Advance Care Planning in Ecuador.

Advance Care Planning is a process by which a patient's health care preferences are established in advance in the event that he or she become temporarily or constantly unable to make decisions for themselves in the future. It is also applied early in emergencies, in intensive care treatment, and after surgery where one's ability to decide is reduced. In Ecuador there is currently no legislation on this subject, however, the National Health Bioethics Commission validated and published the document "Advance Living Will" and as an important advance issued a favorable criterion before the National Assembly for it to be incorporated into the Organic Health Code, the concept, regulations, and the text of Vital Advance Will. Instead of, its use is currently not in force. However, the compliance criteria have been established in the Palliative Care Standard since 2015, but are not yet implemented. There are few studies that demonstrate its application in the country, so it is important to know the cultural and social characteristics of both health professionals and patients, which limit its application.

How to Advance Palliative Care Research in South America? Findings From a Delphi Study.

CONTEXT: Progress in palliative care (PC) necessarily involves scientific development. However, research conducted in South America (SA) needs to be improved. OBJECTIVES: To develop a set of recommendations to advance PC research in SA. METHODS: Eighteen international PC experts participated in a Delphi study. In round one, items were developed (open-ended questions); in round two, each expert scored the importance of each item (from 0 to 10); in round three, they selected the 20 most relevant items. Throughout the rounds, the five main priority themes for research in SA were defined. In Round three, consensus was defined as an agreement of ≥75%. RESULTS: 60 potential suggestions for overcoming research barriers in PC were developed in round one. Also in Round one, 88.2% (15 of 17) of the experts agreed to define a priority research agenda. In Round two, the 36 most relevant suggestions were defined and a new one added. Potential research priorities were investigated (open-ended). In Round three, from the 37 items, 10 were considered the most important. Regarding research priorities, symptom control, PC in primary care, public policies, education and prognosis were defined as the most relevant. CONCLUSION: Potential strategies to improve scientific research on PC in SA were defined, including stimulating the formation of collaborative research networks, offering courses and workshops on research, structuring centers with infrastructure resources and trained researchers, and lobbying governmental organizations to convince about the importance of palliative care. In addition, priority research topics were identified in the region.

Farmacovigilancia intensiva de vacunas SOBERANA®02 y Soberana®Plus en población pediátrica en el Centro de Inmunología Molecular / Intensive pharmacovigilance of SOBERANA®02 and Soberana®Plus vaccines in pediatric population at the Center for Molecular Immunology

Las vacunas SOBERANA®02 y SOBERANA® Plus contra el coronavirus tipo 2 causante del síndrome respiratorio agudo severo, recibieron autorización de uso en emergencia por la autoridad reguladora de Cuba, y de inmediato aconteció una campaña de vacunación masiva en población pediátrica, lo que devino en una inminente movilización de centros de vacunación y vigilancia de sus eventos adversos. El Centro de Inmunología Molecular realizó un estudio de farmacovigilancia intensiva que evalúo el cumplimiento del esquema heterólogo con ambas vacunas, su seguridad y la incidencia de casos positivos a COVID-19 en niños y adolescentes después de completar el esquema de inmunización. Desde el 15 de septiembre al 31 de diciembre del 2021, participaron 529 sujetos entre 2 y 18 años de edad, de ambos sexos, sin antecedentes de infección por coronavirus tipo 2 del síndrome respiratorio agudo severo, procedentes de 35 municipios y 12 provincias cubanas, quienes recibieron vacuna SOBERANA®02 (dos dosis) y SOBERANA®Plus (una dosis). Se realizó vigilancia de eventos adversos hasta 30 días después de la última dosis recibida. Se consultó la plataforma informática nacional Higia Andariego para identificar los casos positivos al virus del síndrome respiratorio agudo severo coronavirus 2, hasta 3 meses de haber completado la vacunación. El 98,5 por ciento de los participantes completó el esquema de vacunación y en el 6,6 por ciento se notificó algún evento adverso con relación consistente a la vacunación. Predominaron las reacciones locales (dolor, eritema, inflamación), sobre las reacciones sistémicas (fatiga y febrícula), de intensidad ligera o moderada. Se logró un elevado cumplimiento del esquema de inmunización, con un perfil de seguridad favorable, los sujetos con esquema completo de inmunización no enfermaron de COVID-19(AU)

