Evaluación de la prueba G8 como tamizaje para valoración geriátrica integral en pacientes adultos mayores con cáncer / Evaluation of the G-8 test as a screening tool for comprehensive geriatric assessment in elderly patients with cancer

RESUMEN Objetivo: evaluar la sensibilidad y especificidad del test G8 en el tamizaje de adultos mayores con cáncer para la realización de la valoración geriátrica integral (VGI). Materiales y métodos: el presente estudio observacional y retrospectivo se realizó en el Servicio de Geriatría del Hospital Almenara de Lima, Perú. Se revisaron los informes de VGI en las historias clínicas electrónicos de adultos mayores (> 60 años) con cáncer, ambulatorios y hospitalizados, durante noviembre de 2022 y julio de 2023. Los pacientes se clasificaron según los criterios SIOG-1 (Sociedad Internacional de Oncología Geriátrica), formando dos grupos: pacientes aptos y pacientes no aptos o unfit (vulnerables + frágiles + muy enfermos). Del test G8 se estimó la sensibilidad, especificidad y valor predictivo positivo, área bajo la curva característica operativa del receptor (AUC). Resultados: ingresaron al estudio 201 pacientes, 91 mujeres (45,3%) y 110 (54,7%) varones, la media de la edad fue de 76,2 ± 7,4 años. Las neoplasias más frecuentes fueron colorrectal, estómago, próstata y vías biliares. La prevalencia de pacientes aptos y no aptos (unfit) fue del 23,4 y 76,6%, respectivamente. Cuando el puntaje de la prueba G8 fue ≤11, la sensibilidad, especificidad, valor predictivo positivo y AUC fueron 73,4% (intervalo de confianza al 95%: 65,7-80,2%), 91,5% (79,6%-97,6%), 96,6% (91,7-98,6%) y 89% (84-93%), respectivamente. Conclusiones: el test G8 con puntaje ≤11 tendría una alta sensibilidad y especificidad, para identificar adultos con cáncer vulnerables o frágiles, que podrían beneficiarse de la VGI.

ABSTRACT Objective: To evaluate sensitivity and specificity of the G8 test in screening older adults with cancer who may benefit from a Comprehensive Geriatric Assessment (CGA). Material and methods: This observational retrospective study was carried out in the Geriatrics Service of the Guillermo Almenara Hospital in Lima, Peru. CGA reports were reviewed in the electronic medical records of older adults (> 60 years) with cancer, both outpatients and inpatients, between November 2022 and July 2023. Patients were classified according to the SIOG-1 (International Society of Geriatric Oncology) criteria into two groups: fit and non-fit patients (vulnerable + frail + too sick). Sensitivity, specificity, and positive predictive value, area under the receiver operating characteristic curve (AUC), were estimated for the G8 test. Results: 201 patients entered the study, 91 women (45.3%) and 110 (54.7%) men; their mean age was 76.2 ± 7.4 years. The most frequent neoplasms were colorectal, stomach, prostate, and bile ducts. The prevalence of eligible and unfit patients was 23.4% and 76.6%, respectively. When the G8 test score was ≤11, sensitivity, specificity, positive predictive value, and AUC were 73.4% (95% Confidence Interval: 65.7- 80.2%), 91.5% (79.6%-97.6%), 96.6% (91.7-98.6%), and 89% (84-93%), respectively. Conclusions: The G8 test with a score ≤11 would have high sensitivity and specificity for identifying vulnerable or frail patients with cancer who could benefit from the CGA.

Association between polymorphisms of the VKORC1 and CYP2C9 genes and warfarin maintenance dose in Peruvian patients.

AIMS: The aim of this study was to investigate the association between VKORC1 and CYP2C9 genes polymorphisms and the maintenance dose of warfarin in Peruvian patients. METHODS: An observational study was conducted on outpatients from the Hospital Grau ESSALUD in Lima, Peru. The participants were selected using nonprobabilistic convenience sampling. Inclusion criteria required patients to have been on anticoagulation therapy for >3 months, maintain stable doses of warfarin (consistent dose for at least 3 outpatient visits), and maintain an international normalized ratio within the therapeutic range of 2.5-3.5. DNA samples were obtained from peripheral blood for gene analysis. RESULTS: Seventy patients (mean age of 69.6 ± 13.4 years, 45.7% female) were included in the study. The average weekly warfarin dose was 31.6 ± 15.2 mg. The genotypic frequencies of VKORC1 were as follows: 7.1% (95% confidence interval, 2.4-15.9) for AA; 44.3% (32.4-56.7) for GA; and 48.6% (36.4-60.8) for GG. No deviation from the Hardy-Weinberg equilibrium was observed in the variants studied (P = .56). The mean weekly warfarin doses for AA, GA and GG genotypes were 16.5 ± 2.9, 26.5 ± 9.5 and 37.9 ± 17.1 mg, respectively (P < .001). The genotypic frequencies of CYP2C9 were as follows: 82.8% (72.0-90.8) for CC (*1/*1); 4.3% (1.0-12.0) for CT (*1/*2); and 12.9% (6.1-23.0) for TT (*2/*2). We did not find a significant association between the CYP2C9 gene polymorphism and the dose of warfarin. CONCLUSIONS: The AA genotype of the VKORC1 gene was associated with a lower maintenance dose of warfarin in Peruvian patients.

