Evidence Based Scarce Resource Allocation During the COVID-19 Pandemic: A Case Study of Bamlanivimab Administration in the Emergency Department.

Background: Patients presenting for emergency department (ED) evaluation may be appropriate for treatment with monoclonal antibodies for mild to moderate COVID-19. While many sites have implemented infusion centers for these agents, EDs will continue to evaluate these patients where appropriate identification and efficient infusion of eligible patients is critical. Objectives: Patients receiving bamlanivimab in the EDs of an academic medical center are described. The primary objective was to describe operational metrics and secondary objectives reported clinical outcomes. Methods: Patients receiving bamlanivimab and discharged from the ED were included from November 16, 2020 to January 16, 2021 in the retrospective, observational cohort. Primary outcome was adherence to institutional criteria. Secondary outcomes included ED visit metrics, clinical characteristics, and return visits within 30 days. Risk factors for return visits were assessed with regression. Results: One hundred nineteen patients were included. Most (71%) were diagnosed with COVID-19 during the ED visit and median symptom duration was 3(IQR 2-5) days. Median number of risk factors for progression to severe disease was 2 (IQR 1-2). Thirty percent had a documented abnormal chest x-ray. Institutional criteria adherence was 99.2%. Median time from ED room to bamlanivimab was 4 (IQR 3.1-5.2) hours. Thirty patients had return visit within 30 days; 19 were COVID-19 related. Two multivariable regression models were analyzed for COVID-19 related return visit. Characteristics on ED presentation were considered in Model I: male gender (OR 3.01[0.97-9.31]), age (per 10 years) (OR 1.49[1.05-2.12]), African-American race (OR 3.46[1.09-11.06]), and symptom duration (per day) (OR 1.34[1.05-1.73]). Model II included labs and imaging acquired in ED. In Model II, age (per 10 years) (OR 1.52[1.07-2.16]) and abnormal CXR (OR 5.74[1.95-16.9]) were associated with COVID-19 related return visits. Conclusions: Administration of bamlanivimab to ED patients can be done efficiently, with the potential to reduce COVID-19 related return visits. Age and abnormal imaging were independent predictors of COVID-19 return visits.

Exercise-induced bronchoconstriction update-2016.

The first practice parameter on exercise-induced bronchoconstriction (EIB) was published in 2010. This updated practice parameter was prepared 5 years later. In the ensuing years, there has been increased understanding of the pathogenesis of EIB and improved diagnosis of this disorder by using objective testing. At the time of this publication, observations included the following: dry powder mannitol for inhalation as a bronchial provocation test is FDA approved however not currently available in the United States; if baseline pulmonary function test results are normal to near normal (before and after bronchodilator) in a person with suspected EIB, then further testing should be performed by using standardized exercise challenge or eucapnic voluntary hyperpnea (EVH); and the efficacy of nonpharmaceutical interventions (omega-3 fatty acids) has been challenged. The workgroup preparing this practice parameter updated contemporary practice guidelines based on a current systematic literature review. The group obtained supplementary literature and consensus expert opinions when the published literature was insufficient. A search of the medical literature on PubMed was conducted, and search terms included pathogenesis, diagnosis, differential diagnosis, and therapy (both pharmaceutical and nonpharmaceutical) of exercise-induced bronchoconstriction or exercise-induced asthma (which is no longer a preferred term); asthma; and exercise and asthma. References assessed as relevant to the topic were evaluated to search for additional relevant references. Published clinical studies were appraised by category of evidence and used to document the strength of the recommendation. The parameter was then evaluated by Joint Task Force reviewers and then by reviewers assigned by the parent organizations, as well as the general membership. Based on this process, the parameter can be characterized as an evidence- and consensus-based document.

Genome-wide association study identifies loci on 12q24 and 13q32 associated with tetralogy of Fallot.