The severe acute respiratory syndrome coronavirus 2 vaccines, SOBERANA®02 and SOBERANA®Plus, received authorization for emergency use by the Cuban regulatory authority; a massive vaccination campaign was immediately launched in the pediatric population, which led to an imminent mobilization of vaccination centers and surveillance of adverse events. The Molecular Immunology Center conducted an intensive pharmacovigilance study to evaluate compliance of the heterologous scheme with both vaccines, their safety, and the incidence of COVID-19 positive cases in children and adolescents after completing the immunization schedule. From September 15 to December 31, 2021, a total of 529 subjects between 2 and 18 years of age, of both sexes, without a history of infection by severe acute respiratory syndrome coronavirus type 2, from 35 municipalities and 12 Cuban provinces, who received SOBERANA®02 (two doses) and SOBERANA®Plus (one dose) vaccines, were included in the study. Surveillance for adverse events was performed up to 30 days after the last dose received. The national computer platform Higia Andariego was consulted to identify positive cases for severe acute respiratory syndrome coronavirus 2 up to 3 months after completing vaccination. According to the report, 98.5percent of the participants completed the vaccination schedule and 6.6percent of them reported some adverse event consistently related to vaccination. Local reactions (pain, erythema, inflammation) prevailed over systemic reactions (fatigue and fever), of light or moderate intensity. High compliance with the immunization schedule was achieved, with a favorable safety profile; subjects with a complete immunization schedule did not become ill with COVID-19(AU)

[Differences among renin-angiotensin system inhibitor drugs in prognosis of hypertense patients with COVID-19]. / Diferencias entre fármacos inhibidores del sistema renina-angiotensina en pacientes hipertensos ingresados por COVID-19.

Introduction: Concerns have been raised about Renin-angiotensin system inhibitors (RASi) in patients with COVID-19. Although recent trials have proved its security, evidence regarding intrinsic differences between RASi is lacking, especially in patients with arterial hypertension. Our objective was to analyse the prognosis of hypertense patients who received angiotensin converting enzyme inhibitors (ACEi) or angiotensin-2 receptor blockers (ARBs) and were hospitalized due to COVID-19. Materials and methods: 392 consecutive patients with hypertension and COVID-19 were analyse. Incidence of the combined event (death or mechanical ventilation need) was the primary endpoint. Secondary, incidence of each event and time to event were analysed. Results: 155 received ACEi and 237 ARBs. During the hospitalization, the combined event was observed in the 31,6 % of patients. No differences were observed between those previously treated with ACEi and ARBs (33.5 vs. 30.9%; p = 0.51). In the survival analysis, no differences were observed regarding time to combined event (p = 0.91). In-hospital mortality was similar in both groups (32.3 vs. 29.1%; p = 0.51), as well as the need of mechanical ventilation (3.2 vs. 5.9%; p = 0.23). Conclusions: The type of RASi was not associated with in-hospital major events in patients with arterial hypertension hospitalized due to COVID-19.

Introducción: Han surgido dudas sobre la seguridad de los fármacos inhibidores del sistema renina-angiotensina (SRA) en pacientes con enfermedad por coronavirus 2019 (COVID-19). Aunque estudios recientes han demostrado la seguridad de este grupo de fármacos, la evidencia sobre la comparativa de los diferentes fármacos inhibidores del SRA es escasa, sobre todo en pacientes hipertensos. Nuestro objetivo fue analizar el pronóstico de los pacientes hipertensos tratados con inhibidores de la enzima convertidora de angiotensina (IECA) o antagonistas del receptor de angiotensina II (ARA II) que presentaron COVID-19. Materiales y métodos: Se analizaron 582 pacientes hipertensos con COVID-19. Se registró la incidencia del evento combinado de muerte o necesidad de ventilación mecánica invasiva (VMI) durante la hospitalización. De forma secundaria, se analizó la incidencia de eventos de manera independiente y se realizó un análisis de supervivencia para analizar el tiempo hasta los eventos. Resultados: 155 pacientes recibían tratamiento previo con IECA y 237 con ARA II. Durante la hospitalización por COVID-19, se observó una incidencia del evento combinado del 31.6%. No se detectaron diferencias entre los pacientes que recibían tratamiento con IECA y los tratados con ARA II (33.5 vs. 30.9%; p = 0.51). En el análisis de supervivencia, no se hallaron diferencias en el tiempo hasta el evento combinado (p = 0.91). La mortalidad intrahospitalaria fue similar en ambos grupos (32.3 vs. 29.1%; p = 0.51), así como la necesidad de VMI (3.2 vs. 5.9%; p = 0.23). Conclusiones: El tipo de inhibidor del SRA no se asoció a diferencias pronósticas significativas entre los pacientes hipertensos ingresados con COVID-19.

Implementation and Knowledge of the Clinical Practice Guide for Palliative Care in the Ecuadorian Primary Care Level.

Ecuador assumed the commitment of including Palliative Care (PC) in its health policies. In 2014, the Ministry of Public Health (Ministerio de Salud Pública, MSP) approved the Clinical Practice Guide for Palliative Care (Guía de Práctica Clínica sobre Cuidados Paliativos, GPCCP), with application at the national level, as a mandatory internal regulation in all institutions belonging to the National Health System. In 2021, there is no evidence about the degree of implementation. The objective was to evaluate the implementation (I) of the GPCCP guide and the knowledge (C) of the health personnel working in the Zone 7 Health Centers (HCs). This is a cross-sectional, descriptive, and prospective study. A total of 292 professionals were interviewed: managers (38), physicians (150), and nurses (104). Three surveys based on the GPCCP guide were elaborated: one for the implementation, which was applied to the individuals in charge, and the others to assess the health professionals' knowledge. The SPSS program was used, version 25. In the three groups, more than half of the participants had no training in PC, 91.2% of the HCs have the GPCCP guide, there is PC medical history (MH) in 38.2%, and morphine is used in 14.7%. The implementation of the GPCCP guide was inadequate in 52.9% of the cases. Only 25% treat the agony symptoms and 30%, delirium; 4.4% acknowledge the use of morphine in dyspnea, and 13.3% identify the subcutaneous route as the first choice for hydration at the end-of-life phase. Strategies to implement the GPCCP guide and to improve the health personnel's knowledge must be implemented in Zone 7 centers.

