) were analyzed in DNA obtained from venous blood of participants using polymerase chain reaction and restriction fragment length polymorphism methods. Results: There was no difference found between the serum vitamin D levels of patients with pterygium and healthy controls. However, tissue expression of vitamin D receptor was higher in the pterygium endothelial cells of micro-vessels (p=0.002), subepithelial stromal (p=0.04), and intravascular inflammatory cells (p=0.0001), in comparison with the adjacent healthy conjunctival tissue. Moreover, while the BBtt haplotype was 2-fold higher, the bbTt haplotype was 2.5-fold lower, and the BbTT haplotype was 2.25-fold lower in the control group than in the pterygium group (p<0.001). Conclusions: Vitamin D serum levels did not differ between the healthy and pterygium groups. Vitamin D receptor expression was increased in the pterygium tissue versus the adjacent healthy tissue. However, vitamin D receptor polymorphism analysis in patients with pterygium did not reveal any significant difference in BsmI, FokI, or TaqI polymorphisms in comparison with the healthy volunteers.(AU)

RESUMO Objetivo: Determinar o papel do receptor da vitamina D na patogênese do pterígio. Os níveis de expressão do receptor da vitamina D no tecido do pterígio, os níveis sanguíneos de vitamina D e a frequência de alguns polimorfismos do gene do receptor da vitamina D (BsmI, FokI e TaqI) foram comparados entre pacientes com pterígio e participantes saudáveis. Métodos: Foram incluídos pacientes com pterígio (n=50) e voluntários saudáveis (n=50). Os níveis séricos de vitamina D foram medidos em ambos os grupos. Foi feita uma coloração imuno-histoquímica para o receptor da vitamina D em cortes obtidos do pterígio e dos tecidos conjuntivais saudáveis adjacentes dos mesmos indivíduos. A existência de polimorfismos do receptor da vitamina D (BsmI, FokI e TaqI) no genoma foi analisada em DNA obtido do sangue venoso dos participantes, usando métodos de Polymerase chain reaction (PCR) e RFLP. Resultados: Não foi observada nenhuma diferença entre os níveis séricos de vitamina D dos pacientes com pterígio e os dos controles saudáveis. Entretanto, a expressão tissular do receptor da vitamina D foi maior nas células endoteliais dos microvasos do pterígio (p=0,002), nas células estromais sub-epiteliais (p=0,04) e nas células inflamatórias intravasculares (p=0,0001), quando comparada à expressão no tecido conjuntival saudável adjacente. Além disso, embora o haplótipo BBtt tenha sido duas vezes mais frequente, o haplótipo bbTt foi 2,5 vezes menos frequente e o haplótipo BbTT foi 2,25 vezes menos frequente no grupo de controle do que no grupo com pterígio (p<0,001). Conclusões: Os níveis séricos de vitamina D não apresentaram diferenças entre o grupo de pessoas saudáveis e o com pterígio. A expressão do receptor da vitamina D mostrou-se maior no grupo com pterígio do que no tecido saudável adjacente. Entretanto, a análise dos polimorfismos do receptor da vitamina D nos pacientes com pterígio não revelou qualquer diferença significativa nos polimorfismos BsmI, FokI ou TaqI em comparação com os voluntários saudáveis.(AU)

Efectos de la suplementación con vitamina D en el control del asma en pacientes adultos: una revisión sistemática / Effects of vitamin D supplementation on asthma control in adult patients: a systematic review