Evaluación geriátrica integral en pacientes con fractura de cadera

Introducción. Las fracturas de cadera son un conjunto de patologías frecuentes en los adultos mayores frágiles, con impacto negativo sobre la funcionalidad. Objetivo. Determinar las características clínicas, funcionales, mentales y sociales basados en la evaluación geriátrica integral. Métodos. Se evaluó a 445 pacientes, la comorbilidad se midió con el índice de Charlson, el estado funcional basal con el índice de Barthel y la escala de Lawton y Brody, el estado mental con el cuestionario de Pfeiffer, el delirio mediante el Confusion Assessment Method y la evaluación social con la Escala Sociofamiliar de Gijón. Las variables categóricas se presentaron como valor absoluto y porcentaje, y las continuas como media y desviación estándar. Resultados. El sexo femenino representó el 71,5%, el promedio de edad en mujeres fue de 81,58 años y en varones de 82,58 años. El deterioro visual fue 48,8% y el auditivo fue 46,1%. El 46,0% tuvieron más de una comorbilidad. 30,3% era independiente para actividades básicas, así como 90,3% de mujeres y 64,3% de hombres fueron dependientes para actividades instrumentales. El deterioro cognitivo estuvo presente en el 53,5% de los pacientes y delirio el 20,4%. En la segunda semana fueron operados 30,5% y en la tercera 21,6%. La mortalidad fue de 2,7% durante la hospitalización. Conclusión. Las características más frecuentes fueron de una octogenaria, con deterioro visual/auditivo, sin comorbilidad, pero pluripatológica, con dependencia leve para actividades básicas de vida diaria y deterioro cognitivo en entorno social de riesgo.

Introduction. Hip fractures are a group of frequent pathologies in frail older adults, with a negative impact on functionality. Objective. To determine the clinical, functional, mental, and social characteristics based on the comprehensive geriatric assessment. Methods. 445 patients were evaluated, comorbidity was measured with the Charlson index, baseline functional state with the Barthel index and the Lawton and Brody scale, mental state with the Pfeiffer questionnaire, delirium using the Confusion Assessment Method and social assessment with the Gijón Socio-Family Scale. Categorical variables were presented as absolute value and percentage and continuous variables as mean and standard deviation. Results. The female sex represented 71.5%, the average age in women was 81.58 years and in men 82.58 years. Visual impairment was 48.8% and hearing impairment 46.1%. 46% had more than one comorbidity. 30.3% were independent for basic activities, as well as 90.3% of women and 64.3% of men were dependent for instrumental activities. Cognitive impairment was present in 53.5% and delirium developed in 20.4%. In the second week, 30.5% were operated and in the third, 21.6%. Mortality was 2.7% during hospitalization. Conclusion. the most frequent characteristics were of an octogenarian, with visual / auditory deterioration, without comorbidity, but multipathological, with slight dependence for basic activities of daily living and cognitive deterioration in a risky social environment.

Hepatotoxicity induced by isoniazid in patients with latent tuberculosis infection: a meta-analysis.

Aim: The aim of the present study was to conduct a meta-analysis of the frequency of isoniazid-induced liver injury (INH-ILI) in patients receiving isoniazid (INH) preventative therapy (IPT). Background: The frequency of hepatotoxicity (drug-induced liver injury: DILI) of antituberculosis drugs has been studied, especially when INH, rifampin, and pyrazinamide are co-administered. However, little is known about the frequency of DILI in patients with latent tuberculosis infection (LTBI), where IPT is indicated. Methods: We searched PubMed, Google Scholar, and the Cochrane Database of Systematic Reviews for studies reporting the frequency of INH-ILI in patients with IPT using one or more diagnostic indicators included in the criteria of the DILI Expert Working Group. Results: Thirty-five studies comprising a total of 22,193 participants were included. The overall average frequency of INH-ILI was 2.6% (95% CI, 1.7-3.7%). The mortality associated with INH-DILI was 0.02% (4/22193). Subgroup analysis revealed no significant differences in the frequency of INH-ILI in patients older or younger than 50 years, children, patients with HIV, candidates for liver, kidney, or lung transplant, or according to the type of study design. Conclusion: The frequency of INH-ILI in patients receiving IPT is low. Studies on INH-ILI are needed where the current DILI criteria are used.

Uso previo de antagonistas de la angiotensina II en pacientes hipertensos hospitalizados y mortalidad por COVID-19

Introducción: Actualmente existe un gran interés en establecer la relación entre la severidad de la infección por SARS-COV-2 en pacientes hipertensos usuarios de antagonistas de la angiotensina II (ARAII). Objetivo: Estudiar la relación entre el uso previo de antagonistas de la ARA II en pacientes hipertensos y la mortalidad por COVID-19. Materiales y métodos: Se realizó un estudio observacional retrospectivo en un hospital de referencia en Lima, Perú, en pacientes hipertensos hospitalizados en marzo del 2021 por COVID-19 severo. Resultados: Ingresaron al estudio 101 pacientes, con una media de edad de 70.1 + 12.0 y sexo masculino 48%. Los usuarios de ARAII fueron 45 (45.6%) y no los tomaban 56 (54.4%). El Índice de comorbilidad de Charlson fue mayor en el grupo ARAII (3.6 + 1.56 vs 3.04 + 1.24) (p<0.05). La mortalidad total y por sexo (varones vs mujeres), entre los que usaban ARAII o no, fueron 57.8% vs 62% (p = 0.633) y 36.36% vs 63.64 % (p<0.05), respectivamente. La media de la concentración de deshidrogenasa láctica fue menor en los que tomaban ARAII comparado con los no usuarios, 394.18 + 152.3 vs 503.5 + 252.7 (p<0.05); no se observó diferencia significativa en el recuento de leucocitos, niveles séricos de Proteína C Reactiva, Ferritina, dímero D y fibrinógeno. Conclusión: Entre los pacientes hospitalizados con COVID-19 con hipertensión, el uso previo de ARAII no se asoció con riesgo de mortalidad.