Psychological Inflexibility and Loneliness Mediate the Impact of Stress on Anxiety and Depression Symptoms in Healthcare Students and Early-Career Professionals During COVID-19.

Background: The current mental health state of healthcare professionals and students during the COVID-19 pandemic in Ecuador remains understudied and how to improve their mental health is a challenge. Objective: This study aimed to explore the anxiety and depressive symptomatology among healthcare students and professionals in Ecuador and to examine the role of psychological inflexibility, loneliness, and psychological stress as predictors of anxiety and depression symptoms. Methods: A total of 191 undergraduate and graduate healthcare students in clinical practice (early-career healthcare professionals) in Ecuador were surveyed between January and March 2021 using standardized measures of psychological stress (PSS), psychological inflexibility (AAQ), loneliness (UCLA), alcohol consumption (AUDIT-C), and anxiety and depressive symptomatology (PHQ). Macro Process for SPSS (models 4 and 7) were used to test mediation effects. Results: Alcohol consumption varied between men and women and anxiety and depression symptomatology was generally low among the sample. Psychological inflexibility and loneliness mediated the impact of stress on anxiety and depressive mood in participants, regardless of gender and previous personal history of COVID-19. Discussion: Implications of psychological inflexibility and the prevention and coping with stress in healthcare professionals during COVID-19 are further discussed.

The Suffering of Advanced Chronic Renal Patients and Their Relationship with Symptoms in Loja, Ecuador.

Advanced Chronic Kidney Disease (ACKD) supposes a public health problem in Ecuador that requires a comprehensive approach. In view of the scarcity of studies on the subject in this country, the objective of this research was to determine the signs and symptoms associated with the patients' physical, social and psychological spheres that allow properly developing palliative care. A longitudinal, prospective and observational study was conducted with ACKD patients. In order to assess the symptomatic burden and suffering of these patients, the Edmonton Symptom Assessment System Revised: renal (ESAS-r) for renal patients and the Distress Thermometer (DT) were used. The sample consisted of a total of 246 patients. The most common symptoms that affect them, causing them suffering in their daily lives, are those related to well-being, difficulty falling asleep and itching. It is necessary that health professionals adapt care measures and help patients undergoing renal treatment, especially those who have suffered the disease for a longer period of time, in order to alleviate the patients' suffering and therefore improve their daily lives. To such an end, a care plan could be designed that includes early palliative care.

Compassionate Engagement and Action in the Education for Health Care Professions: A Cross-Sectional Study at an Ecuadorian University.

Objective: This study aimed at exploring the compassion attitudes and needs for awareness and training related to a compassionate approach for Medicine, Nursing, and Psychology students, as well as for the academic and administration personnel from the Universidad Técnica Particular de Loja (UTPL, Ecuador) Health Sciences area. Methods: A cross-sectional observational study, based on a self-administered questionnaire through a sample of 788 UPTL students. STROBE guidelines were followed and applied. Results: A positive correlation was found between life engagement and compassion for others, from others, and self-compassion. The Nursing students were those who reported having previous experiences of contact with people with an advanced disease or in an end-of-life situation and having received some type of training compared to Medicine and Psychology students and lecturers (faculty members). Differences were found on the "self-compassion" and "compassion for others" subscales, noting a higher level of compassion among Psychology students. Conclusions: To implement the philosophy of compassionate universities it is necessary to design trainings that include the students, the faculty members, and the administrative staff, centered on sensitization and training about assistance, care, and accompaniment at the end of life, as well as cultivating compassion in the workplace.

Chronic Diseases and Associated Factors among Older Adults in Loja, Ecuador.

(1) Background: This study aimed to explore the symptoms, functional status, and depression in patients with chronic diseases in Loja, Ecuador. (2) Methods: A cross-sectional study was carried out with patients over 60 years old having at least one chronic disease and cared for in healthcare centers of the Health Ministry of Ecuador or living in associated geriatric centers. (3) Results: The sample comprised 283 patients with a mean age of 76.56 (SD 7.76) years. The most prevalent chronic diseases were chronic obstructive pulmonary disease, followed by arterial hypertension and diabetes. Patients with a joint disease had the worst scores for the majority of the symptoms assessed with the Edmonton Scale. Cancer, dementia, and arterial hypertension contributed the most to the dependence levels assessed with the Barthel Index. Dementia contributed the most to the poor performance status evaluated with the Karnofsky Performance Status. Cancer and diabetes contributed the most to depression. Patients with a higher number of chronic diseases reported worse functional status. (4) Conclusions: Targeted interventions to address symptoms, functional status, and depression in patients with chronic diseases are needed.

