Disponibilidad y distribución de los recursos de hemostasia y trombosis en Argentina en el año 2022 / Availability and distribution of hemostasis and thrombosis resources in Argentina in 2022

Resumen Introducción. En Argentina la información sobre la disponibilidad de los recursos en hemostasia y trombosis es muy escasa. El grupo Promoción del Acceso a los Recursos del grupo CAHT (Cooperativo Argentino de Hemostasia y Trombosis) desarrolló un amplio relevamiento de los recursos en Argentina para conocer el estado de situación de la especialidad. Objetivos. Describir la disponibilidad de los recursos humanos y físicos (diagnósticos y terapéuticos) en hemostasia y trombosis en los centros asistenciales de Argentina en 2022 e identificar diferencias regionales y/o entre los sectores privado y público. Materiales y métodos. Estudio de cohorte transversal. Se incluyeron centros asistenciales de la República Argentina: instituciones con internación, centros ambulatorios y laboratorios. Se obtuvieron datos respecto a la disponibilidad de recursos humanos, diagnósticos, y terapéuticos en hemostasia y trombosis, en algún momento del año 2022, mediante una encuesta a profesionales de la salud. En los recursos analíticos se definió disponibilidad cuando la prueba se realizaba en la institución o se derivaba la muestra/paciente. Resultados. En el estudio se incluyeron 215 centros de 77 ciudades argentinas. El 85,5% de los centros contaban con internación. La mediana de especialistas en hematología por institución fue de 3 (RIC 1-5). Se encontraron diferencias entre las medianas de las regiones: CABA-Ciudad Autónoma de Buenos Aires-(5), Centro/Cuyo (3,5) GBA/LP-Gran Buenos Aires/La Plata-(2), NOA-Noroeste Argentino-(2), NEA-Nordeste Argentino-(1) y SUR (1). El 27% de los centros contaban con 1 ("trabajo solitario") o ningún especialista en hematología. El 59% de los centros reportaron que contaban con bioquímicos especialistas en hemostasia/hematología. La región con menor porcentaje de centros con especialistas fue GBA/LP (37%). Se observó una alta disponibilidad de pruebas básicas de la coagulación. Por el contrario, en las estudios de mayor complejidad la disponibilidad fue subóptima y se detectaron marcadas asimetrías regionales (GBA/LP, NOA y NEA presentaron la menor proporción de centros con los recursos). Algunas pruebas, como la agregación plaquetaria o el anti-factor plaquetario 4 / heparina (anti-PF4/hep), no estuvieron disponibles en amplias áreas del país. En la mayoría de los recursos terapéuticos se detectó una mayor disponibilidad en el sector privado. Conclusiones. Detectamos una disponibilidad sub-óptima de los recursos físicos de alta complejidad y disparidades público-privada y regionales. Consideramos que el establecimiento de redes integradas es una estrategia que permitirá reducir las inequidades de acceso. Desde su lugar, las sociedades científicas podrían realizar valiosos aportes para obtener esa meta.

