Eventos adversos a medicamentos en los servicios de Medicina Interna del Hospital de Caldas

Para establecer la frecuencia de eventos adversosa medicamentos en el servicio de Medicina Internase llevó a cabo un estudio descriptivo de casos, recolectando la información a través del reporteespontáneo del evento adverso por parte de losmédicos, los residentes y las enfermeras. En unperíodo de 4 meses (Enero a Abril de 1998) fueronreportados 29 eventos adversos quecomprometieron al 7% de los pacientes queegresaron del servicio. El 62.6% de los pacienteseran menores de 65 años y la mayoría de sexomasculino. Los eventos adversos reportados conmayor frecuencia fueron los trastornoselectrolíticos (hipokalemia) en el 44.8% de loscasos, seguidos por manifestaciones en piel(20,7%), hematológicas (10,3%),gastrointestinales (6.9%) y cardiovasculares(6.9%). El medicamento más implicado en loseventos adversos fue furosemida con un 27,6%, lesiguieron en frecuencia antibióticos con el 24.1%,antiagregantes plaquetarios y anticoagulantes conel 13.8% y antihipertensivos con un 10.3%. Lasindicaciones más frecuentes para el uso de losmedicamentos fueron las enfermedadescardiovasculares y las infecciones. A diferenciade otros estudios, los trastornos electrolíticos comoefectos adversos, aparecen con mucha frecuencialo cual sugirió revisar el uso de los diuréticos conespecial énfasis en los pacientes ancianos ycontinuar con la recolección de eventos adversospara poder establecer un programa defarmacovigilancia

Eventos adversos a medicamentos en los servicios de Medicina Interna del Hospital de Caldas

Para establecer la frecuencia de eventos adversosa medicamentos en el servicio de Medicina Internase llevó a cabo un estudio descriptivo de casos, recolectando la información a través del reporteespontáneo del evento adverso por parte de losmédicos, los residentes y las enfermeras. En unperíodo de 4 meses (Enero a Abril de 1998) fueronreportados 29 eventos adversos quecomprometieron al 7% de los pacientes queegresaron del servicio. El 62.6% de los pacienteseran menores de 65 años y la mayoría de sexomasculino. Los eventos adversos reportados conmayor frecuencia fueron los trastornoselectrolíticos (hipokalemia) en el 44.8% de loscasos, seguidos por manifestaciones en piel(20,7%), hematológicas (10,3%),gastrointestinales (6.9%) y cardiovasculares(6.9%). El medicamento más implicado en loseventos adversos fue furosemida con un 27,6%, lesiguieron en frecuencia antibióticos con el 24.1%,antiagregantes plaquetarios y anticoagulantes conel 13.8% y antihipertensivos con un 10.3%. Lasindicaciones más frecuentes para el uso de losmedicamentos fueron las enfermedadescardiovasculares y las infecciones. A diferenciade otros estudios, los trastornos electrolíticos comoefectos adversos, aparecen con mucha frecuencialo cual sugirió revisar el uso de los diuréticos conespecial énfasis en los pacientes ancianos ycontinuar con la recolección de eventos adversospara poder establecer un programa defarmacovigilancia

UV-R mitigation strategies in encapsulated embryos of the intertidal gastropod Acanthina monodon: A way to compensate for lack of parental care

