Harmonization of individual case safety reports transmission requirements among PAHO reference authorities: a review of their current regulation.

To perform optimal monitoring of the safety profile in the postmarketing phase, Marketing Authorization Holders and National Regulatory Authorities (NRAs) must evaluate the adverse drug reactions (ADRs) that occurred and characterize their nature, frequency, and severity. Management is possible through Individual Case Safety Reports (ICSRs), which are the reports of organized and processed data. Globally, the International Council for Harmonisation (ICH) E2B guideline suggests harmonized activities for the ICSR electronic content and transmission. In America, the Pan American Health Organization (PAHO) is the agency responsible to implement cooperation among its members, which are recognized as National Regulatory Authorities of Reference (NRARs) such as Argentina, Brazil, Canada, Chile, Colombia, Cuba, Mexico, and the United States. PAHO published the 'Good Pharmacovigilance Practices for the Americas' suggesting improvement and harmonization in the region. After reviewing the regulatory framework, it is assumed that all NRARs have a regulated ICSR transmission system (i.e. a systematic vigilance system for collecting, analyzing, and disseminating information from ADRs). However, significant differences exist, such as the requirement for social media vigilance, expedited and non-expedited ICSRs, coding, severity, and transmission. The volume of ICSRs has significantly increased, due to using electronic standards managed by the NRAs, which facilitates early identification of new ADRs, allowing the implementation of novel minimization activities, contributing to the continuous assessment of the benefit-risk balance of medicines. Nevertheless, there is still area for improvement, especially in Latin America.

Transmission of spontaneous adverse drug reactions by industry in countries designated as a reference by the Pan American Health Organization (PAHO): comparison on regulatory requirements This review aims to describe regulatory criteria and compare harmonization across regions that marketing authorization holders must fulfill when transmitting spontaneous adverse drug reactions to the authorities for postmarketing surveillance. It centers on the regulatory requirements of authorities designated as a reference by the PAHO. Consequently, it is important to review the regulatory framework, to evaluate the requirements for transmission and have the context of the current harmonization among these agencies in America. This review contains the minimum criteria for transmission and harmonized guidelines according to the International Council for Harmonisation (ICH) and PAHO. However, identifying the differences is only the first step, future research in harmonization must continue to advance the understanding and establish guidelines that allow a better evaluation of the safety profile of medical products.

Impact of exclusive enteral nutrition on the gut microbiome of children with medical complexity.

BACKGROUND: Children with medical complexity (CMC) often require enteral tube feedings to meet their nutrition needs. Many, however, experience symptoms of feeding intolerance, such as vomiting and pain. The goal of this analysis was to examine the relationship between diet and the gut microbiome, controlling for medications, among CMC receiving enteral tube feedings, CMC consuming oral nutrition, and healthy controls. Given the variety of available commercial formula preparations, we were also interested in examining the impact of different formula types on the CMC microbiome. METHODS: Fecal samples from 91 children (57 CMC and 34 healthy controls) were collected and analyzed. Parents completed clinical and dietary questionnaires. 16S ribosomal RNA amplicon sequencing was completed using the QIIME2 pipeline. RESULTS: A significant decrease in alpha diversity among CMC receiving exclusive enteral nutrition (CMC EEN) compared with healthy controls (Shannon P = 0.006 and Faith's phylogenetic distance P = 0.006) was found that was not observed between CMC receiving oral nutrition and healthy controls. Significant differences in beta diversity were also observed between CMC EEN and healthy controls, with CMC EEN having a greater relative abundance of Enterobacteriaceae and obligate anaerobes. Differences were also noted between CMC EEN and CMC receiving oral nutrition (Aitchison distance P = 0.001); however, no differences were observed between CMC receiving oral nutrition and healthy controls. CONCLUSION: Despite similarities in medication profiles, CMC EEN have decreased alpha diversity and differences in beta diversity compared with healthy controls not observed in CMC receiving oral nutrition, highlighting the impact of diet over medications.

Ocular Cyclopentolate: A Mini Review Concerning Its Benefits and Risks.