Subtyping of Clostridium difficile PCR ribotypes 591, 106 and 002, the dominant strain types circulating in Medellin, Colombia.

We aimed to achieve a higher typing resolution within the three dominant Clostridium difficile ribotypes (591,106 and 002) circulating in Colombia. A total of 50 C. difficile isolates we had previously typed by PCR-ribotyping, representing the major three ribotypes circulating in Colombia, were analyzed. Twenty-seven isolates of ribotype 591, 12 of ribotype 106 and 11 of ribotype 002 were subtyped by multiple locus variable-number tandem-repeat analysis (MLVA). The presence of the PaLoc genes (tcdA/tcdB), toxin production in culture and antimicrobial susceptibility were also determined. From the total C. difficile ribotypes analyzed, 20 isolates (74%) of ribotype 591, nine (75%) of ribotype 106 and five (45.5%) of ribotype 002 were recovered from patients with Clostridium difficile infection (CDI). MLVA allowed us to recognize four and two different clonal complexes for ribotypes 591 and 002, respectively, having a summed tandem-repeat difference (STRD) <2, whereas none of the ribotype 106 isolates were grouped in a cluster or clonal complex having a STRD >10. Six ribotype 591 and three ribotype 002 isolates belonging to a defined clonal complex were isolated on the same week in two different hospitals. All ribotypes harbored either tcdA+/tcdB+ or tcdA-/tcdB+ PaLoc genes. Moreover, 94% of the isolates were positive for toxin in culture. All isolates were susceptible to vancomycin and metronidazole, while 75% to 100% of the isolates were resistant to clindamycin, and less than 14.8% of ribotype 591 isolates were resistant to moxifloxacina. No significant differences were found among ribotypes with respect to demographic and clinical patients' data; however, our results demonstrated a high molecular heterogeneity of C. difficile strains circulating in Colombia.

Molecular, microbiological and clinical characterization of Clostridium difficile isolates from tertiary care hospitals in Colombia.

In Colombia, the epidemiology and circulating genotypes of Clostridium difficile have not yet been described. Therefore, we molecularly characterized clinical isolates of C.difficile from patients with suspicion of C.difficile infection (CDI) in three tertiary care hospitals. C.difficile was isolated from stool samples by culture, the presence of A/B toxins were detected by enzyme immunoassay, cytotoxicity was tested by cell culture and the antimicrobial susceptibility determined. After DNA extraction, tcdA, tcdB and binary toxin (CDTa/CDTb) genes were detected by PCR, and PCR-ribotyping performed. From a total of 913 stool samples collected during 2013-2014, 775 were included in the study. The frequency of A/B toxins-positive samples was 9.7% (75/775). A total of 143 isolates of C.difficile were recovered from culture, 110 (76.9%) produced cytotoxic effect in cell culture, 100 (69.9%) were tcdA+/tcdB+, 11 (7.7%) tcdA-/tcdB+, 32 (22.4%) tcdA-/tcdB- and 25 (17.5%) CDTa+/CDTb+. From 37 ribotypes identified, ribotypes 591 (20%), 106 (9%) and 002 (7.9%) were the most prevalent; only one isolate corresponded to ribotype 027, four to ribotype 078 and four were new ribotypes (794,795, 804,805). All isolates were susceptible to vancomycin and metronidazole, while 85% and 7.7% were resistant to clindamycin and moxifloxacin, respectively. By multivariate analysis, significant risk factors associated to CDI were, staying in orthopedic service, exposure to third-generation cephalosporins and staying in an ICU before CDI symptoms; moreover, steroids showed to be a protector factor. These results revealed new C. difficile ribotypes and a high diversity profile circulating in Colombia different from those reported in America and European countries.

The role of tramadol in pain management in Latin America: a report by the Change Pain Latin America Advisory Panel.

OBJECTIVE: Change Pain Latin America (CPLA) was created to enhance chronic pain understanding and develop pain management improving strategies in this region. During its seventh meeting (August 2016), the main objective was to discuss tramadol's role in treating pain in Latin America. Furthermore, potential pain management consequences were considered, if tramadol was to become more stringently controlled. METHODS: Key topics discussed were: main indications for prescribing tramadol, its pharmacological characteristics, safety and tolerability, effects of restrictions on its availability and use, and consequent impact on pain care quality. RESULTS: The experts agreed that tramadol is used to treat a wide spectrum of non-oncological pain conditions (e.g. post-surgical, musculoskeletal, post-traumatic, neuropathic, fibromyalgia), as well as cancer pain. Its relevance when treating special patient groups (e.g. the elderly) is recognized. The main reasons for tramadol's high significance as a treatment option are: its broad efficacy, an inconspicuous safety profile and its availability, considering that access to strong analgesics - mainly controlled drugs (classical opioids) - is highly restricted in some countries. The CPLA also agreed that tramadol is well tolerated, without the safety issues associated with long-term nonsteroidal anti-inflammatory drug (NSAID) use, with fewer opioid-like side effects than classical opioids and lower abuse risk. CONCLUSIONS: In Latin America, tramadol is a valuable and frequently used medication for treating moderate to severe pain. More stringent regulations would have significant impact on its availability, especially for outpatients. This could cause regression to older and frequently inadequate pain management methods, resulting in unnecessary suffering for many Latin American patients.