Intracapsular embryonic development in the intertidal zone exposes embryos to various stress sources characteristic of this environment, including UV-R. They require defensive mechanisms to mitigate its adverse effects. The presence of total carotenoids (TC), and mycosporine-like amino acids (MAAs) was studied in adults, in encapsulated embryos, and in the egg capsule walls of the intertidal gastropod Acanthina monodon. Oxygen consumption rates (OCR) were determined in encapsulated and excapsulated embryos exposed to photosynthetically active radiation (PAR) and PAR + UV-A + UV-B to understand if the capsule wall is a protective structure for encapsulated embryos. The results showed the presence of TC in adult pedal and gonad tissues, and in all encapsulated stages. MAAs were not detected. The physical structure of the capsule wall retained most wavelengths, being particularly efficient in the UV-B range. Excapsulated embryos exposed to PAR + UV-A + UV-B radiation increased its OCR compared to encapsulated embryos, indicating the protective character of the capsule wall.Fil: Cubillos, Victor M.. Universidad Austral de Chile; ChileFil: Salas Yanquin, Luis P.. Universidad Austral de Chile; ChileFil: Buchner Miranda, Joseline. Universidad Austral de Chile; ChileFil: Ramirez, Felipe. Universidad Austral de Chile; ChileFil: Zabala, Maria Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto de Biología de Organismos Marinos; ArgentinaFil: Averbuj, Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto de Biología de Organismos Marinos; ArgentinaFil: Marquez, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto de Biología de Organismos Marinos; Argentina. Universidad Nacional de la Patagonia. Facultad de Ciencias Naturales. Sede Puerto Madryn; ArgentinaFil: Jaramillo, Hans. Universidad Austral de Chile; ChileFil: Chaparro, Oscar R.. Universidad Austral de Chile; Chil

Physical activity and sedentary behavior patterns and sociodemographic correlates in 116,982 adults from six South American countries: the South American physical activity and sedentary behavior network (SAPASEN).

BACKGROUND: Physical inactivity and sedentary behavior are major concerns for public health. Although global initiatives have been successful in monitoring physical activity (PA) worldwide, there is no systematic action for the monitoring of correlates of these behaviors, especially in low- and middle-income countries. Here we describe the prevalence and distribution of PA domains and sitting time in population sub-groups of six south American countries. METHODS: Data from the South American Physical Activity and Sedentary Behavior Network (SAPASEN) were used, which includes representative data from Argentina (n = 26,932), Brazil (n = 52,490), Chile (n = 3719), Ecuador (n = 19,851), Peru (n = 8820), and Suriname (n = 5170). Self-reported leisure time (≥150 min/week), (≥150 min/week), transport (≥10 min/week), and occupational PA total (≥10 min/week), as well as sitting time (≥4 h/day) were captured in each national survey. Sex, age, income, and educational status were exposures. Descriptive statistics and harmonized random effect meta-analyses were conducted. RESULTS: The prevalence of PA during leisure (Argentina: 29.2% to Peru: 8.6%), transport (Peru: 69.7% to Ecuador: 8.8%), and occupation (Chile: 60.4 to Brazil 18.3%), and ≥4 h/day of sitting time (Peru: 78.8% to Brazil: 14.8%) differed widely between countries. Moreover, total PA ranged between 60.4% (Brazil) and 82.9% (Chile) among men, and between 49.4% (Ecuador) and 74.9% (Chile) among women. Women (low leisure and occupational PA) and those with a higher educational level (low transportation and occupational PA as well as high sitting time) were less active. Concerning total PA, men, young and middle-aged adults of high educational status (college or more) were, respectively, 47% [OR = 0.53 (95% CI = 0.36-0.78), I2 = 76.6%], 25% [OR = 0.75 (95% CI = 0.61-0.93), I2 = 30.4%] and 32% [OR = 0.68 (95% CI = 0.47-1.00), I2 = 80.3%] less likely to be active. CONCLUSIONS: PA and sitting time present great ranges and tend to vary across sex and educational status in South American countries. Country-specific exploration of trends and population-specific interventions may be warranted

Cd98hc (slc3A2) sustains amino acid and nucleotide availability for cell cycle progression

