Análisis de un algoritmo de riesgo de errores de medicación: una experiencia portuguesa / Analysis of a medication error risk algorithm: a portuguese experience

Los errores de medicación son cada vez más comunes lo cual pone en peligro la salud de los pacientes, de ahí la importancia de prevenirlos y controlarlos. El concepto de crear una herramienta de decisión clínica que permita gestionar mejor estos eventos no es nuevo. Utilizando una experiencia danesa, decidimos aplicar el algoritmo de MERIS (Medication Risk Score) en un servicio de accidente cerebrovascular de un hospital portugués con el fin de probar su aplicabilidad, determinar volumen de pacientes de riesgo y comprobar cual variable del algoritmo se correlaciona más con paciente de riesgo. Con una muestra de 65 pacientes con sus respectivos reportes MERIS se determinó que durante dos meses más de la mitad de los pacientes admitidos eran de alto riesgo para errores en su medicación. Se seleccionó la prueba de correlación de Spearman para determinar cuál de todas las variables de MERIS estaba más relacionada a un puntaje alto. Encontramos correlaciones positivas fuertes y estadísticamente significativas entre el puntaje de Meris y: función renal reducida, número de fármacos con bajo riesgo de daño, número de fármacos con alto riesgo de daño, número de fármacos, número de fármacos con riesgo medio de daño y número de fármacos con riesgo de interacción bajo a medio, siendo estos últimos tres los más significativos. No hubo una correlación estadísticamente significativa entre el puntaje MERIS y el número de fármacos con alto riesgo de interacción. Finalmente, modificamos la lista de medicamentos propuesta por los autores anteriores adaptada a nuestro hospital. (AU)

Medication errors are gradually more common, risking patients health, hence the importance of preventing and controlling them. The concept of creating a clinical decision tool to better manage these events is not new. Using a Danish experience, we applied the MERIS (Medication Risk Score) algorithm in a stroke unit of a Portuguese hospital in order to test its applicability, determine the volume of patients at risk and check which variable of the algorithm correlates more with patient risk. Using a sample of 65 patients with their respective MERIS reports, we determined that for two months more than half of the admitted patients were at high risk of errors in their medication. The Spearman correlation test was selected to determine which MERIS variable was most related to a high score. We found strong and statistically significant positive correlations between the Meris score and: reduced kidney function, number of drugs with low risk of damage, number of drugs with high risk of damage, number of drugs, number of drugs with medium risk of damage and number of drugs with low to medium risk of interaction, the latter three being the most significant. There was no statistically significant correlation between the MERIS score and the number of drugs with a high risk of interaction. Finally, we modify the list of medications proposed by the previous authors adapted to our hospital. (AU)

Environmental benchmarks based on ecotoxicological assessment with planktonic species might not adequately protect benthic assemblages in lotic systems.

Freshwater ecosystems face widespread diffuse and point-source contamination. Species Sensitivity Distributions (SSDs) have been used as a tool to determine chemical concentration benchmarks that represent protective levels for most species in the environment. Here we used a SSD approach to assess on the adequacy of standard planktonic organisms to reflect the response of benthic communities, critically supporting the structure and function of lotic ecosystems. For the purpose, SSDs reflecting non-lethal responses of standard planktonic and selected benthic organisms were built based on EC50 values (collected in the literature or estimated following testing herein) regarding three model contaminants: potassium dichromate (PD), 3,5-dichlorophenol (DCP) and lead chloride (LC). The derived HC5 estimates were discriminatory between chemicals and the uncertainty associated with the estimate was remarkably low. The HC5 estimates with corresponding uncertainty were generally within the same order of magnitude for the three chemicals tested, with better discrimination between chemicals regarding their hazardous potential being achieved for benthic organisms: DCP was clearly less hazardous than PD, but LC tends to be as hazardous as PD and DCP (assuming the confidence interval ranges). Moreover, benthic communities were more sensitive to both DCP and PD, in this later case the HC5 being lower by more than one order of magnitude than that found for planktonic communities; for LC, confidence intervals overlapped, preventing a feasible assumption regarding differential sensitivity of the compared communities. Microphytobenthos was highlighted as the most sensitive group to the three tested chemicals in SSDs covering the benthic compartment, while SSDs with planktonic organisms did not consistently show trends in sensitivity ordering. Overall, our results suggest that protective benchmarks retrieved from SSDs built with the responses of standard planktonic organisms (which are the most commonly used for regulation purposes) do not adequately protect benthic communities.

