Healthcare risk stratification model for emergency departments based on drugs, income and comorbidities: the DICER-score.

BACKGROUND: During the last decade, the progressive increase in age and associated chronic comorbidities and polypharmacy. However, assessments of the risk of emergency department (ED) revisiting published to date often neglect patients' pharmacotherapy plans, thus overseeing the Drug-related problems (DRP) risks associated with the therapy burden. The aim of this study is to develop a predictive model for ED revisit, hospital admission, and mortality based on patient's characteristics and pharmacotherapy. METHODS: Retrospective cohort study including adult patients visited in the ED (triage 1, 2, or 3) of multiple hospitals in Catalonia (Spain) during 2019. The primary endpoint was a composite of ED visits, hospital admission, or mortality 30 days after ED discharge. The study population was randomly split into a model development (60%) and validation (40%) datasets. The model included age, sex, income level, comorbidity burden, measured with the Adjusted Morbidity Groups (GMA), and number of medications. Forty-four medication groups, associated with medication-related health problems, were assessed using ATC codes. To assess the performance of the different variables, logistic regression was used to build multivariate models for ED revisits. The models were created using a "stepwise-forward" approach based on the Bayesian Information Criterion (BIC). Area under the curve of the receiving operating characteristics (AUCROC) curve for the primary endpoint was calculated. RESULTS: 851.649 patients were included; 134.560 (15.8%) revisited the ED within 30 days from discharge, 15.2% were hospitalized and 9.1% died within 30 days from discharge. Four factors (sex, age, GMA, and income level) and 30 ATC groups were identified as risk factors and combined into a final score. The model showed an AUCROC values of 0.720 (95%CI:0.718-0.721) in the development cohort and 0.719 (95%CI.0.717-0.721) in the validation cohort. Three risk categories were generated, with the following scores and estimated risks: low risk: 18.3%; intermediate risk: 40.0%; and high risk: 62.6%. CONCLUSION: The DICER score allows identifying patients at high risk for ED revisit within 30 days based on sociodemographic, clinical, and pharmacotherapeutic characteristics, being a valuable tool to prioritize interventions on discharge.

PREDICTION OF MULTIDRUG-RESISTANT BACTERIA IN URINARY TRACT INFECTIONS IN THE EMERGENCY DEPARTMENT.

BACKGROUND: Urinary tract infections (UTI) due to multidrug-resistant bacteria are a frequent reason for visiting the emergency department (ED). OBJECTIVES: The aim of this study was to evaluate the applicability of a predictive model of infection by multidrug-resistant microorganisms in UTIs treated in an ED. METHODS: This is a retrospective observational study. Adult patients admitted to an ED with a diagnosis of UTI and positive urine culture were included. The main objective was to evaluate the area under the curve of the receiver operating characteristic (AUC-ROC), the scale proposed by González-del-Castillo, considering infection by a resistant pathogen as the dependent variable and the scale score of the predictive model used as the independent variable. RESULTS: The study included 414 patients with UTIs, 125 (30.2%) of which were caused by multidrug-resistant microorganisms. A total of 38.4% of patients were treated with antibiotics during the previous 3 months and a multidrug-resistant pathogen was isolated from 10.4% of the total during the previous 6 months. The AUC-ROC of the scale for predicting UTIs due to multidrug-resistant microorganisms was 0.79 (95% confidence interval 0.76-0.83), the optimal cut-off point being 9 points, with a sensitivity of 76.8% and a specificity of 71.6%. CONCLUSIONS: The use of the predictive model evaluated is a useful tool in real clinical practice to improve the success of empirical treatment of patients presenting to the ED with a diagnosis of UTI and positive urine culture pending identification.

Development of an Emergency Revisit Score for Patients With Drug-Related Problems.