INTRODUCCIÓN: El asma es una enfermedad crónica inflamatoria de la vía aérea e inmunomediada en su patogénesis. La vitamina D es un inmunomodulador que regula el perfil secretor de citoquinas, entre otras funciones celulares. Una asociación entre la suficiencia de vitamina D y mejoría en la función pulmonar, control de asma y número de exacerbaciones se ha propuesto en adultos, importante dada la elevada prevalencia de insuficiencia de vitamina D globalmente. OBJETIVO: Conocer los efectos de la suplementación con vitamina D en el control del asma en adultos. MÉTODOS: Se realizó una revisión sistemática de la literatura a través de una búsqueda en la base de datos PubMed y EMBASE. Los desenlaces primarios fueron cambios en VEF1, control sintomático, frecuencia de exacerbaciones, además de eventos adversos y FEM como desenlaces secundarios. La calidad de evidencia de los desenlaces fue evaluada a través del modelo GRADE. RESULTADOS: Siete estudios fueron seleccionados después de remover duplicados y aplicar los criterios de inclusión y exclusión, con calidad de evidencia muy baja aplicando sistema GRADE. DISCUSIÓN: No se encontraron diferencias estadísticamente significativas tras la suplementación con vitamina D en los desenlaces evaluados en general, pero dada la calidad de evidencia muy baja y que no se reportaron efectos adversos serios, es necesario tomar cautelosamente estos resultados. Asímismo no se puede descartar la utilidad de esta terapia como tratamiento auxiliar a los pacientes asmáticos con este déficit vitamínico.

BACKGROUND: Asthma is an airway chronic disease, with an important inflammatory component within its pathogenesis, driven by a dysregulated immune response. Vitamin D is an immunomodulator that regulates cell proliferation, differentiation and cytokine secretion profile. An association between vitamin D sufficiency and improvement in pulmonary function, asthma control and a decrease in exacerbations have been proposed in the adult population, which falls into importance given the high prevalence of vitamin D insufficiency globally. OBJECTIVE: To know vitamin D supplementation effects in asthma control in adults. METHODS: Through a PubMed and EMBASE database search, a systematic review of the literature was conducted. Primary outcomes were: changes in FEV1, symptomatic control, exacerbation frequency and PEF and adverse events as secondary outcomes. Outcome evidence quality assessment was made using the GRADE model. Results: Seven studies were selected after taking out duplicates, applying inclusion and exclusion criteria. In all cases, evidence quality assessed by the GRADE system yielded very low quality. CONCLUSIONS: No statistically significant differences were found after vitamin D supplementation in the overall evaluated outcomes. Nonetheless, a cautious interpretation of studies is mandatory, because evidence quality was very low and no serious adverse events were reported. Hence this treatment usefulness as an ancillary therapy for vitamin D deficient asthmatic patients cannot be dismissed.

Resultados perinatales tras la suplementación de una cohorte de gestantes con vitamina D / Perinatal results after vitamin D supplementation in a pregnant women cohort

