Search

Background: The major membrane currents responsible for sinoatrial (SA) rhythm generation are generally studied in isolated cardiac cells using electrophysiological tools. Such studies are resource and labor-intensive. Materials and Methods: Here, we have studied four major currents in isolated rat heart preparations, perfused in Langendorff mode, and demonstrate that this is a good preparation for such studies. Heart rates of isolated perfused rat hearts were recorded using surface electrocardiogram before and after perfusion with drugs and solutions that affect the four major currents responsible for SA rhythm generation. Results: The rates of whole isolated hearts beating with SA rhythm decreased with cesium and decreased by about half with ivabradine, both blockers of the funny current (If). Importantly, the rhythm was not abolished even with a high dose of ivabradine at which total blockade of If is expected. The rate was not affected by nickel, a blocker of T-type calcium current. The SA rhythm was abolished by the reduction or removal of sodium from the perfusate (interventions that inhibit the calcium-extrusive mode of the sodium-calcium exchanger) or by nifedipine, the L-type calcium channel blocker. Discussion: The inferences made based on these observations are (a) If contributes significantly to pacemaking, (b) ICaT does not play a role and (c) INCX and ICaL are obligatory rhythm-generating currents in the SA node. Cyclical calcium release from SR during diastole (the calcium clock), responsible for driving INCX in its forward mode is probably a phenomenon independent of membrane events, as total If blockade did not abolish rhythm generation. These results corroborate with published literature where most studies were done on single cells.

Abstract Background No research has been conducted to assess whether antibiotic prophylaxis prescribing differs by dental setting. Therefore, the goal of this study was to compare the prescribing of antibiotic prophylaxis in Veterans Affairs (VA) and non-Veterans Affairs settings. Methods This was a retrospective study of veteran and non-veteran dental patients with cardiac conditions or prosthetic joints between 2015–2017. Multivariable log binomial regression analysis was conducted to compare concordant prescribing by setting with a sub-analysis for errors of dosing based on antibiotic duration (i.e., days prescribed). Results A total of 61,124 dental visits that received a prophylactic antibiotic were included. Most were male (61.0%), and 55 years of age or older (76.2%). Nearly a third (32.7%) received guideline concordant prophylaxis. VA dental settings had a lower prevalence of guideline concordant prescribing compared to non-VA settings in unadjusted results (unadjusted prevalence ratio [uPR] = 0.92, 95% CI: 0.90–0.95). After adjustment, prevalence of guideline concordant prescribing was higher in those with prosthetic joints in the VA setting (adjusted prevalence ratio [aPR] = 1.73, 95% CI: 1.59–1.88), with no difference identified in those without a prosthetic joint (aPR = 0.99, 95% CI: 0.96–1.01). Concordance of dosing was higher in VA compared to non-VA settings (aPR = 1.11, 95% CI: 1.07–1.15). Conclusions VA has a higher prevalence of guideline concordant prescribing among those with prosthetic joints and when assessing dosing errors. Though the presence of an integrated electronic health record (EHR) may be contributing to these differences, other system or prescriber-related factors may be responsible. Future studies should focus on to what extent the integrated EHR may be responsible for increased guideline concordant prescribing in the VA setting.

Background: Antibiotics prescribed as infection prophylaxis prior to dental procedures have the potential for serious adverse drug events (ADEs). However, the extent to which guideline concordance and different dental settings are associated with ADEs from antibiotic prophylaxis is unknown.Aim: The purpose was to assess guideline concordance and antibiotic-associated ADEs and whether it differs by VA and non-VA settings.Methods: Retrospective cohort study of antibiotic prophylaxis prescribed to adults with cardiac conditions or prosthetic joints from 2015 to 2017. Multivariable logistic regression models were fit to assess the impact of ADEs, guideline concordance and dental setting. An interaction term of concordance and dental setting evaluated whether the relationship between ADEs and concordance differed by setting.Results: From 2015 to 2017, 61,124 patients with antibiotic prophylaxis were identified with 62 (0.1%) having an ADE. Of those with guideline concordance, 18 (0.09%) had an ADE while 44 (0.1%) of those with a discordant antibiotic had an ADE (unadjusted OR: 0.84, 95% CI: 0.49–1.45). Adjusted analyses showed that guideline concordance was not associated with ADEs (OR: 0.78, 95% CI: 0.25–2.46), and this relationship did not differ by dental setting (Wald χ^2 p-value for interaction = 0.601).Conclusion: Antibiotic-associated ADEs did not differ by setting or guideline concordance.