Nasal administration of the neuroprotective candidate NeuroEPO to healthy volunteers: a randomized, parallel, open-label safety study.

BACKGROUND: Delivery of therapeutic agents as erythropoietin (EPO) into Central Nervous System through intranasal route could benefit patients with neurological disorders. A new nasal formulation containing a non-hematopoietic recombinant EPO (NeuroEPO) has shown neuroprotective actions in preclinical models. In the current study, the safety of NeuroEPO was evaluated for the first time in humans. METHODS: A phase I, randomized, parallel, open-label study was carried out in healthy volunteers. They received, intranasally, 1 mg of NeuroEPO every 8 h during 4 days (Group A) or 0.5 mg of NeuroEPO (Group B) with the same schedule. The working hypothesis was that intranasal NeuroEPO produce <10% of severe adverse reactions in the evaluated groups. Therefore, a rigorous assessment of possible adverse events was carried out, which included tolerance of the nasal mucosa and the effect on hematopoietic activity. Clinical safety evaluation was daily during treatment and laboratory tests were done before and on days 5 and 14 after starting treatment. RESULTS: Twenty-five volunteers, 56% women, with a mean age of 27 yrs. were included. Twelve of them received the highest NeuroEPO dose. Twenty types of adverse events occurred, with headache (20%) and increase of hepatic enzymes (20%) as the most reported ones. Nasopharyngeal itching was the most common local event but only observed in four patients (16%), all of them from the lowest dose group. About half of the events were very probably or probably caused by the studied product. Most of the events were mild (95.5%), did not require treatment (88.6%) and were completely resolved (81.8%). No severe adverse events were reported. During the study the hematopoietic variables were kept within reference values. CONCLUSIONS: NeuroEPO was a safe product, well tolerated at the nasal mucosa level and did not stimulate erythropoiesis in healthy volunteers. TRIAL REGISTRATION: Cuban Public Registry of Clinical Trials RPCEC00000157 , June 10, 2013.

Latin-American guidelines for cancer pain management.

Cancer is a major public health issue. Poor pain management has devastating consequences that seriously affect quality of life, diminish functionality and place a huge emotional burden on patients and their relatives. A group of Latin American opinion leaders were invited to participate in a meeting to discuss areas associated with cancer pain. The expert panel reviewed the latest literature to draft region-specific guidelines for effective pain management. The guidelines make recommendations on tailoring treatment to the specific type of pain and provide local physicians with the state-of-the art findings in the field. Management should be with pharmacological approaches (nonopioid, adjuvant and opioid analgesics, as well as oncologic therapies and interventional procedures) and nonpharmacological approaches.

Latin-American guidelines for opioid use in chronic nononcologic pain.

AIM: Latin-American experts in the use of opioids in patients with chronic nononcologic pain (CNOP) have updated existing recommendations to current Latin-American reality. METHODS: Several key opinion leaders from Latin America participated in a face-to-face meeting in Guatemala (April 2015) to discuss the use of opioids in CNOP. Subgroups of experts worked on specific topics, reviewed the literature and shaped the final manuscript. RESULTS: The expert panel developed guidelines taking into consideration the utility of both opioid and nonopioid analgesics and factors pertaining to their efficacy, safety, adherence, administration and risks for abuse/addiction. CONCLUSION: Latin-American guidelines for the use of opioids in CNOP should improve pain relief and patients' quality of life by increasing access to these effective agents.

Efectividad y seguridad del uso de ior® EPOCIM en pacientes en prediálisis Ensayo clínico / Effectiveness and safety in the use of ior® EPOCIM in predialysis patients:Clinical trial

Introducción: El ior® EPOCIM (eritropoyetina humana recombinante) es un medicamento cubano que se produce en el Centro de Inmunología Molecular, el cual ha resultado ser seguro y no se han reportado eventos adversos graves asociados a su uso en pacientes dialíticos; sin embargo, en pacientes en prediálisis la información divulgada sobre su uso es insuficiente. Objetivo: Evaluar la efectividad y seguridad de ior® EPOCIM en pacientes con Enfermedad Renal Crónica en prediálisis, estadios 3 y 4: Material y Métodos: Se realizó un ensayo clínico multicéntrico, abierto, no aleatorizado, fase IV, que incluyó una muestra de 242 pacientes con y sin anemia. Durante 12 meses se evaluó el tratamiento con iorâ EPOCIM, dosis inicial de 30 U/Kg/dosis e incrementó según respuesta hematológica hasta 150 U/Kg/dosis, para lograr estabilización de la hemoglobina entre 10,5-12,5 g/dl y/o hematocrito entre 33-36 por ciento. Resultados: La hemoglobina inicial promedio fue 10 ± 1,5 g/dl, se incrementó rogresivamente hasta el cuarto mes, estabilizando su valor en 11,7 ± 1,2 g/dl, y el hematocrito tuvo similar comportamiento. La función renal se mantuvo estable; la calidad de vida mejoró; hubo mayor beneficio en las escalas de rol físico y salud general. Se reportaron 147 eventos adversos; tuvieron alguna relación causal 13,6 por ciento. El evento más frecuente fue la hipertensión arterial. Ninguna muerte estuvo relacionada con el producto. Conclusiones: El ior® EPOCIM fue seguro y efectivo en los pacientes estudiados con Enfermedad Renal Crónica en prediálisis, estadios 3 y 4(AU)

