RESUMEN
The growing threat of antibiotic-resistant bacterial pathogens necessitates the development of alternative antimicrobial approaches. This is particularly true for chronic wound infections, which commonly harbor biofilm-dwelling bacteria. A novel electrochemical bandage (e-bandage) delivering low-levels of hypochlorous acid (HOCl) was evaluated against Pseudomonas aeruginosa murine wound biofilms. 5 mm skin wounds were created on the dorsum of mice and infected with 106 colony-forming units (CFU) of P. aeruginosa. Biofilms were formed over 2 days, after which e-bandages were placed on the wound beds and covered with Tegaderm. Mice were administered Tegaderm-only (control), non-polarized e-bandage (no HOCl production), or polarized e-bandage (using an HOCl-producing potentiostat), with or without systemic amikacin. Purulence and wound areas were measured before and after treatment. After 48 hours, wounds were harvested for bacterial quantification. Forty-eight hours of polarized e-bandage treatment resulted in mean biofilm reductions of 1.4 log10 CFUs/g (P = 0.0107) vs non-polarized controls and 2.2 log10 CFU/g (P = 0.004) vs Tegaderm-only controls. Amikacin improved CFU reduction in Tegaderm-only (P = 0.0045) and non-polarized control groups (P = 0.0312) but not in the polarized group (P = 0.3876). Compared to the Tegaderm-only group, there was less purulence in the polarized group (P = 0.009). Wound closure was neither impeded nor improved by either polarized or non-polarized e-bandage treatment. Concurrent amikacin did not impact wound closure or purulence. In conclusion, an HOCl-producing e-bandage reduced P. aeruginosa in wound biofilms with no impairment in wound healing, representing a promising antibiotic-free approach for addressing wound infection.
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Infecciones por Pseudomonas , Infección de Heridas , Animales , Ratones , Pseudomonas aeruginosa , Ácido Hipocloroso , Amicacina , Infecciones por Pseudomonas/microbiología , Infección de Heridas/microbiología , Vendajes , Antibacterianos , BiopelículasRESUMEN
OBJECTIVE: To investigate factors affecting the efficacy and tolerability of verapamil for migraine prevention using individual pharmacogenomic phenotypes. BACKGROUND: Verapamil has a wide range of dosing in headache disorders without reliable tools to predict the optimal doses for an individual. METHODS: This is a retrospective chart review examining adults with existing pharmacogenomic reports at Mayo Clinic who had used verapamil for migraine. Effects of six cytochrome P450 phenotypes on the doses of verapamil for migraine prevention were assessed. RESULTS: Our final analysis included 33 migraine patients (82% with aura). The mean minimum effective and maximum tolerable doses of verapamil were 178.2(20-320) mg and 227.9(20-480) mg. A variety of CYP2C9, CYP2D6, and CYP3A5 phenotypes were found, without significant association with the verapamil doses after adjusting for age, sex, body mass index, and smoking status. CONCLUSIONS: We demonstrated a wide range of effective and tolerable verapamil doses used for migraine in a cohort with various pharmacogenomic phenotypes.
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Trastornos Migrañosos , Verapamilo , Adulto , Humanos , Proyectos Piloto , Verapamilo/uso terapéutico , Pruebas de Farmacogenómica , Farmacogenética , Estudios Retrospectivos , Trastornos Migrañosos/tratamiento farmacológico , Trastornos Migrañosos/genética , Trastornos Migrañosos/prevención & control , FenotipoRESUMEN
The antibiofilm activity of a hypochlorous acid (HOCl)-producing electrochemical bandage (e-bandage) was assessed against 14 yeast isolates in vitro. The evaluated e-bandage was polarized at +1.5 VAg/AgCl to allow continuous production of HOCl. Time-dependent decreases in the biofilm CFU counts were observed for all isolates with e-bandage treatment. The results suggest that the described HOCl-producing e-bandage could serve as a potential alternative to traditional antifungal wound biofilm treatments.
