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70 result(s) for "Mandrekar, Jayawant N."
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Randomized Trial of Rapid Multiplex Polymerase Chain Reaction–Based Blood Culture Identification and Susceptibility Testing
Background. The value of rapid, panel-based molecular diagnostics for positive blood culture bottles (BCBs) has not been rigorously assessed. We performed a prospective randomized controlled trial evaluating outcomes associated with rapid multiplex PCR (rmPCR) detection of bacteria, fungi, and resistance genes directly from positive BCBs. Methods. A total of 617 patients with positive BCBs underwent stratified randomization into 3 arms: standard BCB processing (control, n = 207), rmPCR reported with templated comments (rmPCR, n = 198), or rmPCR reported with templated comments and real-time audit and feedback of antimicrobial orders by an antimicrobial stewardship team (rmPCR/AS, n = 212). The primary outcome was antimicrobial therapy duration. Secondary outcomes were time to antimicrobial de-escalation or escalation, length of stay (LOS), mortality, and cost. Results. Time from BCB Gram stain to microorganism identification was shorter in the intervention group (1.3 hours) vs control (22.3 hours) (P < .001). Compared to the control group, both intervention groups had decreased broad-spectrum piperacillin-tazobactam (control 56 hours, rmPCR 44 hours, rmPCR/AS 45 hours; P = .01) and increased narrow-spectrum β-lactam (control 42 hours, rmPCR 71 hours, rmPCR/AS 85 hours; P = .04) use, and less treatment of contaminants (control 25%, rmPCR 11%, rmPCR/AS 8%; P = .015). Time from Gram stain to appropriate antimicrobial de-escalation or escalation was shortest in the rmPCR/AS group (de-escalation: rmPCR/AS 21 hours, control 34 hours, rmPCR 38 hours, P < .001; escalation: rmPCR/AS 5 hours, control 24 hours, rmPCR 6 hours, P = .04). Groups did not differ in mortality, LOS, or cost. Conclusions. rmPCR reported with templated comments reduced treatment of contaminants and use of broad-spectrum antimicrobials. Addition of antimicrobial stewardship enhanced antimicrobial de-escalation. Clinical Trials Registration. NCT01898208.
Sonication of Removed Hip and Knee Prostheses for Diagnosis of Infection
Current techniques for the identification of the infecting organism in prosthetic-joint (e.g., hip or knee) infection remain insensitive. In this study of 331 surgeries involving prosthetic joint replacement, a new technique that sonicates the removed artificial joint is found to be more sensitive in identifying the infecting organism than are standard culture techniques. In surgeries involving prosthetic joint replacement, a new technique that sonicates the removed artificial joint is found to be more sensitive in identifying the infecting organism than are standard culture techniques. In the United States, 638,000 patients underwent hip or knee replacement in 2003. 1 Although they may improve the quality of life, these procedures are associated with complications, including aseptic failure and prosthetic-joint infection. 2 It is important to distinguish prosthetic-joint infection from other causes of joint failure, because its management is different. 3 Nonmicrobiologic methods developed for diagnosing native-joint infection use different criteria from those used to diagnose prosthetic-joint infection. 4 Microbiologic diagnosis of prosthetic-joint infection may also require different criteria from those used for the microbiologic diagnosis of native-joint infection. Most clinicians and laboratory workers culture periprosthetic tissue (hereafter referred to as . . .
Exposure of Bacterial Biofilms to Electrical Current Leads to Cell Death Mediated in Part by Reactive Oxygen Species
Bacterial biofilms may form on indwelling medical devices such as prosthetic joints, heart valves and catheters, causing challenging-to-treat infections. We have previously described the 'electricidal effect', in which bacterial biofilms are decreased following exposure to direct electrical current. Herein, we sought to determine if the decreased bacterial quantities are due to detachment of biofilms or cell death and to investigate the role that reactive oxygen species (ROS) play in the observed effect. Using confocal and electron microscopy and flow cytometry, we found that direct current (DC) leads to cell death and changes in the architecture of biofilms formed by Gram-positive and Gram-negative bacteria. Reactive oxygen species (ROS) appear to play a role in DC-associated cell death, as there was an increase in ROS-production by Staphylococcus aureus and Staphylococcus epidermidis biofilms following exposure to DC. An increase in the production of ROS response enzymes catalase and superoxide dismutase (SOD) was observed for S. aureus, S. epidermidis and Pseudomonas aeruginosa biofilms following exposure to DC. Additionally, biofilms were protected from cell death when supplemented with antioxidants and oxidant scavengers, including catalase, mannitol and Tempol. Knocking out SOD (sodAB) in P. aeruginosa led to an enhanced DC effect. Microarray analysis of P. aeruginosa PAO1 showed transcriptional changes in genes related to the stress response and cell death. In conclusion, the electricidal effect results in death of bacteria in biofilms, mediated, at least in part, by production of ROS.