Triacontyl p-coumarate: an inhibitor of snake venom metalloproteinases.

Snake venom metalloproteinases (SVMPs) participate in a number of important biological, physiological and pathophysiological processes and are primarily responsible for the local tissue damage characteristic of viperid snake envenomations. The use of medicinal plant extracts as antidotes against animal venoms is an old practice, especially against snake envenomations. Such plants are sources of many pharmacologically active compounds and have been shown to antagonize the effects of some venoms and toxins. The present study explores the activity of triacontyl p-coumarate (PCT), an active compound isolated from root bark of Bombacopsis glabra vegetal extract (Bg), against harmful effects of Bothropoides pauloensis snake venom and isolated toxins (SVMPs or phospholipase A(2)). Before inhibition assays, Bg or PCT was incubated with venom or toxins at ratios of 1:1 and 1:5 (w/w; venom or isolated toxins/PCT) for 30 min at 37°C. Treatment conditions were also assayed to simulate snakebite with PCT inoculated at either the same venom or toxin site. PCT neutralized fibrinogenolytic activity and plasmatic fibrinogen depletion induced by B. pauloensis venom or isolated toxin. PCT also efficiently inhibited the hemorrhagic (3MDH - minimum hemorrhagic dose injected i.d into mice) and myotoxic activities induced by Jararhagin, a metalloproteinase from B. jararaca at 1:5 ratio (toxin: inhibitor, w/w) when it was previously incubated with PCT and injected into mice or when PCT was administered after toxin injection. Docking simulations using data on a metalloproteinase (Neuwiedase) structure suggest that the binding between the protein and the inhibitor occurs mainly in the active site region causing blockade of the enzymatic reaction by displacement of catalytic water. Steric hindrance may also play a role in the mechanism since the PCT hydrophobic tail was found to interact with the loop associated with substrate anchorage. Thus, PCT may provide a alternative to complement ophidian envenomation treatments.

The use of polymerase chain reaction for early diagnosis of tuberculosis in Mycobacterium tuberculosis culture

Early diagnosis plays a vital role in controlling tuberculosis. The conventional methodology is slow, with results taking several weeks, in addition to having low sensitivity, especially in clinical paucibacillary samples. The objective of this study was to evaluate the use of polymerase chain reaction (PCR) on solid medium culture for a rapid diagnosis of tuberculosis, mainly in cases of negative sputum smears. Forty sputum samples were collected from inpatients with tuberculosis treated for less than 2 days. Bacilloscopy, PCR for sputum, culture on Lõwestein-Jensen (LJ) solid medium, and daily PCR from culture were performed on each sample. DNA extracted from the BCG vaccine, which contains attenuated bacillus Calmette-Guérin, was used as the positive control. Smear microscopy showed 68.6 percent sensitivity, 80 percent specificity, 96 percent positive predictive value, and 26.7 percent negative predictive value, with culture on LJ medium as the gold standard. Culture at day 28 showed 74.3 percent sensitivity and 100 percent specificity. PCR of DNA extracted from sputum amplified a 1027-bp fragment of the 16s RNA gene, showing 22.9 percent sensitivity and 60 percent specificity. PCR performed with DNA extracted from daily culture showed that, from the 17th to the 40th day, the sensitivity (85.7 percent) and specificity (60 percent) were constant. We conclude that a 17-day culture is a good choice for rapid diagnosis and to interfere with the transmission chain of tuberculosis.

The use of polymerase chain reaction for early diagnosis of tuberculosis in Mycobacterium tuberculosis culture.

