Management results of a cohort of rheumatoid arthritis patients in a specialized comprehensive healthcare institution in Colombia / Resultados de gestión en una cohorte de pacientes con artritis reumatoide en una institución de atención integral especializada en Colombia

ABSTRACT Objective: To determine the management results in a cohort of patients with rheumatoid arthritis in a specialized integral healthcare institution for this disease in Colombia. Materials and methods: Descriptive cross-sectional study based on a cohort of rheumatoid arthritis patients according to ACR/EULAR 2010 criteria. The information was analysed based on consolidated data from clinical records and national reports in the period 2015-2018. Administrative records related to medication authorizations and prescriptions were considered. Sociodemographic variables, outcome indicators related to disease activity status and medication use percentage were evaluated. Results: As of June 30th 2018, 698 patients were identified, of which the female sex represented 83.8%, the general average age was 55.47 years, and the highest number of cases were in the 60-64 year age group. Of the patients, 68.3% were between remission and low disease activity. Seventy-three point one percent were managed with conventional disease-modifying antirheumatic drugs and a reduction in the use of biological therapy was recorded from 27.2% in 2016 to 17.8% at the end of the period. Conclusions: This study presents the management results of a comprehensive care model for patients with rheumatoid arthritis in Colombia, which managed to maintain the highest proportion of patients in low activity and remission as they had a longer follow-up time, to decrease the percentage of biological DMARDs use, and establish conventional DMARDs as the main therapeutic alternative.

RESUMEN Objetivo: Conocer los resultados de gestión en una cohorte de pacientes con artritis reumatoide en una institución de atención integral especializada en esta enfermedad en Colombia. Materiales y métodos: Estudio descriptivo de corte transversal, a partir de una cohorte de pacientes de artritis reumatoide, según criterios ACR/EULAR 2010. La información se analizó con base en los datos consolidados de historia clínica y reportes nacionales en el periodo 2015-2018. Se tuvieron en cuenta los registros administrativos relacionados con autorizaciones y prescripciones de medicamentos. Se evaluaron variables sociodemográficas, indicadores de resultado relacionados con el estado de actividad de la enfermedad y porcentaje de uso de medicamentos. Resultados: A 30 de junio de 2018, se identificaron 698 pacientes, de los cuales el 83,8% correspondió a sexo femenino; el promedio general de edad fue de 55,47 años y el grupo de edad de 60 a 64 años concentró el mayor número de casos. El 68,3% se ubicó entre remisión y actividad baja de la enfermedad. El 73,1% se encontró manejado con fármacos antirreumáticos modificadores de enfermedad convencionales y se registró una reducción de uso de terapia biológica desde el 27,2% en 2016 al 17,8% al final del periodo. Conclusiones: Este estudio presenta los resultados de gestión de un modelo de atención integral para pacientes con artritis reumatoide en Colombia, que logró mantener la mayor proporción de pacientes en actividad baja y remisión a medida que estos contaban con mayor tiempo de seguimiento, también logró disminuir el porcentaje de uso de FARME biológicos y establecer los FARME convencionales como la principal alternativa terapéutica.

Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC): The First Reported Case in Brazil Using Standardized Technique with the Capnopen® Nebulizer Device.

BACKGROUND Peritoneal metastasis is a common progression of abdominal-pelvic cancers, and it is associated with poorer oncological prognosis when compared to other metastasis sites. Its treatment has limited results, mainly because of poor bioavailability of chemotherapy within the abdominal cavity after systemic administration. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) has been proposed as a novel method to deliver chemotherapy directly into the peritoneal surface; it combines the effectiveness and response of an intraperitoneal therapy with benefits of a minimally invasive approach. The laparoscopic capnoperitoneum is used to instill chemotherapy particles in a more efficient way for distribution and penetration when compared to peritoneal lavage. In the present study, we describe the first PIPAC performed in Brazil, according to the standard technique previously described with the Capnopen® nebulizer device, as well as technique details based on our literature review. CASE REPORT A 67-year-old man with pancreatic adenocarcinoma metastatic to the liver at first diagnosis underwent systemic treatment with the FOLFIRINOX protocol. After a major clinical response due to systemic treatment, pancreaticoduodenectomy was performed with resection and radiofrequency ablation of hepatic nodules. After 7 months of follow-up, the patient's condition evolved with symptomatic relapse in the peritoneum. Aiming at better control of this site, multiple PIPAC procedures were performed, showing excellent control of the peritoneal cavity disease. The patient had a sustained response in the peritoneal cavity and showed systemic disease progression 6 months after the first PIPAC procedure, which deceased at 20 months after the first PIPAC procedure and 42 months after the primary diagnosis. CONCLUSIONS This report shows that the PIPAC procedure is reproducible elsewhere, with safety and good functional results.