Background: Drug-related problems (DRPs) are a frequent reason for emergency departments (EDs) visits. However, data about the risk factors associated with EDs revisits are limited. Objective: To develop and validate a predictive model indicating the risk factors associated with EDs revisit within 30 days of the first visit. Methods: A retrospective cohort study was conducted involving patients who attended an ED for DRPs related to cardiovascular drugs. A 30-day prediction model was created in a derivation cohort by logistic regression. An integer score proportional to the regression coefficient was assigned to the variables with P < .100 in the multivariate analysis. Results: 581 patients (mean age: 80.0 [12.6] years) were included, 133 (22.9%) revisited the ED within 30 days from discharge. Six factors (chronic kidney disease, chronic heart failure, visit to an ED in the preceding 3 months, high anticholinergic burden, DRPs associated with heparin, and safety-related DRPs) were identified as risk factors and combined into a final score, termed the DREAMER score. The model reached an area under the receiver operating curve values of 0.72 (95% confidence interval [CI] = 0.67-0.77) in the referral cohort and 0.71 (95% CI = 0.65-0.74) in the validation cohort (P = .273). Three risk categories were generated, with the following scores and estimated risks: low risk (0-8 points): 11.6%; intermediate risk (9-14 points): 21.3%; and high risk (>14 points): 41.2%. Conclusion and Relevance: The DREAMER score identifies patients at high risk for ED revisit within 30 days from the first visit for a DRPs, being a useful tool to prioritize interventions on discharge.

Factors associated with inappropriate intravenous antibiotic prescription in patients discharged from the emergency department.

WHAT IS KNOWN AND OBJECTIVE: Since 2011, a collaborative territorial network for urgent care has been deployed in Hospital de la Santa Creu i Sant Pau area, which allows direct and early transfer of patients with frailty from the hospital emergency department (ED) to other healthcare settings according to the destination's adequacy. This study aimed to identify factors associated with inappropriate intravenous antibiotic treatment prescribed on referral of patients with frailty based on microbiological culture and analyse the effect of inappropriate prescription on ED reconsultations for any cause 30 days after hospital discharge. METHODS: This observational, retrospective study was performed at a tertiary hospital between March 2018 and February 2019 and included 264 patients. A multivariate analysis, including variables with a P-value <.2 in the previous univariate analysis, was conducted. The variables included in the analysis were age, sex, patient comorbidities (COPD, diabetes and chronic kidney disease), antibiotic treatment in the last 30 days and patient referral (nursing home or family home). RESULTS AND DISCUSSION: Multidrug-resistant bacteria were isolated from 85 patients (51.5% of the isolates). In total, 159 patients received carbapenem, of whom 87 (54.7%) had non-drug-resistant bacteria. The antibiotic was considered inappropriate in 33 patients (12.5%) according to an antibiogram. Only 71 (26.8%) patients had a definitive culture on discharge. Moreover, 73 (28.3%) patients were readmitted after 30 days. Patients with an inappropriate antibiotic treatment had more reconsultations within 30 days than those with adequate treatment (59.3% vs 24.5%; P < .001). In a multivariate analysis, an inappropriate prescription was significantly associated with a higher number of reconsultations at 30 days (OR, 3.22 [1.37-7.57]). WHAT IS NEW AND CONCLUSION: In patients discharged from the ED with intravenous antibiotics, the empirical prescription of an inappropriate drug according to the final culture is a frequent problem and is related to a higher number of reconsultations. This highlights the need to implement early communication strategies with outpatient units to optimize antibiotic therapy once microbiological results are known.

Cost-effectiveness analysis of pharmacogenomics-guided clopidogrel treatment in Spanish patients undergoing percutaneous coronary intervention.

