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Cefiderocol, a novel siderophore cephalosporin, demonstrates promising in vitro activity against multidrug-resistant Gram-negative bacteria, including carbapenemase-producing strains. Nonetheless, only a few reports are available regarding the acquisition of resistance in clinical settings, primarily due to its recent usage. This study aimed to investigate cefiderocol resistance using an in vitro resistance development model to gain insights into the underlying molecular resistance mechanisms. Cefiderocol susceptible reference strains (Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa) and a clinical Acinetobacter baumannii complex isolate were exposed to increasing cefiderocol concentrations using a high-throughput resistance development model. Cefiderocol susceptibility testing was performed using broth microdilution. Whole-genome sequencing was employed to identify newly acquired resistance mutations. Our in vitro resistance development model led to several clones of strains exhibiting cefiderocol resistance, with MIC values 8-fold to 512-fold higher than initial levels. In total, we found 42 different mutations in 26 genes, of which 35 could be described for the first time. Putative loss-of-function mutations were detected in the envZ, tonB, and cirA genes in 13 out of 17 isolates, leading to a decrease in cefiderocol influx. Other potential resistance mechanisms included multidrug efflux pumps (baeS, czcS, nalC), antibiotic-inactivating enzymes (ampR, dacB), and target mutations in penicillin-binding-protein genes (mrcB). This study reveals new insights into underlying molecular resistance mechanisms against cefiderocol. While mutations leading to reduced influx via iron transporters was the most frequent resistance mechanism, we also detected several other novel resistance mutations causing cefiderocol resistance.
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BACKGROUND: Target Product Profiles (TPPs) are instrumental to help optimise the design and development of therapeutics, vaccines, and diagnostics - these products, in order to achieve the intended impact, should be aligned with users' preferences and needs. However, patients are rarely involved as key stakeholders in building a TPP. METHODOLOGY: Thirty-three cutaneous leishmaniasis (CL) patients from Brazil, Colombia, and Austria, infected with New-World Leishmania species, were recruited using a maximum variation approach along geographic, sociodemographic and clinical criteria. Semi-structured interviews were conducted in the respective patient's mother tongue. Transcripts, translated into English, were analysed using a framework approach. We matched disease experiences, preferences, and expectations of CL patients to a TPP developed by DNDi (Drug for Neglected Diseases initiative) for CL treatment. PRINCIPAL FINDINGS: Patients' preferences regarding treatments ranged from specific efficacy and safety endpoints to direct and significant indirect costs. Respondents expressed views about trade-offs between efficacy and experienced discomfort/adverse events caused by treatment. Reasons for non-compliance, such as adverse events or geographical and availability barriers, were discussed. Considerations related to accessibility and affordability were relevant from the patients' perspective. CONCLUSIONS/SIGNIFICANCE: NTDs affect disadvantaged populations, often with little access to health systems. Engaging patients in designing adapted therapies could significantly contribute to the suitability of an intervention to a specific context and to compliance, by tailoring the product to the end-users' needs. This exploratory study identified preferences in a broad international patient spectrum. It provides methodological guidance on how patients can be meaningfully involved as stakeholders in the construction of a TPP of therapeutics for NTDs. CL is used as an exemplar, but the approach can be adapted for other NTDs.