Background: There is caurrently great interest in establishing the relationship between the severity of SARS-COV-2 infection in hypertensive patients who use angiotensin II antagonists (AIIRAs). Objective: To study the relationship between the previous use of angiotensin II antagonists (ARB) in hypertensive patients and mortality from COVID-19. Materials and methods: A retrospective observational study was carried out in a tertiary care hospital in Lima, Peru, in hypertensive patients hospitalized in March 2021 for severe COVID-19. Results: A total of 101 patients entered the study, with a mean age of 70.1 + 12.0 and 48% male. ARB users and non-users were 45 (45.6%) and 56 (54.4%), respectively. The Charlson Comorbidity Index was higher in the ARB group (3.6 + 1.56 vs 3.04 + 1.24) (p<0.05). Total and male vs women mortality, among those using ARBs or not, were 57.8% vs 62% (p = 0.633) and 36.36% vs 63.64% (p <0.05), respectively. Mean lactate dehydrogenase concentration was lower in those taking ARBs compared to non-users, 394.18 + 152.3 vs 503.5 + 252.7 (p<0.05); No significant difference was observed in the leukocyte count and serum levels of C-Reactive Protein, Ferritin, D-dimer and fibrinogen. Conclusion: Among hospitalized COVID-19 patients with hypertension, prior use of ARBSs was not associated with mortality risk.

Metodología de investigación en farmacogenética: estudios de casos y controles / Methodology for research in pharmacogenetics: Case-control studies

RESUMEN La farmacogenética estudia la asociación entre el fenotipo farmacológico de un individuo con su constitución genética, y el diseño de estudios de casos y controles es una metodología de uso frecuente. Este diseño consiste en que se analiza la frecuencia de las variantes genéticas en los casos, es decir, de los pacientes que presentan el fenotipo (desenlaces o resultados) comparado con los controles. Para obtener una calidad metodológica adecuada en este tipo de estudios es importante trabajar con fenotipos precisos, adecuada selección de los casos y controles y tamaño de la muestra; seleccionar una metodología adecuada para la identificación de variantes genéticas; y en el momento del análisis de resultados utilizar el Equilibrio de Hardy-Weinberg (EHW) e interpretar los resultados considerando la posibilidad de un fenómeno de fenoconversión.

ABSTRACT Pharmacogenetics studies the association between the pharmacological phenotype of an individual with his/her genetic constitution. Case-control studies is a commonly used methodology when performing pharmacogenetics research. This design analyses the frequency of genetic variants in cases; that is, of those patients who have a particular phenotype (outcomes or results) compared with controls. For obtaining adequate methodological quality in pharmacogenetic case-control studies, it is important to work with precise phenotypes, have adequate case and control selection and appropriate sample size; select an adequate methodology for the identification of genetic variants, analyze the results using Hardy-Weinberg Equilibrium (HWE); and interpret the results considering the possibility of a phenoconversion phenomenon.

Relación entre los grupos sanguíneos A, B y O y mortalidad por infección con SARS-CoV-2 en pacientes hospitalizados

El objetivo del estudio fue investigar la relación entre los grupos sanguíneos A, B y O y la mortalidad en pacientes hospitalizados por una infección grave por SARS-CoV-2. La investigación fue observacional retrospectiva en un hospital de tercer nivel en Lima, Perú. Se incluyó a 203 pacientes, con una edad media de 62,58 ± 16,45 años, y el 71,92 % eran varones. La frecuencia de los grupos sanguíneos O, A y B fue del 75,37 %, 17,24 % y 7,39 %, respectivamente. Se encontró asociación con la mortalidad por infección grave por COVID-19 con los grupos sanguíneos que no son A (grupo O, grupo B), con un PR (razón de prevalencia) de 2,25 IC (intervalo de confianza) 95 % 1,07-4,71. Al ajustar por las principales variables, la asociación con RP persistió en 2,78 IC 95 % 1,06-7,24. En conclusión, en los pacientes hospitalizados por una infección grave por SARS-CoV-2, los grupos sanguíneos O y B estarían asociados con una mayor mortalidad que los pacientes del grupo sanguíneo A.

This study aimed to determine the relationship between ABO blood groups and mortality in patients hospitalized for severe SARS-CoV-2 infection. An observational and retrospective research was conducted in a tertiary care hospital in Lima, Peru. A total of 203 patients with a mean age of 62.58 ± 16.45 years were included in the research, out of whom 71.92 % were males. The frequency of O, A and B blood groups were 75.37 %, 17.24 % and 7.39 %, respectively. An association with mortality from severe COVID-19 infection was found with non-A blood groups (O group or B group), with a PR (prevalence ratio) of 2.25 and 95% CI (confidence interval) of 1.07 - 4.71. When adjusting the main variables, the association with PR remained in 2.78 and 95% CI in 1.06 - 7.24. In conclusion, patients hospitalized for severe SARS-CoV-2 infection with O and B blood groups seem to be associated with higher mortality rates than those with A blood group.