Clopidogrel is an antiplatelet drug given to patients before and after having a percutaneous coronary intervention (PCI). Genomic variants in the CYP2C19 gene are associated with variable enzyme activities affecting drug metabolism and hence, patients with reduced or increased enzymatic function have increased risk of bleeding. We conducted a cost-effectiveness analysis to compare a pharmacogenomics versus a non-pharmacogenomics-guided clopidogrel treatment for coronary artery syndrome patients undergoing PCI in the Spanish healthcare setting. A total of 549 patients diagnosed with coronary artery disease followed by PCI were recruited. Dual antiplatelet therapy was administrated to all patients from 1 to 12 months after PCI. Patients were classified into two groups: the Retrospective group was treated with clopidogrel based on the clinical routine practice and the Prospective group were initially genotyped for the presence of CYP2C19 variant alleles before treatment with those carrying more than one CYP2C19 variant alleles given prasugrel treatment. We collected data on established clinical and health outcome measures, including, per treatment arm: the percentage of patients that suffered from (a) myocardial infraction, (b) major bleeding and minor bleeding, (c) stroke, (d) the number of hospitalization days, and (e) the number of days patients spent in Intensive Care Unit. Our primary outcome measure for the cost-effectiveness analysis was Quality Adjusted Life Years (QALYs). To estimate the treatment cost for each patient, individual data on its resource used were combined with unit price data, obtained from Spanish national sources. The analysis predicts a survival of 0.9446 QALYs in the pharmacogenomics arm and 0.9379 QALYs in the non-pharmacogenomics arm within a 1-year horizon. The cumulative costs per patient were €2971 and €3205 for the Prospective and Retrospective groups, respectively. The main cost driver of total cost in both arms was hospitalization costs. The incremental cost-effectiveness ratio (ICER) was negative indicating that the PGx was a dominant option. Our data show that pharmacogenomics-guided clopidogrel treatment strategy may represent a cost-effective choice compared with non-pharmacogenomics-guided strategy for patients undergoing PCI.

Implication of Haemodiafiltration Flow Rate on Amikacin Pharmacokinetic Parameters in Critically Ill Patients.

BACKGROUND: To analyse the effect of haemodiafiltration (CVVHDF) flow rate on amikacin pharmacokinetics and blood concentrations. METHODS: Prospective observational study. Patients receiving CVVHDF and amikacin treatment were included. Pharmacokinetic parameters were calculated using Bayesian analysis. Spearman correlation test was used in order to assess the influence of CVVHDF flux on amikacin minimum concentration (Cmin) and plasma clearance. RESULTS: Thirty patients undergoing CVVHDF procedures were included. The treatment with amikacin started at an initial mean dose of 12.4 (4.1) mg/kg/day. An association between the flow rate and Cmin value (r = 0.261; p = 0.161) and plasma clearance was found (r = 0.268; p = 0.152). Four patients (13.3%) were not able to achieve peak concentration over MIC value higher than 8. In 4 patients, amikacin had to be discontinued due to a high Cmin value. CONCLUSIONS: Amikacin clearance in patients with CVVHDF is affected by the flow rate used. Therefore, CVVHDF dose should be taken into account when dosing amikacin.

Whole genome sequence of Mycobacterium kansasii isolates of the genotype 1 from Brazilian patients with pulmonary disease demonstrates considerable heterogeneity.

Mycobacterium kansasii is an opportunistic pathogen and one of the most commonly encountered species in individuals with lung disease. We here report the complete genome sequence of 12 clinical isolates of M. kansasii from patients with pulmonary disease in Brazil.

Decontamination Strategies and Bloodstream Infections With Antibiotic-Resistant Microorganisms in Ventilated Patients: A Randomized Clinical Trial.