INTRODUCCIÓN Y OBJETIVOS: La deficiencia de vitamina D es muy prevalente durante la gestación, siendo cada vez más numerosos los estudios que relacionan esta condición con peores resultados perinatales. El objetivo del presente trabajo es describir los resultados perinatales y el curso del embarazo de una cohorte de gestantes deficitarias en vitamina D durante el primer trimestre del embarazo, suplementándolas con colecalciferol, así como establecer una comparación entre los resultados perinatales de aquellas pacientes con déficit o insuficiencia que lograron niveles normales de vitamina D en el tercer trimestre frente a aquellas que no lo lograron. Como objetivo secundario se describe el curso del embarazo de una cohorte de pacientes que durante el mismo periodo de tiempo del estudio presentaban normovitaminosis al inicio de la gestación. MÉTODOS: La cohorte de 190 pacientes analizada procede de casos consecutivos en la primera consulta de embarazo. Se determinaron los niveles de 25-hidroxivitamina D (25-OH-D) en la analítica del primer trimestre de 190 gestantes diferenciando entre valores normales (>30ng/mL), insuficiencia (30-15 ng/mL) y deficiencia (<15 ng/mL). Las pacientes con insuficiencia se suplementaron con 1000 UI/día de colecalciferol y las pacientes con deficiencia con 2000 UI/día. En el tercer trimestre se determinaron de nuevo los niveles de 25-OH-D en las pacientes suplementadas, suspendiendo la prescripción en caso de haberse normalizado los valores. Se comparan estadísticamente los resultados perinatales entre aquellas pacientes que mejoraron con la suplementación frente a aquellas que no lo hicieron. RESULTADOS: De las 190 pacientes analizadas, un 45% presentaban insuficiencia; un 27,5% deficiencia; y un 27,5% valores normales. De forma global, un 61% de las pacientes suplementadas habían normalizado sus niveles de vitamina D en la analítica del tercer trimestre, suspendiéndose la prescripción. De ese 61% normalizado, un 63% pertenecían al grupo de insuficiencia y un 37% al de deficiencia. Dentro del grupo suplementado con colecalciferol, un 1,4% de las pacientes desarrollaron hipertensión arterial, mientras que un 33% desarrollaron diabetes en el embarazo, de las cuales un 87% la controlaron exclusivamente con dieta y un 13% precisaron insulina. Un 3,6% de las gestaciones cursaron con retraso del crecimiento y la tasa de prematuridad fue igualmente del 3,6%. La tasa de cesáreas fue del 23%, de las cuales un 77% fueron indicadas intraparto y un 23% cesáreas programadas. El peso medio al nacimiento fue 3205g. Dentro del grupo con valores normales de 25-OH-D en el primer trimestre de la gestación, ninguna paciente desarrolló hipertensión arterial, mientras que un 15% presentaron diabetes gestacional controlada con dieta. Un 3,8% de dichas gestaciones cursaron con retrasos del crecimiento y la tasa de prematuridad fue del 1,9%. La tasa de cesáreas fue del 23%, de las cuales un 50% fueron indicadas intraparto y el 50% restante programadas. El peso medio al nacimiento fue de 3280g. En el análisis comparativo de los resultados perinatales entre el grupo de pacientes suplementadas que normalizaron sus cifras de vitamina D y aquellas que no lo hicieron, no se hallan diferencias estadísticamente significativas para ninguno de los parámetros analizados. CONCLUSIONES: La elevada tasa de hipovitaminosis D en la muestra analizada apoya la extensión del cribado y suplementación a todas las embarazadas y no solamente a aquellas con factores de riesgo. Dado que no se observaron diferencias estadísticamente significativas entre los niveles de vitamina D en el tercer trimestre y las variables perinatales estudiadas, podemos concluir que en nuestro estudio la suplementación con vitamina D no se ha comportado como factor protector de eventos obstétricos adversos.

INTRODUCTION AND OBJECTIVES: Vitamin D deficiency is highly prevalent during pregnancy, with an increasing number of studies linking this condition with worse perinatal outcomes. The objective of this present work is to describe the perinatal results and the course of pregnancy in a cohort of pregnant women deficient in vitamin D during the first trimester of pregnancy, supplementing them with cholecalciferol, as well as to establish a comparison between perinatal results of those patients with deficiencnieve or insufficiency who achieved normal levels of vitamin D in the third trimester compared to those who did not. As a secondary objective, the course of pregnancy is described in a cohort of patients who presented normal levels at the beginning of gestation during the same period of time of the study. METHODS: The cohort of 190 patients analyzed comes from consecutive cases in the first pregnancy visit. The levels of 25-hydroxyvitamin D (25-OH-D) were determined in the analysis of the first trimester of 190 pregnant women, differentiating between normal values (> 30ng / mL), insufficiency (30-15 ng / mL) and deficiency (<15 ng / mL). Patients with insufficiency were supplemented with 1000 IU/day of cholecalciferol and patients with deficiency with 2000 IU/day. In the third trimester, the 25-OH-D levels were determined again in the supplemented patients, suspending the prescription if the values had normalized. Perinatal outcomes are statistically compared between those patients who improved with supplementation versus those who did not. RESULTS: Of the 190 patients analyzed, 45% had insufficiency; 27.5% deficiency; and 27.5% normal values. Overall, 61% of the supplemented patients had normalized their vitamin D levels in the third trimester analysis, suspending the prescription. Within that 61% normalized, 63% belonged to the insufficiency group and 37% to the deficiency group. In the group supplemented with cholecalciferol, 1.4% of the patients developed arterial hypertension, while 33% developed diabetes in pregnancy, of which 87% controlled it exclusively with diet and 13% required insulin. 3.6% of pregnancies had intrauterine growth restriction and the prematurity rate was also 3.6%. The caesarean section rate was 23%, of which 77% were indicated intrapartum and 23% scheduled caesarean sections. The mean weight at birth was 3205g. Within the group with normal 25-OH-D values in the first trimester of pregnancy, no patient developed hypertension, while 15% had diet-controlled gestational diabetes. 3.8% of these pregnancies had intrauterine growth restriction and the prematurity rate was 1.9%. The cesarean section rate was 23%, of which 50% were indicated intrapartum and the remaining 50% scheduled. The mean weight at birth was 3280g. In the comparative analysis of the perinatal results between the group of supplemented patients who normalized their vitamin D levels and those who did not, no statistically significant differences were found for any of the parameters analyzed. CONCLUSIONS: The high rate of hypovitaminosis D in the analyzed sample supports the extension of screening and supplementation to all pregnant women and not only to those with risk factors. Since no statistically significant differences were observed between vitamin D levels in the third trimester and the perinatal outcomes studied, we can conclude that in our study vitamin D supplementation has not behaved as a protective factor against adverse obstetric events.