Early diagnosis plays a vital role in controlling tuberculosis. The conventional methodology is slow, with results taking several weeks, in addition to having low sensitivity, especially in clinical paucibacillary samples. The objective of this study was to evaluate the use of polymerase chain reaction (PCR) on solid medium culture for a rapid diagnosis of tuberculosis, mainly in cases of negative sputum smears. Forty sputum samples were collected from inpatients with tuberculosis treated for less than 2 days. Bacilloscopy, PCR for sputum, culture on Löwestein-Jensen (LJ) solid medium, and daily PCR from culture were performed on each sample. DNA extracted from the BCG vaccine, which contains attenuated bacillus Calmette-Guérin, was used as the positive control. Smear microscopy showed 68.6% sensitivity, 80% specificity, 96% positive predictive value, and 26.7% negative predictive value, with culture on LJ medium as the gold standard. Culture at day 28 showed 74.3% sensitivity and 100% specificity. PCR of DNA extracted from sputum amplified a 1027-bp fragment of the 16s RNA gene, showing 22.9% sensitivity and 60% specificity. PCR performed with DNA extracted from daily culture showed that, from the 17th to the 40th day, the sensitivity (85.7%) and specificity (60%) were constant. We conclude that a 17-day culture is a good choice for rapid diagnosis and to interfere with the transmission chain of tuberculosis.

Interaction of zinc or vitamin A supplementation and specific parasite infections on Mexican infants' growth: a randomized clinical trial.

BACKGROUND: The efficacy of micronutrient supplementation on growth may be modified by specific gastrointestinal parasite infections. METHODS: We carried out a double-blind placebo-controlled trial to evaluate the effect of vitamin A and zinc supplementation on gastro-intestinal pathogen infections and growth among 584 infants in Mexico City. Children aged 5-15 months were assigned to receive either a vitamin A supplement every 2 months (20,000 IU of retinol for infants < or =; 1 year or 45,000 IU for infants >1 year), a daily supplement of 20 mg of zinc, a combined vitamin A-zinc supplement or a placebo, and were followed up for 1 year. Weight and length were measured once a month and morbidity histories were recorded twice a week for 12 months. Monthly stool samples were screened for Giardia duodenalis, Ascaris lumbricoides and Entamoeba spp. Growth velocity slopes, generated from the linear regression of individual child length, and height-for-age z-scores on time were analyzed as end points in regression models, adjusting for the presence of parasite infections. RESULTS: The main effect of vitamin A supplementation was in height improvement (P<0.05), and was only found in the model evaluating infants with any parasite. There was an interaction effect of slower growth (P<0.05) found in infants infected with any parasite and supplemented with vitamin A in slower growth (P<0.05). In addition, the interaction of zinc supplementation and Giardia duodenalis or A. lumbricoides was associated with reduced growth (P<0.05). CONCLUSION: Gastro-intestinal parasite infections may modify the effect that zinc or vitamin A supplementation has on childhood growth.

Trichophyton rubrum isolated from aids and human immunodeficiency virus-infected patients in São Paulo, Brazil: antifungal susceptibility and extracellular enzyme production.

BACKGROUND: In order to identify intraspecific variations in Trichophyton rubrum and to correlate them to the immunological status of the host, sixty strains isolated from AIDS, HIV-positive and HIV-negative patients were compared for the production of extracellular enzymes and for their susceptibility to several antifungal drugs. METHODS: The isolates were tested for their ability to secrete keratinases, proteinases, phospholipases, lipases and DNases. Likewise, we investigated their susceptibility to amphotericin B, ketoconazole, ciclopiroxolamine, griseofulvin, miconazole and tolnaftate. RESULTS: Variations in the Minimal Inhibitory Concentration (MIC80)) values were observed for all antifungals tested, but they were similarly distributed among the three clinical groups. Griseofulvin showed the most prominent differences among the three groups of isolates. Regarding enzyme secretion, all samples secreted keratinases and DNases, while none secreted phospholipases. Proteinases and lipases were secreted by some of them. CONCLUSIONS: The differences among isolates of the three groups were not statistically significant and therefore could not be ascribed to a given clinical status. Intraspecific variations similarly occurred in each group, irrespective of the immunological status of the patients.

Determination of serum aluminum, platelet aggregation and lipid peroxidation in hemodialyzed patients.