Importance: The effects of chlorhexidine (CHX) mouthwash, selective oropharyngeal decontamination (SOD), and selective digestive tract decontamination (SDD) on patient outcomes in ICUs with moderate to high levels of antibiotic resistance are unknown. Objective: To determine associations between CHX 2%, SOD, and SDD and the occurrence of ICU-acquired bloodstream infections with multidrug-resistant gram-negative bacteria (MDRGNB) and 28-day mortality in ICUs with moderate to high levels of antibiotic resistance. Design, Setting, and Participants: Randomized trial conducted from December 1, 2013, to May 31, 2017, in 13 European ICUs where at least 5% of bloodstream infections are caused by extended-spectrum ß-lactamase-producing Enterobacteriaceae. Patients with anticipated mechanical ventilation of more than 24 hours were eligible. The final date of follow-up was September 20, 2017. Interventions: Standard care was daily CHX 2% body washings and a hand hygiene improvement program. Following a baseline period from 6 to 14 months, each ICU was assigned in random order to 3 separate 6-month intervention periods with either CHX 2% mouthwash, SOD (mouthpaste with colistin, tobramycin, and nystatin), or SDD (the same mouthpaste and gastrointestinal suspension with the same antibiotics), all applied 4 times daily. Main Outcomes and Measures: The occurrence of ICU-acquired bloodstream infection with MDRGNB (primary outcome) and 28-day mortality (secondary outcome) during each intervention period compared with the baseline period. Results: A total of 8665 patients (median age, 64.1 years; 5561 men [64.2%]) were included in the study (2251, 2108, 2224, and 2082 in the baseline, CHX, SOD, and SDD periods, respectively). ICU-acquired bloodstream infection with MDRGNB occurred among 144 patients (154 episodes) in 2.1%, 1.8%, 1.5%, and 1.2% of included patients during the baseline, CHX, SOD, and SDD periods, respectively. Absolute risk reductions were 0.3% (95% CI, -0.6% to 1.1%), 0.6% (95% CI, -0.2% to 1.4%), and 0.8% (95% CI, 0.1% to 1.6%) for CHX, SOD, and SDD, respectively, compared with baseline. Adjusted hazard ratios were 1.13 (95% CI, 0.68-1.88), 0.89 (95% CI, 0.55-1.45), and 0.70 (95% CI, 0.43-1.14) during the CHX, SOD, and SDD periods, respectively, vs baseline. Crude mortality risks on day 28 were 31.9%, 32.9%, 32.4%, and 34.1% during the baseline, CHX, SOD, and SDD periods, respectively. Adjusted odds ratios for 28-day mortality were 1.07 (95% CI, 0.86-1.32), 1.05 (95% CI, 0.85-1.29), and 1.03 (95% CI, 0.80-1.32) for CHX, SOD, and SDD, respectively, vs baseline. Conclusions and Relevance: Among patients receiving mechanical ventilation in ICUs with moderate to high antibiotic resistance prevalence, use of CHX mouthwash, SOD, or SDD was not associated with reductions in ICU-acquired bloodstream infections caused by MDRGNB compared with standard care. Trial Registration: ClinicalTrials.gov Identifier: NCT02208154.

Cry1A(b)16 toxin from Bacillus thuringiensis: Theoretical refinement of three-dimensional structure and prediction of peptides as molecular markers for detection of genetically modified organisms.

Transgenic maize produced by the insertion of the Cry transgene into its genome became the second most cultivated crop worldwide. Cry gene from Bacillus thuringiensis kurstaki expresses protein derivatives of crystalline endotoxins which confer insect resistance onto the maize crop. Mandatory labeling of processed food containing or made by genetically modified organisms is in force in many countries, so, it is very urgent to develop fast and practical methods for GMO identification, for example, biosensors. In the absence of an available empirical structure of Cry1A(b)16 protein, a theoretical model was effectively generated, in this work, by homology modeling and molecular dynamics simulations based on two available homologous protein structures. Molecular dynamics simulations were carried out to refine the selected model, and an analysis of its global structure was performed. The refined models of Cry1A(b)16 showed a standard fold and structural characteristics similar to those seen in Bacillus thuringiensis Cry1A(a) insecticidal toxin and Bacillus thuringiensis serovar kurstaki Cry1A(c) toxin. After in silico analysis of Cry1A(b)16, two immunoreactive candidate peptides were selected and specific polyclonal antibodies were produced resulting in antibody-peptide interaction. Biosensing devices are expected to be developed for detection of the Cry1A(b) protein as a marker of transgenic maize in food. Proteins 2017; 85:1248-1257. © 2017 Wiley Periodicals, Inc.

Papiliotrema leoncinii sp. nov. and Papiliotrema miconiae sp. nov., two tremellaceous yeast species from Brazil.