We conducted a genome-wide association study to search for risk alleles associated with Tetralogy of Fallot (TOF), using a northern European discovery set of 835 cases and 5159 controls. A region on chromosome 12q24 was associated (P = 1.4 × 10(-7)) and replicated convincingly (P = 3.9 × 10(-5)) in 798 cases and 2931 controls [per allele odds ratio (OR) = 1.27 in replication cohort, P = 7.7 × 10(-11) in combined populations]. Single nucleotide polymorphisms in the glypican 5 gene on chromosome 13q32 were also associated (P = 1.7 × 10(-7)) and replicated convincingly (P = 1.2 × 10(-5)) in 789 cases and 2927 controls (per allele OR = 1.31 in replication cohort, P = 3.03 × 10(-11) in combined populations). Four additional regions on chromosomes 10, 15 and 16 showed suggestive association accompanied by nominal replication. This study, the first genome-wide association study of a congenital heart malformation phenotype, provides evidence that common genetic variation influences the risk of TOF.

Eucapnic Voluntary Hyperventilation to Detect Exercise-Induced Bronchoconstriction in Cystic Fibrosis.

BACKGROUND: Exercise-induced bronchoconstriction (EIB) has not been well studied in cystic fibrosis (CF), and eucapnic voluntary hyperventilation (EVH) testing has not been used as an objective assessment of EIB in CF to date. METHODS: A prospective cohort pilot study was completed where standard EVH testing was completed by 10 CF patients with forced expiratory volume in 1 s (FEV1) ≥70% of predicted. All patients also completed a cardiopulmonary exercise test (CPET) with pre- and post-CPET spirometry as a comparative method of detecting EIB. RESULTS: No adverse events occurred with EVH testing. A total of 20% (2/10) patients were diagnosed with EIB by means of EVH. Both patients had clinical symptoms consistent with EIB. No patient had a CPET-based exercise challenge consistent with EIB. CONCLUSIONS: EVH testing was safe and effective in the objective assessment for EIB in patients with CF who had well-preserved lung function. It may be a more sensitive method of detecting EIB then exercise challenge.

An official American Thoracic Society clinical practice guideline: exercise-induced bronchoconstriction.

BACKGROUND: Exercise-induced bronchoconstriction (EIB) describes acute airway narrowing that occurs as a result of exercise. EIB occurs in a substantial proportion of patients with asthma, but may also occur in individuals without known asthma. METHODS: To provide clinicians with practical guidance, a multidisciplinary panel of stakeholders was convened to review the pathogenesis of EIB and to develop evidence-based guidelines for the diagnosis and treatment of EIB. The evidence was appraised and recommendations were formulated using the Grading of Recommendations, Assessment, Development, and Evaluation approach. RESULTS: Recommendations for the treatment of EIB were developed. The quality of evidence supporting the recommendations was variable, ranging from low to high. A strong recommendation was made for using a short-acting ß(2)-agonist before exercise in all patients with EIB. For patients who continue to have symptoms of EIB despite the administration of a short-acting ß(2)-agonist before exercise, strong recommendations were made for a daily inhaled corticosteroid, a daily leukotriene receptor antagonist, or a mast cell stabilizing agent before exercise. CONCLUSIONS: The recommendations in this Guideline reflect the currently available evidence. New clinical research data will necessitate a revision and update in the future.

Low-frequency intermediate penetrance variants in the ROCK1 gene predispose to Tetralogy of Fallot.

