Premature Ventricular Contractions (PVCs): A Narrative Review.

Premature ventricular complexes/contractions (PVCs) are relatively common, occurring in 3%-20% of the general population, and are often found during work-up of palpitations or incidentally on routine electrocardiographic testing. They are usually considered benign but can be a sign of underlying cardiac disease and cause significantly impairing symptoms. While often thought of as a problem for the cardiologist, it is not uncommon for PVCs to be identified initially in a primary care or inpatient general medicine setting. This paper will review etiologies, epidemiology, evaluation, and management of PVCs for the internist.

Knowledge, Attitudes, and Beliefs of Pediatric Health Care Workers: Understanding the Response to COVID-19.

INTRODUCTION: This research aims to assess knowledge, attitudes, and beliefs of PHCW regarding COVID-19. METHOD: Data collected using an electronic survey sent to pediatric health care workers. RESULTS: Age was not likely to influence willingness to care for patients with COVID-19. Males were more likely to be willing to care for patients than female. Nurse practitioners were more likely to be willing to care for patients with COVID-19 than physicians. Availability of proper personal protective equipment, COVID-19 knowledge, and training did not influence willingness to care for COVID-19 patients. Healthcare workers with a higher risk of COVID-19-related sickness, and who received most of their COVID-19 information from social media, were less likely to be willing to care for COVID positive patients. As perception of hospital preparedness increased, reluctance to care for COVID-19 positive patients decreased. DISCUSSION: Hospital preparedness and social media exposure play a significant role in willingness to care for patients with COVID-19.

Impact of Different Electronic Cohort Definitions to Identify Patients With Atrial Fibrillation From the Electronic Medical Record.

Background Electronic medical records (EMRs) allow identification of disease-specific patient populations, but varying electronic cohort definitions could result in different populations. We compared the characteristics of an electronic medical record-derived atrial fibrillation (AF) patient population using 5 different electronic cohort definitions. Methods and Results Adult patients with at least 1 AF billing code from January 1, 2010, to December 31, 2017, were included. Based on different electronic cohort definitions, we trained 5 different logistic regression models using a labeled training data set (n=786). Each model yielded a predicted probability; patients were classified as having AF if the probability was higher than a specified cut point. Test characteristics were calculated for each model. These models were then applied to the full cohort and resulting characteristics were compared. In the training set, the comprehensive model (including demographics, billing codes, and natural language processing results) performed best, with an area under the curve of 0.89, sensitivity of 0.90, and specificity of 0.87. Among a candidate population (n=22 000), the proportion of patients identified as having AF varied from 61% in the model using diagnosis or procedure International Classification of Diseases (ICD) billing codes to 83% in the model using natural language processing of clinical notes. Among identified AF patients, the proportion of patients with a CHA2DS2-VASc score ≥2 varied from 69% to 85%; oral anticoagulant treatment rates varied from 50% to 66% depending on the model. Conclusions Different electronic cohort definitions result in substantially different AF study samples. This difference threatens the quality and reproducibility of electronic medical record-based research and quality initiatives.

Burkholderia cenocepacia utilizes ferritin as an iron source.

Burkholderia cenocepacia is a member of the Burkholderia cepacia complex, a group of genetically similar species that inhabit a number of environmental niches, including the lungs of patients with cystic fibrosis (CF). To colonize the lung, this bacterium requires a source of iron to satisfy its nutritional requirements for this important metal. Because of the high potential for damage in lung tissue resulting from oxygen-iron interactions, this metal is sequestered by a number of mechanisms that render it potentially unavailable to invading micro-organisms. Such mechanisms include the intracellular and extracellular presence of the iron-binding protein ferritin. Ferritin has a highly stable macromolecular structure and may contain up to 4500 iron atoms per molecule. To date, there has been no known report of a pathogenic bacterial species that directly utilizes iron sequestered by this macromolecule. To examine the ability of ferritin to support growth of B. cenocepacia J2315, iron-deficient media were supplemented with different concentrations of ferritin and the growth kinetics characterized over a 40 h period. The results indicated that B. cenocepacia J2315 utilizes iron bound by ferritin. Further studies examining the mechanisms of iron uptake from ferritin indicated that iron utilization results from a proteolytic degradation of this otherwise stable macromolecular structure. Since it is known that the ferritin concentration is significantly higher in the CF lung than in healthy lungs, this novel iron-acquisition mechanism may contribute to infection by B. cenocepacia in people with CF.