Two yeast species, Papiliotrema leoncinii sp. nov. and Papiliotrema miconiae sp. nov., in the family Rhynchogastremataceae of the Tremellales are proposed. The two species are related to six species of the genus Papiliotrema: Papiliotrema aureus, P. flavescens, P. terrestris, P. baii, P. ruineniae and P. wisconsinensis. The novel species are proposed on the basis of the sequence-based phylogenetic species concept with analysis of the D1/D2 region of the large subunit (LSU) rRNA gene and the internal transcribed spacer (ITS) region. A total of 16 strains of Papiliotrema leoncinii sp. nov. were obtained from freshwater and bromeliad leaves collected in Brazil. Papiliotrema leoncinii sp. nov. differs by 11, 12, 16, 14, 11 and 13 substitutions in the D1/D2 domain from the related species P. aureus, P. flavescens, P. terrestris, P. baii, P. ruineniae and P. wisconsinensis, respectively. Differences of 11 substitutions and 21 or more substitutions in ITS regions were found when the sequences of Papiliotrema leoncinii sp. nov. were compared with P. wisconsinensis and its closest relatives. The type strain of Papiliotrema leoncinii sp. nov. is UFMG-CM-Y374T (=CBS 13918T). Papiliotrema miconiae sp. nov. is represented by two strains isolated from a flower of Miconia sp. and a water sample in Brazil. Papiliotrema miconiae sp. nov. differs from the related species P. aureus and P. ruineniae by eight substitutions, from P. flavescens and P. terrestris by 11 substitutions, from P. baii by 10 substitutions and from P. wisconsinensis by 6 substitutions in the D1/D2 domain, and by 7 substitutions from P. wisconsinensis and more than 19 substitutions in the ITS region from its closest relatives. The type strain of Papiliotrema miconiae sp. nov. is CBS 8358T (ML 3666T=DBVPG-4492T). The MycoBank numbers for Papiliotrema leoncinii sp. nov. and Papiliotrema miconiae sp. nov. are MB 813594 and MB 814882, respectively.

Influence of the HER2 Ile655Val polymorphism on trastuzumab-induced cardiotoxicity in HER2-positive breast cancer patients: a meta-analysis.

BACKGROUND: The HER2 655 A>G genetic variant has recently been associated with trastuzumab-induced cardiotoxicity in HER2 breast cancer patients. Considering previous results, the aim of our study was to validate the role of this polymorphism as a predictor of the cardiac toxicity of trastuzumab in breast cancer patients. METHODS: Our study population was composed of 78 HER2 breast cancer patients receiving trastuzumab. The HER2 655 A>G (rs1136201) genetic variant was genotyped using TaqMan allelic discrimination technology. Patients were classified on the basis of the occurrence of cardiotoxic events or the absence of cardiotoxic events during 1 year after the first infusion. RESULTS: The HER2 655 A>G polymorphism was significantly associated with cardiotoxicity: AG versus AA [P=0.012, odds ratio (OR)=5.12, 95% confidence interval (CI) 1.43-18.36], AG+GG versus AA (P=0.01, OR=5.72, 95% CI 1.50-21.76), AG versus AA+GG (P=0.005, OR=7.17, 95% CI 1.82-28.29). A meta-analysis combining these data with the results from previous studies confirmed this association. CONCLUSION: Our results support the role of the HER2 655 A>G polymorphism as a genetic marker of trastuzumab-induced cardiotoxicity in HER2-positive breast cancer patients.

Bullera vrieseae sp. nov., a tremellaceous yeast species isolated from bromeliads.