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Leishmaniasis Cutánea , Enfermedades Desatendidas , Humanos , Enfermedades Desatendidas/prevención & control , Leishmaniasis Cutánea/tratamiento farmacológico , Desarrollo de Medicamentos , Investigación Cualitativa , Costos y Análisis de CostoRESUMEN
Background: The esophageal-tracheal Combitube (ETC) was developed for the management of difficult airways but can also be used for general anaesthesia. Methods: This clinical study collected data from patients undergoing anaesthesia with the ETC in order to assess the rate of complications. Results: Five hundred forty patients were ventilated with the ETC. In 94.8% (512/540), insertion was performed for the first time by the respective physician. The following minor complications were observed: 38.7% sore throat, 30.9% blood on tube as sign of mucosal lesions and 17.0% cyanotic tongue. Experience decreased the risk of mucosal lesions (odds ratio [OR]: 2.3, 95% confidence interval [CI]: 1.5-3.5). A higher than recommended volume of the oropharyngeal cuff was associated with blood on the ETC (OR: 1.5, 95% CI: 1.0-2.3) and tongue cyanosis (OR: 2.3, 95% CI: 1.4-3.7). Ventilation for more than 2 h was associated with tongue cyanosis (OR: 2.2, 95% CI: 1.6-3.1) and tongue protrusion (OR: 1.4, 95% CI: 1.1-1.9). Conclusion: We conclude that the Combitube may be used for short procedures requiring general anaesthesia, but the high rate of minor complications limits its value when other alternatives such as a laryngeal mask airway are available. The tested method appears safe regarding major complications, but minor complications are common. Adherence to recommended cuff volumes, experience with the ETC and limiting its use to surgeries lasting less than 2 h might reduce the rate of complications.
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Intubación Intratraqueal , Máscaras Laríngeas , Humanos , Intubación Intratraqueal/métodos , Máscaras Laríngeas/efectos adversos , Respiración , Anestesia General/efectos adversos , Cianosis/etiologíaRESUMEN
INTRODUCTION: Neutrophilic granulocytes represent the first line of defense against microorganisms. Granulocytes phagocytose microorganisms and specifically synthesize oxygen radicals against them, which eventually kills the invaders. METHODS: Neutrophilic granulocytes were isolated from peripheral blood of healthy volunteer donors. Putative interference of new-generation antibiotics with neutrophil function was tested using a collection of granulocyte-stimulating agents and Amplex™ Red-based plate assay and flow cytometry-based respiratory burst assays. In addition, phagocytosis of E. coli, IL-8 production, bactericidal activity, and CD62L expression of granulocytes were evaluated. RESULTS: Of note, we found that the two glycopeptide antibiotics dalbavancin and teicoplanin inhibited ROS production upon granulocyte activation via different signaling pathways in a dose-dependent manner. Dalbavancin also blocked the PMA-induced shedding of CD62L. In contrast, the oxazolidinone antibiotics tedizolid and linezolid had no effect on neutrophil function, while the combination of ceftazidime/avibactam dose dependently inhibited the fMLP/Cytochalasin B-induced granulocyte burst in a dose-dependent manner. Additionally, we showed that dalbavancin and teicoplanin as well as sulfametrole/trimethoprim and ceftazidime/avibactam inhibited baseline and PMA-induced IL-8 production by neutrophilic granulocytes. Moreover, dalbavancin impaired the bactericidal activity of neutrophilic granulocytes. CONCLUSION: We here identified hitherto unknown inhibitory effects of several classes of antibiotics on the effector functions of neutrophilic granulocytes.
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Ceftazidima , Neutrófilos , Humanos , Ceftazidima/metabolismo , Ceftazidima/farmacología , Teicoplanina/farmacología , Teicoplanina/metabolismo , Escherichia coli , Interleucina-8/metabolismo , Antibacterianos/farmacologíaRESUMEN
Patients after hematopoietic stem cell transplantation (HSCT) are vulnerable to infections due to severe immunosuppression. Live-attenuated vaccines are contraindicated for two years after HSCT. The aim of this study was to assess the persistence of antibodies against measles, mumps, rubella and varicella in the first year after HSCT. Forty patients undergoing autologous (n = 12) or allogeneic (n = 28) HSCT were included in this study. Specific IgG antibodies to measles, mumps, rubella and varicella virus in serum samples were assessed by the LIAISON XL, a fully automated chemiluminescence analyzer, at seven different time points starting one week before HSCT and up to 12 months after HSCT. At baseline, before HSCT, most patients showed antibodies against measles (100%), mumps (80%), rubella (97.5%) and varicella (92.5%). Although titers declined over time, most patients retained antibodies against measles (92.5%), mumps (62.5%), rubella (87.5%) and varicella (85%) up to 12 months after HSCT. There was no significant difference between patients with and without GvHD concerning persistence of antibody titers. Significantly higher varicella titers were detected in autologous patients compared to patients with chronic GvHD. Considering that live-attenuated vaccines should not be administered during the first year after HSCT, the persistence of antibodies against these diseases is relevant.