Aluminum (Al3+) overload is frequently associated with lipid peroxidation and neurological disorders. Aluminum accumulation is also reported to be related to renal impairment, anemia and other clinical complications in hemodialysis patients. The aim of the present study was to determine the degree of lipid peroxidation, platelet aggregation and serum aluminum in patients receiving regular hemodialytic treatment. The level of plasma lipid peroxidation was evaluated on the basis of thiobarbituric acid reactive substances (TBARS). Mean platelet peroxidation in patients undergoing hemodialysis was significantly higher than in normal controls (2.7 +/- 0.03 vs. 1.8 +/- 0.06 nmol/l, P<0.05). Platelet aggregation and serum aluminum levels were determined by a turbidimetric method and atomic absorption spectrophotometry, respectively. Serum aluminum was significantly higher in patients than in normal controls (44.5 +/- 29 vs. 10.8 +/- 2.5 microg/l, P<0.05). Human blood platelets were stimulated with collagen (2.2 microg/ml), adenosine diphosphate (6 microM) and epinephrine (6 microM) and showed reduced function with the three agonists utilized. No correlation between aluminum levels and platelet aggregation or between aluminum and peroxidation was observed in hemodialyzed patients.

Determination of serum aluminum, platelet aggregation and lipid peroxidation in hemodialyzed patients

Aluminum (Al3+) overload is frequently associated with lipid peroxidation and neurological disorders. Aluminum accumulation is also reported to be related to renal impairment, anemia and other clinical complications in hemodialysis patients. The aim of the present study was to determine the degree of lipid peroxidation, platelet aggregation and serum aluminum in patients receiving regular hemodialytic treatment. The level of plasma lipid peroxidation was evaluated on the basis of thiobarbituric acid reactive substances (TBARS). Mean platelet peroxidation in patients undergoing hemodialysis was significantly higher than in normal controls (2.7 ± 0.03 vs 1.8 ± 0.06 nmol/l, P<0.05). Platelet aggregation and serum aluminum levels were determined by a turbidimetric method and atomic absorption spectrophotometry, respectively. Serum aluminum was significantly higher in patients than in normal controls (44.5 ± 29 vs 10.8 ± 2.5 æg/l, P<0.05). Human blood platelets were stimulated with collagen (2.2 æg/ml), adenosine diphosphate (6 æM) and epinephrine (6 æM) and showed reduced function with the three agonists utilized. No correlation between aluminum levels and platelet aggregation or between aluminum and peroxidation was observed in hemodialyzed patients

Production of extracellular enzymes by Microsporum canis and their role in its virulence.

Microsporum canis is the most prevalent dermatophyte of domestic animals. Several enzymes produced by dermatophytes, particularly keratinases, are considered to play a role in the virulence of this fungus. To investigate the possible relationship between the clinical status of M. canis infection and enzymatic activity of isolates, we studied the relationship between keratinase, elastase, lipase and DNase levels produced in vitro by different isolates and virulence as expressed in a guinea pig model. Samples isolated from symptomatic dogs and cats showed a statistically significantly (P < 0.05) higher keratinase activity than samples isolated from asymptomatic animals. Experimental infection of guinea pigs showed that a strain with high in vitro keratinase activity induced acute infection, which resolved clinically and mycologically faster than the infection induced by a strain with low keratinase activity. This suggested a strong correlation between high keratinase activity and the development of symptoms. The same correlation was not observed for other enzymes tested.

Phenotypic characterization of Trichophyton rubrum isolates from two geographic locations in Brazil.

To characterize possible Trichophyton rubrum phenotypes, which circulate in two Brazilian localities, we tested 53 isolates of this dermatophyte for their ability to assimilate several carbon sources, for keratinase, proteinase, phospholipase, lipase and desoxiribonuclease (DNase) secretions, and for their susceptibility to the antifungals fluconazole, ketoconazole and itraconazole. For each method, the isolates were submitted to similarity analysis and the methods were evaluated for their discriminatory indexes. None of the isolates were capable of assimilating arabinose, dulcitol, lactose, melibiose, ribose and xylose, while all of the isolates assimilated maltose, sucrose and sorbitol. However, adonitol, cellobiose, dextrin, erythritol, fructose, galactose, inulin, mannitol, mannose, raffinose, rhamnose and trehalose were assimilated by some isolates but not by others. All isolates secreted keratinase and DNase, while none secreted phospholipase. Proteinase and lipase were secreted only by some isolates. All but four isolates were resistant to fluconazole, most of them were sensitive to ketoconazole and all were sensitive to itraconazole. Carbohydrate assimilation was the method that presented the highest discriminatory index, and also the method that displayed the largest number of biotypes. Taken together, these data suggest that significant phenotypic variations exist among T. rubrum isolates. They seem to occur independently from their geographic origins.