Two independent surveys of yeasts associated with different bromeliads in different Brazilian regions led to the proposal of a novel yeast species, Bullera vrieseae sp. nov., belonging to the Tremellales clade (Agaricomycotina, Basidiomycota). Analysis of the sequences in the internal transcribed spacer (ITS) region and D1/D2 domain of the LSU rRNA gene suggested affinity to a phylogenetic lineage that includes Bullera miyagiana and Bullera sakaeratica. Six isolates of the novel species were obtained from different bromeliads and regions in Brazil. Sequence analysis of the D1/D2 domains of the large subunit of the rRNA gene showed that the novel species differs from B. miyagiana and B. sakaeratica by 85 and 64 nt substitutions, respectively and by more than 75 nt substitutions in the ITS region. Phenotypically, Bullera vrieseae sp. nov. can be distinguished from both species based on the assimilation of meso-erythritol, which was negative for B. vrieseae sp. nov. but positive for the others, assimilation of d-glucosamine, which was positive for B. vrieseae sp. nov. but negative for B. miyagiana and of l-sorbose, which was negative for B. vrieseae sp. nov. but positive for B. sakaeratica. The novel species Bullera vrieseae sp. nov. is proposed to accommodate these isolates. The type strain of Bullera vrieseae sp. nov. is UFMG-CM-Y379T (BRO443T; ex-type CBS 13870T).

Multilocus sequence typing scheme versus pulsed-field gel electrophoresis for typing Mycobacterium abscessus isolates.

Outbreaks of infections by rapidly growing mycobacteria following invasive procedures, such as ophthalmological, laparoscopic, arthroscopic, plastic, and cardiac surgeries, mesotherapy, and vaccination, have been detected in Brazil since 1998. Members of the Mycobacterium chelonae-Mycobacterium abscessus group have caused most of these outbreaks. As part of an epidemiological investigation, the isolates were typed by pulsed-field gel electrophoresis (PFGE). In this project, we performed a large-scale comparison of PFGE profiles with the results of a recently developed multilocus sequence typing (MLST) scheme for M. abscessus. Ninety-three isolates were analyzed, with 40 M. abscessus subsp. abscessus isolates, 47 M. abscessus subsp. bolletii isolates, and six isolates with no assigned subspecies. Forty-five isolates were obtained during five outbreaks, and 48 were sporadic isolates that were not associated with outbreaks. For MLST, seven housekeeping genes (argH, cya, glpK, gnd, murC, pta, and purH) were sequenced, and each isolate was assigned a sequence type (ST) from the combination of obtained alleles. The PFGE patterns of DraI-digested DNA were compared with the MLST results. All isolates were analyzable by both methods. Isolates from monoclonal outbreaks showed unique STs and indistinguishable or very similar PFGE patterns. Thirty-three STs and 49 unique PFGE patterns were identified among the 93 isolates. The Simpson's index of diversity values for MLST and PFGE were 0.69 and 0.93, respectively, for M. abscessus subsp. abscessus and 0.96 and 0.97, respectively, for M. abscessus subsp. bolletii. In conclusion, the MLST scheme showed 100% typeability and grouped monoclonal outbreak isolates in agreement with PFGE, but it was less discriminative than PFGE for M. abscessus.

Hannaella pagnoccae sp. nov., a tremellaceous yeast species isolated from plants and soil.

Several independent surveys of yeasts associated with different plant materials and soil led to the proposal of a novel yeast species belonging to the Tremellales clade (Agaricomycotina, Basidiomycota). Analysis of the sequences of the D1/D2 domains and internal transcribed spacer region of the large subunit of the rRNA gene suggested affinity to a phylogenetic lineage that includes Hannaella coprosmaensis, Hannaella oryzae and Hannaella sinensis. Thirty-two isolates were obtained from different sources, including bromeliads, nectar of Heliconia psittacorum (Heliconiaceae), flowers of Pimenta dioica (Myrtaceae), roots and leaves of sugar cane (Saccharum spp.) in Brazil, leaves of Cratoxylum maingayi, Arundinaria pusilla and Vitis vinifera in Thailand, soil samples in Taiwan, and prairie soil in the USA. Sequence analysis of the D1/D2 domains of the large subunit of the rRNA gene showed that the novel species differs from Hannaella coprosmaensis and Hannaella oryzae by 36 and 46 nt substitutions, respectively. A novel species is suggested to accommodate these isolates, for which the name Hannaella pagnoccae sp. nov. is proposed. The type strain is BI118(T) ( = CBS 11142(T) = ATCC MYA-4530(T)).

Drug Interaction Between Oral Cyclosporine Modified and Iron.