CD98 heavy chain (CD98hc) forms heteromeric amino acid (AA) transporters by interacting with different light chains. Cancer cells overexpress CD98hc-transporters in order to meet their increased nutritional and antioxidant demands, since they provide branched-chain AA (BCAA) and aromatic AA (AAA) availability while protecting cells from oxidative stress. Here we show that BCAA and AAA shortage phenocopies the inhibition of mTORC1 signalling, protein synthesis and cell proliferation caused by CD98hc ablation. Furthermore, our data indicate that CD98hc sustains glucose uptake and glycolysis, and, as a consequence, the pentose phosphate pathway (PPP). Thus, loss of CD98hc triggers a dramatic reduction in the nucleotide pool, which leads to replicative stress in these cells, as evidenced by the enhanced DNA Damage Response (DDR), S-phase delay and diminished rate of mitosis, all recovered by nucleoside supplementation. In addition, proper BCAA and AAA availability sustains the expression of the enzyme ribonucleotide reductase. In this regard, BCAA and AAA shortage results in decreased content of deoxynucleotides that triggers replicative stress, also recovered by nucleoside supplementation. On the basis of our findings, we conclude that CD98hc plays a central role in AA and glucose cellular nutrition, redox homeostasis and nucleotide availability, all key for cell proliferation

Unmet Diagnostic and Therapeutic Opportunities for COPD in Low- and Middle-Income Countries

RATIONALE: Chronic obstructive pulmonary disease (COPD) is a prevalent and burdensome condition in low- and middle-income countries (LMICs). Challenges to better care include more effective diagnosis, and access to affordable interventions. There are no previous reports describing therapeutic needs in LMIC populations with COPD identified through screening. OBJECTIVE: To describe unmet therapeutic need in screening-detected COPD in LMIC settings. METHODS: We compared interventions recommended by the international 'GOLD' COPD strategy document, with that received, in 1000 people with COPD identified by population screening at three LMIC sites in Nepal, Peru and Uganda. We calculated costs using data on the availability and affordability of medicines. MEASUREMENT AND MAIN RESULTS: The greatest unmet need for non-pharmacological interventions was for education and vaccinations (applicable to all), pulmonary rehabilitation (49%), smoking cessation (30%) and advice on biomass smoke exposure (26%). 95% of cases were previously undiagnosed and few were receiving therapy (4.5% had short-acting beta-agonists). Only three of 47 people (6%) with a previous COPD diagnosis had access to drugs consistent with recommendations. None of those with more severe COPD were accessing appropriate maintenance inhalers. Even when available, maintenance treatments were unaffordable with 30 days of treatment more than a low-skilled workers' daily average wage. CONCLUSION: We found significant missed opportunity to reduce the burden of COPD in LMIC settings, with most cases undiagnosed. Whilst there is unmet need in developing novel therapies, in LMICs where the burden is greatest, better diagnosis together with access to affordable interventions could translate to immediate benefit. This article is open access and distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/)

Chronic Obstructive Pulmonary Disease Self-Management in Three LMICs: A Pilot Randomized Trial

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) disproportionately affects low- and middle-income countries (LMICs). Health systems are ill-prepared to manage the increase in COPD cases. METHODS: We carried out a pilot effectiveness-implementation randomized field trial of a community health worker (CHW)-supported, one-year self-management intervention in individuals with COPD grade B-D. The study took place in low-resource settings of Nepal, Peru, and Uganda. The primary outcome was the St. George's Respiratory Questionnaire (SGRQ) score at one year. We evaluated differences in moderate-to-severe exacerbations, all-cause hospitalizations and the EuroQol score (EQ5D-3L) at 12 months. RESULTS: We randomly assigned 239 participants (119 control, 120 intervention) with grade B-D COPD to a multi-component, CHW-supported intervention or standard of care and COPD education. 25 participants (21%) died or were lost to follow-up in the control arm compared to 11 (9%) in the intervention arm. At 12 months, there was no difference in mean total SGRQ scores between intervention and control arms (34.7 vs. 34.0 points; adjusted mean difference 1.0, 95% CI -4.2 to 6.1; p=0.71). The intervention arm had a higher proportion of hospitalizations (10% vs 5.2%; adjusted odds ratio 2.2, 95% CI 0.8-7.5; p=0.15) at 12 months compared to controls. CONCLUSION: A CHW-based intervention to support self-management of acute exacerbations of COPD in three resource-poor settings did not result in differences in SGRQ scores at one year. Fidelity was high, and intervention engagement was moderate. While results cannot differentiate between a failed intervention or implementation, it nonetheless suggests that we need to revisit our strategy. Clinical trial registration available at www. CLINICALTRIALS: gov, ID: NCT03359915