Multiresistant extended-spectrum beta-lactamase-producing Klebsiella pneumoniae causing an outbreak of nosocomial bloodstream infection.

This article describes an outbreak of bloodstream infection due to clonal dissemination of multiresistant Klebsiella pneumoniae in a neonatal area, during August 1999, in Mexico City General Hospital. The intestinal tract was the likely reservoir, and intensification of Contact Precaution measures contained the outbreak.

Outbreak of nosocomial sepsis and pneumonia in a newborn intensive care unit by multiresistant extended-spectrum beta-lactamase-producing Klebsiella pneumoniae: high impact on mortality.

We describe a case-control study of a small outbreak of nosocomial sepsis and pneumonia with high mortality due to clonal dissemination of a multiresistant Klebsiella pneumoniae in the neonatal intensive care unit of a Mexican institution. Our study helped to change nosocomial infection control policy in this hospital.

Phenotypic characterization of Microsporum canis isolated from cats and dogs.

To characterize strains of Microsporum canis that infect dogs and cats in São Paulo city, 30 isolates of this dermatophyte were tested for their ability to assimilate carbon and nitrogen sources, for proteinase and phospholipase secretion, for susceptibility to yeast killer toxins, and for susceptibility to the antifungals fluconazole, ketoconazole, itraconazole, 5-fluorocytosine and amphotericin B, in E test. All samples assimilated the nitrogen sources asparagine, ammonium sulphate, urea and sodium nitrate, as well as the carbon sources inulin, mannitol, trehalose, meso-erythritol, maltose, mannose, sorbitol, cellobiose, fructose and dextrin. Not all the samples assimilated adonitol, galactose, arabinose, rhamnose, raffinose, melibiose, ribose and sucrose, and none of them was capable of growing with dulcitol, lactose, or xylose as the only carbon source. Proteinase and phospholipase secretion was observed for most isolates. In the test of yeast killer toxin, 10 types could be identified, with four types exclusively observed in isolates from dogs and two types exclusively observed in isolates from cats. In the E test, all isolates were found to be resistant to the fluconazole and 5-fluorocytosine, while they were variably sensitive to amphotericin B, ketoconazole and itraconazole. When the data were submitted to the qualitative analysis in the matrix distance program FITOPAC, the similarity of the isolates could be assessed.

Genomic variability of Haemophilus influenzae isolated from Mexican children determined by using enterobacterial repetitive intergenic consensus sequences and PCR.

Genomic fingerprints from 92 capsulated and noncapsulated strains of Haemophilus influenzae from Mexican children with different diseases and healthy carriers were generated by PCR using the enterobacterial repetitive intergenic consensus (ERIC) sequences. A cluster analysis by the unweighted pair-group method with arithmetic averages based on the overall similarity as estimated from the characteristics of the genomic fingerprints, was conducted to group the strains. A total of 69 fingerprint patterns were detected in the H. influenzae strains. Isolates from patients with different diseases were represented by a variety of patterns, which clustered into two major groups. Of the 37 strains isolated from cases of meningitis, 24 shared patterns and were clustered into five groups within a similarity level of 1.0. One fragment of 1.25 kb was common to all meningitis strains. H. influenzae strains from healthy carriers presented fingerprint patterns different from those found in strains from sick children. Isolates from healthy individuals were more variable and were distributed differently from those from patients. The results show that ERIC-PCR provides a powerful tool for the determination of the distinctive pathogenicity potentials of H. influenzae strains and encourage its use for molecular epidemiology investigations.

Klebsiella pneumoniae 35 and 36 kDa porins are common antigens in different serotypes and induce opsonizing antibodies.