OBJECTIVE: To describe a recent case of suspected interaction between oral cyclosporine modified and iron. CASE SUMMARY: A 33-year-old man underwent urgent cardiac transplantation for refractory cardiogenic shock caused by acute myocarditis. The patient had persistently low levels of cyclosporine despite a dose increase of the drug after the change of administration route from intravenous to oral. Spacing the administration of cyclosporine modified from oral iron resolved the problem. This drug interaction was reported as "probable" as determined by a Drug Interaction Probability Scale score of 7. Using this scoring system, the patient experienced a probable drug interaction between cyclosporine and iron both administered orally, and we surmise that the mechanism is that iron physicochemically destabilizes the cyclosporine microemulsion when both are administered concurrently. DISCUSSION: This may be because of the interaction between cyclosporine microemulsion and iron because this cation can destabilize the immunosuppressant dosage form. CONCLUSIONS: Taking into account that joint administration of oral iron and cyclosporine modified can generate a physicochemical interaction that involves a decrease in the absorption of cyclosporine modified, we believe that it is necessary to recommend spacing administrations of both drugs as well as monitoring levels of cyclosporine in order to ensure optimal levels of immunosuppression.

[Experience in the management of immunosuppressant treatment with hepatitis C virus protease inhibitors]. / Experiencia en el manejo de inmunosupresores con los fármacos inhibidores de proteasa frente al virus de la hepatitis C.

INTRODUCTION: Antiviral drugs for the treatment of hepatitis C virus (HCV) infections have a large number of interactions. The aim of this study was to describe the interactions of telaprevir, boceprevir and sofosbuvir with immunosuppressive drugs in liver transplant recipients. METHODS: A retrospective observational study was performed in liver transplant patients with HCV infection who started treatment with telaprevir, boceprevir or sofosbuvir. Dose, regimens and plasma levels of tacrolimus, cyclosporine and sirolimus before and after antiviral treatment initiation were collected. Average variations in dose, dosing interval and immunosuppressive plasma levels after the start of treatment were calculated. RESULTS: Thirty-five patients were included. In patients treated with telaprevir (n = 18), the cyclosporine dose was reduced by an average of 59.1% (SD = 14.6%), yielding an average reduction of 14.6% (18.8%) in plasma levels. The dose of tacrolimus was reduced by 34.3% (31.7%), increasing the dosing interval by a mean of 73.4 (38.2) hours. After this variation, tacrolimus levels were increased by an average of 59.7% (89.6%). In patients treated with boceprevir (n = 4), tacrolimus started with a reduction of 18.1% (9.8%) of the initial dose and an average increase in the dosing interval of 12.0 (16.9) hours, showing a mean reduction in plasma levels of 37.7% (21.8%). Sofosbuvir therapy (n = 13) showed no significant variations in immunosuppressive drug levels. CONCLUSIONS: The interaction of telaprevir and boceprevir with immunosuppressive drugs requires a substantial dose reduction at the beginning of treatment and close monitoring of plasma levels.

[Environmental factors associated with habitat preferences by caddisfly larvae in tropical dry forest watersheds (Tolima, Colombia)]. / Factores ambientales asociados con la preferencia de hábitat de larvas de tricópteros en cuencas con bosque seco tropical (Tolima, Colombia).