Improved Diagnosis of Prosthetic Joint Infection by Culturing Periprosthetic Tissue Specimens in Blood Culture Bottles
Despite known low sensitivity, culture of periprosthetic tissue specimens on agars and in broths is routine. Culture of periprosthetic tissue samples in blood culture bottles (BCBs) is potentially more convenient, but it has been evaluated in a limited way and has not been widely adopted. The aim of this study was to compare the sensitivity and specificity of inoculation of periprosthetic tissue specimens into blood culture bottles with standard agar and thioglycolate broth culture, applying Bayesian latent class modeling (LCM) in addition to applying the Infectious Diseases Society of America (IDSA) criteria for prosthetic joint infection. This prospective cohort study was conducted over a 9-month period (August 2013 to April 2014) at the Mayo Clinic, Rochester, MN, and included all consecutive patients undergoing revision arthroplasty. Overall, 369 subjects were studied; 117 (32%) met IDSA criteria for prosthetic joint infection, and 82% had late chronic infection. Applying LCM, inoculation of tissues into BCBs was associated with a 47% improvement in sensitivity compared to the sensitivity of conventional agar and broth cultures (92.1 versus 62.6%, respectively); this magnitude of change was similar when IDSA criteria were applied (60.7 versus 44.4%, respectively; P = 0.003). The time to microorganism detection was shorter with BCBs than with standard media ( P < 0.0001), with aerobic and anaerobic BCBs yielding positive results within a median of 21 and 23 h, respectively. Results of our study demonstrate that the semiautomated method of periprosthetic tissue culture in blood culture bottles is more sensitive than and as specific as agar and thioglycolate broth cultures and yields results faster. IMPORTANCE Prosthetic joint infections are a devastating complication of arthroplasty surgery. Despite this, current microbiological techniques to detect and diagnose infections are imperfect. This study examined a new approach to diagnosing infections, through the inoculation of tissue samples from around the prosthetic joint into blood culture bottles. This study demonstrated that, compared to current laboratory practices, this new technique increased the detection of infection. These findings are important for patient care to allow timely and accurate diagnosis of infection. Prosthetic joint infections are a devastating complication of arthroplasty surgery. Despite this, current microbiological techniques to detect and diagnose infections are imperfect. This study examined a new approach to diagnosing infections, through the inoculation of tissue samples from around the prosthetic joint into blood culture bottles. This study demonstrated that, compared to current laboratory practices, this new technique increased the detection of infection. These findings are important for patient care to allow timely and accurate diagnosis of infection.
Associations between Doximity internal medicine residency navigator reputation rank and publicly available metrics
Background The U.S. News & World Report has used the Doximity social networking site to determine rankings for 27 medical specialties, which influence medical students' choices. Despite concerns about the validity of these rankings, few studies have explored whether Doximity rankings correlate with program characteristics. We aim to determine associations between Doximity internal medicine reputation rank and publicly available program characteristics. Methods We performed a cross-sectional study of the 566 internal medicine residencies with a Doximity reputation rank from 2020. Doximity rankings were linked with publicly available sources, including the American Medical Association’s FREIDA, the American Board of Internal Medicine, the Accreditation Council for Graduate Medical Education, the Centers for Medicare and Medicaid Services Quality System, and U.S. News Best Hospitals Ranking. Variables included resident demographics, faculty characteristics, and program features. Statistical analyses involved univariable and multivariable linear regression. Results In multivariable analysis (parameter estimate ± standard error), higher ABIM pass rates (-1.30 ± 0.41), higher physician faculty-to-resident ratios (-14.10 ± 4.45), older programs (-1.07 ± 0.25), availability of research rotations (-38.56 ± 16.23), and larger program sizes (-1.09 ± 0.16) were associated with better Doximity ranks. Conversely, a higher percentage of international medical graduates (1.07 ± 0.19) and Doctors of Osteopathy (1.12 ± 0.27) were linked to lower rankings. Variables had an adjusted R2 of 0.53. Conclusions Doximity rankings were positively associated with publicly available characteristics of residency programs including higher ABIM pass rates, lower physician faculty-to-resident ratio, older program age, availability of a research rotation, and larger program size. Doximity rankings were negatively associated with a higher percentage of IMG and DO residents. These findings suggest that while Doximity rankings may be influenced by larger program sizes and higher self-reporting rates, they may also reflect meaningful indicators of program quality. The findings highlight the importance of research productivity and faculty ratios in enhancing program reputation and underscore potential disadvantages for community-based programs.