Hepatotoxicidad por antituberculosos en pacientes con tuberculosis multidrogorresistente / Hepatotoxicity due to antitubercular drugs in multidrug-resistant tuberculosis patients

RESUMEN Objetivo: Describir las características clínicas de la injuria hepática inducida por antituberculosos (IHIA) en pacientes con tuberculosis multirresistente (MDR-TB). Materiales y métodos: Estudio retrospectivo de pacientes hospitalizados con TB-MDR e IHIA. Se utilizó los criterios de la DILI-Expert Working Group, y el instrumento de análisis de causalidad fue el RUCAM (Roussel Uclaf Causality Assessment Method). La asociación específica de la IHIA con un antituberculoso fue por un proceso de reexposición o suspensión y recuperación. Resultados: Reportamos 7 casos de MDR-TB e IHIA; la edad media (desviación estándar) fue de 39,1 (3,3) años. La media de la IHIA apareció después de 30,4 (27,70) días de iniciar el tratamiento. Tres (43,00 %) pacientes presentaron ictericia. En cuanto al patrón, en 4 (57,00 %) fue hepatocelular y en 3 (43,00 %), colestásico. En 4 pacientes, la IHIA fue leve, y moderada en 3. En todos los casos estuvo involucrada la pirazinamida (pirazinamida sola, 4; pirazinamida y etionamida, 1; pirazinamida, rifampicina e isoniazida, 1; pirazinamida y rifampicina, 1). La estancia hospitalaria media fue de 48,10 (48,70) días. Los promedios de fosfatasa alcalina (FA), alanina aminotransferasa (ALT) y gamma-glutamiltranspeptidasa (GGT) sérica fueron 2,40 (1,10), 7,9 (7,10) y 5,60 (3,70) veces el límite superior normal (NUL), respectivamente. La bilirrubina total media fue 2,30 (2,10), rango de 0,50 a 6,40 mg/dl. Como parte del esquema de alta del paciente, se administraron quinolonas a 7 pacientes (levofloxacino, 6; ofloxacino, 1), y en un paciente se agregó ácido amoxicilina/ácido clavulánico. Conclusiones: La IHIA en pacientes con TB-MDR puede aparecer después del primer mes de tratamiento. El patrón de lesión común fue hepatocelular, y la pirazinamida fue el antimicobacteriano involucrado con mayor frecuencia.

ABSTRACT Objective: To describe the clinical characteristics of drug-induced liver injury (DILI) in multidrug-resistant tuberculosis (MDR-TB) patients. Materials and methods: A retrospective study conducted in hospitalized patients with MDR-TB and DILI. The criteria of the DILI Expert Working Group were used for the diagnosis of DILI, and the RUCAM (Roussel Uclaf Causality Assessment Method) for the causality analysis. The specific association between DILI and antitubercular drugs was established by drug rechallenge or discontinuation and recovery. Results: Seven cases of MDR-TB and DILI are described in this research. The mean age (standard deviation) was 39.10 (3.30) years. Mean DILI occurred 30.40 (27.70) days after starting the treatment. Three (43.00 %) patients presented jaundice. Regarding the type of injury, four (57.00 %) had hepatocellular injury and three (43.00 %) cholestatic injury. Four patients showed mild DILI and three moderate DILI. All the patients had taken pyrazinamide (pyrazinamide alone: four patients; pyrazinamide and ethionamide: one patient; pyrazinamide, rifampin and isoniazid: one patient; pyrazinamide and rifampicin: one patient). The mean hospital stay was 48.10 (48.70) days. The mean serum alkaline phosphatase (AP), alanine aminotransferase (ALT) and gamma-glutamyl- transpeptidase (GGT) were 2.40 (1.10), 7.90 (7.10) and 5.60 (3.70) times the upper limit of normal (ULN), respectively. The mean total bilirubin was 2.30 (2.00), with a range of 0.50 to 6.40 mg/dl. As part of the discharge plan, quinolones were given to seven patients (levofloxacin: six patients; ofloxacin: one patient) and amoxicillin/clavulanic acid was added to one patient. Conclusions: MDR-TB patients may develop DILI after the first month of treatment. Hepatocellular injury was the most common type of liver injury, and pyrazinamide was the most frequently used antimycobacterial.

Hepatic disorders associated with the use of Ivermectin for SARS-CoV-2 infection in adults: a pharmacovigilance study in VigiBase.

Aim: The aim of the present study was to review in VigiBase the reports of serious hepatic disorders associated with the use of ivermectin for COVID-19 in adults. Background: In the face of the global health emergency caused by SARS-CoV-2, ivermectin, among other drugs, has been repurposed in some Latin American countries to treat COVID-19. Studies are needed on the safety of ivermectin for this new indication. VigiBase is the WHO pharmacovigilance database that registers all individual case safety reports (ICSRs) from more than 130 countries. Methods: We extracted the ICSRs of men or women aged ≥ 18 years and dated between 1 January 2020 and 7 March 2021 which included an association with the use of ivermectin. Results: Of 1393 ICSRs associated with ivermectin, 60 (4.3%) were registered as "serious." Ivermectin had been used for COVID-19 in 25 of those cases. Among the latter, 6 experienced hepatic disorders (hepatitis, hepatocellular injury, cholestasis, increased alanine aminotransferase and/or aspartate aminotransferase levels, abnormal liver function tests). Conclusion: The safety of the use of ivermectin should be studied more exhaustively, especially as regards the possibility of hepatic disorders developing when the drug is used for COVID-19.