River ecosystems, mainly those draining tropical dry forests, are among the most endangered tropical ecosystems and a major conservation priority in South America, as elsewhere. In this study, we assessed the influence of environmental factors (e.g., precipitation) and riparian vegetation on Trichoptera larval assemblages colonizing four substrates (rock, gravel, sand, and litter) in the Venadillo and Opia watersheds (Tolima, Colombia). In each river, five 20m reaches nested into two 100m segments (one at -550 and another at -250masl), were surveyed for benthic invertebrates in the above mentioned substrates. In addition, water samples were collected for physicochemical analyses and the QBR index ("qualitat del bosc de ribera" or riparian forest quality) was applied in both rivers. A total of 6,282 larvae were collected, belonging to 11 families and 22 genera, representing 73.30% and 43.13% of the Trichoptera fauna reported to Colombia, respectively. The most abundant families were Hydropsychidae (49.86%) and Philopotamidae (25.44%) and the least abundant Odontoceridae (0.16%) and Hydrobiosidae (0.06%). The genera Smicridea, Chimarra, Protoptila, Neotrichia, and Leptonema, were common during dry and rainy seasons. The main factors related to changes in composition, richness, and abundance of larval Trichoptera were seasonality and riparian vegetation, which can influence organic matter supply, availability and stability of substrates, and colonization and population dynamics. Trichoptera assemblages showed no significant differences among substrates. However sampling points located at high elevation and in non-urbanized areas offered the largest variety of substrates and richness. Our results indicate that Trichoptera larvae are an important biotic element in freshwater ecosystems and that they are sensitive to environmental changes. Hence, our study suggests that caddisflies may be used as potential organisms for the biomonitoring of tropical dry forest rivers. The implementation of these studies is urgent, considering that degradation of freshwater ecosystems tends to be severe and persistent in dry forest.

Design of a panel of indicators for antibiotic stewardship programs in the Emergency Department. / Diseño de un panel de indicadores para programas de optimización del uso de antimicrobianos en los Servicios de Urgencias.

OBJECTIVE: To develop a panel of indicators to monitor antimicrobial stewardship programs activity in the emergency department. METHODS: A multidisciplinary group consisting of experts in the management of infection in emergency departments and the implementation of antimicrobial stewardship programs (ASP) evaluated a proposal of indicators using a modified Delphi methodology. In the first round, each expert classified the relevance of each proposed indicators in two dimensions (healthcare impact and ease of implementation) and two attributes (prioritization level and frequency). The second round was conducted based on the modified questionnaire according to the suggestions raised and new indicators suggested. Experts modified the prioritization order and rated the new indicators in the same manner as in the first round. RESULTS: 61 potential indicators divided into four groups were proposed: consumption indicators, microbiological indicators, process indicators, and outcome indicators. After analyzing the scores and comments from the first round, 31 indicators were classified as high priority, 25 as intermediate priority, and 5 as low priority. Moreover, 18 new indicators were generated. Following the second round, all 61 initially proposed indicators were retained, and 18 new indicators were incorporated: 11 classified as high priority, 3 as intermediate priority, and 4 as low priority. CONCLUSIONS: The experts agreed on a panel of ASP indicators adapted to the emergency services prioritized by level of relevance. This is as a helpful tool for the development of these programs and will contribute to monitoring the appropriateness of the use of antimicrobials in these units.

Targeted next-generation sequencing panel to investigate antiplatelet adverse reactions in acute coronary syndrome patients undergoing percutaneous coronary intervention with stenting.

Antiplatelet therapy, the gold standard of care for patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI), is one of the therapeutic approaches most associated with the development of adverse drug reactions (ADRs). Although numerous studies have shown that pharmacological intervention based on a limited number of high-evidence variants (primarily CYP2C19*2 and *3) can reduce the incidence of major adverse cardiovascular events (MACEs), ADRs still occur at variable rates (10.1 % in our case) despite personalized therapy. This study aimed to identify novel genetic variants associated with the endpoint of MACEs 12 months after PCI by designing and analyzing a targeted gene panel. We sequenced 244 ACS-PCI-stent patients (109 with event and 135 without event) and 99 controls without structural cardiovascular disease and performed an association analysis to search for unexpected genetic variants. No single nucleotide polymorphisms reached genomic significance after correction, but three novel variants, including ABCA1 (rs2472434), KLB (rs17618244), and ZNF335 (rs3827066), may play a role in MACEs in ACS patients. These genetic variants are involved in regulating high-density lipoprotein levels and cholesterol deposition, and as they are regulatory variants, they may affect the expression of nearby lipid metabolism-related genes. Our findings suggest new targets (both at the gene and pathway levels) that may increase susceptibility to MACEs, but further research is needed to clarify the role and impact of the identified variants before these findings can be incorporated into the therapeutic decision-making process.