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Ácido Hipocloroso , Saccharomyces cerevisiae , Ácido Hipocloroso/farmacología , Antifúngicos/farmacología , Vendajes , BiopelículasRESUMEN
AIMS: As antimicrobial resistance is on the rise, treating chronic wound infections is becoming more complex. The presence of biofilms in wound beds contributes to this challenge. Here, the activity of a novel hypochlorous acid (HOCl) producing electrochemical bandage (e-bandage) against monospecies and dual-species bacterial biofilms formed by bacteria commonly found in wound infections was assessed. METHODS AND RESULTS: The system was controlled by a wearable potentiostat powered by a 3V lithium-ion battery and maintaining a constant voltage of + 1.5V Ag/AgCl, allowing continuous generation of HOCl. A total of 19 monospecies and 10 dual-species bacterial biofilms grown on polycarbonate membranes placed on tryptic soy agar (TSA) plates were used as wound biofilm models, with HOCl producing e-bandages placed over the biofilms. Viable cell counts were quantified after e-bandages were continuously polarized for 2, 4, 6, and 12 hours. Time-dependent reductions in colony forming units (CFUs) were observed for all studied isolates. After 12 hours, average CFU reductions of 7.75 ± 1.37 and 7.74 ± 0.60 log10 CFU/cm2 were observed for monospecies and dual-species biofilms, respectively. CONCLUSIONS: HOCl producing e-bandages reduce viable cell counts of in vitro monospecies and dual-species bacterial biofilms in a time-dependent manner in vitro. After 12 hours, >99.999% reduction in cell viability was observed for both monospecies and dual-species biofilms.
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Ácido Hipocloroso , Infección de Heridas , Humanos , Ácido Hipocloroso/farmacología , Bacterias , Vendajes , BiopelículasRESUMEN
Wound infections are caused by bacteria and/or fungi. The presence of fungal biofilms in wound beds presents a unique challenge, as fungal biofilms may be difficult to eradicate. The goal of this work was to assess the in vitro antibiofilm activity of an H2O2-producing electrochemical bandage (e-bandage) against 15 yeast isolates representing commonly encountered species. Time-dependent decreases in viable biofilm CFU counts of all isolates tested were observed, resulting in no visible colonies with 48 h of exposure by plate culture. Fluorescence microscopic analysis showed extensive cell membrane damage of biofilm cells after e-bandage treatment. Reductions in intracellular ATP levels of yeast biofilm cells were recorded post e-bandage treatment. These results suggest that exposure to H2O2-producing e-bandages reduces in vitro viable cell counts of yeast biofilms, making this a potential new topical treatment approach for fungal wound infections.
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Vendajes , Biopelículas , Peróxido de Hidrógeno , Infección de Heridas , Electroquímica , Humanos , Peróxido de Hidrógeno/farmacología , Infección de Heridas/microbiología , Infección de Heridas/prevención & control , Levaduras/patogenicidadRESUMEN
Omadacycline, vancomycin, and rifampin, as well as rifampin combination therapies, were evaluated in an experimental rat model of methicillin-resistant Staphylococcus aureus (MRSA) osteomyelitis. All treatment groups had less MRSA recovered than saline-treated animals. The emergence of rifampin resistance was observed in 3 of 16 animals with rifampin monotherapy and none with rifampin combination therapy. After treatment, the median tibial bacterial loads were 6.04, 0.1, 4.81, and 5.24 log10 CFU/g for saline-, rifampin-, vancomycin-, and omadacycline-treated animals, respectively. Omadacycline or vancomycin administered with rifampin yielded no detectable MRSA. Omadacycline administered with rifampin deserves evaluation in humans as a potential treatment for osteomyelitis.