Abstract Introduction. In Argentina, information regarding the availability of resources in hemostasis and thrombosis is very scarce. The "Grupo Promoción del Acceso" del grupo CAHT (Cooperativo Argentino de Hemostasia y trombosis) conducted an extensive survey of resources in Argentina to understand the current state of the specialty. Objectives. To describe the availability of human and physical resources (diagnostic and therapeutic) in hemostasis and thrombosis in healthcare centers across Argentina in 2022 and to identify regional differences or disparities between the private and public sectors. Materials and methods. Cross-sectional cohort study. Healthcare centers from the Argentine Republic were included: institutions with inpatient services, outpatient centers, and laboratories. Data regarding the availability of human, diagnostic, and therapeutic resources in hemostasis and thrombosis were obtained at some point during the year 2022 through surveys conducted among healthcare professionals. Availability in analytical resources was defined when the test was performed within the institution or when the sample/patient was referred elsewhere for testing. Results. The study included 215 centers from 77 cities across Argentina. 85.5% of the centers had inpatient services. The median number of hematologists per institution was 3 (IQR 1-5). Differences were found among the median numbers across regions: CABA-Ciudad Autónoma de Buenos Aires-(5), Centro/Cuyo (3.5), GBA/LP-Gran Buenos Aires/La Plata-(2), NOA-Noroeste Argentino-(2), NEA-Nordeste Argentino-(1), and SUR (1). 27% of the centers had 1 or no hematologist. 59% of the centers reported employing specialized biochemists in hemostasis/ hematology. The region with the lowest percentage of centers with specialists was GBA/LP (37%). There was a high availability of basic coagulation tests observed. Conversely, for more complex tests, availability was suboptimal and marked regional asymmetries were detected (GBA/LP, NOA, and NEA presented the lowest proportion of centers with resources). Some tests, such as platelet aggregation or anti-platelet factor 4/heparin, were not available in wide areas of the country. In most therapeutic resources, greater availability was detected in the private sector. Conclusions. We identified suboptimal availability of high-complexity physical resources and public-private and regional disparities. We believe that the establishment of integrated networks is a strategy that will help reduce access inequities. Scientific societies, from their position, can make valuable contributions to achieve this goal.

Analysis of mismatch repair (MMR) proteins expression in a series of malignant pleural mesothelioma (MPM) patients.

BACKGROUND: Promising results have been reported with immune checkpoint inhibitors (ICI) in a small proportion of MPM patients. MMR deficiency (dMMR) has been well described in several malignancies and was approved as a biomarker for anti-PD-1 inhibitors. Next generation sequencing (NGS) data demonstrated that 2% of MPM harbor microsatellite instability. The aim of this study is to characterize MMR by immunohistochemistry (IHC) in a series of MPM including a subset of patients treated with immunotherapy. METHODS: Tumors of 159 MPM p diagnosed between 2002 and 2017 were reviewed. Formalin-fixed, paraffin-embedded tissue was stained for MLH1, MSH2, MSH6 and PMS2 and tumors were classified as dMMR (MMR protein expression negative) and MMR intact (all MMR proteins positively expressed). We retrospectively collected clinical outcomes under standard chemotherapy and experimental immunotherapy in the entire cohort. RESULTS: MMR protein expression was analyzed in 158 samples with enough tissue and was positive in all of the cases. Twenty two patients received ICI with anti-CTLA4 or anti-PD-1 blockade in clinical trials, 58% had a response or stable disease for more than 6 m, with median progression-free survival (PFS) of 5.7 m (2.1-26.1 m). The median overall survival (mOS) in all population was 15 months (m) (13.5-18.8 m). In a multivariable model factors associated to improved mOS were PS 0, neutrophil-lymphocyte ratio (NLR) < 5 and epithelioid histology (p < 0.001). CONCLUSIONS: In our series we were unable to identify any MPM patient with dMMR by IHC. Further studies are needed to elucidate potential predictive biomarkers of ICI benefit in MPM.

Thin-layer voltammetry of soluble species on screen-printed electrodes: proof of concept.

Thin-layer diffusion conditions were accomplished on screen-printed electrodes by placing a controlled-weight onto the cast solution and allowing for its natural spreading. The restricted diffusive conditions were assessed by cyclic voltammetry at low voltage scan rates and electrochemical impedance spectroscopy. The relationship between the weight exerted over the drop and the thin-layer thickness achieved was determined, in such a way that the simple experimental set-up designed for this work could be developed into a commercial device with variable control of the thin-layer conditions. The experimental results obtained resemble those reported for the voltammetric features of electroactive soluble species employing electrodes modified with carbon nanotubes or graphene layers, suggesting that the attainment of the benefits reported for these nanomaterials could be done simply by forcing the solution to spread over the screen-printed electrodic system to form a thin layer solution. The advantages of thin-layer voltammetry in the kinetic characterization of quasi-reversible and irreversible processes are highlighted.