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During the last few years, we have experienced a shift in how we evaluate the effectiveness of vaccines [...].
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The aim of this prospective study was to assess lymphocyte proliferative and cytokine response prior to and following tick-borne encephalitis (TBE) immunization among patients after allogeneic hematopoietic stem cell transplantation (HSCT). Seventeen adult patients 11-13 months after HSCT and eight unvaccinated healthy adults received up to three TBE vaccinations. Following in vitro stimulation with TBE-antigen, lymphocyte proliferation and cytokine secretion (IL-2, IL-10, IL-13, TNF-alpha, IFN-gamma, GM-CSF) were analyzed by thymidine incorporation assay and the Luminex system. Ten patients (59%) showed significant baseline TBE-specific lymphocyte proliferation (stimulation index (SI) > 3) prior to vaccination, but none of the unvaccinated controls (p = 0.002). All patients with a TBE-specific antibody response after two vaccinations (at least 2-fold increase of neutralization test titers) exhibited a strong TBE-specific lymphocyte proliferative response at baseline (SI > 10). Patients with sibling donors had a significantly stronger baseline TBE-specific lymphocyte proliferative and IL-13 cytokine response than patients with unrelated donors (p < 0.05). In conclusion, a relevant proportion of patients showed TBE-specific lymphocyte proliferative and cytokine responses prior to vaccination after HSCT, which predicted the humoral response to the vaccine. Patients with vaccinated sibling donors were more likely to elicit a cellular immune response than patients with unrelated donors of unknown vaccination status.
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[This corrects the article DOI: 10.1038/s41541-020-00215-1.].
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The aim of this prospective study was to characterize the humoral immune response to TBE vaccination after hematopoietic stem cell transplantation (HSCT). Nineteen adult patients 11-13 months after HSCT and 15 age-matched immunocompetent adults received up to three TBE vaccinations. Antibodies against TBE virus were measured by neutralization test (NT). As primary endpoint, the antibody response (NT titer of ≥10 and at least a twofold increase from baseline 4 weeks after second vaccination) was compared between patients and controls using Fisher exact test. Prior vaccination, 15 (79%) HSCT patients still had detectable neutralizing antibodies. At primary endpoint, the antibody response was significantly lower in patients than in controls (35% versus 93%; p < 0.001). The CD4+ cell count was a predictor for an antibody response in patients (p = 0.019). Interestingly, the majority of HSCT patients still had detectable antibodies prior vaccination. Following vaccination, antibody response in HSCT patients was associated with the CD4+ cell count.
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Although the costs of dengue illness to patients and households have been extensively studied in endemic populations, international travelers have not been the focus of costing studies. As globalization and human travel activities intensify, travelers are increasingly at risk for emerging and reemerging infectious diseases, such as dengue. This exploratory study aims to investigate the impact and out-of-pocket costs of dengue illness among travelers. We conducted a prospective study in adult travelers with laboratory-confirmed dengue and recruited patients at travel medicine clinics in eight different countries from December 2013 to December 2015. Using a structured questionnaire, we collected information on patients and their health-care utilization and out-of-pocket expenditures, as well as income and other financial losses they incurred because of dengue illness. A total of 90 patients participated in the study, most of whom traveled for tourism (74%) and visited countries in Asia (82%). Although 22% reported hospitalization and 32% receiving ambulatory care while traveling, these percentages were higher at 39% and 71%, respectively, after returning home. The out-of-pocket direct and indirect costs of dengue illness were US$421 (SD 744) and US$571 (SD 1,913) per episode, respectively, averaging to a total out-of-pocket cost of US$992 (SD 2,052) per episode. The study findings suggest that international travelers incur important direct and indirect costs because of dengue-related illness. This study is the first to date to investigate the impact and out-of-pocket costs of travel-related dengue illness from the patient's perspective and paves the way for future economic burden studies in this population.
