Kathryn N. Rankin

Understanding the human salivary metabolome.

Saliva is a readily accessible biofluid that is important for the overall health, aiding in the chewing, swallowing, and tasting of food as well as the regulation mouth flora. As a first step to determining and understanding the human saliva metabolome, we have measured salivary metabolite concentrations under a variety of conditions in a healthy population with reasonably good oral hygiene. Using 1H NMR spectroscopy, metabolite concentrations were measured in resting (basal) and stimulated saliva from the same subject and compared in a cohort of healthy male non‐smoking subjects (n = 62). Almost all metabolites were higher in the unstimulated saliva when compared to the stimulated saliva. Comparison of the salivary metabolite profile of male smokers and non‐smokers (n = 46) revealed citrate, lactate, pyruvate, and sucrose to be higher and formate to be lower in concentration in smokers compared with non‐smokers (p < 0.05). Gender differences were also investigated (n = 40), and acetate, formate, glycine, lactate, methanol, propionate, propylene glycol, pyruvate, succinate, and taurine were significantly higher in concentration in male saliva compared to female saliva (p < 0.05). These results show that differences between male and female, stimulated and unstimulated, as well as smoking status may be observed in the salivary metabolome. Copyright

Pneumococcal Pneumonia: Potential for Diagnosis through a Urinary Metabolic Profile

Pneumonia, an infection of the lower respiratory tract, is caused by any of a number of different microbial organisms including bacteria, viruses, fungi, and parasites. Community-acquired pneumonia (CAP) causes a significant number of deaths worldwide, and is the sixth leading cause of death in the United States. However, the pathogen(s) responsible for CAP can be difficult to identify, often leading to delays in appropriate antimicrobial therapies. In the present study, we use nuclear magnetic resonance spectroscopy to quantitatively measure the profile of metabolites excreted in the urine of patients with pneumonia caused by Streptococcus pneumoniae and other microbes. We found that the urinary metabolomic profile for pneumococcal pneumonia was significantly different from the profiles for viral and other bacterial forms of pneumonia. These data demonstrate that urinary metabolomic profiles may be useful for the effective diagnosis of CAP.

Streptococcus pneumoniae and Staphylococcus aureus pneumonia induce distinct metabolic responses

Pneumonia is an infection of the lower respiratory tract caused by microbial pathogens. Two such pathogens, Streptococcus pneumoniae and Staphylococcus aureus, are the most common causes of community-acquired and hospital-acquired pneumonia respectively. Each expresses strains highly resistant to penicillin and other antibiotics, and a significant number of people succumb to infection by these pathogens every year. Urinary metabolite changes in a C57Bl/6 mouse model with lung infection from either S. pneumoniae or S. aureus were characterized using multivariate targeted profiling data obtained from (1)H NMR spectra. Marked changes in the urinary metabolite profile occurred within 24 h after infection with either pathogen. Specifically, significant decreases in TCA cycle intermediates, coupled with increases in fucose, creatine, and taurine were observed in the urine of S. pneumoniae-treated mice. Infection with S. aureus resulted in the decrease of a number of urinary metabolites including 1-methylnicotinamide, 3-methyl-2-oxovalerate, 2-oxoisocaproate, N-isovaleroylglycine and others. Disturbances in gut-derived microbial metabolites were also observed. Analysis of metabolic trajectory data indicated that, as the mice recovered from infection, their urinary metabolic profile became similar to that of the preinfected state. These results underline the potential of metabolomics as a tool for diagnosis, health monitoring, and drug development, and show its usefulness for understanding microbial-host interactions.

Healthcare transition for youth with heart disease: a clinical trial

Objectives Adolescents with heart disease have complex health needs and require lifelong cardiology follow-up. Interventions to facilitate paediatric to adult healthcare transition are recommended, although outcomes are unknown. We sought to determine the impact of a transition intervention on improving knowledge and self-management skills among this population. Methods We conducted a clinical trial of 15–17 year olds with moderate or complex congenital heart disease (CHD) or cardiomyopathy. Participants were systematically allocated to either usual care (controls) or a 1 h nurse-led one-on-one teaching session about their heart. Allocation was determined by week of attendance in the cardiology clinic. The primary outcome was change in Transition Readiness Assessment Questionnaire (TRAQ) score at 6 months, possible scores ranging from 1 (low) to 5 (optimal). Cardiac knowledge (MyHeart score, range 0–100) was a secondary outcome. Analysis was intention to treat. Results Of 58 participants (48% female), 52 had CHD and 6 had cardiomyopathy. 27 were allocated to the intervention group; 3 declined the intervention and received usual care. When comparing the intervention group with the usual care group at 6 months postintervention, the mean self-management TRAQ score was 3.59 (±0.83) vs 3.16 (±1.05), respectively (p=0.048, adjusted for baseline score); the mean self-advocacy TRAQ score was 4.38 (±0.56) vs 4.01 (±0.95) (p=0.18) and the mean MyHeart score was 75% (±15) vs 61% (±25) (p=0.019). Conclusions A 1 h nurse-led transition intervention resulted in a significant improvement in self-management and cardiac knowledge scores. An educational intervention should be routine for youth with congenital or acquired heart disease. Trial registration number NCT01286480