Elevación de los niveles de transaminasas inducidos por tocilizumab durante el tratamiento para infección severa por SARS-CoV-2: Estudio meta-analítico

Objetivo: estudio sistemático de incremento de los niveles de transaminasas hepáticas inducidos por tocilizumab (TCZ) en pacientes con infección por SARS-CoV-2. Material y métodos: Se realizaron búsquedas en PubMed, EMBASE y Google Scholar, de estudios publicados entre enero 2020 y agosto 2021. Se incluyeron estudios que reportaban datos con niveles de transaminasas hepáticas (aspartato-aminotransferasa o AST y alanino- aminotransferasa o ALT) en pacientes infección por SARS-CoV-2 en tratamiento con TCZ, ya sea en estudios de casos y controles o cuando se median dichos niveles antes y después de terapia en un mismo paciente. La calidad de los artículos fue evaluada de acuerdo con la escala Newcastle Ottawa (NOS). Se extrajeron datos sobre el diseño del estudio, país, número de pacientes, edad y sexo. Se aplicó un modelo de efectos aleatorios para la construcción del diagrama de árbol en base a la delta de la media y desviación estándar de los niveles de ALT y GPT de los casos y controles, de cada uno de los reportes incluidos, con un intervalo de confianza (IC) del 95%. Resultados: Se identificaron 5 estudios de casos y controles para su inclusión, que totalizaron un total de 511 pacientes. La media de edad fue 62,3 + 5,0 años y el 78,8 % fueron varones. La puntuación media de NOS de los estudios incluidos fue 7,8 + 0,4. La dosis utilizada de TCZ fue de 8mg/kg/día. En el diagrama de árbol se observó que la delta de la media de variación de la ALT y AST fueron 0,33 (delta 95% intervalo de confianza: 0,17-0,5; I2 =73% p<0,05) y 0,34 (95% IC: 0,17-0,51; I2=84% p<0,05), respectivamente. En un estudio se reportó normalización de ALT y AST a la 3ra semana, y el resto de estudios no reportó datos de evolución. Conclusión: El uso de TCZ en la infección por SARS-CoV-2 está asociado con elevación de ALT y AST, sin embargo, sus niveles no cumplen criterios de injuria hepática inducida por medicamento y aparentemente es autolimitado. Se requieren más estudios para confirmar la naturaleza temporal de la elevación de las transaminasas asociada al TCZ.

The relationship between the severity and mortality of SARS-CoV-2 infection and 25-hydroxyvitamin D concentration - a metaanalysis.

INTRODUCTION: There is increasing scientific interest in the possible association between hypovitaminosis D and the risk of SARS-CoV-2 infection severity and/or mortality. OBJECTIVE: To conduct a metanalysis of the association between 25-hydroxyvitamin D (25(OH)D) concentration and SARS-CoV-2 infection severity or mortality. MATERIAL AND METHODS: We searched PubMed, EMBASE, Google scholar and the Cochrane Database of Systematic Reviews for studies published between December 2019 and December 2020. Effect statistics were pooled using random effects models. The quality of included studies was assessed with the Newcastle-Ottawa Scale (NOS). Targeted outcomes: mortality and severity proportions in COVID-19 patients with 25(OH)D deficiency, defined as serum 25(OH)D < 50 nmol/L. RESULTS: In the 23 studies included (n = 2692), the mean age was 60.8 (SD ± 15.9) years and 53.8% were men. Results suggested that vitamin 25(OH)D deficiency was associated with increased risk of severe SARS-CoV-2 disease (RR 2.00; 95% CI 1.47-2.71, 17 studies) and mortality (RR 2.45; 95% CI 1.24-4.84, 13 studies). Only 7/23 studies reported C-reactive protein values, all of which were > 10 mg/L. Conclusions 25(OH)D deficiency seems associated with increased SARS-CoV-2 infection severity and mortality. However, findings do not imply causality, and randomized controlled trials are required, and new studies should be designed to determine if decreased 25(OH)D is an epiphenomenon or consequence of the inflammatory process associated with severe forms of SARS-CoV-2. Meanwhile, the concentration of 25(OH)D could be considered as a negative acute phase reactant and a poor prognosis in COVID-19 infection.

Angiotensin-Receptor Blockers and the Risk of Alzheimer´s Disease: A Meta-analysis.

BACKGROUND: Anti-hypertensive medications may reduce the incidence of cognitive disorders. This may be due to reasons beyond their pure hypotensive effect. This study aimed to systematically review the association between the use of Angiotensin-Receptor Blockers (ARBs) and the incidence of Alzheimer's disease (AD). METHODS: We systematically searched studies reporting the association between ARB use and the incidence of AD. RESULTS: Ten studies (1 RCT, 2 case-control and 7 cohort studies) met the inclusion criteria. When all observational studies (9) were analyzed, ARB use was associated with a reduced risk of incident AD (HR 0.72, 95% CI: 0.58-0.88, p<0.001). In the only RCT, decrease in the incidence of AD was also significant (HR= 0.31, 95% CI: 0.14-0.68). CONCLUSION: ARB use may reduce the risk of incident AD. This association does not imply causation and further research is required to clarify potential mechanisms.

Clinical characteristics of pyrazinamide-associated hepatotoxicity in patients at a hospital in Lima, Peru. / Características clínicas de la hepatotoxicidad asociada a la pirazinamida en pacientes de un hospital de Lima, Perú.