Cycloplegic and mydriatic agents are essential in ophthalmological clinical practice since they provide the means for diagnosing and treating certain eye conditions. In addition, cyclopentolate has proven to possess certain benefits compared to other available cycloplegics and mydriatics. Still, the incidence of some adverse drug reactions related to this drug, especially in susceptible patients, has created interest in reviewing the literature about the benefits and risks of using cyclopentolate. A literature search was conducted in Medline/PubMed and Google Scholar, focusing on identifying cyclopentolate's benefits and risks; the most important benefit was its usefulness for evaluating refractive errors, especially for hyperopic children, pseudomyopia, anterior uveitis, treatment of childhood myopia, idiopathic vision loss, and during examinations before refractive surgery, with particular advantages compared to other cycloplegics. While the risks were divided into local adverse drug reactions such as burning sensation, photophobia, hyperemia, punctate keratitis, synechiae, and blurred vision, which are relatively frequent but mild and temporary; and systemic adverse drug reactions such as language problems, visual or tactile hallucinations and ataxia, but unlike ocular, systemic adverse drug reactions are rare and occur mainly in patients with risk factors. In addition, six cases of abuse were found. The treatment with cyclopentolate is effective and safe in most cases; nevertheless, special care must be taken due to the potential severe ADRs that may occur, especially in susceptible patients like children, geriatrics, patients with neurological disorders or Down's syndrome, patients with a low blood level of pseudocholinesterase, users of substances with CNS effects, and patients with a history of drug addiction. The recommendations are avoiding the use of 2% cyclopentolate and instead employing solutions with lower concentrations, preferably with another mydriatic such as phenylephrine. Likewise, the occlusion of the nasolacrimal duct after instillation limits the drug's absorption, reducing the risk of systemic adverse events.

Underreporting and Triggering Factors for Reporting ADRs of Two Ophthalmic Drugs: A Comparison between Spontaneous Reports and Active Pharmacovigilance Databases.

(1) Aims of the study: calculating the underreporting ratio for two different medications, a fixed combination of 0.5% timolol + 0.2% brimonidine + 2.0% dorzolamide (antiglaucoma) and a fixed combination of sodium hyaluronate 0.1% + chondroitin sulfate 0.18% (artificial tears) for characterizing the features influencing the reporting of adverse drug reactions (ADRs) in spontaneous reporting. (2) Methods: The underreporting ratio was calculated by comparing the adverse drug reactions reported in the spontaneous reporting database for every 10,000 defined daily doses marketed and the adverse drug reactions from an active surveillance study for every 10,000 defined daily doses used for different drugs (antiglaucoma and artificial tears). The factors related to the report in spontaneous reporting through statistical tests were also determined. (3) Results: The underreporting ratio of spontaneous reporting was 0.006029% for antiglaucoma and 0.003552% for artificial tears. Additionally, statistically significant differences were found for severity, unexpected adverse drug reactions, and incidence of adverse drug reactions in females when compared with spontaneous reporting and active surveillance. (4) Conclusions: The underreporting ratio of ADRs related to ophthalmic medications indicates worry since the cornerstone of pharmacovigilance focuses on spontaneous reporting. Additionally, since underreporting seems to b selective, the role of certain aspects, such as gender, seriousness, severity, and unexpected ADRs, must be considered in future research.

Enhancing untargeted metabolomics using metadata-based source annotation.

Human untargeted metabolomics studies annotate only ~10% of molecular features. We introduce reference-data-driven analysis to match metabolomics tandem mass spectrometry (MS/MS) data against metadata-annotated source data as a pseudo-MS/MS reference library. Applying this approach to food source data, we show that it increases MS/MS spectral usage 5.1-fold over conventional structural MS/MS library matches and allows empirical assessment of dietary patterns from untargeted data.

Guided Self-Help for Pediatric Obesity in Primary Care: A Randomized Clinical Trial.