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Staphylococcus aureus Resistente a Meticilina , Osteomielitis , Infecciones Estafilocócicas , Animales , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Quimioterapia Combinada , Pruebas de Sensibilidad Microbiana , Osteomielitis/tratamiento farmacológico , Osteomielitis/microbiología , Ratas , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/microbiología , TetraciclinasRESUMEN
BACKGROUND: Drug-resistant epilepsy (DRE) patients not amenable to epilepsy surgery can benefit from neurostimulation. Few data compare different neuromodulation strategies. OBJECTIVE: Compare five invasive neuromodulation strategies for the treatment of DRE: anterior thalamic nuclei deep brain stimulation (ANT-DBS), centromedian thalamic nuclei DBS (CM-DBS), responsive neurostimulation (RNS), chronic subthreshold stimulation (CSS), and vagus nerve stimulation (VNS). METHODS: Single center retrospective review and phone survey for patients implanted with invasive neuromodulation for 2004-2021. RESULTS: N = 159 (ANT-DBS = 38, CM-DBS = 19, RNS = 30, CSS = 32, VNS = 40). Total median seizure reduction (MSR) was 61 % for the entire cohort (IQR 5-90) and in descending order: CSS (85 %), CM-DBS (63 %), ANT-DBS (52 %), RNS (50 %), and VNS (50 %); p = 0.07. The responder rate was 60 % after a median follow-up time of 26 months. Seizure severity, life satisfaction, and quality of sleep were improved. Cortical stimulation (RNS and CSS) was associated with improved seizure reduction compared to subcortical stimulation (ANT-DBS, CM-DBS, and VNS) (67 % vs. 52 %). Effectiveness was similar for focal epilepsy vs. generalized epilepsy, closed-loop vs. open-loop stimulation, pediatric vs. adult cases, and high frequency (>100 Hz) vs. low frequency (<100 Hz) stimulation settings. Delivered charge per hour varied widely across approaches but was not correlated with improved seizure reduction. CONCLUSIONS: Multiple invasive neuromodulation approaches are available to treat DRE, but little evidence compares the approaches. This study used a uniform approach for single-center results and represents an effort to compare neuromodulation approaches.
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Núcleos Talámicos Anteriores , Estimulación Encefálica Profunda , Epilepsia Refractaria , Epilepsia , Adulto , Humanos , Niño , Estimulación Encefálica Profunda/métodos , Epilepsia/terapia , Epilepsia Refractaria/terapia , Convulsiones , Resultado del TratamientoRESUMEN
Helicobacter pylori infection is mainly diagnosed noninvasively, with susceptibility testing traditionally requiring endoscopy. Treatment is empirical, with clarithromycin-based triple therapy recommended where resistance rates are below 15%. Rising rates of clarithromycin resistance, resulting in high clarithromycin-based therapy failure rates, are seen worldwide, but U.S. data are limited. We developed a real-time PCR assay for simultaneous detection of H. pylori and genotypic markers of clarithromycin resistance directly from stool specimens. The assay was validated by testing 524 stool samples using an H. pylori stool antigen test as the reference method for detection accuracy and Sanger sequencing to confirm genotypic susceptibility results. A separate set of 223 antigen-positive stool samples was tested and retrospective medical record review conducted to define clinical utility. PCR resulted in 88.6% and 92.8% sensitivity in the validation and clinical study sets, respectively. Sequencing confirmed correct detection of clarithromycin resistance-associated mutations in all positive validation samples. The PCR-predicted clarithromycin resistance rate was 39% in the clinical data set overall and 31% in treatment-naive patients; the clarithromycin-based triple therapy eradication rate in treatment-naive patients was 62%. The clarithromycin-based triple therapy success was lower when resistance was predicted by PCR (41%) than when no resistance was predicted (70%; P = 0.03). PCR results were positive in 98% of antigen-positive stools from patients tested for eradication. The described PCR assay can accurately and noninvasively diagnose H. pylori, provide genotypic susceptibility, and test for eradication. Our findings support the need for susceptibility-guided therapy in our region if a clarithromycin-based regimen is considered.