Introduction: The ior® EPOCIM (human recombinant erythropoietin) is a Cuban medicament produce by the Molecular Immunology Center, which result safety, not being adverse results associated to its use in dialytic patients, but regarding predialysis patients the disclosed information is not enough. Objective: To evaluate effectiveness and safety of ior® EPOCIM in patients with Chronic Kidney Disease (CKD) in pre-dialysis, stages 3 and 4. Material and Methods: Was performed a multicenter, opened, non-randomized phase IV clinical trial, which included 242 patients with and without anemia. During a 12 months period was evaluated the treatment with iorâ EPOCIM, with an initial dose of 30 U/kg/dose; and them increase according to the hematologic response up to a dose of 150 U/Kg/ to achieve the hemoglobinas stabilization between 10.5-12.5 g/dL and/or hematocrit between 33-36 percent. Results: The initial mean value for hemoglobin was 10 (SD ± 1.5 g / dl) it gradually increased until the 4th month stabilizing its value in 11.7 (SD ± 1.2 g / dl); hematocrit had similar behavior. Renal function remained stable. The life quality improved, was a greater benefit in the scale of the physical role and general health. 147 adverse events were reported; they had some causal relationship 13.6 percent. The most frequent event was hypertension (44.9 percent). No death was related with the product. Conclusions: ior® EPOCIM was safe and effective in this population(AU)

A Phase III Clinical Trial of the Epidermal Growth Factor Vaccine CIMAvax-EGF as Switch Maintenance Therapy in Advanced Non-Small Cell Lung Cancer Patients.

PURPOSE: EGFR is a well-validated target for patients with non-small cell lung cancer (NSCLC). CIMAvax-EGF is a therapeutic cancer vaccine composed of human recombinant EGF conjugated to a carrier protein and Montanide ISA51 as adjuvant. The vaccine is intended to induce antibodies against self EGFs that block EGF-EGFR interaction. EXPERIMENTAL DESIGN: To evaluate overall survival, safety, immunogenicity, and EGF concentration in serum after CIMAvax-EGF, a randomized phase III trial was done in patients with advanced NSCLC. Four to 6 weeks after first-line chemotherapy, 405 patients with stage IIIB/IV NSCLC were randomly assigned to a vaccine group, which received CIMAvax-EGF or a control group, treated with best supportive care. RESULTS: Long-term vaccination was very safe. Most frequent adverse reactions were grade 1 or 2 injection-site pain, fever, vomiting, and headache. Vaccination induced anti-EGF antibodies and decreased serum EGF concentration. In the safety population, median survival time (MST) was 10.83 months in the vaccine arm versus 8.86 months in the control arm. These differences were not significant according the standard log rank (HR, 0.82; P = 0.100), but according a weighted log rank (P = 0.04) that was applied once the nonproportionality of the HR was verified. Survival benefit was significant (HR, 0.77; P = 0.036) in the per-protocol setting (patients receiving at least four vaccine doses): MST was 12.43 months for the vaccine arm versus 9.43 months for the control arm. MST was higher (14.66 months) for vaccinated patients with high EGF concentration at baseline. CONCLUSIONS: Switch maintenance with CIMAvax-EGF was well tolerated and significantly increased MST of patients that completed induction vaccination. Baseline EGF concentration predicted survival benefit. Clin Cancer Res; 22(15); 3782-90. ©2016 AACR.

Caracterización molecular de un brote de Klebsiella pneumoniae resistente a carbapenémicos en un hospital de alto nivel de complejidad de Medellín, Colombia / Molecular characterization of an outbreak of carbapenem-resistant Klebsiella pneumoniae in a tertiary care hospital in Medellín, Colombia