OBJECTIVES: Our aim was to compare the effect of 2 treatment models on attendance and child weight status: a less intense guided self-help (GSH) program delivered in the primary care setting versus traditional family-based behavioral treatment (FBT) delivered in an academic center. METHODS: We conducted a randomized clinical trial among 164 children between 5 and 13 years old with a BMI ≥85th percentile and their parents. The intervention group (GSH) received 14 individual sessions over 6 months, with 5.3 hours of treatment. The control group (FBT) received 20 group-based sessions over 6 months, with 20 hours of treatment. Main outcomes included proportion of sessions families attended and change in child BMI z-score (BMIz), percentage from the 95th BMI percentile, difference from the 95th BMI percentile at the end of treatment, and 6-month follow-up. RESULTS: Mean age of children was 9.6 years, BMI z-score 2.1, 49% female, and >90% Latino. The odds of attending GSH compared to FBT was 2.2 (P < 0.01). Those assigned to GSH had a 67% reduced risk of attrition (hazard ratio = 0.33, 95% confidence interval 0.22-0.50, P < .001). Intent-to-treat analysis showed no between-group differences in change in BMIz and percentage from the 95th BMI percentile over time. Combined, there was a significant reduction in BMIz from baseline to posttreatment (ß = -0.07 (0.01), P < .01, d: 0.60) and a slight increase from posttreatment to follow-up (ß = 0.007 (0.13), P = .56). CONCLUSIONS: This study provides support for a novel, less intense GSH model of obesity treatment, which can be implemented in the primary care setting. Future studies should examine effective approaches to dissemination and implementation of GSH in different settings to increase access to treatment.

Real-Life Active Surveillance of a Naphazoline/ Hypromellose Fixed Combination's Safety Profile in Peruvian Population.

OBJECTIVE: Identifying the adverse reactions and the possible risks associated with the use of naphazoline 0.1% + hypromellose 0.5% (NAPH), thereby evaluating its tolerability and safety profile. METHODS: A total of 236 Peruvian patients were included in an active pharmacovigilance study drug event monitoring consisting in 2 phone calls conducted in order to register adverse drug reactions (ADRs), the product's tolerability and to assess the risk concerning specific clinical and demographic characteristics using a binary logistic regression model. RESULTS: A total of 54 ADRs (one per patient) were reported after the use of NAPH; classified (according to the Medical Dictionary for Regulatory Activities) into two groups of System Organ Class (SOC): eye disorders and nervous system disorders; and four groups of preferred term (PT): eye irritation, vision blurred, eye pruritus and headache. All ADRs were expected, mild and not serious. No risk factors related to the clinical and demographic characteristics of the patients were identified. CONCLUSION: The low incidence of ADRs, their short recovery time, and their categorization as "mild" and "not serious" demonstrates the high tolerability in the studied population; therefore, according to the study, the safety profile for NAPH seems to be adequate, with a suitable tolerability.

Ophthalmic Solution Safety Profile: Active Surveillance of a Sodium Hyaluronate/Chondroitin Sulfate Combination in Peruvian Population.

BACKGROUND: Sodium hyaluronate/chondroitin sulfate fixed combination plays an essential role in the treatment of keratoconjunctivitis sicca, a multifactorial disease accompanied by ocular symptoms like alteration of the tear film. Despite low or no absorption of such drugs, these can cause secondary effects. An essential tool in the study of medication behavior is active pharmacovigilance. Unlike spontaneous reporting pharmacovigilance, this tool allows an appraisal of adverse drug reactions (ADRs)' real incidence, a higher capacity to identify safety signals, the relationship with concomitant drugs and pathologies prevalent in the study population. This study aimed to evaluate the safety profile and identify and/or assess adverse reactions in an uncontrolled population. METHODS: Active pharmacovigilance by Drug Event Monitoring was performed. A total of 3 follow-up calls were made for 30 days for the identification of the ADRs, tolerability (ADR severity, seriousness, long term sequelae, and duration) and the possible risks (safety signals, medical interactions) of sodium hyaluronate and chondroitin sulfate (HUM). RESULTS: Thirty-five ADRs were identified in the 212 patients included in the study (0.17 ADR/patient). The 35 ADRs were classified into 3 System Organ Class (SOC) groups: general disorders and administration site conditions (74.2%), eye disorders (22.9%), and nervous system disorders (2.9%); and 4 Preferred Term (PT) groups: burning sensation (74.2%), followed by blurred vision (20%), ocular pain (2.9%) and headache (2.9%). All the ADRs were categorized as mild and not serious. No statistically significant differences were found in concomitantly medications, posology and age groups. CONCLUSION: Good tolerability to the solution was identified, with a low incidence of ADRs. Just the same, all the associated ADRs were consistent with the information found in HUM's physicochemical profile and the physiopathology of DED. No unknown risks were identified, reinforcing HUM's safety profile.

Design of the GOT Doc study: A randomized controlled trial comparing a Guided Self-Help obesity treatment program for childhood obesity in the primary care setting to traditional family-based behavioral weight loss.