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Infecciones por Helicobacter , Helicobacter pylori , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Claritromicina/farmacología , Farmacorresistencia Bacteriana/genética , Infecciones por Helicobacter/diagnóstico , Infecciones por Helicobacter/tratamiento farmacológico , Helicobacter pylori/genética , Humanos , Pruebas de Sensibilidad Microbiana , Reacción en Cadena en Tiempo Real de la Polimerasa , Estudios RetrospectivosRESUMEN
BACKGROUND: Owing to patient intolerance or drug interactions, alternative agents to rifampin are needed for management of staphylococcal periprosthetic joint infection. In the current study, we evaluated rifabutin, rifapentine and rifampin, with and without vancomycin, in a rat model of foreign body osteomyelitis. METHODS: Proximal tibiae were inoculated with methicillin-resistant Staphylococcus aureus (MRSA) and a Kirschner wire (K-wire) implanted in each. After 4 weeks of infection, rifampin, rifabutin, or rifapentine were administered, alone or with vancomycin. Tibiae and K-wires were cultured, and medians were reported as log10 colony-forming units (CFUs) per gram of bone or log10 CFUs per K-wire, respectively. RESULTS: Rifampin, rifabutin or rifapentine administered with vancomycin yielded less MRSA from bones (0.10, 3.02, and 0.10 log10 CFUs/g, respectively) than did no treatment (4.36 log10 CFUs/g) or vancomycin alone (4.64 log10 CFUs/g) (both Pâ ≤â .02). The K-wires of animals receiving no treatment or vancomycin monotherapy recovered medians of 1.76 and 2.91 log10 CFUs/g per K-wire, respectively. In contrast, rifampin, rifabutin and rifapentine administered with vancomycin yielded medians of 0.1 log10 CFUs per K-wire, respectively. Rifampin resistance was detected in a single animal in the rifampin monotherapy group. CONCLUSIONS: Rifabutin or rifapentine with vancomycin were as active as rifampin with vancomycin against MRSA in rat foreign body osteomyelitis, suggesting that rifabutin and/or rifapentine may be alternatives to rifampin in the clinical management of staphylococcal periprosthetic joint infections.
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Antibacterianos/uso terapéutico , Cuerpos Extraños/microbiología , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Osteomielitis/microbiología , Rifabutina/uso terapéutico , Rifampin/análogos & derivados , Infecciones Estafilocócicas/tratamiento farmacológico , Animales , Modelos Animales de Enfermedad , Quimioterapia Combinada , Cuerpos Extraños/complicaciones , Masculino , Osteomielitis/etiología , Ratas , Ratas Wistar , Rifampin/administración & dosificación , Rifampin/uso terapéutico , Infecciones Estafilocócicas/etiología , Vancomicina/administración & dosificación , Vancomicina/uso terapéuticoRESUMEN
BACKGROUND: Continuing medical education (CME) often uses passive educational models including lectures. However, numerous studies have questioned the effectiveness of these less engaging educational strategies. Studies outside of CME suggest that engaged learning is associated with improved educational outcomes. However, measuring participants' engagement can be challenging. We developed and determined the validity evidence for a novel instrument to assess learner engagement in CME. METHODS: We conducted a cross-sectional validation study at a large, didactic-style CME conference. Content validity evidence was established through review of literature and previously published engagement scales and conceptual frameworks on engagement, along with an iterative process involving experts in the field, to develop an eight-item Learner Engagement Instrument (LEI). Response process validity was established by vetting LEI items on item clarity and perceived meaning prior to implementation, as well as using a well-developed online platform with clear instructions. Internal structure validity evidence was based on factor analysis and calculating internal consistency reliability. Relations to other variables validity evidence was determined by examining associations between LEI and previously validated CME Teaching Effectiveness (CMETE) instrument scores. Following each presentation, all participants were invited to complete the LEI and the CMETE. RESULTS: 51 out of 206 participants completed the LEI and CMETE (response rate 25%) Correlations between the LEI and the CMETE overall scores were strong (r = 0.80). Internal consistency reliability for the LEI was excellent (Cronbach's alpha = 0.96). To support validity to internal structure, a factor analysis was performed and revealed a two dimensional instrument consisting of internal and external engagement domains. The internal consistency reliabilities were 0.96 for the internal engagement domain and 0.95 for the external engagement domain. CONCLUSION: Engagement, as measured by the LEI, is strongly related to teaching effectiveness. The LEI is supported by robust validity evidence including content, response process, internal structure, and relations to other variables. Given the relationship between learner engagement and teaching effectiveness, identifying more engaging and interactive methods for teaching in CME is recommended.