Treatment Satisfaction, Patient Preferences, and the Impact of Suboptimal Disease Control in a Large International Rheumatoid Arthritis Cohort: SENSE Study.

BACKGROUND: Patients' needs and perspectives are important determinants of treatment success in rheumatoid arthritis (RA). Assessing patients' perspectives can help identify unmet needs and enhance the understanding of treatment benefits. OBJECTIVE: The SENSE study assessed the impact of inadequate response to disease-modifying antirheumatic drugs (DMARDs) on treatment satisfaction, disease outcomes, and patient perspectives related to RA disease management. METHODS: SENSE was a noninterventional, cross-sectional study conducted in 18 countries across Europe, Asia, and South America. Adult patients with poorly controlled RA of moderate/high disease activity were eligible. Patient satisfaction was assessed by the Treatment Satisfaction Questionnaire for Medication (TSQM v1.4). Treatment adherence, healthcare resource utilization (HRU), quality of life (QoL), work ability, digital health literacy (DHL), patient preference information, and treatment strategy were also assessed. RESULTS: A total of 1624 patients were included in the study: most were female (84.2%) and middle-aged, and mean disease duration was 10.5 years. Mean TSQM global satisfaction subscore was 60.9, with only 13.5% of patients reporting good treatment satisfaction (TSQM global ≥80). The strongest predictor of good treatment satisfaction was treatment with advanced therapies. Most patients (87.4%) reported good treatment adherence. In general, patients had impaired QoL and work ability, high HRU, and 67.4% had poor DHL. Leading treatment expectations were "general improvement of arthritis" and "less joint pain". Most patients preferred oral RA medications (60.7%) and rapid (≤1 week) onset of action (71.1%). "Increased risk for malignancies" and "increased risk for cardiovascular disease" were the least acceptable side effects. Despite suboptimal control, advanced therapies were only used in a minority of patients, and DMARD switches were planned for only half of the patients. CONCLUSION: Suboptimal disease control negatively impacts treatment satisfaction, work ability, QoL, and HRU. Data collected on patient perspectives may inform shared decision-making and optimize treat-to-target strategies for improving patient outcomes in RA.

SQ109 inhibits proliferation of Leishmania donovani by disruption of intracellular Ca2+ homeostasis, collapsing the mitochondrial electrochemical potential (ΔΨm) and affecting acidocalcisomes.

Leishmania donovani is the causative agent of visceral leishmaniasis. Annually, 500 million new cases of infection are reported mainly in poor communities, decreasing the interest of the pharmaceutical industries. Therefore, the repositioning of new drugs is an ideal strategy to fight against these parasites. SQ109, a compound in phase IIb/III of clinical trials to treat resistant Mycobacterium tuberculosis, has a potent effect against Trypanosoma cruzi, responsible for Chagas' disease, and on Leishmania mexicana, the causative agent of cutaneous and muco-cutaneous leishmaniasis. In the latter, the toxic dose against intramacrophagic amastigotes is very low (IC50 ~ 11 nM). The proposed mechanism of action on L. mexicana involves the disruption of the parasite intracellular Ca2+ homeostasis through the collapse of the mitochondrial electrochemical potential (ΔΨm). In the present work, we show a potent effect of SQ109 on L. donovani, the parasite responsible for visceral leishmaniasis, the more severe and uniquely lethal form of these infections, obtaining a toxic effect on amastigotes inside macrophages even lower to that obtained in L. mexicana (IC50 of 7.17 ± 0.09 nM) and with a selectivity index > 800, even higher than in L. mexicana. We also demonstrated for first time that SQ109, besides collapsing ΔΨm of the parasite, induced a very rapid damage to the parasite acidocalcisomes, essential organelles involved in the bioenergetics and many other important functions, including Ca2+ homeostasis. Both effects of the drug on these organelles generated a dramatic increase in the intracellular Ca2+ concentration, causing parasite death.