Currently one-third of children in the United States have overweight or obesity (OW/OB). The goal of Healthy People 2020 is to reduce the proportion of children with OW/OB and increase the proportion of primary care visits that include nutrition and weight-related counseling. Unfortunately, many health care providers find it difficult to offer effective weight-related counseling and treatment in the primary care setting. Therefore, new models of care are needed that allow a greater proportion of children with OW/OB and their parents to access care and receive quality weight management treatment. The current paper describes the GOT Doc study which is designed to test the effectiveness of a Guided Self-Help (GSH) model of obesity treatment that can be delivered in the primary care setting compared to a traditional Family-Based Behavioral weight loss treatment (FBT) delivered at an academic center. We will assess the impact of this program on attendance (access to care) and changes in child BMI percentile/z-score. We will also examine the impact of this treatment model on change in child lifestyle behaviors, parent support behaviors, and parent self-efficacy and empowerment to make behavior change. Finally, we will assess the cost-effectiveness of this model on changes in child BMI percentile/z-score. We believe the GSH intervention will be a cost-effective model of obesity management that can be implemented in community practices around the country, thereby increasing access to treatment for a broader proportion of our population and decreasing rates of childhood obesity.

Active Pharmacovigilance in Peruvian Population: Surveillance of a Timolol/Brimonidine/Dorzolamide Ophthalmic Fixed Combination.

PURPOSE: In this study active pharmacovigilance was used in an uncontrolled population to enrich the safety profile and canvass the Adverse Drug Reactions (ADRs) associated with the use of a fixed combination of 0.5% timolol + 0.2% brimonidine + 2.0% dorzolamide (TBD). METHODS: Active pharmacovigilance consisting of 3 follow-up calls within 60 days was used to monitor the product's safety and identify new risks by searching for unexpected ADRs and increased incidence, tolerability, drug interactions and special population-related ADRs. RESULTS: Ninety-four ADRs were reported by a total of 246 patients (0.38 ADRs/patient); all of them were classified as "mild". We found an increased risk of ADRs with a Relative Risk (RR) for simultaneous use of TBD + ophthalmic ciprofloxacin and TBD + oral atorvastatin; 2.0309 (95% CI, 1.2467-3.3083) and 1.8864 (95% CI, 1.0543-3.3754), respectively. Two unexpected ADRs were discovered, both of which presented belonged to the System Organ Class (SOC) of "infections and infestations" and the preferred term (PT) of "nasopharyngitis.". CONCLUSION: Three safety signals were identified, two of them corresponded to an increase in the incidence of ADRs and the last one is associated with 2 unexpected ADR. Nevertheless, we found a good tolerability profile for TBD in the study population.

A Drug Safety Surveillance Study of a Ciprofloxacin/Dexamethasone Ophthalmic Fixed Combination in Peruvian Population.

(1) Background: drugs provide a significant benefit for patients who require medical treatment; however, their use implies an intrinsic potential danger, with the possibility of causing unwanted effects. These effects are known as adverse drug reactions (ADRs). Post-marketing drug safety surveillance detects unknown risks that have not been identified in clinical trials, and it is necessary to monitor marketed medications under real-life practice. Due to the scarce information about fixed combination of ciprofloxacin 0.3%/dexamethasone 0.1% (SDO), we performed a drug safety surveillance study. (2) Methods: A prospective non-controlled drug safety surveillance study was conducted in Peruvian population. A total of 236 patients prescribed SDO were included derived from 12 sites. Patients' standardized information was collected through two phone calls, including demographics, medical history, prescribing patterns of SDO, concomitant medication, and ADRs in detail. The ADRs were classified by causality and severity, followed by outcome measures to identify new risk. (3) Results: 236 patients prescribed with SDO participated in the study and 220 were included. A total of 82 ADRs/220 patients were reported after the use of SDO, presenting a ratio 0.37 ADR/patient. The most frequent ADR with SDO administration was eye irritation (30%). All ADRs were classified as non-serious, and 97.5% (n = 80) were classified as mild while 2.5% as moderate (n = 2). No cases under the severe category were identified. (4) Conclusion: No new risks were found in the population where this study was conducted.