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Educación Médica Continua , Estudiantes , Estudios Transversales , Humanos , Aprendizaje , Reproducibilidad de los ResultadosRESUMEN
PURPOSE: Experiential learning has been suggested as a framework for planning continuing medical education (CME). We aimed to (1) determine participants' learning styles at traditional CME courses and (2) explore associations between learning styles and participant characteristics. MATERIALS AND METHODS: Cross-sectional study of all participants (n = 393) at two Mayo Clinic CME courses who completed the Kolb Learning Style Inventory and provided demographic data. RESULTS: A total of 393 participants returned 241 surveys (response rate, 61.3%). Among the 143 participants (36.4%) who supplied complete demographic and Kolb data, Kolb learning styles included diverging (45; 31.5%), assimilating (56; 39.2%), converging (8; 5.6%), and accommodating (34; 23.8%). Associations existed between learning style and gender (p = 0.02). For most men, learning styles were diverging (23 of 63; 36.5%) and assimilating (30 of 63; 47.6%); for most women, diverging (22 of 80; 27.5%), assimilating (26 of 80; 32.5%), and accommodating (26 of 80; 32.5%). CONCLUSIONS: Internal medicine and psychiatry CME participants had diverse learning styles. Female participants had more variation in their learning styles than men. Teaching techniques must vary to appeal to all learners. The experiential learning theory sequentially moves a learner from Why? to What? to How? to If? to accommodate learning styles.
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Logro , Educación Médica Continua/métodos , Satisfacción Personal , Adulto , Actitud del Personal de Salud , Estudios Transversales , Femenino , Humanos , Masculino , Factores Sexuales , Encuestas y CuestionariosRESUMEN
We have previously demonstrated that culturing periprosthetic tissue in blood culture bottles (BCBs) improves sensitivity compared to conventional agar and broth culture methods for diagnosis of prosthetic joint infection (PJI). We have also shown that prosthesis sonication culture improves sensitivity compared to periprosthetic tissue culture using conventional agar and broth methods. The purpose of this study was to compare the diagnostic accuracy of tissue culture in BCBs (subsequently referred to as tissue culture) to prosthesis sonication culture (subsequently referred to as sonicate fluid culture). We studied 229 subjects who underwent arthroplasty revision or resection surgery between March 2016 and October 2017 at Mayo Clinic in Rochester, Minnesota. Using the Infectious Diseases Society of America (IDSA) PJI diagnostic criteria (omitting culture criteria) as the gold standard, the sensitivity of tissue culture was similar to that of the sonicate fluid culture (66.4% versus 73.1%, P = 0.07) but was significantly lower than that of the two tests combined (66.4% versus 76.9%, P < 0.001). Using Bayesian latent class modeling, which assumes no gold standard for PJI diagnosis, the sensitivity of tissue culture was slightly lower than that of sonicate fluid culture (86.3% versus 88.7%) and much lower than that of the two tests combined (86.3% versus 99.1%). In conclusion, tissue culture in BCBs reached sensitivity similar to that of prosthesis sonicate fluid culture for diagnosis of PJI, but the two tests combined had the highest sensitivity without compromising specificity. The combination of tissue culture in BCBs and sonicate fluid culture is recommended to achieve the highest level of microbiological diagnosis of PJI.
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Técnicas Bacteriológicas/instrumentación , Técnicas Bacteriológicas/métodos , Infecciones Relacionadas con Prótesis/diagnóstico , Manejo de Especímenes/métodos , Técnicas de Cultivo de Tejidos/métodos , Adulto , Anciano , Anciano de 80 o más Años , Teorema de Bayes , Técnicas de Cultivo de Célula/instrumentación , Técnicas de Cultivo de Célula/métodos , Recuento de Colonia Microbiana , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Infecciones Relacionadas con Prótesis/microbiología , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Sonicación , Manejo de Especímenes/instrumentación , Infecciones Estafilocócicas/diagnóstico , Staphylococcus/crecimiento & desarrollo , Staphylococcus/aislamiento & purificación , Técnicas de Cultivo de Tejidos/instrumentaciónRESUMEN
Metagenomic shotgun sequencing has the potential to transform how serious infections are diagnosed by offering universal, culture-free pathogen detection. This may be especially advantageous for microbial diagnosis of prosthetic joint infection (PJI) by synovial fluid analysis since synovial fluid cultures are not universally positive and since synovial fluid is easily obtained preoperatively. We applied a metagenomics-based approach to synovial fluid in an attempt to detect microorganisms in 168 failed total knee arthroplasties. Genus- and species-level analyses of metagenomic sequencing yielded the known pathogen in 74 (90%) and 68 (83%) of the 82 culture-positive PJIs analyzed, respectively, with testing of two (2%) and three (4%) samples, respectively, yielding additional pathogens not detected by culture. For the 25 culture-negative PJIs tested, genus- and species-level analyses yielded 19 (76%) and 21 (84%) samples with insignificant findings, respectively, and 6 (24%) and 4 (16%) with potential pathogens detected, respectively. Genus- and species-level analyses of the 60 culture-negative aseptic failure cases yielded 53 (88%) and 56 (93%) cases with insignificant findings and 7 (12%) and 4 (7%) with potential clinically significant organisms detected, respectively. There was one case of aseptic failure with synovial fluid culture growth; metagenomic analysis showed insignificant findings, suggesting possible synovial fluid culture contamination. Metagenomic shotgun sequencing can detect pathogens involved in PJI when applied to synovial fluid and may be particularly useful for culture-negative cases.