Neuroserpin polymorphisms and stroke risk in a biracial population: the stroke prevention in young women study

<p>Abstract</p> <p>Background</p> <p>Neuroserpin, primarily localized to CNS neurons, inhibits the adverse effects of tissue-type plasminogen activator (tPA) on the neurovascular unit and has neuroprotective effects in animal models of ischemic stroke. We sought to evaluate the association of neuroserpin polymorphisms with risk for ischemic stroke among young women.</p> <p>Methods</p> <p>A population-based case-control study of stroke among women aged 15–49 identified 224 cases of first ischemic stroke (47.3% African-American) and 211 age-matched control subjects (43.1% African-American). Neuroserpin single nucleotide polymorphisms (SNPs) chosen through HapMap were genotyped in the study population and assessed for association with stroke.</p> <p>Results</p> <p>Of the five SNPs analyzed, the A allele (frequency; Caucasian = 0.56, African-American = 0.42) of SNP rs6797312 located in intron 1 was associated with stroke in an age-adjusted dominant model (AA and AT vs. TT) among Caucasians (OR = 2.05, p = 0.023) but not African-Americans (OR = 0.71, p = 0.387). Models adjusting for other risk factors strengthened the association. Race-specific haplotype analyses, inclusive of SNP rs6797312, again demonstrated significant associations with stroke among Caucasians only.</p> <p>Conclusion</p> <p>This study provides the first evidence that neuroserpin is associated with early-onset ischemic stroke among Caucasian women.</p

Modulating Pharmacokinetics, Tumor Uptake and Biodistribution by Engineered Nanoparticles

Inorganic nanoparticles provide promising tools for biomedical applications including detection, diagnosis and therapy. While surface properties such as charge are expected to play an important role in their in vivo behavior, very little is known how the surface chemistry of nanoparticles influences their pharmacokinetics, tumor uptake, and biodistribution.Using a family of structurally homologous nanoparticles we have investigated how pharmacological properties including tumor uptake and biodistribution are influenced by surface charge using neutral (TEGOH), zwitterionic (Tzwit), negative (TCOOH) and positive (TTMA) nanoparticles. Nanoparticles were injected into mice (normal and athymic) either in the tail vein or into the peritoneum.Neutral and zwitterionic nanoparticles demonstrated longer circulation time via both i.p. and i.v. administration, whereas negatively and positively charged nanoparticles possessed relatively short half-lives. These pharmacological characteristics were reflected on the tumor uptake and biodistribution of the respective nanoparticles, with enhanced tumor uptake by neutral and zwitterionic nanoparticles via passive targeting

Identifying New Therapeutic Targets via Modulation of Protein Corona Formation by Engineered Nanoparticles

We introduce a promising methodology to identify new therapeutic targets in cancer. Proteins bind to nanoparticles to form a protein corona. We modulate this corona by using surface-engineered nanoparticles, and identify protein composition to provide insight into disease development.Using a family of structurally homologous nanoparticles we have investigated the changes in the protein corona around surface-functionalized gold nanoparticles (AuNPs) from normal and malignant ovarian cell lysates. Proteomics analysis using mass spectrometry identified hepatoma-derived growth factor (HDGF) that is found exclusively on positively charged AuNPs ((+)AuNPs) after incubation with the lysates. We confirmed expression of HDGF in various ovarian cancer cells and validated binding selectivity to (+)AuNPs by Western blot analysis. Silencing of HDGF by siRNA resulted s inhibition in proliferation of ovarian cancer cells.We investigated the modulation of protein corona around surface-functionalized gold nanoparticles as a promising approach to identify new therapeutic targets. The potential of our method for identifying therapeutic targets was demonstrated through silencing of HDGF by siRNA, which inhibited proliferation of ovarian cancer cells. This integrated proteomics, bioinformatics, and nanotechnology strategy demonstrates that protein corona identification can be used to discover novel therapeutic targets in cancer