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Dengue/economía , Dengue/terapia , Gastos en Salud , Enfermedad Relacionada con los Viajes , Viaje , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Aceptación de la Atención de Salud , Estudios Prospectivos , Adulto JovenRESUMEN
Accurate assessment is essential to implementing effective mental health treatment; however, little research has explored child clinicians' assessment practices in applied settings. The current study thus examines practitioners' use of evidence-based assessment (EBA) instruments (i.e., self-report measures and structured interviews), specificity of identified diagnoses (i.e., use of specific diagnostic labels vs. nonstandardized labels, not otherwise specified [NOS] diagnoses, and adjustment disorder diagnoses), and documentation of Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev., DSM-IV-TR, American Psychiatric Association, 2000) criteria. Use of these practices was evaluated via analysis of documentation contained within a regional medical center's medical records. This analysis was limited to 2,499 session notes from patient appointments associated with psychiatric disorders newly diagnosed during 2013. In total, session notes were linked to 694 children aged 7 to 17. Results indicated that EBA use was low overall, although self-report measures were utilized relatively frequently versus structured interviews. Diagnostic specificity was also low overall and clinicians rarely documented full diagnostic criteria; however, EBA use was associated with increased diagnostic specificity. Further, clinicians practicing in psychological, psychiatric, and primary care settings were more likely to use self-report measures as compared to those practicing in an integrated behavioral health social work setting. In addition, structured interviews were most likely to be utilized by clinicians practicing in a psychological services setting. Finally, clinicians were more likely to use self-report measures when the identified primary concern was a mood disorder or attention-deficit/hyperactivity disorder (ADHD). Based on these results, we provide suggestions and references to resources for clinicians seeking to improve the quality of their assessments via implementation of EBA. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
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Prestación Integrada de Atención de Salud/estadística & datos numéricos , Práctica Clínica Basada en la Evidencia/estadística & datos numéricos , Entrevista Psicológica , Trastornos Mentales/diagnóstico , Servicios de Salud Mental/estadística & datos numéricos , Calidad de la Atención de Salud/estadística & datos numéricos , Autoinforme/estadística & datos numéricos , Adolescente , Trastorno por Déficit de Atención con Hiperactividad/diagnóstico , Niño , Femenino , Humanos , Masculino , Trastornos del Humor/diagnósticoRESUMEN
This study analyzed the performance of different molecular technologies along with blood culture (BC) in the diagnosis of bloodstream infections (BSI) in patients from internal medicine wards - including intensive care units (ICUs) - and the emergency room. Patients with systemic inflammatory response syndrome were prospectively included. BCs and EDTA whole blood were obtained simultaneously. The latter was analyzed by PCR combined with electrospray ionization mass spectrometry (PCR/ESI-MS; IRIDICA BAC BSI assay, Abbott) and by SeptiFast (Roche). Cases were classified as BSI according to adapted European Centre for Disease Prevention and Control criteria. Out of 462 analyzed episodes, 193 with valid test results fulfilled the inclusion criteria and were further evaluated. Sixty-nine (35.8%) were classified as BSI. PCR/ESI-MS showed a significantly better overall performance than BC (p = 0.004) or SeptiFast (p = 0.034). Only in patients from the ICU the performance of SeptiFast was comparable to that of PCR/ESI-MS. Mainly due to the negative effect of antimicrobial pre-treatment on BC results, the cumulative performance of each of the molecular tests with BC was significantly higher than that of BC alone (p < 0.001). SeptiFast and in particular the broad-range pathogen detection system PCR/ESI-MS proved to be an essential addition to BC-based diagnostics in BSI.