Abstract Background Carbapenem-resistant Acinetobacter baumannii (CRAB) and carbapenem-resistant Pseudomonas aeruginosa (CRPA) are a growing threat. The objective of this study was to describe CRAB and CRPA epidemiology and identify factors associated with mortality and length of stay (LOS) post-culture. Methods This was a national retrospective cohort study of Veterans with CRAB or CRPA positive cultures from 2013 to 2018, conducted at Hines Veterans Affairs Hospital. Carbapenem resistance was defined as non-susceptibility to imipenem, meropenem and/or doripenem. Multivariable cluster adjusted regression models were fit to assess the association of post-culture LOS among inpatient and long-term care (LTC) and to identify factors associated with 90-day and 365-day mortality after positive CRAB and CRPA cultures. Results CRAB and CRPA were identified in 1,048 and 8,204 unique patients respectively, with 90-day mortality rates of 30.3% and 24.5% and inpatient post-LOS of 26 and 27 days. Positive blood cultures were associated with an increased odds of 90-day mortality compared to urine cultures in patients with CRAB (OR 6.98, 95% CI 3.55–13.73) and CRPA (OR 2.82, 95% CI 2.04–3.90). In patients with CRAB and CRPA blood cultures, higher Charlson score was associated with increased odds of 90-day mortality. In CRAB and CRPA, among patients from inpatient care settings, blood cultures were associated with a decreased LOS compared to urine cultures. Conclusions Positive blood cultures and more comorbidities were associated with higher odds for mortality in patients with CRAB and CRPA. Recognizing these factors would encourage clinicians to treat these patients in a timely manner to improve outcomes of patients infected with these organisms.

Abstract Background Infections caused by carbapenem-resistant Enterobacteriaceae (CRE) and carbapenemase-producing (CP) CRE are difficult to treat, resulting in high mortality in healthcare settings every year. The Veterans Health Administration (VHA) disseminated guidelines in 2015 and an updated directive in 2017 for control of CRE focused on laboratory testing, prevention, and management. The Consolidated Framework for Implementation Research (CFIR) framework was used to analyze qualitative interview data to identify contextual factors and best practices influencing implementation of the 2015 guidelines/2017 directive in VA Medical Centers (VAMCs). The overall goals were to determine CFIR constructs to target to improve CRE guideline/directive implementation and understand how CFIR, as a multi-level conceptual model, can be used to inform guideline implementation. Methods Semi-structured interviews were conducted at 29 VAMCs with staff involved in implementing CRE guidelines at their facility. Survey and VHA administrative data were used to identify geographically representative large and small VAMCs with varying levels of CRE incidence. Interviews addressed perceptions of guideline dissemination, laboratory testing, staff attitudes and training, patient education, and technology support. Participant responses were coded using a consensus-based mixed deductive-inductive approach guided by CFIR. A quantitative analysis comparing qualitative CFIR constructs and emergent codes to sites actively screening for CRE (vs. non-screening) and any (vs. no) CRE-positive cultures was conducted using Fisher’s exact test. Results Forty-three semi-structured interviews were conducted between October 2017 and August 2018 with laboratory staff (47%), Multi-Drug-Resistant Organism Program Coordinators (MPCs, 35%), infection preventionists (12%), and physicians (6%). Participants requested more standardized tools to promote effective communication (e.g., electronic screening). Participants also indicated that CRE-specific educational materials were needed for staff, patient, and family members. Quantitative analysis identified CRE screening or presence of CRE as being significantly associated with the following qualitative CFIR constructs: leadership engagement, relative priority, available resources, team communication, and access to knowledge and information. Conclusions Effective CRE identification, prevention, and treatment require ongoing collaboration between clinical, microbiology, infection prevention, antimicrobial stewardship, and infectious diseases specialists. Our results emphasize the importance of leadership’s role in promoting positive facility culture, including access to resources, improving communication, and facilitating successful implementation of the CRE guidelines.

Abstract Objective: To describe national trends in testing and detection of carbapenemases produced by carbapenem-resistant Enterobacterales (CRE) and associate testing with culture and facility characteristics. Design: Retrospective cohort study. Setting: Department of Veterans’ Affairs medical centers (VAMCs). Participants: Patients seen at VAMCs between 2013 and 2018 with cultures positive for CRE, defined by national VA guidelines. Interventions: Microbiology and clinical data were extracted from national VA data sets. Carbapenemase testing was summarized using descriptive statistics. Characteristics associated with carbapenemase testing were assessed with bivariate analyses. Results: Of 5,778 standard cultures that grew CRE, 1,905 (33.0%) had evidence of molecular or phenotypic carbapenemase testing and 1,603 (84.1%) of these had carbapenemases detected. Among these cultures confirmed as carbapenemase-producing CRE, 1,053 (65.7%) had molecular testing for ≥1 gene. Almost all testing included KPC (n = 1,047, 99.4%), with KPC detected in 914 of 1,047 (87.3%) cultures. Testing and detection of other enzymes was less frequent. Carbapenemase testing increased over the study period from 23.5% of CRE cultures in 2013 to 58.9% in 2018. The South US Census region (38.6%) and the Northeast (37.2%) region had the highest proportion of CRE cultures with carbapenemase testing. High complexity (vs low) and urban (vs rural) facilities were significantly associated with carbapenemase testing (P < .0001). Conclusions: Between 2013 and 2018, carbapenemase testing and detection increased in the VA, largely reflecting increased testing and detection of KPC. Surveillance of other carbapenemases is important due to global spread and increasing antibiotic resistance. Efforts supporting the expansion of carbapenemase testing to low-complexity, rural healthcare facilities and standardization of reporting of carbapenemase testing are needed.