In order to determine the characteristics of drug-induced liver injury (DILI), adult patients diagnosed with tuberculosis and with an anti-tuberculosis treatment scheme including pyrazinamide were studied. The re-exposure process was used for the cause-effect analysis of the DILI. A total of 10 patients were found with pyrazinamide-associated DILI; the median age and hospital stay were 40.5 years (from 22 to 76 years) and 41 days (from 11 to 130 days), respectively. The median time in which the events appeared was 14 days (from 3 to 46 days); jaundice was observed in 4 patients and radiological patterns such as hepatocellular, mixed and cholestatic were found in 5, 3 and 2 patients, respectively. Mild presentation of DILI was observed in 6 cases (60%) and moderate in 3 (30%). In conclusion, pyrazinamide-associated DILI required prolonged hospital stay, presented jaundice in little more than a third of the cases, and radiologically, the hepatocellular pattern predominated.

Con el objetivo de determinar las características de la enfermedad hepática inducida por el medicamento (DILI) se realizó un estudio de pacientes adultos con diagnóstico de tuberculosis y esquema de tratamiento antituberculoso con pirazinamida. El análisis de causa efecto de la DILI fue mediante el proceso de reexposición. Se encontraron 10 pacientes con DILI asociada a pirazinamida, la mediana de edad y de estancia hospitalaria fue de 40,5 años (rango 22-76) y 41 días (rango 11-130), respectivamente. La mediana de presentación del evento fue de 14 días (rango 3-46), 4 pacientes presentaron ictericia, 5 tuvieron patrón hepatocelular, 3 mixtas y 2 colestásicos. La presentación de la DILI fue leve en 6 casos (60%) y moderados en 3 (30%). En conclusión, la DILI asociada a la pirazinamida requiere estancia hospitalaria prolongada, se presenta con ictericia en un poco más de un tercio de los casos siendo el patrón predominante el hepatocelular.

Frequency of Long QT in Patients with SARS-CoV-2 Infection Treated with Hydroxychloroquine: A Meta-analysis.

Introduction Hydroxychloroquine (HCQ) has been proposed as a SARS-CoV-2 treatment but the frequency of long QT (LQT) during use is unknown. Objective To conduct a meta-analysis of the frequency of LQT in patients with SARS-CoV-2 infection treated with HCQ. Data Sources PubMed, EMBASE, Google Scholar, the Cochrane Database of Systematic Reviews and preprint servers (medRxiv, Research Square) were searched for studies published between December 2019 and June 30, 2020. Methods Effect statistics were pooled using random effects. The quality of observational studies and randomized controlled trials was appraised with STROBE and the Cochrane Risk of Bias Assessment tools, respectively. Outcomes Critical LQT was defined as: (1) maximum QT corrected (QTc)≥500 ms (if QRS<120 ms) or QTc≥550 ms (if QRS≥120 ms), and (2) QTc increase ≥60 ms. Results In the 28 studies included (n=9124), the frequency of LQT during HCQ treatment was 6.7% (95% confidence interval [CI]: 3.7-10.2). In 20 studies (n=7825), patients were also taking other QT-prolonging drugs. The frequency of LQT in the other 8 studies (n=1299) was 1.7% (95% CI: 0.3-3.9). Twenty studies (n=6869) reported HCQ discontinuation due to LQT, with a frequency of 3.7% (95% CI: 1.5-6.6). The frequency of ventricular arrhythmias during HCQ treatment was 1.68% (127/7539) and that of arrhythmogenic death was 0.69% (39/5648). Torsades de Pointes occurred in 0.06% (3/5066). Patients aged >60 years were at highest risk of HCQ-associated LQT (P<0.001). Conclusions HCQ-associated cardiotoxicity in SARS-CoV-2 patients is uncommon but requires ECG monitoring, particularly in those aged >60 years and/or taking other QT-prolonging drugs.

A pharmacological perspective of chloroquine in SARS-CoV-2 infection: An old drug for the fight against a new coronavirus?

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is having serious consequences on health and the economy worldwide. All evidence-based treatment strategies need to be considered to combat this new virus. Drugs need to be considered on scientific grounds of efficacy, safety and cost. Chloroquine (CQ) and hydroxychloroquine (HCQ) are old drugs used in the treatment of malaria. Moreover, their antiviral properties have been previously studied, including against coronaviruses, where evidence of efficacy has been found. In the current race against time triggered by the COVID-19 pandemic, the search for new antivirals is very important. However, consideration should be given to old drugs with known anti-coronavirus activity, such as CQ and HCQ. These could be integrated into current treatment strategies while novel treatments are awaited, also in light of the fact that they display an anticoagulant effect that facilitates the activity of low-molecular-weight heparin, aimed at preventing acute respiratory distress syndrome (ARDS)-associated thrombotic events. The safety of CQ and HCQ has been studied for over 50 years, however recently published data raise concerns for cardiac toxicity of CQ/HCQ in patients with COVID-19. This review also re-examines the real information provided by some of the published alarming reports, although concluding that cardiac toxicity should in any case be stringently monitored in patients receiving CQ/HCQ.