Disease activity improvements with optimal discriminatory ability between treatment arms: applicability in early and established rheumatoid arthritis clinical trials.

BACKGROUND: The ACR20 has been validated as the best discriminator of efficacy in placebo-controlled trials, but not in head-to-head trials comparing effective therapies in patients with rheumatoid arthritis (RA). We assessed the most discriminatory ACR response and most discriminatory percent improvement in disease activity measures for Simplified Disease Activity index (SDAI), Clinical Disease Activity index (CDAI), and 28-joint Disease Activity Score based on C-reactive protein (DAS28(CRP)) using different patient populations and trial designs. METHODS: Data from two placebo-controlled studies in established RA and two head-to-head studies in early RA were analyzed. The numeric ACR response for each treatment and P value for the difference between treatments were calculated at multiple time points to determine the ACR response associated with the lowest P value. Similarly, values for percent improvement from baseline in SDAI, CDAI, and DAS28(CRP) with the most discrimination between treatments were examined. RESULTS: In the head-to-head early RA trials, the minimum P value and greatest treatment difference between the active comparator arms at 6 months was achieved at higher ACR rates and greater percent improvements in other disease activity measures. In established RA, lower responses (minimum P value and maximum treatment difference) and smaller improvements in disease activity scores had better discriminatory ability at 6 months. CONCLUSIONS: The most discriminatory ACR response rate and percent improvement in disease activity measures were higher in head-to-head active comparator trials in early RA versus placebo-controlled trials in established RA. This difference should be considered in future clinical trial designs. TRIAL REGISTRATION: NCT00195663, NCT00420927, NCT00195702.

Health Care Cost for Multiple Sclerosis: The Case of a Health Insurer in Colombia.

BACKGROUND: There have been many studies on the cost of multiple sclerosis in countries with high prevalence, whereas in Latin America such analyses are few. Taking into consideration the burden of this disease and the high financial impact of treatment on the health care system, it is necessary to know the behavior of cost of illness. OBJECTIVES: To describe the direct costs associated with health care in patients with multiple sclerosis affiliated with a health insurer in Colombia. METHODS: An analysis of direct costs of disease was performed from the perspective of the third-party payer. A direct measurement from the technical costing "top-down" approach was used. Data were adjusted for inflation and expressed in 2014 US dollars. RESULTS: The average annual cost per patient for the country was $29,339 (2010), $20,956 (2011), $23,892 (2012), $24,148 (2013), and $22,688 (2014). Drug therapy represented 86.1% of the total cost. Between 2010 and 2013, interferons accounted for the largest proportion of the costs of drug treatment (98.5% to 53%), whereas fingolimod showed an increase and accounted for 47% in 2014. CONCLUSIONS: Medications account for the largest proportion of disease costs, with few variations in the last 5 years; nevertheless, the increase in the use of new pharmaceuticals poses a challenge to maintain the financial balance of health insurance.

Cost-Effectiveness of a Care Program for HIV/AIDS Patients Affiliated with a Health Insurer in Colombia, Comparing Three Health Care Providers Nationwide.

BACKGROUND: In Colombia, HIV and AIDS constitute one of the major diseases of high cost to the health system, making necessary health risk management of patients with this disease through comprehensive health care programs with their respective evaluation of results. OBJECTIVE: To evaluate the relative cost-effectiveness of a care program for patients with HIV/AIDS affiliated to a health insurer in Colombia, comparing their results in three Health care provider (HCP). METHODS: The study population corresponded to a cohort of patients older than 18 years with HIV/AIDS and affiliated to a health insurer in Colombia during 2011 and 2012. A cost-effectiveness and cost-utility analysis of a health care program for this population was performed on the basis of a Markov model, in which quality-adjusted life-years (QALYs) and life-years gained were assessed. This analysis was conducted from the insurer perspective. The time horizon was life expectancy. A discount rate of 3% was applied. RESULTS: Drugs accounted for 80.54% of care costs. The average annual cost of patients in health state 5 was 3 times higher than that of patients in state 1. HCP A compared with HCP B generated an additional 1.53 QALYs, with a rate of incremental cost-effectiveness of $2400 per QALY gained. HCP C showed a dominated behavior. The variables that most influence the uncertainty were the cost of HCP A in health state 5 (55.52%) and the cost of HCP B in state 3 (27.51%). CONCLUSIONS: HCP A is a very cost-effective option considering a threshold of 1 time the per-capita gross domestic product.