Anticuerpos Antifosfolípidos en Enfermedad Periodontal / Antiphospholipid Antibodies in Periodontal Disease

INTRODUCCIÓN Las complicaciones obstétricas observadas en la enfermedad periodontal (EP) son similares a las del síndrome antifosfolípido (SAF). Se desconoce la prevalencia de los anticuerpos antifosfolípidos (aPL) en mujeres con EP y su relación con complicaciones obstétricas. Objetivo/s: Investigar la prevalencia de aPL, criterio y no criterio, en mujeres en edad fértil con EP; y su asociación con antecedentes obstétricos adversos. MÉTODOS El estudio se llevó a cabo en el Hospital Odontológico Universitario de la Facultad de Odontología de la Universidad de Buenos Aires (UBA); las determinaciones de laboratorio se realizaron en el Laboratorio de Hemostasia del Departamento de Bioquímica Clínica de la Facultad de Farmacia y Bioquímica, UBA. Se realizó un estudio de casos y controles. Se definió como caso a pacientes con EP. Se incluyeron mujeres entre 30 y 45 años, que hubieran tenido embarazos en los últimos 5 años. RESULTADOS El estudio no alcanzó el tamaño muestral calculado. Se incluyeron 50 pacientes; se informan los datos 28 casos (edad: 34.8±2.2) y 21 controles (edad: 31±1.8) con resultados de laboratorio completos. El 75% de los casos y el 62% de los controles tuvieron partos normales en los últimos 5 años. Sólo los casos tuvieron positividad de aPL criterio (28%, 8/28 pacientes); únicamente se constataron AL y títulos altos de aCL y aB2GPI en 2 pacientes con enfermedad periodontal (frecuencia: 7.1%). Se observó positividad de Ac. "no criterio" en 4 pacientes (1 caso y 3 controles). Ninguna paciente con EP y aPL criterio positivos tuvo antecedentes obstétricos adversos. Un caso con EP y Ac. Anti Anexina V IgM había tenido un parto prematuro un año antes. DISCUSIÓN Sólo se observaron aPL en pacientes con EP; no se observó asociación con antecedentes obstétricos adversos. Se requiere mayor número de pacientes para confirmar estas observaciones así como para valorar su asociación con complicaciones bstétricas.

[Prevalence of anti-Toxoplasma gondii antibodies in blood donors in Buenos Aires city, from 1967 to 2017]. / Prevalencia de anticuerpos anti-Toxoplasma gondii en hemodonantes en la ciudad de Buenos Aires, desde 1967 a 2017.

A prevalence study of antibodies anti Toxoplasma gondii in voluntary blood donors who attended the hemotherapy service at the Hospital Alemán during the first four months of the years 1997, 2007 and 2017 was carried out and the results were compared to the study carried out in 1967. The sera where processed with the Sabin Feldman Dye Test. The global average seroprevalence in 1967 was 67.0% (CI95%, 64.4%-69.6%); in 1997, 35.0% (CI95%, 33.3%-38.3%); in 2007, 31.9% (CI95%, 29.6%-34.2%) and in 2017, 21.2% (CI95%, 19.0%-23.3%). In the fifty years covered by the study the decline in prevalence was 45.8%, which represents an average annual decline of 0.9%.The decline was statistically significant between 1967 and 1997, and between 2007 and 2017. The four studies demonstrate that infection prevalence increased depending on age. The infection rate for 1967 was 1.0% per year and declined in the next studies to 0.8% in 1997, 0.8% in 2007, and 0.5% in 2017. Donors from the last study responded to a survey that showed a statistically significant correlation between seroprevalence of Toxoplasma gondii antibodies and lack of tap water, unfinished secondary studies or residence in the western or southern part of the Buenos Aires metropolitan area. No significant association was found with having a cat as a pet, the consumption of undercooked meat or the practice of gardening.

Prevalencia de anticuerpos anti Toxoplasma gondii en hemodonantes en la ciudad de Buenos Aires, desde 1967 a 2017 / Prevalence of anti-Toxoplasma gondii antibodies in blood donors in Buenos Aires city, from 1967 to 2017