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Cultivo de Sangre , Reacción en Cadena de la Polimerasa , Sepsis/diagnóstico , Espectrometría de Masa por Ionización de Electrospray , Cultivo de Sangre/métodos , Cultivo de Sangre/normas , Femenino , Humanos , Masculino , Reacción en Cadena de la Polimerasa/métodos , Reacción en Cadena de la Polimerasa/normas , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Sepsis/sangre , Sepsis/etiología , Sepsis/terapia , Espectrometría de Masa por Ionización de Electrospray/métodos , Espectrometría de Masa por Ionización de Electrospray/normasRESUMEN
BACKGROUND: Patients with inflammatory rheumatic diseases are at higher risk for influenza and current guidelines recommend vaccination for this group of patients. The aim of this study was to evaluate the vaccination coverage and predictors for influenza vaccination among patients with inflammatory rheumatic diseases. METHODS: This survey was conducted at the outpatient rheumatology clinic at the Medical University of Vienna between July and October 2017. All patients diagnosed with an inflammatory rheumatic disease and receiving immunosuppressive therapy were asked to complete a questionnaire about their influenza vaccination status for 2016/17. RESULTS: 490 patients with rheumatic diseases completed a questionnaire (33% male, mean age 55.3â¯years). The influenza vaccination rate for the previous season was 25.3% (nâ¯=â¯124/490). Predictors for a positive influenza vaccination status were higher age (Adjusted Odds Ratio 5.0, 95% Confidence Interval 2.4-10.4) and treatment with biological disease-modifying antirheumatic drugs (AOR 2.0, 95% CI 1.3-3.1). Patients who received a recommendation for influenza vaccination by their general practitioner were significantly more likely to be vaccinated than those who did not (57% vs. 15%, AOR 6.6, 95% CI 4.1-10.8); even more so if they received a recommendation by their rheumatologist (62% vs. 19%, AOR 9.0, 95% CI 4.9-16.5). The main reasons for patients to decline influenza vaccination were fear of side effects (36%), concerns that vaccination might not be effective due to their immunosuppressed condition (38%) or that it might worsen the rheumatic disease (20%). CONCLUSIONS: A moderate influenza vaccination rate of 25.3% was detected among patients with inflammatory rheumatic diseases. Recommendation of the influenza vaccine by a physician exerts the most effective impact on a positive vaccination status.
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Vacunas contra la Influenza/uso terapéutico , Enfermedades Reumáticas/prevención & control , Humanos , Gripe Humana/inmunología , Gripe Humana/prevención & control , Aceptación de la Atención de Salud , Enfermedades Reumáticas/inmunología , Encuestas y Cuestionarios , Vacunación/métodosRESUMEN
There is a well-established association between chronic inflammation and an elevated risk of heart disease among patients with systemic autoimmune conditions. This review aims to summarize existing literature on the relationship between inflammatory bowel disease and ischemic heart disease, heart failure, arrhythmia, and pericarditis, with particular attention to approaches to management and treatment.