Obesity and eating behaviour in a three-generation Chilean family with carriers of the Thrl50Ile mutation in the melanocortin-4 receptor gene.

It has been proposed that functional mutations in the melanocortin 4 receptor (MC4R) gene have an important impact in body mass index, being considered as a major susceptibility gene for obesity. A number of mutations have been reported in the MC4R gene in subjects from different countries and ethnic groups. However, no reports of MC4R mutations are have been published for South American populations. In this study, DNA samples of thirty-two unrelated obese women of Chilean origin were examined to search for genetic variants in the single exon of the gene through the use of single strand conformational polymorphism techniques and direct sequencing, leading to the identification of a Thr150Ile mutation in heterozygous status. The evaluation of family relatives of the index case for this mutation using PCR-RFLP analysis, identified two additional carriers in a three-generation family. Obesity, eating behavior and body composition phenotypes in this family revealed a possible relation of this variant with obesity in the presence of reduced penetrance. According to our knowledge, this is the first report of MC4R mutations in South American populations.

Random delays and the synchronization of chaotic maps.

We investigate the dynamics of an array of chaotic logistic maps coupled with random delay times. We report that for adequate coupling strength the array is able to synchronize, in spite of the random delays. Specifically, we find that the synchronized state is a homogeneous steady state, where the chaotic dynamics of the individual maps is suppressed. This synchronization behavior is largely independent of the connection topology and depends mainly on the average number of links per node. We carry out a statistical linear stability analysis that confirms the numerical results and provides a better understanding of the nontrivial roles of random delayed interactions.

Delay-induced synchronization phenomena in an array of globally coupled logistic maps.

We study the synchronization of a linear array of globally coupled identical logistic maps. We consider a time-delayed coupling that takes into account the finite velocity of propagation of the interactions. We find globally synchronized states in which the elements of the array evolve along a periodic orbit of the uncoupled map, while the spatial correlation along the array is such that an individual map sees all other maps in his present, current, state. For values of the nonlinear parameter such that the uncoupled maps are chaotic, time-delayed mutual coupling suppresses the chaotic behavior by stabilizing a periodic orbit that is unstable for the uncoupled maps. The stability analysis of the synchronized state allows us to calculate the range of the coupling strength in which global synchronization can be obtained.

Association between prematurity and maternal anemia in Venezuelan pregnant women during third trimester at labor.

To determine the association and its magnitude between prematurity and anemia in women in their third trimester of pregnancy and at labor. An incident case-control study was conducted using 2 controls per case. Data was obtained in a tertiary hospital in Valencia, Venezuela. A total of 543 women who delivered between May and December 1996 entered into the study. Women having a preterm delivery, less than 37 weeks of gestation at delivery, were defined as cases (n = 181). Anemia was defined according to WHO as Hb less than 11 g/dL. Logistic regression was used to analyze the data and likelihood ratio test was done for model comparison. Maternal anemia was found to be significantly associated with prematurity (Odds Ratio: 1.70; 95% CI = 1.18 to 2.57 P = .001), after adjusting for Placental Abruption, PROM, Previous Premature Labor, Prenatal Care Visits, and Uterine Bleeding during more than one trimester. Maternal anemia at the end of the third trimester of pregnancy, at labor, was associated with an increased risk of prematurity.

Surveillance of arbovirus infections in the Atlantic Forest Region, State of São Paulo, Brazil. I. Detection of hemagglutination-inhibiting antibodies in wild birds between 1978 and 1990.