BACKGROUND: Epidemiological studies indicate a substantial excess familial recurrence of non-syndromic Tetralogy of Fallot (TOF), implicating genetic factors that remain largely unknown. The Rho induced kinase 1 gene (ROCK1) is a key component of the planar cell polarity signalling pathway, which plays an important role in normal cardiac development. The aim of this study was to investigate the role of genetic variation in ROCK1 on the risk of TOF. RESULTS: ROCK1 was sequenced in a discovery cohort of 93 non-syndromic TOF probands to identify rare variants. TagSNPs were selected to capture commoner variation in ROCK1. Novel variants and TagSNPs were genotyped in a discovery cohort of 458 TOF cases and 1331 healthy controls, and positive findings were replicated in a further 209 TOF cases and 1290 healthy controls. Association between genotypes and TOF was assessed using LAMP.A rare SNP (c.807C > T; rs56085230) discovered by sequencing was associated with TOF risk (p = 0.006) in the discovery cohort. The variant was also significantly associated with the risk of TOF in the replication cohort (p = 0.018). In the combined cohorts the odds ratio for TOF was 2.61 (95% CI 1.58-4.30); p < 0.0001. The minor allele frequency of rs56085230 in the cases was 0.02, and in the controls it was 0.007. The variant accounted for 1% of the population attributable risk (PAR) of TOF. We also found significant association with TOF for an uncommon TagSNP in ROCK1, rs288979 (OR 1.64 [95% CI 1.15-2.30]; p = 1.5x10⁻5). The minor allele frequency of rs288979 in the controls was 0.043, and the variant accounted for 11% of the PAR of TOF. These association signals were independent of each other, providing additional internal validation of our result. CONCLUSIONS: Low frequency intermediate penetrance (LFIP) variants in the ROCK1 gene predispose to the risk of TOF.

Exercise-induced bronchospasm, asthma control, and obesity.

Exercise-induced bronchospasm (EIB) commonly affects patients with asthma. However, the relationship between EIB and asthma control remains unclear. Exercise limitation due to asthma might lead to reduced physical activity, but little information is available regarding obesity and EIB in asthma. A recent survey evaluated the frequency of EIB and exercise-related respiratory symptoms in a large number of patients with asthma. The survey results were reanalyzed to address any relationship between EIB and asthma control and obesity. A nationwide random sample of children aged 4-12 years (n = 250), adolescents aged 13-17 years (n = 266), and adults aged ≥18 years (n = 1001) with asthma were interviewed by telephone. Questions in the survey addressed asthma symptoms in general, medication use, and height and weight. Asthma control was categorized using established methods in the Expert Panel Report 3. Body mass index (BMI) was calculated using standard nomograms and obesity was defined as a BMI ≥ 30 kg/m(2). Most children (77.6%), adolescents (71.1%), and adults (83.1%) had either "not well" or "very poorly" controlled asthma. Children with "not well" controlled asthma reported a history of EIB significantly more often than those with "well" controlled" asthma. Asthma patients of all ages who had "not well" and "very poorly" controlled asthma described multiple (four or more) exercise-related respiratory symptoms significantly more often than those with "well-controlled" asthma. Obesity was significantly more common in adolescents with "not well" and "very poorly" controlled asthma and adults with "very poorly" controlled asthma. Children, adolescents, and adults with asthma infrequently have well-controlled disease. A history of EIB and exercise-related respiratory symptoms occur more commonly in patients with not well and very poorly controlled asthma. Obesity was found more often in adolescents and adults, but not children, with asthma, which was not well and very poorly controlled.

Blind Subgrouping of Task-based fMRI.

Significant heterogeneity in network structures reflecting individuals' dynamic processes can exist within subgroups of people (e.g., diagnostic category, gender). This makes it difficult to make inferences regarding these predefined subgroups. For this reason, researchers sometimes wish to identify subsets of individuals who have similarities in their dynamic processes regardless of any predefined category. This requires unsupervised classification of individuals based on similarities in their dynamic processes, or equivalently, in this case, similarities in their network structures of edges. The present paper tests a recently developed algorithm, S-GIMME, that takes into account heterogeneity across individuals with the aim of providing subgroup membership and precise information about the specific network structures that differentiate subgroups. The algorithm has previously provided robust and accurate classification when evaluated with large-scale simulation studies but has not yet been validated on empirical data. Here, we investigate S-GIMME's ability to differentiate, in a purely data-driven manner, between brain states explicitly induced through different tasks in a new fMRI dataset. The results provide new evidence that the algorithm was able to resolve, in an unsupervised data-driven manner, the differences between different active brain states in empirical fMRI data to segregate individuals and arrive at subgroup-specific network structures of edges. The ability to arrive at subgroups that correspond to empirically designed fMRI task conditions, with no biasing or priors, suggests this data-driven approach can be a powerful addition to existing methods for unsupervised classification of individuals based on their dynamic processes.