Introducción. La resistencia a los carbapenémicos constituye una seria amenaza para la salud pública a nivel mundial, ya que estos antibióticos son una de las últimas opciones terapéuticas contra las bacterias multirresistentes. La caracterización molecular de los brotes causados por bacterias resistentes aporta información relevante para el diseño de estrategias de control de infecciones. Objetivo. Describir las características moleculares de un brote de Klebsiella pneumoniae resistente a carbapenémicos ocurrido en un hospital de alto nivel de complejidad de Medellín entre 2010 y 2011. Materiales y métodos. A partir de una colección de cepas del brote ocurrido en la institución hospitalaria, se recuperaron 84 aislamientos de 32 pacientes infectados y 52 colonizados. La identificación y la sensibilidad de los aislamientos se establecieron mediante el sistema Vitek2 ® . La detección de carbapenemasas se hizo mediante el test de Hodge modificado y usando la reacción en cadena de la polimerasa. La relación genética entre los aislamientos se evaluó mediante electroforesis en gel de campo pulsado y tipificación de secuencias de locus múltiple. Resultados. Todos los aislamientos analizados fueron multirresistentes; el análisis molecular reveló que todos eran portadores del gen bla KPC-3 . El análisis genético mostró que los aislamientos de pacientes infectados y colonizados (58/64 aislamientos) estaban estrechamente relacionados (>80 %) y pertenecían al linaje ST258. Conclusión. Mediante el empleo de técnicas de tipificación molecular fue posible confirmar un brote ocasionado por K. pneumoniae ST258 portador del bla KPC-3 con un perfil de multirresistencia, el cual había sido asociado a uno anterior ocurrido en otro hospital de Medellín. El ST258 es un clon de alto riesgo presente a nivel mundial, lo que debe alertar sobre la posible diseminación de resistencia en el país. El empleo de herramientas moleculares en la vigilancia epidemiológica, es útil para evaluar la diseminación de microorganismos de interés en salud pública.

Introduction: Resistance to carbapenems is considered to represent a serious threat to public health at the global level, since these antibiotics are one of the last therapeutic options for the treatment of multidrug-resistant bacteria. Molecular characterization of outbreaks due to resistant bacteria provides information that can be used in the design of infection control strategies. Objective: To describe the molecular characteristics of an outbreak of carbapenem-resistant Klebsiella pneumoniae that occurred in a tertiary care hospital in Medellín in 2010-2011. Materials and methods: Eighty-four isolates were obtained from a collection of strains associated with the hospital outbreak, of which 32 were from patients infected at that time and 52 were carriers. Identification and susceptibility of the isolates was performed using Vitek2 ® . Carbapenemases were detected using a modified Hodge test and polymerase chain reaction. Genetic relationships between the isolates were evaluated using pulsed field gel electrophoresis and multiple locus sequence typing. Results: All the isolates analyzed were multidrug resistant; molecular analysis revealed that all harbored bla KPC-3 . The genetic analysis showed that 58/64 of the isolates from both infected and colonized patients were closely related (Dice similarity index >80%) and belonged to the ST258 lineage. Conclusion: Using molecular typing techniques it was possible to confirm the occurrence of an outbreak caused by K. pneumoniae ST258, a carrier of bla KPC-3 with a multidrug-resistant profile which had been associated with a previous outbreak in another hospital in the city of Medellín. ST258 is a high risk clone at the global level, demonstrating the potential for dissemination of resistance in this country. Implementation of molecular tools in support of epidemiological surveillance is useful for evaluating the spread of microorganisms of public health significance.

Bacteriemia por enterobacterias resistentes a carbapenems: Un estudio transversal / Bacteremia due to carbapenem-resistant Enterobacteriaceae: A cross-sectional study

Objetivos: Describir las características clínicas, los esquemas de antibiótico empleados y el pronóstico en términos de mortalidad intrahospitalaria y efectos adversos en pacientes con bacteriemia por enterobacterias con prueba fenotípica para carbapenemasas positiva. Material y métodos: Estudio de corte trasversal en un hospital de tercer nivel (Medellín, Colombia), en pacientes con bacteriemia por enterobacterias resistentes a carbapenems (CRE) detectados entre enero del 2010 y diciembre del 2013. Se presentan las variables continuas con medianas y rangos intercuartiles (RIQ) y las categóricas con porcentajes. Resultados: Se incluyeron 64 casos con un promedio de edad de 62 ± 14 años, 66% (n = 42) hombres. El 60% (n = 38) se encontraban en la UCI, y la mediana de APACHE-II fue de 17 (RIQ: 12-22), con alta comorbilidad (puntaje Charlson de 3; RIQ: 2-5). La mediana de estancia previa a la bacteriemia fue de 21 días (RIQ: 13-39). El 64% correspondieron a Klebsiella pneumoniae , el 20% a Serratia marcescens y el 11% a Enterobacter spp. El 45% tenían tamización positiva previa a la bacteriemia. La mortalidad a los 28 días fue del 51,6% (n = 33) y ocurrió con una mediana de 5 días luego de detectada la bacteriemia (RIQ: 2-17). El tratamiento definitivo fue combinado en el 76,6% de los casos, pero no hubo un esquema de combinación prevalente. Se reportaron efectos adversos en uno de cada 3 pacientes, y la mediana de estancia hospitalaria fue de 46 días (RIQ: 26-76). La mortalidad a 28 días de pacientes tratados con carbapenems (n = 27), colistina (n = 27) o tigeciclina (n = 18), solos o en cualquier combinación, fue del 40,7, del 55,2 y del 55,7%, respectivamente. Discusión: Los pacientes incluidos tenían altos índices de comorbilidad y exposición al ambiente nosocomial, como en estudios previamente publicados. La mortalidad a 28 días fue comparable a la reportada en otros estudios. Se encontró menor mortalidad en pacientes tratados con terapias combinadas que incluían carbapenems, similar a lo reportado en un estudio clínico reciente en pacientes con bacteriemia por Klebsiella pneumoniae productora de carbapenemasas. Conclusiones: La bacteriemia por CRE afecta pacientes muy enfermos y se acompaña de elevadamortalidad. Se detecta colonización en casi la mitad de los pacientes antes del desarrollo deinfección. Hay heterogeneidad en el manejo antimicrobiano, pero la inclusión de carbapenemsen el esquema de tratamiento combinado podría asociarse con menor mortalidad.