[Urology training in Mexico: Residents' perspective]. / Entrenamiento de urología en México: Perspectiva del residente.

OBJECTIVE: To assess and identify from the resident's perspective the current state of the urology residency training in the surgical, research, affective domain and its working future. MATERIAL AND METHODS: We performed an anonymous survey of 98 urology residents during 2014. The survey included 62 questions and assesses the surgical, the clinical research, and the affective domain, and also its working future. RESULTS: We reviewed a total of 98 surveys, average age 29 years, 92% men and 8% women. The scholarship average was 12,000-14,000 pesos. Most of them have had at least one research work in a national congress, but not in an international one. Less than 10% has published papers in PubMed, although most consider clinical research as mandatory in their urology training programs. Most residents consider their training in laparoscopy to be inadequate, but they consider the relationship between partners and teachers is adequate and most of them are satisfied with their program.

The Psychological Impact of Prostate Biopsy: Anxiety and Depression Associated with a Positive Biopsy Result.

INTRODUCTION: We evaluated the psychological impact on patients caused by transrectal prostate biopsy and the emotional stress in those with a positive prostate cancer finding. METHODS: We performed a psychological evaluation of 328 men who underwent transrectal prostate biopsy using HADS (Hospital Anxiety and Depression Scale) at 3 time points. In addition we analyzed events related to the procedure, compared anxiety and depression levels in men with a negative result vs those diagnosed with prostate cancer, and evaluated anxiety and depression associated with events related to the procedure. RESULTS: Of the 328 men 99.08% completed the evaluation, including 51.2% with a biopsy positive for prostate cancer and 48.8% with a negative prostate cancer result. The group with a positive biopsy scored an average of 6.85 in the anxiety category and 3.48 for depressive symptoms with a 2.02 point difference in respect to the original evaluation (p = 0.01). Prostate cancer with prostate specific antigen greater than 20 ng/ml was associated with significant anxiety (p = 0.03). CONCLUSIONS: Biopsy positive for prostate cancer with prostate specific antigen greater than 20 ng/ml is associated with significant anxiety. However, events related to the procedure and marital status are not associated with significant anxiety.

Prevalencia del cáncer en una aseguradora en salud en Colombia, 2013 / Cancer prevalence in a health insurance organization in Colombia, 2013

Resumen Introducción: El cáncer es una de las principales causas de muerte no violenta en el mundo, se calcula que anualmente se presentan más de 11 millones de casos nuevos, de los cuales 80% se presentan en países en vías de desarrollo. Objetivo: Conocer la prevalencia del cáncer en una población afiliada a una aseguradora en salud en Colombia. Materiales y métodos: Se realizó un estudio descriptivo de corte transversal en una cohorte de 11.500 pacientes con cáncer de una aseguradora en salud, identificados a partir de los sistemas de información de la compañía, durante los años 2010 a 2013, se analizaron los datos a través de frecuencias, tasas y razón de prevalencias. Resultados: La prevalencia general de cáncer fue de 543 por 100.000 afiliados. La mayor proporción de los casos (67%) se presentaron en mayores de 50 años. Las ciudades con mayor prevalencia fueron Manizales, Cali, Pereira y Neiva. Los tipos de cáncer más prevalentes fueron mama, otros sólidos, próstata, piel y tiroides. La prevalencia de cáncer infantil fue de 65 por 100.000 menores de 18 años afiliados. Las leucemias linfoides agudas, los tumores malignos cerebrales y los linfomas fueron las neoplasias más frecuentes en la población infantil. Conclusiones: Este es el primer estudio de prevalencia de cáncer en una población asegurada en Colombia, con lo cual se establece una herramienta que permite planear servicios, proporcionar estrategias de tamización, auditoría y evaluación de resultados en un contexto de aseguramiento y gestión del riesgo en salud.