Understanding Solid-State Photochemical Energy Storage in Polymers with Azobenzene Side Groups.

Solar thermal fuel (STF) materials store energy through light-induced changes in the structures of photoactive molecular groups, and the stored energy is released as heat when the system undergoes reconversion to the ground-state structure. Solid-state STF devices could be useful for a range of applications; however, the light-induced structural changes required for energy storage are often limited or prevented by dense molecular packing in condensed phases. Recently, polymers have been proposed as effective solid-state STF platforms, as they can offer the bulk properties of solid materials while retaining the molecular-level free volume and/or mobility to enable local structural changes in photoresponsive groups. Light-induced energy storage and macroscopic heat release have been demonstrated for polymers with photoisomerizable azobenzene side groups. However, the mechanism of energy storage and the link between the polymer structure, energy density and storage duration has not yet been explored in detail. In this work, we present a systematic study of methacrylate- and acrylate-based polymers with azobenzene side groups to establish the mechanism of energy storage and release and the factors affecting energy density and reconversion kinetics. For polymers with directly attached azobenzene side groups, the energy storage properties are in line with previous work on similar systems, and the photoisomerization and reconversion properties of the azobenzene side groups mirror those of molecular azobenzene. However, the inclusion of an alkyl linker between the azobenzene side group and the backbone significantly increases the photoswitching efficiency, giving almost quantitative conversion to the Z isomeric state. The presence of the alkyl linker also reduces the glass transition temperature and leads to faster spontaneous thermal reconversion to the E isomeric form, but in all cases, half-lives of more than 4 days are observed in the solid state, which provides scope for applications requiring daily energy storage-release cycles. The maximum gravimetric energy density observed is 143 J g-1, which represents an increase of up to 44% compared to polymers with directly attached azobenzene moieties.

Design, synthesis and biological evaluation of potent NAD+-dependent DNA ligase inhibitors as potential antibacterial agents. Part 2: 4-amino-pyrido[2,3-d]pyrimidin-5(8H)-ones.

A series of 4-amino-pyrido[2,3-d]pyrimidin-5(8H)-ones were designed and synthesized as a novel class of inhibitors of NAD(+)-dependent DNA ligase that possess potency against Gram-positive bacteria.

Design, synthesis and biological evaluation of potent NAD+-dependent DNA ligase inhibitors as potential antibacterial agents. Part I: aminoalkoxypyrimidine carboxamides.

A series of 2,6-disubstituted aminoalkoxypyrimidine carboxamides (AAPCs) with potent inhibition of bacterial NAD(+)-dependent DNA ligase was discovered through the use of structure-guided design. Two subsites in the NAD(+)-binding pocket were explored to modulate enzyme inhibitory potency: a hydrophobic selectivity region was explored through a series of 2-alkoxy substituents while the sugar (ribose) binding region of NAD(+) was explored via 6-alkoxy substituents.

Screening for exercise-induced bronchoconstriction in college athletes.