Objectives: To describe the clinical features, antibiotic regimes and prognosis in terms of inpatient mortality and adverse effects in patients with Enterobacteriaceae bacteremia anda positive carbapenemase-detecting phenotypic test. Materials and methods: A cross-sectional study was conducted at a tertiary hospital (Medellín,Colombia). Patients with blood stream infections by carbapenems-resistant Enterobacteriaceae(CRE) diagnosed from January, 2010 to December, 2013 were included. Continuous variables are presented as medians and interquartile ranges (IQR), and categorical variables are presentedas percentages. Results: Sixty-four cases were included, with a mean age of 62 ± 14; 66% were male (n = 42).A total of 60% (n = 38) were admitted to the ICU and the median APACHE-II score was 17 (IQR:12-22), with high comorbidity (Charlson score = 3, IQR: 2-5). The median hospital stay prior to the diagnosis of bacteremia was 21 days (IQR: 13-39). Klebsiella pneumoniae was isolated in 64%, Serratia marcescens in 20% and Enterobacter spp. in 11% of the cases. Some 45% had apositive screening before the diagnosis of bacteremia. Mortality at 28 days was 51.6% (n = 33)and occurred in a median of 5 days (IQR: 2-17) after bloodstream infection was detected. Definitive treatment was a combination of antibiotics for 76.6%, but no combination scheme was prevalent. Adverse effects were observed in one of 3 patients and the median hospital stay was46 days (IQR: 26-76). Mortality at 28 days was 40.7% when patients were treated with a combination that included carbapenems agents (n = 27), compared with 55.2% for colistin (n = 27) and 55,7% for tigecycline (n = 18). Discussion: A high comorbidity index and nosocomial environment exposure were observed,as in previously published studies. The 28-day mortality was comparable to that reported inother studies. There was less mortality in patients treated with a combination that includeda carbapenem agent, as was reported in a recent clinical study on patients with bacteremia Klebsiella pneumoniae carbapenemase. Conclusions: CRE bacteremia is seen in very ill patients and is associated with high mortality. Bacterial colonization was detected in nearly half the patients prior to development of infection. The current antimicrobial therapy is heterogeneous, but the inclusion of a carbapenems agent in combination therapy may be associated with lower mortality.

[Molecular characterization of an outbreak of carbapenem-resistant Klebsiella pneumoniae in a tertiary care hospital in Medellín, Colombia]. / Caracterización molecular de un brote de Klebsiella pneumoniae resistente a carbapenémicos en un hospital de alto nivel de complejidad de Medellín, Colombia.

INTRODUCTION: Resistance to carbapenems is considered to represent a serious threat to public health at the global level, since these antibiotics are one of the last therapeutic options for the treatment of multidrug-resistant bacteria. Molecular characterization of outbreaks due to resistant bacteria provides information that can be used in the design of infection control strategies. OBJECTIVE: To describe the molecular characteristics of an outbreak of carbapenem-resistant Klebsiella pneumoniae that occurred in a tertiary care hospital in Medellín in 2010-2011. MATERIALS AND METHODS: Eighty-four isolates were obtained from a collection of strains associated with the hospital outbreak, of which 32 were from patients infected at that time and 52 were carriers. Identification and susceptibility of the isolates was performed using Vitek2®. Carbapenemases were detected using a modified Hodge test and polymerase chain reaction. Genetic relationships between the isolates were evaluated using pulsed field gel electrophoresis and multiple locus sequence typing. RESULTS: All the isolates analyzed were multidrug resistant; molecular analysis revealed that all harbored bla KPC-3 . The genetic analysis showed that 58/64 of the isolates from both infected and colonized patients were closely related (Dice similarity index >80%) and belonged to the ST258 lineage. CONCLUSION: Using molecular typing techniques it was possible to confirm the occurrence of an outbreak caused by K. pneumoniae ST258, a carrier of bla KPC-3 with a multidrug-resistant profile which had been associated with a previous outbreak in another hospital in the city of Medellín. ST258 is a high risk clone at the global level, demonstrating the potential for dissemination of resistance in this country. Implementation of molecular tools in support of epidemiological surveillance is useful for evaluating the spread of microorganisms of public health significance.