The relationship between learner engagement and teaching effectiveness: a novel assessment of student engagement in continuing medical education
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.
Ureaplasma urealyticum Causes Hyperammonemia in an Experimental Immunocompromised Murine Model
Hyperammonemia syndrome is an often fatal complication of lung transplantation which has been recently associated with Ureaplasma infection. It has not been definitely established that Ureaplasma species can cause hyperammonemia. We established a novel immunocompromised murine model of Ureaplasma urealyticum infection and used it to confirm that U. urealyticum can cause hyperammonemia. Male C3H mice were pharmacologically immunosuppressed with mycophenolate mofetil, tacrolimus and oral prednisone for seven days, and then challenged intratracheally (IT) and/or intraperitoneally (IP) with 107 CFU U. urealyticum over six days, while continuing immunosuppression. Spent U. urealyticum-free U9 broth was used as a negative control, with uninfected immunocompetent mice, uninfected immunosuppressed mice, and infected immunocompetent mice serving as additional controls. Plasma ammonia concentrations were compared using Wilcoxon ranks sum tests. Plasma ammonia concentrations of immunosuppressed mice challenged IT/IP with spent U9 broth (n = 14) (range 155-330 μmol/L) were similar to those of normal mice (n = 5), uninfected immunosuppressed mice (n = 5), and U. urealyticum IT/IP challenged immunocompetent mice (n = 5) [range 99-340 μmol/L, p = 0.60]. However, immunosuppressed mice challenged with U. urealyticum IT/IP (n = 20) or IP (n = 15) had higher plasma ammonia concentrations (range 225-945 μmol/L and 276-687 μmol/L, respectively) than those challenged IT/IP with spent U9 broth (p<0.001). U. urealyticum administered IT/IP or IP causes hyperammonemia in mice pharmacologically immunosuppressed with a regimen similar to that administered to lung transplant recipients.
C-Reactive Protein, Erythrocyte Sedimentation Rate and Orthopedic Implant Infection
C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) have been shown to be useful for diagnosis of prosthetic hip and knee infection. Little information is available on CRP and ESR in patients undergoing revision or resection of shoulder arthroplasties or spine implants. We analyzed preoperative CRP and ESR in 636 subjects who underwent knee (n=297), hip (n=221) or shoulder (n=64) arthroplasty, or spine implant (n=54) removal. A standardized definition of orthopedic implant-associated infection was applied. Receiver operating curve analysis was used to determine ideal cutoff values for differentiating infected from non-infected cases. ESR was significantly different in subjects with aseptic failure infection of knee (median 11 and 53.5 mm/h, respectively, p=<0.0001) and hip (median 11 and 30 mm/h, respectively, p=<0.0001) arthroplasties and spine implants (median 10 and 48.5 mm/h, respectively, p=0.0033), but not shoulder arthroplasties (median 10 and 9 mm/h, respectively, p=0.9883). Optimized ESR cutoffs for knee, hip and shoulder arthroplasties and spine implants were 19, 13, 26, and 45 mm/h, respectively. Using these cutoffs, sensitivity and specificity to detect infection were 89 and 74% for knee, 82 and 60% for hip, and 32 and 93% for shoulder arthroplasties, and 57 and 90% for spine implants. CRP was significantly different in subjects with aseptic failure and infection of knee (median 4 and 51 mg/l, respectively, p<0.0001), hip (median 3 and 18 mg/l, respectively, p<0.0001), and shoulder (median 3 and 10 mg/l, respectively, p=0.01) arthroplasties, and spine implants (median 3 and 20 mg/l, respectively, p=0.0011). Optimized CRP cutoffs for knee, hip, and shoulder arthroplasties, and spine implants were 14.5, 10.3, 7, and 4.6 mg/l, respectively. Using these cutoffs, sensitivity and specificity to detect infection were 79 and 88% for knee, 74 and 79% for hip, and 63 and 73% for shoulder arthroplasties, and 79 and 68% for spine implants. CRP and ESR have poor sensitivity for the diagnosis of shoulder implant infection. A CRP of 4.6 mg/l had a sensitivity of 79 and a specificity of 68% to detect infection of spine implants.