Definiciones, criterios diagnósticos y valoración de terminalidad en enfermedades crónicas oncológicas y no oncológicas / Definitions, diagnostic criteria and terminality assessment of cancer and non- cancer chronic diseases

RESUMEN Los cambios demográficos mundiales han producido nuevos retos en el sistema de salud. La atención de pacientes de mayor edad y con problemas de salud más complejos se ha incrementado de manera importante y sobrepasan nuestra capacidad de respuesta; el Perú no escapa a esta realidad. Estos pacientes necesitan cada vez mayores cuidados y la enfermedad crónica en fase avanzada requiere un cambio de enfoque; de los tratamientos agresivos con fines curativos hacia un enfoque paliativo, de mejora de la calidad de vida, asociado a un importante contenido social. La enfermedad en fase terminal se sitúa en la etapa final de la vida, en la que existe daño irreversible y múltiples síntomas somáticos, psicológicos y espirituales, con gran impacto en el paciente y su familia. Se ha estudiado con relativa frecuencia la enfermedad oncológica en fase terminal, sin embargo, las no oncológicas tienen mayor frecuencia y sobrevida. El objetivo de la presente revisión es hacer un compendio de las definiciones operacionales de esta condición, describir criterios diagnósticos específicos de terminalidad, resumir instrumentos para identificar necesidad de cuidados paliativos y escalas de pronóstico publicadas en la literatura científica.

ABSTRACT Global demographic changes have generated new challenges in the health system. Treating increasingly older patients with more complex health problems has significantly raised and exceeded our response capacity, and Peru is not indifferent to this situation. These patients need more and more care, and late-stage chronic diseases require an approach change: from aggressive healing treatments to palliative ones which improve quality of life and are associated with an important social content. Late-stage diseases occur in the final stage of life, where irreversible damage; multiple somatic, psychological and spiritual symptoms; as well as great impact in the patients and their families take place. Late-stage cancer diseases have been studied on a relatively frequent basis; however, non-cancer diseases occur more often and result in better survival rates. This review article aims at gathering the operational definitions of this condition, describing the specific diagnostic criteria of terminality, and summarizing the instruments to identify the need of palliative care and the prognostic scales published in the scientific literature.

Características clínicas de la hepatotoxicidad asociada a la pirazinamida en pacientes de un hospital de Lima, Perú / Clinical characteristics of pyrazinamide-associated hepatotoxicity in patients at a hospital in Lima, Peru

RESUMEN Con el objetivo de determinar las características de la enfermedad hepática inducida por el medicamento (DILI) se realizó un estudio de pacientes adultos con diagnóstico de tuberculosis y esquema de tratamiento antituberculoso con pirazinamida. El análisis de causa efecto de la DILI fue mediante el proceso de reexposición. Se encontraron 10 pacientes con DILI asociada a pirazinamida, la mediana de edad y de estancia hospitalaria fue de 40,5 años (rango 22-76) y 41 días (rango 11-130), respectivamente. La mediana de presentación del evento fue de 14 días (rango 3-46), 4 pacientes presentaron ictericia, 5 tuvieron patrón hepatocelular, 3 mixtas y 2 colestásicos. La presentación de la DILI fue leve en 6 casos (60%) y moderados en 3 (30%). En conclusión, la DILI asociada a la pirazinamida requiere estancia hospitalaria prolongada, se presenta con ictericia en un poco más de un tercio de los casos siendo el patrón predominante el hepatocelular.

ABSTRACT In order to determine the characteristics of drug-induced liver injury (DILI), adult patients diagnosed with tuberculosis and with an anti-tuberculosis treatment scheme including pyrazinamide were studied. The re-exposure process was used for the cause-effect analysis of the DILI. A total of 10 patients were found with pyrazinamide-associated DILI; the median age and hospital stay were 40.5 years (from 22 to 76 years) and 41 days (from 11 to 130 days), respectively. The median time in which the events appeared was 14 days (from 3 to 46 days); jaundice was observed in 4 patients and radiological patterns such as hepatocellular, mixed and cholestatic were found in 5, 3 and 2 patients, respectively. Mild presentation of DILI was observed in 6 cases (60%) and moderate in 3 (30%). In conclusion, pyrazinamide-associated DILI required prolonged hospital stay, presented jaundice in little more than a third of the cases, and radiologically, the hepatocellular pattern predominated.

Angiotensin-Converting Enzyme (ACE) genetic variation and longevity in Peruvian older people: a cross-sectional study.

Background: Some studies have suggested that the insertion(I)/deletion(D) polymorphism of the Angiotensin-Converting Enzyme (ACE) gene may be associated with human longevity, especially in centenarians. However, this association is still controversial. Besides, there have been no studies in Peruvians.Aim: To describe the age distribution of the ACE polymorphism in a convenience sample of Peruvian older people.Subjects and methods: This was a cross-sectional study in 104 Geriatric Day Hospital patients in Lima, Perú. The ACE polymorphism was determined in all patients. For the purpose of association with age, the sample was divided into four categories: young (< 65), youngest-old (65-74), middle-old (75-84) and oldest-old (85 or more).Results: The distribution of genotype frequencies was consistent with a population in Hardy-Weinberg equilibrium (p = 0.62). The number (%) of D/D, I/D and I/I genotypes in the young was 2 (14.3%), 3 (21.4%) and 9 (64.3%), respectively; in youngest-old: 4 (11.4%), 15 (42.9%) and 16 (45.7%); in middle-old: 6 (12.2%), 20 (40.8%) and 23 (46.9%); and in oldest-old: 0 (0.0%), 4 (66.7%) and 2 (33.3%). A chi-square analysis showed no significant differences in genotype distribution between age groups (p = 0.647).Conclusion: No significant age differences were found in the distribution of the ACE polymorphism in this sample. Further studies with greater statistical power are recommended.