Se estudió la prevalencia de anticuerpos anti Toxoplasma gondii a los dadores voluntarios de sangre que concurrieron durante el primer cuatrimestre de los años 1997, 2007 y 2017 al Servicio de Hemoterapia del Hospital Alemán de Buenos Aires y se compararon los resultados con el estudio efectuado en el año 1967. Los sueros fueron procesados con el Sabin Feldman Dye Test. La seroprevalencia promedio en 1967 fue 67.0% (IC95%, 64.4%-69.6%), en 1997, 35% (IC95%, 33.3%-38.3%), en 2007, 31.9 % (IC95%, 29.6%-34.2%) y en 2017, 21.2% (IC95%, 19.0%-23.3%). En los cincuenta años que abarca el estudio la disminución de la prevalencia fue de 45.8%, que representa una declinación anual promedio del 0.9%. El descenso fue estadísticamente significativo entre los años 1967 y 1997 y entre 2007 y 2017. En los cuatro estudios se observó un incremento de la prevalencia de infección en función de la edad. La tasa de infección calculada para el año 1967 fue 1.0% y disminuyó en los estudios posteriores, a 0.8% en 1997, 0.7% en 2007 y 0.5% en 2017. Los donantes del último estudio respondieron una encuesta que mostró una correlación estadísticamente significativa entre seroprevalencia de anticuerpos anti-Toxoplasma gondii y la carencia de agua corriente, estudios secundarios no concluidos o la residencia en zona oeste o sur del conurbano bonaerense. No se encontró una asociación significativa con tener un gato como mascota, consumo de carne poco cocida o práctica de jardinería.

A prevalence study of antibodies anti Toxoplasma gondii in voluntary blood donors who attended the hemotherapy service at the Hospital Alemán during the first four months of the years 1997, 2007 and 2017 was carried out and the results were compared to the study carried out in 1967. The sera where processed with the Sabin Feldman Dye Test. The global average seroprevalence in 1967 was 67.0% (CI95%, 64.4%-69.6%); in 1997, 35.0% (CI95%, 33.3%-38.3%); in 2007, 31.9% (CI95%, 29.6%-34.2%) and in 2017, 21.2% (CI95%, 19.0%-23.3%). In the fifty years covered by the study the decline in prevalence was 45.8%, which represents an average annual decline of 0.9%.The decline was statistically significant between 1967 and 1997, and between 2007 and 2017. The four studies demonstrate that infection prevalence increased depending on age. The infection rate for 1967 was 1.0% per year and declined in the next studies to 0.8% in 1997, 0.8% in 2007, and 0.5% in 2017. Donors from the last study responded to a survey that showed a statistically significant correlation between seroprevalence of Toxoplasma gondii antibodies and lack of tap water, unfinished secondary studies or residence in the western or southern part of the Buenos Aires metropolitan area. No significant association was found with having a cat as a pet, the consumption of undercooked meat or the practice of gardening.

Analysis of salivary cortisol levels to determine the association between depression level and differences in circadian rhythms of shift-working nurses.

OBJECTIVE: The aim of this study was to clarify whether there are differences in the circadian rhythms of shift-working nurses by assessing depression, fatigue and salivary cortisol levels. METHODS: Forty nurses working in a two-shift system at "Hospital A", Fukuoka City, Japan, used a self-rated depression scale (SDS) to assess their depression levels. Fatigue levels were measured with the visual analogue scale for fatigue (VAS-F); saliva was collected before and during shifts for three days. Results were analyzed with analysis of variance (ANOVA). RESULTS: Thirty-six valid records were obtained, and subjects were classified according to SDS scores into a normal group (NG), moderate group (MG) and severe group (SG). There were no significant differences in the day shift salivary cortisol values of the three groups. However, the night shift salivary cortisol value for the SG was 0.132 µg/dl at 16:00, before starting the shift, and decreased to 0.036 µg/dl at 20:00. It increased slightly up to 0.057 µg/dl by 24:00 and formed a peak between 5:00 and 7:00, with the levels being 0.322 µg/dl and 0.305 µg/dl respectively. Meanwhile, the NG cortisol value was 0.154 µg/dl before the shift, decreased to 0.034 µg/dl by 20:00, slightly increased up to 0.093 µg/dl by 5:00 and presented its peak value, 0.253 µg/dl, at 7:00 next morning. CONCLUSIONS: SG nurses presented significantly increased salivary cortisol levels early in the morning during night shifts, showing a phase deviation in the circadian rhythm. Because subjective fatigue levels did not differ with time, SG nurses should understand and deal with physical changes in the early morning. This approach may reduce medical accidents and malpractice in the early morning.

Statins but not aspirin reduce thrombotic risk assessed by thrombin generation in diabetic patients without cardiovascular events: the RATIONAL trial.