Fractura de fémur proximal (31-A3. 2) asociada al uso de tenofovir en paciente VIH+: reporte de caso / Proximal femur fracture (31-A3. 2) associated with the use of tenofovir in an HIV-positive patient: case report

Presentamos el primer reporte de caso en paciente adulto con virus de la inmunodeficiencia humana (VIH + ) con fractura por fragilidad en fémur proximal asociada al uso de terapia antirretroviral (TARV) con fumarato de disoproxilo de tenofovir (FDT) en Chile. Actualmente, los pacientes diagnosticados con VIH inician tratamiento precoz con TARV, lo que implica mayor cantidad de años de exposición a los fármacos de la terapia. El tiempo de exposición acumulado al FDT se ha asociado a disminución de la densidad mineral ósea y falla renal progresiva, pudiendo el paciente desarrollar síndrome de Fanconi adquirido y osteomalacia, con riesgo aumentado de fractura. Presentamos el caso de un hombre de 44 años, VIH+ , evaluado en urgencia tras caída a nivel que resultó en fractura patológica del fémur proximal. Los exámenes de ingreso destacaron hipocalemia, hipocalcemia, hipofosfatemia e hipovitaminosis D. Se realizó manejo multidisciplinario, con suspensión del FDT, un cambio en la TARV, y suplementación con calcio y carga de vitamina D. Se realizó reducción cerrada y fijación con clavo cefalomedular largo, que evolucionó favorablemente con rehabilitación motora precoz; el paciente recuperó su funcionalidad previa, y se observó consolidación ósea a las 12 semanas. La aparición de dolor osteomuscular en pacientes VIH+ en TARV debe levantar alta sospecha clínica de efecto adverso a medicamento; el seguimiento de estos pacientes debe incluir el control seriado de la función renal y de los niveles séricos de calcio y fósforo. La búsqueda y sospecha de estas complicaciones permitiría una intervención precoz, mejorando la condición de los pacientes y previniendo fracturas patológicas.

We present the first case report of a human immunodeficiency virus (HIV)-positive adult patient with a fragility fracture of the proximal femur associated with antiretroviral therapy (ART) with tenofovir disoproxil fumarate (TDF) in Chile. Currently, patients diagnosed with HIV start ART early, resulting in more years of exposure to these drugs. The accumulated exposure time to TDF has been associated with a decreased bone mineral density and progressive renal failure, potentially leading to acquired Fanconi syndrome, osteomalacia, and an increased risk of fracture. We present a case of a 44-year-old, HIV-positive man assessed at the emergency room after a fall from standing height which resulted in a proximal femoral pathological fracture. Laboratory findings at admission revealed hypokalemia, hypocalcemia, hypophosphatemia, and hypovitaminosis D. Multidisciplinary management was performed, with TDF discontinuation, ART change, and supplementation with calcium and vitamin D. Closed reduction and fixation with a long cephalomedullary nail was successful, with early motor rehabilitation, functional recovery, and bone consolidation at 12 weeks. Musculoskeletal pain in HIV-positive patients on ART must raise the clinical suspicion of an adverse drug effect; the follow-up of these subjects must include serial monitoring of renal function and serum calcium and phosphorus levels. Screening and suspicion of such complications would enable an early intervention, improving the patients' condition and preventing pathological fractures.