We report data related to arbovirus antibodies detected in wild birds periodically captured from January 1978 to December 1990 in the counties of Salesópolis (Casa Grande Station), Itapetininga and Ribeira Valley, considering the different capture environments. Plasmas were examined using hemagglutination-inhibition (HI) tests. Only monotypic reactions were considered, except for two heterotypic reactions in which a significant difference in titer was observed for a determined virus of the same antigenic group. Among a total of 39,911 birds, 269 birds (0.7%) belonging to 66 species and 22 families were found to have a monotypic reaction for Eastern equine encephalitis (EEE), Venezuelan equine encephalitis (VEE), Western equine encephalitis (WEE), Ilheus (ILH), Rocio (ROC), St. Louis encephalitis (SLE), SP An 71686, or Caraparu (CAR) viruses. Analysis of the data provided information of epidemiologic interest with respect to these agents. Birds with positive serology were distributed among different habitats, with a predominance of unforested habitats. The greatest diversity of positive reactions was observed among species which concentrate in culture fields.

Controlled release of theophylline from inert matrices: effect of channeling material on release rate.

Sustained release theophylline tablets containing stearic acid wax and lactose fast flo as chanelling agent were prepared and evaluated. The fusion technique was used for dispersing the drug in the different levels of stearic acid. The release rate of theophylline from the prepared tablets increased with the increase of the level of the channeling material in the formula. The drug release from tablets containing high level of wax (30 and 60%) and low level of channeling material (59% and 29%) followed the diffusion controlled model for inert porous matrix. The drug release increased significantly with the increase of lactose fast flow level in the formula. After 2 hours of testing dissolution, the tablets start to erode and the mechanism of drug release deviate from the diffusion controlled model. The mechanism of drug release was dependent on the level of the channeling material in the matrix.

Sustained release phenylpropanolamine hydrochloride from ATO 888 matrix.

Sustained release phenylpropanolamine HCl tablets were prepared with compritol as a retardant material. The effects of varying wax levels and methods of matrix formation on drug release were investigated. Also the compaction profiles were recorded for all formulations. The amount of drug in the formula was held constant (10% w/w), while the wax level was varied from 10% to 50% w/w. Two methods were used for the preparation of drug: wax systems; physical mixture and solid dispersion. The drug release from tablets containing 10% Compritol and prepared by solid dispersion was 97% after six hours of testing dissolution. Tablets prepared with 30% wax released 72% of the drug, while tablets containing 50% wax released only 30% of the drug after six hours. Tablets prepared by physical mixture gave higher drug release than tablets prepared by solid dispersion method. The incorporation of Compritol decreased the ejection forces of tablets during compaction. The drug release from tablets prepared by solid dispersion followed the diffusion controlled model described by Higuchi for inert porous matrix.

Physicochemical characterization of acetaminophen-ethylcellulose solid dispersion.

In this study, ethylcellulose was evaluated as a carrier for the preparation of sustained release of acetaminophen via solid dispersion technique. Physical mixture at the same level of acetaminophen and ethylcellulose was prepared. Differential scanning calorimetry and scanning electron microscope were used to characterize the physical properties of the various systems and to determine if there is possible interaction between acetaminophen and ethylcellulose.

Sustained release phenylpropanolamine hydrochloride from ATO 888 matrix

Sustained release phenylpropanolamine HCl tablets were prepared with compritol as a retardant material. The effects of varying wax levels and methods of matrix formation on drug release were investigated. Also the compaction profiles were recorded for all formulations. The amount of drug in the formula was held constant (10 per cent w/w), while the wax level was varied from 10 per cent to 50 per cent w/w. Two methods were used for the preparation of drug: wax systems; physical mixture and solid dispersion. The drug release from tablets containing 10 per cent Compritol and prepared by solid dispersion was 97 per cent after six hours of testing dissolution. Tablets prepared with 30 per cent wax released 72 per cent of the drug, while tablets containing 50 per cent wax released only 30 per cent of the drug after six hours. Tablets prepared by physical mixture gave higher drug release than tablets prepared by solid dispersion method. The incorporation of Compritol decreased the ejection forces of tablets during compaction. The drug release from tablets prepared by solid dispersion followed the diffusion controlled model described by Higuchi for inert porous matrix

Physicochemical characterization of acetaminophen-ethylcellulose solid dispersion

In this study, ethylcellulose was evaluated as a carrier for the preparation of sustained release of acetaminophen via solid dispersion technique. Physical mixture at the same level of acetaminophen and ethylcellulose was prepared. Differential scanning calorimetry and scanning electron microscope were used to characterize the physical properties of the various systems and to determine if there is possible interaction between acetaminophen and ethylcellulose

[Report about drug interactions in a hospital emergency department]. / Consecuencias de un reporte sobre interacciones medicamentosas en una emergencia hospitalaria.