BACKGROUND: The systematic use of aspirin and statins in patients with diabetes and no previous cardiovascular events is controversial. We sought to assess the effects of aspirin and statins on the thrombotic risk assessed by thrombin generation (TG) among patients with type II diabetes mellitus and no previous cardiovascular events. METHODOLOGY/PRINCIPAL FINDINGS: Prospective, randomized, open, blinded to events evaluation, controlled, 2×2 factorial clinical trial including 30 patients randomly allocated to aspirin 100 mg/d, atorvastatin 40 mg/d, both or none. Outcome measurements included changes in TG levels after treatment (8 to 10 weeks), assessed by a calibrated automated thrombogram. At baseline all groups had similar clinical and biochemical profiles, including TG levels. There was no interaction between aspirin and atorvastatin. Atorvastatin significantly reduced TG measured as peak TG with saline (85.09±55.34 nmol vs 153.26±75.55 nmol for atorvastatin and control groups, respectively; p = 0.018). On the other hand, aspirin had no effect on TG (121.51±81.83 nmol vs 116.85±67.66 nmol, for aspirin and control groups, respectively; p = 0.716). The effects of treatments on measurements of TG using other agonists were consistent. CONCLUSIONS/SIGNIFICANCE: While waiting for data from ongoing large clinical randomized trials to definitively outline the role of aspirin in primary prevention, our study shows that among diabetic patients without previous vascular events, statins but not aspirin reduce thrombotic risk assessed by TG. TRIAL REGISTRATION: ClinicalTrials.gov NCT00793754.

Los tiempos difíciles y la inteligencia emocional en el ejercicio odontológico

El odontólogo contemporáneo esta sometido a infinidad de situaciones personales, académicas y de trabajo que afectan directamente su comportamiento, esto se evidencia en el manejo de las emociones que le corresponde experimentar en su día a día. Las últimas teorías acerca de la inteligencia emocional marcan una nueva tendencia cognitiva, unida a ellos los hallazgos de la programación neurolinguística y los descubrimientos relacionados con el desarrollo del cerebro, la motivación y las relaciones interpersonales vitales en el campo odontológico, fundamentan la importancia de este tema.

Contemporaneous odontologist is professional is submitted to infiniteness personal, academics and work situations that affects directly his behavior; this make clear in the driven of emotions that he does correspond experiment in his day to day. Last theories about emotional intelligence mark a new cognitive tendency, besides, the new searching about neurolinguist programmes and discoveries engaged with the development of brain, motivation, and interpersonal relationships, which are vital in odontological field, the bases of the importance of this theme.

Influencia de un programa educativo brindado por la enfermera sobre hipertensión arterial, complicaciones y medidas higiénico - dietéticas a pacientes de la consulta externa de cardiología del Hospital Nacional Arzobispo Loayza febrero - abril 1997 / Influence of an educative program offered by the nurse on arterial hypertension, complications and measures hygienic - dietetic to patients of the external consultation of cardiology of the Hospital Nacional Arzobispo Loayza February - April 1997

El presente trabajo de investigación es un estudio cuasi - experimental, prospectivo y de corte longitudinal, que tuvo como finalidad mostrar el valor de la función educativa, asistencial y científica de la enfermera sobre todo en el nivel preventivo - promocional de la salud al medir la influencia de un programa educativo brindado por la enfermera sobre hipertensión arterial, complicaciones y medidas higiénico dietéticas a pacientes hipertensos, realizados en la consulta externa de Cardiología del Hospital Nacional Arzobispo Loayza. Se tomó una población de 29 personas, utilizando como instrumento un cuestionario de preguntas que se aplicó en tres oportunidades, uno antes de impartir el contenido educativo y los otros dos después del mismo. El estudio se llevó a cabo entre los meses de febrero - abril de 1997. El estudio establece que la enfermera profesional aplicando un programa educativo de salud con costos mínimos y dedicación exclusiva, interviene directamente en el nivel de prevención y control de la hipertensión arterial, lográndose un nivel de conocimientos aceptables de los pacientes sobre su enfermedad, complicaciones y medidas higiénico - dietéticas que se refleja en los resultados óptimos obtenidos, comprobándose así la hipótesis alterna. No se encontró influencia de los factores edad, sexo y estado laboral en el nivel de conocimientos alcanzados por el paciente hipertenso. Se sugiere realizar seguimiento a los pacientes que recibieron para medir el cambio de hábitos y la mejora de su calidad de vida.