OBJECTIVE: Previous studies have reported that the prevalence of exercise-induced bronchoconstriction (EIB) in athletes is higher than that of the general population. There is increasing evidence that athletes fail to recognize and report symptoms of EIB. As a result, there has been debate whether athletes should be screened for EIB, particularly in high-risk sports. METHODS: We prospectively studied 144 athletes from six different varsity sports at a large National Collegiate Athletic Association Division I collegiate athletic program. Baseline demographics and medical history were obtained and the presence of asthma symptoms during exercise was documented. Each athlete subsequently underwent a eucapnic voluntary hyperventilation (EVH) test to document the presence of EIB. Exhaled nitric oxide (eNO) quantification was performed immediately before EVH testing. EIB was defined as a ≥10% decline in forced expiratory volume in 1 second compared with baseline. RESULTS: Only 4 of 144 (2.7%) athletes were EIB-positive after EVH testing. The presence of symptoms was not predictive of EIB as only 2 of the 64 symptomatic athletes (3%) were EIB-positive based on EVH testing. Two of the four athletes who were found to be EIB-positive denied such symptoms. The mean baseline eNO in the four EIB-positive athletes was 13.25 parts per billion (ppb) and 24.5 ppb in the EIB-negative athletes. CONCLUSIONS: Our data argue that screening for EIB is not recommended given the surprisingly low prevalence of EIB in the population we studied. In addition, the presence or absence of symptoms was not predictive of EIB and eNO testing was not effective in predicting EIB.

Managing respiratory problems in athletes.

Respiratory problems are common in athletes of all abilities and can significantly impact upon their health and performance. In this article, we provide an overview of respiratory physiology in athletes. We also discuss the assessment and management of common clinical respiratory conditions as they pertain to athletes, including airways disease, respiratory tract infection and pneumothorax. We focus on providing a pragmatic approach and highlight important caveats for the physician treating respiratory conditions in this highly specific population.

Etiology of dyspnea in elite and recreational athletes.

BACKGROUND: Breathing complaints are common in athletes. Studies have suggested that the prevalence of asthma and exercise-induced bronchoconstriction (EIB) is higher in elite athletes than the general population. Vocal cord dysfunction (VCD) may mimic asthma and EIB as a cause of dyspnea in athletes. However, the majority of studies to date have primarily relied on symptoms to diagnose VCD, and there are limited data on coexistence of asthma, EIB, and/or VCD. It is well established that symptoms alone are inadequate to accurately diagnose EIB and VCD. Our goal was to define via objective testing the prevalence of asthma, EIB, VCD alone, or in combination in a cohort of athletes with respiratory complaints. METHODS: A retrospective chart review was done of 148 consecutive athletes (collegiate, middle school, high school, and recreational) referred to a tertiary care center's asthma center for evaluation of respiratory complaints with exercise. An evaluation including medical history, physical examination, and objective testing including pulmonary function testing (PFT), eucapnic voluntary hyperventilation, and video laryngostroboscopy, were performed. RESULTS: The most common symptom was dyspnea on exertion (96%), with < 1% complaining of either hoarseness or stridor. The most common diagnosis prior to referral was asthma (40%). Only 16% had PFTs prior to referral. Following evaluation by a pulmonologist, 52% were diagnosed with EIB, 17% with asthma, and 70% with VCD. Of those diagnosed with asthma before our evaluation, the diagnosis of asthma was confirmed, with PFTs in only 19 of 59 (32%) athletes based on our testing. Vocal cord dysfunction was more common in females and in adolescent athletes. Coexistence of multiple disorders was common, such as EIB and asthma (8%), EIB and VCD (31%), and VCD and asthma (6%). CONCLUSIONS: Asthma and EIB are common etiologies of dyspnea in athletes, both competitive and recreational. However, VCD is also common and can coexist with either asthma or EIB. Vocal cord dysfunction may contribute to exercise-related respiratory symptoms more frequently in middle school- and high school-aged athletes than in college athletes. Effective treatment of dyspnea requires appropriate identification and treatment of all disorders. Classic symptoms of stridor and/or hoarseness are often not present in athletes with VCD. Accurate diagnosis of asthma, EIB, and VCD requires objective testing and can prevent exposure of patients to medications that are ineffective and have potential adverse side effects. Furthermore, there is need for increased awareness of VCD as a common cause of respiratory complaints in athletes, either as a single diagnosis or in combination with EIB, especially in females, as well as middle school and high school athletes.