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Artritis Infecciosa/diagnóstico , Bacterias/aislamiento & purificación , Técnicas Bacteriológicas/métodos , Metagenómica/métodos , Técnicas de Diagnóstico Molecular/métodos , Infecciones Relacionadas con Prótesis/diagnóstico , Líquido Sinovial/microbiología , Adulto , Anciano , Anciano de 80 o más Años , Artroplastia de Reemplazo de Rodilla/efectos adversos , Bacterias/clasificación , Bacterias/genética , Técnicas Bacteriológicas/normas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Falla de Prótesis , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: We conducted a prospective validation study to develop a physician assistant (PA) clinical rotation evaluation (PACRE) instrument. The specific aims of this study were to 1) develop a tool to evaluate PA clinical rotations, and 2) explore associations between validated rotation evaluation scores and characteristics of the students and rotations. METHODS: The PACRE was administered to rotating PA students at our institution in 2016. Factor analysis, internal consistency reliability, and associations between PACRE scores and student or rotation characteristics were determined. RESULTS: Of 206 PACRE instruments sent, 124 were returned (60.2% response). Factor analysis supported a unidimensional model with a mean (SD) score of 4.31 (0.57) on a 5-point scale. Internal consistency reliability was excellent (Cronbach α=0.95). PACRE scores were associated with students' gender (P = .01) and rotation specialty (P = .006) and correlated with students' perception of being prepared (r = 0.32; P < .001) and value of the rotation (r = 0.57; P < .001). CONCLUSIONS: This is the first validated instrument to evaluate PA rotation experiences. Application of the PACRE questionnaire could inform rotation directors about ways to improve clinical experiences. The findings of this study suggest that PA students must be adequately prepared to have a successful experience on their rotations. PA programs should consider offering transition courses like those offered in many medical schools to prepare their students for clinical experiences. Future research should explore whether additional rotation characteristics and educational outcomes are associated with PACRE scores.
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Asistentes Médicos/educación , Encuestas y Cuestionarios , Adulto , Análisis Factorial , Femenino , Humanos , Masculino , Asistentes Médicos/organización & administración , Evaluación de Programas y Proyectos de Salud , Estudios Prospectivos , Reproducibilidad de los Resultados , Factores Sexuales , Estudiantes de Medicina , Wisconsin , Adulto JovenRESUMEN
OBJECTIVE: Little is known about factors associated with effective continuing medical education (CME) in psychiatry. The authors aimed to validate a method to assess psychiatry CME teaching effectiveness and to determine associations between teaching effectiveness scores and characteristics of presentations, presenters, and participants. METHODS: This cross-sectional study was conducted at the Mayo Clinic Psychiatry Clinical Reviews and Psychiatry in Medical Settings. Presentations were evaluated using an eight-item CME teaching effectiveness instrument, its content based on previously published instruments. Factor analysis, internal consistency and interrater reliabilities, and temporal stability reliability were calculated. Associations were determined between teaching effectiveness scores and characteristics of presentations, presenters, and participants. RESULTS: In total, 364 participants returned 246 completed surveys (response rate, 67.6%). Factor analysis revealed a unidimensional model of psychiatry CME teaching effectiveness. Cronbach α for the instrument was excellent at 0.94. Item mean score (SD) ranged from 4.33 (0.92) to 4.71 (0.59) on a 5-point scale. Overall interrater reliability was 0.84 (95% CI, 0.75-0.91), and temporal stability was 0.89 (95% CI, 0.77-0.97). No associations were found between teaching effectiveness scores and characteristics of presentations, presenters, and participants. CONCLUSIONS: This study provides a new, validated measure of CME teaching effectiveness that could be used to improve psychiatry CME. In contrast to prior research in other medical specialties, CME teaching effectiveness scores were not associated with use of case-based or interactive presentations. This outcome suggests the need for distinctive considerations regarding psychiatry CME; a singular approach to CME teaching may not apply to all medical specialties.