Dental Procedures as Risk Factors for Prosthetic Hip or Knee Infection: A Hospital-Based Prospective Case-Control Study
Background The actual risk of prosthetic joint infection as a result of dental procedures and the role of antibiotic prophylaxis have not been defined. Methods To examine the association between dental procedures with or without antibiotic prophylaxis and prosthetic hip or knee infection, a prospective, single-center, case-control study for the period 2001–2006 was performed at a 1200-bed tertiary care hospital in Rochester, Minnesota. Case patients were patients hospitalized with total hip or knee infection. Control subjects were patients who underwent a total hip or knee arthroplasty but without a prosthetic joint infection who were hospitalized during the same period on the same orthopedic floor. Data regarding demographic features and potential risk factors were collected. Logistic regression was used to assess the association of variables with the odds of infection. Results A total of 339 case patients and 339 control subjects were enrolled in the study. There was no increased risk of prosthetic hip or knee infection for patients undergoing a high-risk or low-risk dental procedure who were not administered antibiotic prophylaxis (adjusted odds ratio [OR], 0.8; 95% confidence interval [CI], 0.4–1.6), compared with the risk for patients not undergoing a dental procedure (adjusted OR, 0.6; 95% CI, 0.4–1.1) respectively. Antibiotic prophylaxis in high-risk or low-risk dental procedures did not decrease the risk of subsequent total hip or knee infection (adjusted OR, 0.9 [95% CI, 0.5–1.6] and 1.2 [95% CI, 0.7–2.2], respectively). Conclusions Dental procedures were not risk factors for subsequent total hip or knee infection. The use of antibiotic prophylaxis prior to dental procedures did not decrease the risk of subsequent total hip or knee infection.
Using Social Media to Improve Continuing Medical Education: A Survey of Course Participants
To determine continuing medical education (CME) course participants' use of social media (SM) and their attitudes about the value of SM for enhancing CME education and to examine associations between participants' characteristics and attitudes toward SM. We conducted a cross-sectional survey and validation study of 539 participants at a Mayo Clinic Internal Medicine CME course in November 2011. The Social Media Use and Perception Instrument (SMUPI) consisted of 10 items (5-point Likert scales) and categorical response options. The main outcome measures were psychometric characteristics of the SMUPI scale, course participants' use of SM, and their attitudes regarding the importance of SM for enhancing CME. Of 539 CME course participants, 327 (61%) responded to the SMUPI survey. Most respondents (291 [89%]) reported using SM, with the most common types being YouTube (189 of the 327 participants [58%]) and Facebook (163 of 327 [50%]). Factor analysis revealed a 2-dimensional assessment of course participants' attitudes. Internal consistency reliability (Cronbach α) was excellent for factor 1 (0.94), factor 2 (0.89), and overall (0.94). The CME course participants' favorable attitudes toward SM were associated with younger age (20-29 years, mean score 3.13; 30-39 years, 3.40; 40-49 years, 3.39; 50-59 years, 3.18; 60-69 years, 2.93; and ≥70 years, 2.92; P=.02), using SM frequently (never, mean score 2.49; less than once monthly, 2.75; once monthly, 3.21; weekly, 3.31; and daily, 3.81; P<.0001), and professional degree (PhD, mean score 3.00; MD, 3.05; DO, 3.35; PA, 3.42; and NP, 3.50; P=.01). We describe the first validated measure of CME course participants' use of and attitudes toward SM. Our results suggest that CME course directors should guide SM strategies toward more youthful, technology-savvy CME participants and that SM will become increasingly worthwhile in CME as younger learners continue to enter the profession.