Vocal cord dysfunction and asthma.

PURPOSE OF REVIEW: Vocal cord dysfunction can occur independently or can co-exist with asthma. It often mimics asthma in presentation and can be challenging to diagnose, particularly in those with known asthma. Vocal cord dysfunction remains under-recognized, which may result in unnecessary adjustments to asthma medicines and increased patient morbidity. There is a need to review current literature to explore current theories regarding disease presentation, diagnosis, and treatment. RECENT FINDINGS: The underlying cause of vocal cord dysfunction is likely multifactorial but there has been increased interest in hyper-responsiveness of the larynx. Many intrinsic and extrinsic triggers have been identified which in part may explain asthma-like symptomatology. A variety of techniques have been reported to provoke vocal cord dysfunction during testing which may improve diagnosis. There is a significant gap in the literature regarding specific laryngeal control techniques, duration of therapy, and the effectiveness of laryngeal control as a treatment modality. SUMMARY: Those with vocal cord dysfunction and asthma report more symptoms on standardized asthma control questionnaires, which can result in increasing amounts of medication if vocal cord dysfunction is not identified and managed appropriately. Clinicians need to maintain a high index of suspicion to identify these patients. Videolaryngostroboscopy remains the diagnostic method of choice. Evidence-based guidelines are needed for the most effective diagnostic techniques. Laryngeal control taught by speech pathologists is the most common treatment. Effectiveness is supported in case reports and clinical experience, but not in larger randomized trials which are needed.

Exercise-induced bronchospasm in children with asthma in the United States: results from the Exercise-Induced Bronchospasm Landmark Survey.

Despite the availability of effective therapies, uncontrolled asthma remains a common problem. Previous large surveys suggest that exercise-related respiratory symptoms may be a significant element of uncontrolled asthma. The Exercise-Induced Bronchospasm (EIB) Landmark Survey is the first comprehensive, national survey evaluating EIB awareness and impact among the general public, asthma patients, and health care providers. This study was designed to evaluate the prevalence and impact of exercise-related respiratory symptoms in children (aged 4-17 years) with asthma. A national survey was conducted with parents of 516 children diagnosed with asthma or taking medications for asthma in the prior year. The majority of parents reported that their child experienced one or more exercise-related respiratory symptom and almost one-half (47.4%) experienced four or more symptoms. Most commonly reported symptoms were coughing, shortness of breath, and wheezing. Respondents reported that asthma limited their child's ability to participate either "a lot" or "some" in sports (30%), other outdoor activities (26.3%), and normal physical exertion (20.9%). Only 23.1% of children with exercise-related respiratory symptoms were reported to take short-acting beta-agonists such as albuterol "always" or "most of the time" before exercising. Exercise-related respiratory symptoms among pediatric asthma patients are common and substantially limit the ability of children to participate normally and perform optimally in physical activities. Such symptoms may reflect uncontrolled underlying asthma that should be evaluated and treated with appropriate controller medications. Despite the availability of preventative therapy, many children do not use short-acting bronchodilators before exercise as recommended in national guidelines.

Impact of exercise-related respiratory symptoms in adults with asthma: Exercise-Induced Bronchospasm Landmark National Survey.