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Braquiterapia/normas , Educación Médica Continua/normas , Psiquiatría/educación , Enseñanza/normas , Estudios Transversales , Educación Médica Continua/métodos , Humanos , Reproducibilidad de los ResultadosRESUMEN
Staphylococcal prosthetic joint infections (PJIs) are associated with biofilm formation, making them difficult to treat; if managed with debridement and implant retention, rifampin-based therapy is usually employed. Rifampin resistance potentially challenges PJI treatment. In investigating the effects of rifampin monotherapy on methicillin-resistant Staphylococcus aureus (MRSA) foreign-body osteomyelitis in rats, we previously demonstrated that rifampin resistance was selected but that it disappeared 14 days following rifampin monotherapy (1) and that rifampin resistance occurred less frequently following two rounds than following one round of rifampin monotherapy (2). Here, we compared rifampin monotherapy followed by rifampin-vancomycin combination therapy to rifampin-vancomycin combination therapy alone in experimental MRSA foreign-body osteomyelitis. Animals treated with rifampin monotherapy followed by rifampin-vancomycin combination therapy had decreased quantities of bacteria 14 days following treatment completion (P = 0.034) compared to those in animals treated with combination therapy alone. Additionally, some isolates recovered from animals treated with combination therapy alone, although still susceptible to rifampin, had higher MIC, minimum biofilm-inhibitory concentration (MBIC), and minimum biofilm-bactericidal concentration (MBBC) values than those of the inoculating strain. This suggests that rifampin may remain a feasible treatment option in foreign-body-associated orthopedic infections following the selection of rifampin resistance.
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Osteomielitis/tratamiento farmacológico , Rifampin/farmacología , Infecciones Estafilocócicas/tratamiento farmacológico , Animales , Antibacterianos/farmacología , Biopelículas/efectos de los fármacos , Quimioterapia Combinada , Cuerpos Extraños/microbiología , Masculino , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Osteomielitis/microbiología , Ratas Wistar , Infecciones Estafilocócicas/microbiología , Vancomicina/farmacologíaRESUMEN
We developed a rat model of methicillin-resistant Staphylococcus epidermidis (MRSE) foreign body-associated osteomyelitis and used it to compare tedizolid alone and in combination with rifampin against rifampin alone, vancomycin plus rifampin, and vancomycin alone. A clinical strain of MRSE was inoculated into the proximal tibia, and a stainless steel wire with a precolonized MRSE biofilm was implanted. Following a 1-week infection period, 92 rats received either no treatment (n = 17) or 14 days of intraperitoneal tedizolid (n = 15), tedizolid plus rifampin (n = 15), rifampin (n = 15), vancomycin plus rifampin (n = 15), or vancomycin (n = 15). Quantitative bone and wire cultures were performed after treatment completion and also 1 week after infection in a separate group of five rats. The median quantity of staphylococci in bone after the 1-week infection period was 4.89 log10 CFU/g bone (interquartile range, 3.83 to 5.33 log10 CFU/g bone); staphylococci were recovered from all associated wires. A median quantity of staphylococci of 3.70 log10 CFU/g bone was detected in bones of untreated control rats after 3 weeks. Quantities of staphylococci in bones of all treatment groups except the group receiving vancomycin alone (2.78 log10 CFU/g) were significantly lower than those for untreated controls, with no staphylococci being detected in the groups receiving rifampin monotherapy, tedizolid-plus-rifampin combination therapy, and vancomycin-plus-rifampin combination therapy. Quantities of staphylococci on wires from all treatment groups that included rifampin were significantly lower than those for untreated controls. No resistance to rifampin, tedizolid, or vancomycin was detected. Tedizolid combined with rifampin was active in a rat model of MRSE foreign body-associated osteomyelitis.