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Cardiopatías/etiología , Enfermedades Inflamatorias del Intestino/complicaciones , Cardiopatías/patología , Humanos , PronósticoRESUMEN
Supraglottic airway devices (SADs) have been introduced to assist medical professionals in emergency situations with limited experience in securing airways via conventional endotracheal intubation (ETI). Literature on the use of SADs for securing an airway during pediatric critical settings is scarce, and there is a lack of studies comparing different SADs to each other and to conventional ETI. We conducted a study comparing five different SADs to ETI with regard to success rate, time to first ventilation, and personal rating in a pediatric manikin under simulated physiologic and pathologic airway conditions in 41 pediatricians of varying clinical experience and training. Only the AirQ, AuraG, and laryngeal tube (LT) were inserted within 30 s correctly by all participants under physiologic conditions. In tongue edema (TE), AirQ and LT had the highest success rate. In limited mobility of the cervical spine (CS), AirQ, AuraG, and LT again all were inserted within 30 s. In a multivariate analysis, factors influencing the success were experience with the respective device and level of medical education. Under TE conditions, there were significantly longer insertion times for the ETI, laryngeal mask airway (LMA), and EzT. Under CS conditions, there were significantly longer insertion times for the ETI, LMA, LT, and EzT. A multivariate analysis showed experience with the respective device to be the only factor of influence on time to first ventilation. CONCLUSION: LT, AuraG, and AirQ were superior in providing fast and effective ventilation during simulated difficult airway situations in pediatricians. What is Known: ⢠Supraglottic airway devices have been introduced for medical professionals who lack experience for managing difficult airway situations. ⢠A variety of these devices have been developed so far, but not compared to each other yet. What is New: ⢠We compared five different supraglottic airway devices with regard to success rate, time to first ventilation, and personal rating in a pediatric manikin under simulated physiologic and pathologic airway conditions. ⢠Laryngeal tube, AuraG, and AirQ were superior in providing fast and effective ventilation during simulated difficult airway situations in pediatricians with varying clinical experience.
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Competencia Clínica , Educación Médica Continua , Máscaras Laríngeas , Maniquíes , Pediatría/educación , Retención en Psicología , Entrenamiento Simulado , Adulto , Austria , Niño , Femenino , Humanos , Masculino , Factores de TiempoRESUMEN
Skin and soft tissue infections (SSTIs) are among the most common health problems in travellers returning from tropical and subtropical countries. Importantly, the prevalence of Staphylococcus aureus, the most common pathogen for purulent SSTIs, with specific drug resistance, such as methicillin resistant Staphylococcus aureus (MRSA) and those expressing virulence genes, such as Panton-Valentine-leukocidin is higher in tropical regions than in most high resource settings. This poses challenges for the empirical antimicrobial treatment of SSTIs in returning travellers. This short report describes a patient with a recent travel history to Hong Kong, Singapore and the Philippines who presented with multiple mosquito bites on both upper extremities and secondary bacterial superinfection. He had previously been prescribed oral beta-lactam antimicrobial therapy but lacked adherence to this treatment. Based on the risk for MRSA infection and problems with treatment adherence to oral therapy an outpatient parenteral antimicrobial therapy with dalbavancin was administered on days 0 and 7. Microbiological culture confirmed presence of MRSA and clinical follow-up demonstrated complete remission of the SSTI within 2 weeks. Dalbavancin is a promising treatment option for empirical parenteral treatment of SSTIs in returning travellers, a population at high risk for beta-lactam resistant S. aureus skin infections.
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Absceso/tratamiento farmacológico , Celulitis (Flemón)/tratamiento farmacológico , Staphylococcus aureus Resistente a Meticilina , Infecciones de los Tejidos Blandos/tratamiento farmacológico , Infecciones Cutáneas Estafilocócicas/tratamiento farmacológico , Teicoplanina/análogos & derivados , Enfermedad Relacionada con los Viajes , Adulto , Atención Ambulatoria , Austria , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Servicio de Urgencia en Hospital , Humanos , Infusiones Intravenosas , Masculino , Infecciones de los Tejidos Blandos/diagnóstico , Infecciones Cutáneas Estafilocócicas/diagnóstico , Teicoplanina/uso terapéutico , Clima TropicalRESUMEN
Bacterial pathogens not detectable via commercial blood culture assays represent an important challenge for infectious disease physicians, in particular if clinical symptoms of the illness are non-specific. In this report, Anaplasma phagocytophilum was detected directly in a peripheral blood sample from a febrile patient reporting a tick bite. This was done using a commercial system based on PCR followed by electrospray ionization mass spectrometry (ESI-MS). The diagnosis of a human granulocytic anaplasmosis infection was established using this diagnostic methodology for the first time. Human granulocytic anaplasmosis is a neglected zoonotic disease in Europe. Its seroprevalence is similar in North America and Europe, but in contrast to the USA, it is rarely diagnosed in the old world. PCR followed by ESI-MS is a novel, complex, but highly promising diagnostic methodology for the rapid assessment of rare or exotic pathogens, including intracellular bacteria.