BACKGROUND: Klebsiella pneumoniae is a major cause of neonatal sepsis and nosocomial infections in Mexico. Antibiotic therapy is the first choice for treatment but the increase in multiple resistance strains has forced scientists to look for alternative treatments, such as immunotherapy. In this work, we propose that porins could be a common antigen among four different capsular serotypes of Klebsiella pneumoniae for the production of immune sera with opsonizing capacity. METHODS: The 35 and 36 kDa porins from four different serotypes of the bacteria were isolated by the Nikaido method followed by purification in Sephacryl column chromatography. The 36 kDa of serotype K8 was further purified by electroelution. The 35 and 36 kDa porins were used to obtain rabbit polyclonal antibodies (PolyAb) to the four serotypes and the 36 kDa from K8 for the production of monoclonal antibodies (MoAb). Antigenic reactivity of PolyAb and MoAb were analyzed by ELISA and WB and their opsonizing capacity for human PMN was measured by chemiluminescence (CL) using capsulated and non-capsulated bacteria. RESULTS: Porins from the four strains showe electrophoretic homology and cross reaction by ELISA and WB. CL assays indicated that PolyAb opsonized heterologous strains and that MoAb perform this in the absence of capsule. CONCLUSIONS: K.pneumoniae 35 and 36 kDa porins are common antigens for the four serotypes studied and induce opsonizing antibodies.

State of immunization in the Americas.

Countries in the Americas have led the world in conquering infectious diseases preventable through vaccination. In 1971, the Western hemisphere achieved smallpox eradication. In 1991, the Americas were free of indigenous transmission of wild poliovirus. In 1998, overall regional vaccination coverage was 86% for diphtheria-pertussis-tetanus, 89% for oral poliovirus vaccine 3, 98% for bacille Calmette-Guérin vaccine, and 85% for measles. These figures confirm that most of the children in the Americas are protected against these diseases. The breakthroughs obtained in immunization have stimulated countries to promote new initiatives aimed at the control and eradication of other vaccine-preventable diseases and to introduce new vaccines into routine schedules. In the 21st century, vaccines will remain the most cost-effective means of preventing diseases and avoiding expensive treatment costs.

Hepatitis A in Latin America: a changing epidemiologic pattern.

In a multicenter study, hepatitis A virus (HAV) seroprevalence was surveyed in six countries in Latin America in which in 12,000 subjects were stratified for age. The highest rates of seroprevalence were recorded in the Dominican Republic (89.0%) and Mexico (81.0%), with lower rates in Brazil (64.7%), Chile (58.1%), Venezuela (55.7%), and Argentina (55.0%). The seroprevalence of HAV in children between 1 and 5 years of age was less than 50%, except in the Dominican Republic. In the 5-10-year-old age group, seroprevalence rates have also decreased compared with previous reports. This suggests that the epidemiology is shifting from high to intermediate endemicity, with the population susceptible to HAV infection shifting from children to adolescents and adults. Furthermore, data from Brazil, Argentina, and Mexico show that HAV seroprevalence is significantly lower in people living in medium and high socioeconomic conditions. This study suggests the need for appropriate vaccination programs to be implemented targeting children, adolescents, and adults, particularly in higher socioeconomic groups.

Outer membrane protein profiles of paired nasopharyngeal and middle ear isolates of nontypable Haemophilus influenzae from Mexican children with acute otitis media.

We studied nontypable Haemophilus influenzae (NTHi) isolates from simultaneous cultures of nasopharyngeal exudates (NEs) and middle ear fluids (MEFs) obtained by tympanocentesis from 57 children with acute otitis media (AOM). Preparations of outer membrane proteins (OMPs) from 14 pairs of NTHi strains recovered from NEs and MEFs from 10 children with unilateral AOM and four with bilateral AOM were subjected to sodium dodecyl sulfate polyacrylamide gel electrophoresis. The NTHi subtypes were determined by comparing the OMP profiles of the isolated strains with those of eight reference NTHi subtypes. Of the 14 pairs, 10 (71%) were identical, and one (8%) was different; three strains isolated from NEs (21%) did not correspond to any of the reference subtypes (nonsubtypable). Subtypes 4, 6, 5, 3, and 8 were isolated in the present study, thereby showing that their distribution is similar to that of subtypes isolated from children with AOM in the United States and suggesting that common otogenic strains are widely distributed in North America.