Introduction: Cancer is one of the leading causes of non-violent death in the world. An estimated eleven million new cases occur worldwide every year, of which 80% occurred in developing countries. Objective: To determine the prevalence of cancer in a population affiliated to a health care insurance organization in Colombia. Materials and Methods: A descriptive cross-sectional study was conducted on a cohort of 11,500 patients with cancer affiliated to a health care organization. The patients were identified from the information systems of the company, during the years 2010-2013. Data were analysed using frequencies, rates, and prevalence ratio. Results: The overall prevalence of cancer was 543 per 100,000 members. The largest proportion of cases (67%) occurred in patients older than 50 years. The cities with the highest prevalence were Manizales, Cali, Pereira and Neiva. The most prevalent cancer types were breast, other solid tumours, prostate, skin, and thyroid. The prevalence of childhood cancer was 65 per 100,000 members under 18 years. Acute lymphoid leukaemia, malignant brain tumours, and lymphomas were the most common malignancies in children. Conclusions: This is the first study of the prevalence of cancer in an insured population in Colombia, becoming a tool for planning services, provide screening strategies, auditing and evaluation of results in the context of health insurance and risk management.

Abiraterone acetate and castration resistant ductal adenocarcinoma of the prostate.

Ductal adenocarcinoma of the prostate is a rare histological variant that only represents <1% of prostate tumors. This histological variant has several important clinical implications with respect to their evolution, clinical prognosis, and treatment. We report the case of a 64-year-old patient with ductal adenocarcinoma of the prostate, which progresses to castration-resistant prostate cancer, that was treated with abiraterone acetate with good clinical response, to our knowledge, the first case of ductal adenocarcinoma of the prostate in treatment with abiraterone acetate.

Protection of Spanish Ibex (Capra pyrenaica) against Bluetongue virus serotypes 1 and 8 in a subclinical experimental infection.

Many wild ruminants such as Spanish ibex (Capra pyrenaica) are susceptible to Bluetongue virus (BTV) infection, which causes disease mainly in domestic sheep and cattle. Outbreaks involving either BTV serotypes 1 (BTV-1) and 8 (BTV-8) are currently challenging Europe. Inclusion of wildlife vaccination among BTV control measures should be considered in certain species. In the present study, four out of fifteen seronegative Spanish ibexes were immunized with a single dose of inactivated vaccine against BTV-1, four against BTV-8 and seven ibexes were non vaccinated controls. Seven ibexes (four vaccinated and three controls) were inoculated with each BTV serotype. Antibody and IFN-gamma responses were evaluated until 28 days after inoculation (dpi). The vaccinated ibexes showed significant (P<0.05) neutralizing antibody levels after vaccination compared to non vaccinated ibexes. The non vaccinated ibexes remained seronegative until challenge and showed neutralizing antibodies from 7 dpi. BTV RNA was detected in the blood of non vaccinated ibexes from 2 to the end of the study (28 dpi) and in target tissue samples obtained at necropsy (8 and 28 dpi). BTV-1 was successfully isolated on cell culture from blood and target tissues of non vaccinated ibexes. Clinical signs were unapparent and no gross lesions were found at necropsy. Our results show for the first time that Spanish ibex is susceptible and asymptomatic to BTV infection and also that a single dose of vaccine prevents viraemia against BTV-1 and BTV-8 replication.

Characterization of homologous and heterologous adaptive immune responses in porcine reproductive and respiratory syndrome virus infection.

The present study characterized the homologous and heterologous immune response in type-I porcine reproductive and respiratory syndrome virus (PRRSV) infection. Two experiments were conducted: in experiment 1, eight pigs were inoculated with PRRSV strain 3262 and 84 days post-inoculation (dpi) they were challenged with either strain 3262 or strain 3267 and followed for the next 14 days (98 dpi). In experiment 2, eight pigs were inoculated with strain 3267 and challenged at 84 dpi as above. Clinical course, viremia, humoral response (neutralizing and non-neutralizing antibodies, NA) and virus-specific IFN-γ responses (ELISPOT) were evaluated all throughout the study. Serum levels of IL-1, IL-6, IL-8, TNF-α and TGF-ß were determined (ELISA) after the second challenge. In experiment 1 primo-inoculation with strain 3262 induced viremia of ≤ 28 days, low titres of homologous NA but strong IFN-γ responses. In contrast, strain 3267 induced longer viremias (up to 56 days), higher NA titres (≤ 6 log2) and lower IFN-γ responses. Inoculation with 3267 produced higher serum IL-8 levels. After the re-challenge at 84 dpi, pigs in experiment 1 developed mostly a one week viremia regardless of the strain used. In experiment 2, neither the homologous nor the heterologous challenge resulted in detectable viremia although PRRSV was present in tonsils of some animals. Homologous re-inoculation with 3267 produced elevated TGF-ß levels in serum for 7-14 days but this did not occur with the heterologous re-inoculation. In conclusion, inoculation with different PRRSV strains result in different virological and immunological outcomes and in different degrees of homologous and heterologous protection.