Signature-tagging of a bacterial isolate demonstrates phenotypic variability of the progeny in vivo in the absence of defined mutations.

Awareness of the high degree of redundancy that occurs in several nutrient uptake pathways of Haemophilus influenzae led us to attempt to develop a quantitative STM method that could identify both null mutants and mutants with decreased fitness that remain viable in vivo. To accomplish this task we designed a modified STM approach that utilized a set of signature tagged wild-type (STWT) strains (in a single genetic background) as carriers for mutations in genes of interest located elsewhere in the genome. Each STWT strain differed from the others by insertion of a unique, Q-PCR-detectable, seven base pair tag into the same redundant gene locus. Initially ten STWTs were created and characterized in vitro and in vivo. As anticipated, the STWT strains were not significantly different in their in vitro growth. However, in the chinchilla model of otitis media, certain STWTs outgrew others by several orders of magnitude in mixed infections. Removal of the predominant STWT resulted in its replacement by a different predominant STWT on retesting. Unexpectedly we observed that the STWT exhibiting the greatest proliferation was animal dependent. These findings identify an inherent inability of the signature tag methodologies to accurately elucidate fitness in this animal model of infection and underscore the subtleties of H. influenzae gene regulation.

Haemophilus influenzae OxyR: characterization of its regulation, regulon and role in fitness.

To prevent damage by reactive oxygen species, many bacteria have evolved rapid detection and response systems, including the OxyR regulon. The OxyR system detects reactive oxygen and coordinates the expression of numerous defensive antioxidants. In many bacterial species the coordinated OxyR-regulated response is crucial for in vivo survival. Regulation of the OxyR regulon of Haemophilus influenzae was examined in vitro, and significant variation in the regulated genes of the OxyR regulon among strains of H. influenzae was observed. Quantitative PCR studies demonstrated a role for the OxyR-regulated peroxiredoxin/glutaredoxin as a mediator of the OxyR response, and also indicated OxyR self-regulation through a negative feedback loop. Analysis of transcript levels in H. influenzae samples derived from an animal model of otitis media demonstrated that the members of the OxyR regulon were actively upregulated within the chinchilla middle ear. H. influenzae mutants lacking the oxyR gene exhibited increased sensitivity to challenge with various peroxides. The impact of mutations in oxyR was assessed in various animal models of H. influenzae disease. In paired comparisons with the corresponding wild-type strains, the oxyR mutants were unaffected in both the chinchilla model of otitis media and an infant model of bacteremia. However, in weanling rats the oxyR mutant was significantly impaired compared to the wild-type strain. In contrast, in all three animal models when infected with a mixture of equal numbers of both wild-type and mutant strains the mutant strain was significantly out competed by the wild-type strain. These findings clearly establish a crucial role for OxyR in bacterial fitness.

Antibody-dependent enhancement, a possible mechanism in augmented pulmonary disease of respiratory syncytial virus in the Bonnet monkey model.

Bonnet monkeys develop an enhanced disease after immunization with the formalin-inactivated (FI) respiratory syncytial virus (RSV) vaccine that is characterized by increased viral replication in perivascular sites of the lung. These sites contain many mononuclear cells, which are known to be permissive for RSV replication. To test the hypothesis that FI-RSV vaccine stimulates the production of enhancing antibodies that serve to increase the replication of RSV in macrophages, in vitro studies were done. Antibody-dependent enhancement was observed in animals immunized with FI-RSV but not in control animals with primary and tertiary infections or those immunized with FI-Vero cell culture. In the presence of serum samples from animals immunized with FI-RSV, an increased number of U937 cells was infected. The enhancement index correlated positively with the pathologic scores of the FI-RSV-vaccinated monkeys.