An estimated 5-20% of the general population and up to 90% of people with asthma experience exercise-induced bronchospasm (EIB). The EIB Landmark Survey is the first comprehensive study on exercise-related respiratory symptoms in the United States. Two surveys were conducted: the first surveyed adults (≥18 years) in the general public and the second surveyed adults with asthma or taking medications for asthma in the prior year. Parameters assessed included exercise-related respiratory symptoms, activity levels, and short-acting beta-antagonist (SABA) use. In the general public survey (n = 1085), 8% were currently diagnosed with asthma. However, 29% reported experiencing one or more of six respiratory-related symptoms during or immediately after exercising. In the EIB in adult asthma survey (n = 1001), although >80% of adults experienced one or more of six exercise-related respiratory symptoms, only 30.6% reported a diagnosis of EIB. Almost one-half (45.6%) of adults with asthma reported that they avoid physical activities because of symptoms. Despite symptoms, only 22.2% of respondents took SABAs before exercise "always" or "most of the time"; 36.3% took rescue medications after or during exercise. Exercise-related respiratory symptoms limit physical activities and negatively impact daily lives. However, adults in the United States lack awareness of EIB. Although many subjects stated that their asthma symptoms limit their physical activity, few adhered to treatment guidelines by using SABAs appropriately before exercising. Findings from this survey support the need for better communication about the proper evaluation and management of EIB in the community and in asthma patients.

Gastroesophageal reflux disease and asthma.

PURPOSE OF REVIEW: Asthma and gastroesophageal reflux disease (GERD) are both common diseases, and hence they often coexist. However, the coexistence of asthma and GERD is far more frequent than chance association. There remains debate regarding the mechanism of this relationship and whether treatment of GERD improves asthma outcomes. RECENT FINDINGS: Recent data have confirmed the high prevalence of GERD among patients with asthma. Many asthmatic patients with GERD documented by pH probe do not have classic symptoms of GERD and are considered to have 'silent GERD'. On the basis of smaller trials with somewhat conflicting results regarding improved asthma control with treatment of GERD, consensus guidelines recommend a trial of GERD treatment for symptomatic asthmatic patients even without symptoms of GERD. Recently, a large multicenter trial demonstrated that the treatment of asymptomatic GERD with proton pump inhibitors did not improve asthma control in terms of pulmonary function, rate of asthma exacerbations, asthma-related quality of life, or asthma symptom frequency. SUMMARY: Asthmatic patients have more GERD than the general population. There is not a clear understanding of why this is true. Current guidelines recommend that physicians consider treating patients who have poorly controlled asthma for GERD, even without GERD symptoms. Recent data suggest that this is not a useful practice for mild-to-moderate asthmatic patients.

Discovery of pyrazolthiazoles as novel and potent inhibitors of bacterial gyrase.

Bacterial DNA gyrase is an attractive target for the investigation of new antibacterial agents. Inhibitors of the GyrB subunit, which contains the ATP-binding site, are described in this communication. Novel, substituted 5-(1H-pyrazol-3-yl)thiazole compounds were identified as inhibitors of bacterial gyrase. Structure-guided optimization led to greater enzymatic potency and moderate antibacterial potency. Data are presented for the demonstration of selective enzyme inhibition of Escherichia coli GyrB over Staphylococcus aureus GyrB.

The oral health of children considered very high risk for infective endocarditis.

BACKGROUND: Children with previous experience of infective endocarditis or with prosthetic heart valve are considered at very high risk for infective endocarditis. AIM: The aim of this study was to compare the dental health of a group of these children with a group of healthy controls and to determine parental awareness of the importance of good oral health. DESIGN: Oral examination was carried out in 28 children with previous infective endocarditis or a prosthetic heart valve to assess oral health. Findings were compared to a healthy control group of 28. Questionnaires were distributed to the parents to assess awareness of oral health. RESULTS: There was no significant difference in DMFT scores of study and control group (2.43 +/- 3.72 and 1.36 +/- 2.5 respectively) or in DMFT scores of study and control group (1.5 +/- 1.73 and 1.15 +/- 1.42 respectively), 36% of the study group had untreated caries. Parental knowledge of the link between oral health and infective endocarditis was excellent. CONCLUSIONS: There were no significant differences between the oral health of cardiac children and healthy children although the dmft and DMFT scores of the study group were high. Of concern was the proportion of children with untreated caries in spite of good dental awareness and attendance.