Recuperación del genoma del padre recurrente en un programa de retrocruzas asistido por marcadores en arroz / Recurrent parent genome recovery in a marker assisted backcross breeding program in rice

La piricularia (Pyricularia grisea (Cooke) Sacc.) es una de las enfermedades más destructivas del arroz a nivel mundial. El uso de cultivares resistentes es la vía más efectiva y económica de controlar la enfermedad. El método de la retrocruza es el más empleado para la incorporación de genes simples de resistencia. Sin embargo, el proceso se dificulta cuando existe ligamiento de estos genes con características indeseables, el cual puede ser difícil de romper, aún después de muchas generaciones de retrocruzas. La selección asistida por marcadores (SAM) contribuye a facilitar la recuperación del genoma del padre recurrente (PR) en un menor número de generaciones. El objetivo del presente estudio fue la recuperación del genoma del PR utilizando marcadores moleculares en generaciones tempranas de un programa de retrocruzas para la incorporación de un gen de resistencia a P. grisea. En los parentales se evaluaron 36 microsatélites ubicados en los 12 cromosomas del arroz; aquellos que mostraron polimorfismo se evaluaron en plantas de las generaciones RC2F2 y RC3F1. La SAM permitió identificar plantas 100 por ciento similares al PR para los loci evaluados en ambas generaciones de retrocruzas; sin embargo, la proporción fue mayor en la RC3F1 que en RC2F2. Se identificaron regiones cromosómicas candidatas en los cromosomas 4 y 7 para la futura identificación del gen de resistencia incorporado. La aplicación de SAM en el programa de retrocruzas permitió la recuperación del genoma del PR en pocas generaciones, reduciendo el tiempo necesario en el proceso de mejoramiento para incorporar resistencia a piricularia

Enteroparasitosis: estudio prospectivo / Enteroparasitosis: prospectivo study

Analiza que la enteroparasitosis constituye un problema de salud pública a nivel mundial, especialmente en países de bajo nivel social y económico. Sin embargo, es solucionable con la implementación de medidas de salud entre las cuales, por su importancia se destacan la dotación de agua potable, sistemas de alcantarillado y la implementación de programas educativos a nivel poblacional. El presente trabajo analiza en forma prospectiva con un universo de 100 sujetos atendidos en el Hospital Francisco de Orellana, mediante la aplicación de una encuesta que pone en evidencia las costumbres de los habitantes y las deficiencias de servicios básicos como factores de riesgo para enfermedades parasitarias.

Causas del parto prematuro

El presente es un estudio prospectivo, realizado en el hospital Gineco-Obstetrico- Isidro Ayora, entre diciembre de 1991 y julio de 1992. Con el Objeto de establecer las causas principales del parto prematuro. Durante este lapso se presentaron 7269 partos, de los cuales 200 fueron partos prematuros, equivalente al 275 por ciento. Entre las causas más importante se encontraron, la rotura prematura de membranas, hipetension inducida por el embarazo, infección de vías urinarias, embarazo múltiple, hemorragias del tercer trimestre y otras causas.

Esofagitis por reflujo: criterios clinicos quirurgicos

Presentamos una revisión bibliográfica sobre esofgitis por reflujo a la que se designa todos aquellos procesos inflamatorios agudos o crónicos que afectan la mucosa esofágica de etiología multifactorial, fundamentalmente por fallas de la barrera antirreflujo, aclaramiento esofágico, etc. Se analiza los múltiples test diagnosticos destacando la endoscopia, la monitorización ph en 24h. Discutimos el tratamiento que va, desde, medidas generales, bloqueadores H2, Omeprazol. Se hace hincapie en las diferentes opciones quirurgicas utilizadas fundamentalmente para sus complicaciones.