Asunto(s)
Resistencia a la Meticilina/efectos de los fármacos , Organofosfatos/farmacología , Osteomielitis/tratamiento farmacológico , Oxazoles/farmacología , Infecciones Estafilocócicas/tratamiento farmacológico , Staphylococcus epidermidis/efectos de los fármacos , Animales , Antibacterianos/farmacología , Modelos Animales de Enfermedad , Quimioterapia Combinada , Cuerpos Extraños , Masculino , Pruebas de Sensibilidad Microbiana , Osteomielitis/microbiología , Osteomielitis/patología , Ratas Wistar , Rifampin/farmacología , Acero Inoxidable , Infecciones Estafilocócicas/microbiología , Staphylococcus epidermidis/patogenicidad , Vancomicina/farmacologíaRESUMEN
Foreign-body-associated infections are often difficult to treat, given that the associated microorganisms are in a biofilm state. Previously, we showed that a low-amperage direct electrical current (DC) reduces Propionibacterium acnes biofilms formed on implant-associated materials in vitro In this study, low-amperage DC was compared to ceftriaxone treatment or no treatment in a novel rat femur model of foreign-body osteomyelitis. A platinum implant seeded with a P. acnes biofilm (107 CFU/cm2) and 109 CFU of planktonic P. acnes was placed in the femoral medullary cavity. One week later, rats were assigned to one of three treatment groups: no treatment, ceftriaxone treatment, or 200-µA-DC treatment. After 2 weeks of treatment, there were fewer bacteria in the bones of the ceftriaxone group (3.06 log10 CFU/g of bone [P = 0.0209]) and the 200-µA-DC group (0.5 log10 CFU/g [P = 0.0015]) than in those of the control group (6.58 log10 CFU/g). The DC-exposed animals exhibited fewer bacteria than the ceftriaxone-treated animals (P = 0.0330). There were fewer bacteria on the implanted wires in the groups treated with ceftriaxone (0.1 log10 CFU/cm2) or a 200-µA DC (0.1 log10 CFU/cm2) than in the control group (2.53 log10 CFU/cm2 [P, 0.0003 for both comparisons]). Low-amperage DC may be useful for treating, or aiding in the treatment of, foreign-body infections caused by P. acnes.
Asunto(s)
Ceftriaxona/farmacocinética , Terapia por Estimulación Eléctrica/métodos , Infecciones por Bacterias Grampositivas/terapia , Osteomielitis/terapia , Propionibacterium acnes , Animales , Fémur , Cuerpos Extraños/microbiología , Humanos , Masculino , Osteomielitis/tratamiento farmacológico , Osteomielitis/microbiología , Propionibacterium acnes/efectos de los fármacos , Propionibacterium acnes/aislamiento & purificación , Propionibacterium acnes/patogenicidad , Ratas WistarRESUMEN
Failure to eradicate Helicobacter pylori infection is often a result of antimicrobial resistance, which for clarithromycin is typically mediated by specific point mutations in the 23S rRNA gene. The purpose of this study was to define current patterns of antimicrobial susceptibility in H. pylori isolates derived primarily from the United States and to survey them for the presence of point mutations in the 23S rRNA gene and assess the ability of these mutations to predict phenotypic clarithromycin susceptibility. Antimicrobial susceptibility testing was performed using agar dilution on 413 H. pylori isolates submitted to Mayo Medical Laboratories for susceptibility testing. For a subset of these isolates, a 150-bp segment of the 23S rRNA gene was sequenced. A total of 1,970 MICs were reported over the 4-year study period. The rate of clarithromycin resistance was high (70.4%), and elevated MICs were frequently observed for metronidazole (82.4% of isolates had an MIC of >8 µg/ml) and ciprofloxacin (53.5% of isolates had an MIC of >1 µg/ml). A total of 111 archived H. pylori isolates underwent 23S rRNA gene sequencing; we found 95% concordance between genotypes and phenotypes (P = 0.9802). Resistance to clarithromycin was most commonly due to an A2143G mutation (82%), followed by A2142G (14%) and A2142C (4%) mutations. Clinical H. pylori isolates derived primarily from the United States demonstrated a high rate of clarithromycin resistance and elevated metronidazole and ciprofloxacin MICs. The relative distribution of point mutations at positions 2143 and 2142 in the 23S rRNA gene in clarithromycin-resistant H. pylori was similar to that reported from other parts of the world; these mutations predict phenotypic resistance to clarithromycin.