Efecto de la suplementación con vitamina D en dosis única sobre el estado nutricional de vitamina D / Effect of vitamin D supplementation as a single dose on the nutritional status of vitamin D

INTRODUCCIÓN: El primer año de vida es un periodo de riesgo de deficiencia de vitamina D (VD). La administración de 400 UI diarias de VD no tiene una adherencia del 100%, en cambio dosis únicas de 100.000 UI de VD oral son seguras en recién nacidos. OBJETIVO: Comparar el efecto de la suplementación oral de VD en dosis única de 100.000 UI al mes de edad vs dosis diarias de 400 UI sobre las concentraciones séricas de VD, a los 6 meses de vida. SUJETOS Y MÉTODOS: Ensayo clínico aleatorizado, sin enmascaramiento. Se incluyeron 84 lactantes sanos de 1 mes de vida, asignados al azar al grupo de estudio (GE) que recibió una dosis única de VD de 100.000 UI oral o al grupo control (GC), que recibió dosis diarias de VD de 400 UI oral del 1er al 6to mes de vida. A los 6 meses de edad se determinó la concentración sérica de VD. RESULTADOS: 65 lactantes terminaron el estudio, 36 en GE y 29 en GC. No se encontró deficiencia de VD. La insuficiencia de VD fue de 5,5% y 6,8% en el GE y GC, respectivamente. La concentración sérica de VD a los 6 meses de vida, fue de 38,8 ± 5,2 ng/ml y 39,7 ± 6,3 ng/ml para GE y GC, respectivamente (NS). CONCLUSIONES: La suplementación con 100.000 UI de VD única al mes de edad logra concentraciones séricas de VD a los 6 meses de vida, similares a dosis diarias de 400 UI de VD, del 1er al 6to mes.

INTRODUCTION: Infants are a group at risk of vitamin D (VD) deficiency. The administration of 400 IU of VD per day during the first year of life does not achieve 100% adherence. A single dose of 100,000 IU of oral VD is safe in newborns. OBJECTIVE: To compare the effect of oral administration of VD between a single dose of 100,000 IU at one month of age vs daily doses of 400 IU on serum concentrations of VD, at 6 months of age. SUBJECTS AND METHOD: Randomized clinical trial, without masking. 84 healthy infants were included at 1 month of age, randomized to the study group (SG) receiving a single oral dose of 100,000 IU or to the control group (CG), who received daily oral doses of VD of 400 IU from the 1st to the 6th month of life. At 6 months of life, the serum concentration of VD was determined. RESULTS: 65 infants completed the study, 36 in SG and 29 in CG. No VD deficiency was found. VD insufficient was 5.5% and 6.8% in the SG and CG, respectively. The serum concentration of VD at six months of age was 38.8 ± 5.2 ng/ml and 39.7 ± 6.3 ng/ml for the SG and CG, respectively (NS). CONCLUSIONS: Supplementation of 100,000 IU of VD at one month age achieves serum concentrations of VD at 6 months of life similar to the administration of daily doses of 400 IU of VD from the 1st to the 6th month.

Informe diário de evidências COVID-19: busca realizada em 4 de agosto de 2020 / COVID-19 daily evidence report: search conducted on August 4, 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, referentes 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 16 artigos e 13 protocolos.

Informe diário de evidências COVID-19: busca realizada em 13 de agosto de 2020 / COVID-19 daily evidence report: search conducted on August 13, 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, referentes 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 16 artigos e 5 protocolos.

Relación entre Nivel de 25 (OH) D Vitaminas y Deterioro Cognitivo en Enfermedad renal Crónica (ERC) en pacientes en diálisis y sin diálisis mediante el uso de la prueba B / Relationship between Level of 25 (OH) D Vitamins and Cognitive Impairment in Chronic Kidney Disease (CKD) in Dialysis and NonDialysis Patients Using Trial Making Test B