Evaluación del plan curricular de un programa de posgrado en Ciencias de la Salud / Evaluation of a health sciences graduate program curriculum

Objetivo: Evaluar la validez interna del currículo de un programa de posgrado en ciencias de la salud. Materiales y métodos: Estudio descriptivo con análisis documental de un programa de maestría en Docencia e Investigación en Salud de una universidad pública. Se analizó la validez interna mediante identificación de indicadores del perfil profesional, se calificaron los sílabos de las asignaturas y se valoró la congruencia en mapa curricular. Se consideraron indicadores de personalidad (alfa) y ocupacionales (beta). Se calculó estadística descriptiva con Microsoft Excel 2013.Resultados: Se identificaron indicadores alfa (diseña, demuestra, valora y aplica) e indicadores beta (líder, investigador, docente y evaluador). Los sílabos tuvieron calificación aprobatoria, pero deficiencias en metodología, materiales y bibliografía. Los indicadores conocimiento, aplicación, ser investigador y docente, estaban articulados en el mapa curricular, y se detectó desarticulación de indicadores de valoración, comunicación, ser líder y evaluador. Conclusiones: El perfil profesional planteado está representado en el plan curricular, pero los indicadores no están articulados adecuadamente.

Objective: To evaluate the internal validity of a health sciences graduate program curriculum.Materials and methods: A descriptive study using a documentary analysis of a public university's Master of Education and Health Research Program. The internal validity was analyzed through the identification of professional profile indicators, subjects' syllabi were rated, and the congruence in the curriculum map was assessed. Personality (alpha) and occupational (beta) indicators were considered. Descriptive statistics was performed using Microsoft Excel 2013.Results: Alpha indicators such as the ability to design, demonstrate, assess and apply, and beta indicators such as being a leader, researcher, professor and assessor were identified. The syllabi achieved a passing grade, but deficiencies in the methodology, materials and bibliography were observed. The indicators "knowledge", "application", "being a researcher and professor" were interrelated in the curriculum map; however, indicators such as "assessment", "communication", "being a leader and assessor" were not interrelated.Conclusions: The proposed professional profile is represented in the curriculum, but the indicators are not adequately interrelated.

[Anemia as a prognostic factor in cancer patients]. / Anemia como factor pronóstico en pacientes con cáncer.

OBJECTIVE.: To determine the frequency and prognostic value of anemia in cancer patients receiving care at the National Institute of Neoplastic Diseases (Instituto Nacional de Enfermedades Neoplásicas - INEN) between January and April of 2010. MATERIALS AND METHODS.: Anemia was considered for men with hemoglobin levels at <13 g/dL; and for women, at <12 g/dL. Associations between qualitative features were assessed with a Chi-square test. Kaplan-Meier estimator was used for the analysis of the survival curves, and differences between the curves were performed with the log-rank test. RESULTS.: 772 patients were included; 584 (75.7%) had solid tumors and 188 (24.3%) had hematologic malignancies. Anemia was diagnosed in 359 patients (46.5%); hematologic malignancies in 127 patients (67.6%); and solid neoplasms in 235 (40.2%). Hematologic malignancies with the highest frequency of anemia were chronic myeloid leukemia, acute leukemias, and multiple myeloma (100%, 92.5% and 60%, respectively); and were cancer of gastrointestinal, gynecological, and urological origin were in the group of solid neoplasms (62%, 52.1% and 45%, respectively). Two hundred and four (204) patients (26.4%) were transfused. In 762 patients, a significant difference in overall survival was found between groups with and without anemia, estimated at 5 years in 62% and 47% respectively (p <0.001). In the solid tumor subgroup (p = 0.002), and the hematological malignancies subgroup (p = 0.007), such association was also found. CONCLUSIONS.: Anemia is common in cancer patients, and its presence determines an independent prognostic factor in overall survival.

OBJETIVOS.: Determinar la frecuencia y el valor pronóstico de la anemia en pacientes con cáncer atendidos en el Instituto Nacional de Enfermedades Neoplásicas (INEN) entre enero y abril del 2010. MATERIALES Y MÉTODOS.: Se consideró anemia en varones cuando la hemoglobina fue <13 g/dL, y en mujeres cuando fue <12 g/dL. Para determinar asociaciones se usó la prueba Chi-cuadrado. Para el análisis de las curvas de sobrevida se usó el estimador de Kaplan-Meier y log rank test. RESULTADOS.: 772 pacientes fueron incluidos; 584 (75,7%) tuvieron tumores sólidos y 188 (24,3%) neoplasias hematológicas. Se diagnóstico anemia en 359 (46,5%) pacientes, en 124 (66,0%) neoplasias hematológicas, y en 235 (40,2%) neoplasias sólidas. Las neoplasias hematológicas con mayor frecuencia de anemia fueron la leucemia mieloide crónica, las leucemias agudas, y el mieloma múltiple (100%, 92,5% y 60%; respectivamente) y en el grupo de neoplasias sólidas fueron los cánceres de origen: gastrointestinal, ginecológico, y urológico (62%, 52,1% y 45%; respectivamente). Recibieron transfusiones 204 pacientes (26,4%). En 762 pacientes se encontró una diferencia en la sobrevida global entre los grupos sin y con presencia de anemia, estimándose a los cinco años en 62% y 47% respectivamente (p<0,001), además se encontraron diferencias en la sobrevida global para el subgrupo de tumores sólidos (p=0,002) y neoplasias hematológicas (p=0,007). CONCLUSIONES.: La anemia es frecuente en pacientes con cáncer y su presencia determina un factor pronóstico independiente en la sobrevida global.