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Anaplasma phagocytophilum/aislamiento & purificación , Ehrlichiosis/diagnóstico , Zoonosis/microbiología , Adulto , Anaplasma phagocytophilum/genética , Animales , Antibacterianos/uso terapéutico , Doxiciclina/uso terapéutico , Ehrlichiosis/sangre , Ehrlichiosis/tratamiento farmacológico , Ehrlichiosis/microbiología , Humanos , Masculino , Enfermedades Desatendidas/diagnóstico , Enfermedades Desatendidas/tratamiento farmacológico , Enfermedades Desatendidas/microbiología , Reacción en Cadena de la Polimerasa , Espectrometría de Masa por Ionización de Electrospray , Mordeduras de Garrapatas/complicaciones , Zoonosis/diagnóstico , Zoonosis/tratamiento farmacológicoRESUMEN
The importance of outcome measures is steadily increasing due to the rise of "pay for performance" and the advent of population health. In 2007, a quality initiative was started due to poor performance on rankings such as the University Health Consortium (UHC) report card. Inherent to all such efforts are common challenges: how to engage the providers; how to gather and ensure the accuracy of the data; how to attribute results to individuals; how to ensure permanent improvements. After analysis, a strategy was developed that included an initial focus on 3 metrics (mortality, infection rates, and complications), leadership from practicing neurosurgeons, protocol development and adherence, and subspecialization. In addition, it was decided that the metrics would initially apply to attending physicians only, but that the entire team would need to be involved. Once the fundamental elements were established, the process could be extended to other measures and providers. To support this effort, special information system tools were developed and a support team formed. As the program matured, measured outcomes improved and more metrics were added (to a current total of 48). For example, UHC mortality ratios (observed over expected) decreased by 75%. Infection rates decreased 80%. The program now involves all trainee physicians, advanced practice providers, nurses, and other staff. This paper describes the design, implementation, and results of this effort, and provides a practical guide that may be useful to other groups undertaking similar initiatives.
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Neurocirugia , Calidad de la Atención de Salud , Humanos , Evaluación de Resultado en la Atención de Salud , Reembolso de Incentivo , TexasRESUMEN
BACKGROUND: Lr16 is a widely deployed leaf rust resistance gene in wheat (Triticum aestivum L.) that is highly effective against the North American Puccinia triticina population when pyramided with the gene Lr34. Lr16 is a seedling leaf rust resistance gene conditioning an incompatible interaction with a distinct necrotic ring surrounding the uredinium. Lr16 was previously mapped to the telomeric region of the short arm of wheat chromosome 2B. The goals of this study were to develop numerous single nucleotide polymorphism (SNP) markers for the Lr16 region and identify diagnostic gene-specific SNP marker assays for marker-assisted selection (MAS). RESULTS: Forty-three SNP markers were developed and mapped on chromosome 2BS tightly linked with the resistance gene Lr16 across four mapping populations representing a total of 1528 gametes. Kompetitive Allele Specific PCR (KASP) assays were designed for all identified SNPs. Resistance gene analogs (RGAs) linked with the Lr16 locus were identified and RGA-based SNP markers were developed. The diagnostic potential of the SNPs co-segregating with Lr16 was evaluated in a diverse set of 133 cultivars and breeding lines. Six SNP markers were consistent with the Lr16 phenotype and are accurately predictive of Lr16 for all wheat lines/cultivars in the panel. CONCLUSIONS: Lr16 was mapped relative to SNP markers in four populations. Six SNP markers exhibited high quality clustering in the KASP assay and are suitable for MAS of Lr16 in wheat breeding programs.