Deficiency in vitamin D and cognitive dysfunction commonly are associated together in patients suffering from chronic kidney disease (CKD) in both dialysis and non-dialysis patients, vitamin D develop new protective regulatory roles in the functions of CNS. Combination of low levels of vitamin D and CKD can be enrolled for devastating and lead to sever cognitive dysfunction. Patients with CKD mostly associated with Hypovitaminosisand moreover common in elderly patients and related with cognitive decline, one of the hypotheses that CKD patients commonly have a low level of vitamin D and have potential experience in accelerated cognitive decline which rarely link on this topic. Most of CKD patients particularly sensitive for developing in the deficiency of vitamin D. Reduce vitamin D intake, male absorption in compromised GIT patients, loosing of vitamin D binding protein with urine, and α-hydroxylase enzyme reduction in the kidney all are the risk factors included in the causes of 25(OH) D vitamin decrease production. Aim of study: assess cognitive function by using one validated score: trial making test B in patients with CKD in both dialysis and non-dialysis. Patients and methods: a total of 54 patients with CKD and 57 patients with ESRD on hemodialysis enrolled in this study, where CKD defined as GFR < 60 ml/min by MDRD study. Exclusion criteria include CVA, deaf and blind, and low education patients. Cognitive functions assessment done for patients who are on hemodialysis and non- dialysis by using trial B testing, this second assess spatial scanning concentration and executive function by time measuring that needed to connect the series of numbered that are sequentially and littered circles. Catastrophic shorter time completion with a maximum of 300 second indicates better performance. 25 (OH) D vitamins has assessed from each patients using direct immunoassay method, with assay at 4-110 ng/ml. Results: for patients on hemodialysis 27 (39.7%) has deficient 25(OH) D vitamin status 25 (36.7%) insufficient,20 (29.4%) had sufficient vitamin D levels, significant low level in patients on hemodialysis in comparison to those with non-hemodialysis. Trial making test B score was significantly lower in dialysis patients, significant correlation between cognitive function assessment (trial making test B) and low vitamin D level. Conclusions: the prevalence of deficiency in vitamin D in CKD especially hemodialysis patients associated with cognitive decline.

Clinical outcomes of ocular surface in patients treated with vitamin D oral replacement / Resultados clínicos da superfície ocular em pacientes tratados com reposição oral de vitamina D

ABSTRACT Purpose: To analyze the clinical outcomes of the ocular surface in patients with vitamin D deficiency after oral replacement. Methods: A total of 40 patients with vitamin D deficiency were enrolled in the study. The patients received 50,000 units of oral vitamin D weekly over a period of 8 weeks. After 8 weeks, 1,500-2,000 units/d were administered for 24 weeks. Eyelid margin score, meibomian gland expressibility score, Oxford grading, Schirmer I test, tear breakup time, tear osmolarity, and the Ocular Surface Disease Index score were evaluated at baseline, and at 8, 12, and 24 weeks. Results: The meibomian gland expressibility score, Schirmer I, tear breakup time, tear osmolarity, and Ocular Surface Disease Index score showed improvement 8 weeks after vitamin D supplementation (p<0.05). Compared with the pretreatment values, the eyelid margin score and Oxford grading were decreased at week 12 (p<0.05). Conclusion: Vitamin D replacement appears to improve ocular surface in individuals with vitamin D deficiency.

RESUMO Objetivo: Analisar os resultados clínicos da superfície ocular em pacientes com deficiência de vitamina D após reposição oral. Métodos: Foram incluídos no estudo 40 pacientes com deficiência de vitamina D. Os pacientes receberam 50.000 unidades de vitamina D semanalmente por um período de oito semanas. Após esse período, 1.500-2.000 unidades/dia foram administradas por 24 semanas. Escores da margem palpebral, escores de expressibilidade da glândula meibomiana, classificação de Oxford, teste de Schirmer I, tempo de ruptura lacrimal, osmolaridade da lágrima e escore do Índice de Doenças da Superfície Ocular foram avaliados no início e após 8, 12 e 24 semanas. Resultados: O escore de expressibilidade da glândula meibomiana, Schirmer I, tempo de ruptura lacrimal, osmolaridade da lágrima e o Índice de Doenças da Superfície Ocular apresentaram melhoras após 8 semanas de suplementação de vitamina D (p<0,05). Comparado com os valores do pré-tratamento, o escore da margem palpebral e a classificação de Oxford diminuíram na 12ª semana (p<0,05). Conclusão: A reposição de vitamina D parece melhorar a superfície ocular em indivíduos com deficiência de vitamina D.