In 1991, we report drug interactions found through the review of 100 clinical charts of an Emergency Department. Two years later we evaluated again the medical indications done at the same Emergency. There were no differences related to sex, age and number of drug administrated by patient when compared with the former group. There was, however, a significant decrease in the percentage of interactions and those important ones. Also, in the average of interactions and those important ones by patient. Among more used drug, antacid occupied a a second place with 36% and Ranitidine the ninth place with 16%. Cimetidine disappeared among the first ten medications. In those cases where antacid or Ranitidine were indicated, there were interactions in 54% and 25%, respectively, but these interactions were not significant. The results of this new analysis point out a significant decrease of drug interactions, showing that continuing education allows indicate the most adequate therapy to each patient.

Ethylcellulose as a carrier for controlled-release acetaminophen tablets.

In this study ethylcellulose was evaluated as a carrier for preparation of prolonged release acetaminophen tablets. Solid dispersions containing three levels of ethylcellulose and acetaminophen (1:3; 1:1; 3:1) were prepared by the solvent method. Also physical mixtures at the same level of ethylcellulose and acetaminophen were prepared. Systems composed of solid dispersion or physical mixture containing the equivalent weight of 50 mg acetaminophen, Emcompress as diluent and 1% magnesium stearate as lubricant were compressed into tablets and tested for dissolution. The dissolution data showed that the drug release decreased as the level of ethylcellulose increased in the solid dispersion formulations. The drug release from tablets prepared with solid dispersion followed the diffusion controlled model for inert porous matrix, while the drug release from tablets prepared with physical mixture followed the first-order kinetic model.

Ethylcellulose as a carrier for controlled-release acetaminophen tablets

In this study ethylcellulose was evaluated as a carrier for preparation of prolonged release acetaminophen tablets. Solid dispersions containing three levels of ethylcellulose and acetaminophen (1:3; 1:1; 3:1) were prepared by the solvent method. Also physical mixtures at the same level of ethylcellulose and acetaminophen were prepared. Systems composed of solid dispersion or physical mixture containing the equivalent weight of 50 mg acetaminophen, Emcompress as diluent and 1 per cent magnesium stearate as lubricant were compressed into tablets and tested for dissolution. The dissolution data showed that the drug release decreased as the level of ethylcellulose increased in the solid dispersion formulations. The drug release from tablets prepared with solid dispersion followed the diffusion controlled model for inert porous matrix, while the drug release from tablets prepared with physical mixture followed the first-order kinetic model

[Main drug interactions at a hospital emergency department. Analysis of 100 cases]. / Principales interacciones medicamentosas en una emergencia hospitalaria. Analysis de 100 casos.

We prospectively reviewed clinical charts of 100 consecutive patients that were admitted during the first trimester 1991 to the Emergency Department of a general hospital in order to determine the more frequent prescribed drugs and their interactions using a computer program (Drug Interaction Program), emphasizing in those drugs used to treat peptic ulcers. Number of drugs prescribed to each patient was 4.20 +/- 1.39. Antacids (39%) and cimetidine (35%) occupied the third and fourth place. There were interactions in 79 patients and in 66 of them (84%) they were important. Antacid and cimetidine were similarly prescribed, but of 35 patients who received cimetidine only 3 (8.5%) had a primary indication for its use (Gastrointestinal bleeding). Significant clinical interactions of cimetidine with other medications are analyzed. Our results indicate that drug interactions are a permanent risk in our hospitals. We suggest to use a computer program on drug interactions or an updated chart of medications in the emergency rooms of our hospitals.