Importancia de la Vitamina D en la época del COVID-19 / Importance of Vitamin D in the time of COVID-19

"Los coronavirus pertenecen a una gran familia de virus (Coronaviridae) que infectan aves y varios mamíferos. El coronavirus actualmente denominado SARS-CoV-2, fue descubierto en diciembre de 2019 en Wuhan, provincia de Hubei, China, y es el agente causal de la epidemia de neumonía atípica actual" (COVID-19; Coronavirus Disease 2019). Los casos más graves presentan un síndrome de dificultad respiratoria aguda que puede conducir a la muerte. La vitamina D (VD), además del efecto bien conocido y positivo sobre la salud ósea y la homeostasis del calcio, tiene efecto pleiotrópico en varios órganos, con distribución casi universal del receptor de VD y de las enzimas de metabolización de 25 hidroxivitamina D (25OHD) en las células del organismo. Estas acciones extraesqueléticas dependen de la síntesis en dichas células del metabolito activo 1,25 dihidroxivitamina D por regulación paracrina y autocrina, dependiente de niveles circulantes óptimos de 25OHD. Por sus acciones inmunomoduladora, antiinflamatoria, antimicrobiana, reguladora del sistema renina-angiotensina-aldosterona, favorecedora de la indemnidad del epitelio respiratorio y la homeostasis redox celular, la VD podría tener efecto protector en la infección por COVID-19. Entre los grupos de riesgo para COVID-19 figuran los adultos mayores, obesos, diabéticos, hipertensos, con afecciones cardiovasculares, patologías con mayor incidencia en individuos con hipovitaminosis VD. La suplementación con VD, para alcanzar niveles óptimos de 25OHD de 40-60 ng/ml, podría reducir la incidencia, severidad y riesgo de muerte en la actual pandemia por COVID-19, como medida complementaria mientras se desarrollan la vacuna y otras medicaciones específicas. (AU)

Coronaviruses belong to a large family of viruses (Coronaviridae) that infect birds and various mammals. The novel coronavirus currently known as SARS-CoV-2 was discovered in December 2019 in Wuhan, Hubei province, China and is the causal agent of the current atypical pneumonia epidemic (COVID-19: Coronavirus Disease 2019); The most severe cases present with acute respiratory distress syndrome that can lead to death. Vitamin D (VD) has a pleiotropic effect on several organs, in addition to its wellknown and positive effect on bone health and calcium homeostasis, with an almost universal distribution of the VD receptor and the metabolites of 25hydroxyvitamin D (25OHD) in all cells of the body. These extra-skeletal actions depend on the synthesis of the active metabolite 1,25dihydroxyvitamin D in the cells depending on the optimal circulating levels of 25OHD and though paracrine and autocrine regulation. Due to its immunomodulatory, anti-inflammatory, antimicrobial, and regulatory actions on the renin angiotensin aldosterone system, which favors the compensation of the respiratory epithelium and cellular redox homeostasis, the VD could have a protective effect on COVID-19 infection. Among the risk groups for COVID-19 are obese, diabetic, and hypertensive patients, subjects with cardiovascular conditions, and elderly people. All these pathologies show a higher incidence in individuals with VD hypovitaminosis. VD supplementation, to achieve optimal 25OHD levels of 40-60 ng/ml, could reduce the incidence, severity, and risk of death in the current COVID-19 pandemic, as a complementary measure while the vaccine and other specific therapies are being developed. (AU)

Informe diário de evidências COVID-19: busca realizada em 7 de julho de 2020 / COVID-19 daily evidence report: search conducted on July 7, 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.

Informe diário de evidências COVID-19: busca realizada em 10 de julho de 2020 / COVID-19 daily evidence report: search conducted on July 10, 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, referentes 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 20 artigos e 16 protocolos.

Informe diário de evidências COVID-19: busca referente aos dias 11, 12 e 13 de julho de 2020 / COVID-19 daily evidence report: search for July 11, 12 and 13, 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, referentes 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 14 artigos.