Risk factors for loss to follow-up among children and young adults with congenital heart disease

OBJECTIVE To identify risk factors for loss to cardiology follow-up among children and young adults with congenital heart disease. METHODS We used a matched case-control design. Cases were born before January, 2001 with moderate or complex congenital heart disease and were previously followed up in the paediatric or adult cardiology clinic, but not seen for 3 years or longer. Controls had been seen within 3 years. Controls were matched 3:1 to cases by year of birth and congenital heart disease lesion. Medical records were reviewed for potential risk factors for loss to follow-up. A subset of cases and controls participated in recorded telephone interviews. RESULTS A total of 74 cases (66% male) were compared with 222 controls (61% male). A history of missed cardiology appointments was predictive of loss to follow-up for 3 years or longer (odds ratio 13.0, 95% confidence interval 3.3-51.7). Variables protective from loss to follow-up were higher family income (odds ratio 0.87 per

A cluster randomized trial of a transition intervention for adolescents with congenital heart disease: rationale and design of the CHAPTER 2 study.

10,000 increase, 0.77-0.98), cardiac catheterisation within 5 years (odds ratio 0.2, 95% confidence interval 0.1-0.6), and chart documentation of the need for cardiology follow-up (odds ratio 0.4, 95% confidence interval 0.2-0.8). Cases lacked awareness of the importance of follow-up and identified primary care physicians as their primary source of information about the heart, rather than cardiologists. Unlike cases, controls had methods to remember appointments. CONCLUSIONS A history of one or more missed cardiology appointments predicted loss to follow-up for 3 or more years, as did lack of awareness of the need for follow-up. Higher family income, recent catheterisations, and medical record documentation of the need for follow-up were protective.

Computer-aided auscultation of murmurs in children: evaluation of commercially available software.

BackgroundThe population of adolescents and young adults with congenital heart disease (CHD) is growing exponentially. These survivors are at risk of late cardiac complications and require lifelong cardiology care. However, there is a paucity of data on how to prepare adolescents to assume responsibility for their health and function within the adult health care system. Evidence-based transition strategies are required.MethodsThe Congenital Heart Adolescents Participating in Transition Evaluation Research (CHAPTER 2) Study is a two-site cluster randomized clinical trial designed to evaluate the efficacy of a nurse-led transition intervention for 16–17 year olds with moderate or complex CHD. The primary endpoint is excess time to adult CHD care, defined as the time interval between the final pediatric cardiology appointment and the first adult CHD appointment, minus the recommended time interval between these appointments. Secondary endpoints include the MyHeart score (CHD knowledge), Transition Readiness Assessment Questionnaire score, and need for catheter or surgical re-intervention. Participants are enrolled in clusters based on week of attendance in the pediatric cardiology clinic. The intervention consists of two one-hour individualized sessions between a cardiology nurse and study participant. Session One focuses on knowledge of the participant’s CHD, review of their cardiac anatomy and prior interventions, and potential late cardiac complications. Session Two focuses on self-management and communication skills through review and discussion of videos and role-play. The study will recruit 120 participants.DiscussionMany adolescents and young adults experience a gap in care predisposing them to late cardiac complications. The CHAPTER 2 Study will investigate the impact of a nurse-led transition intervention among adolescents with CHD. Fidelity of the intervention is a major focus and priority. This study will build on our experience by (i) enrolling at two tertiary care programs, (ii) including a self-management intervention component, and (iii) evaluating the impact of the intervention on time to ACHD care, a clinically relevant outcome. The results of this study will inform pediatric cardiology programs, patients and policy makers in judging whether a structured intervention program provides clinically meaningful outcomes for adolescents and young adults living with CHD.Trial registrationClinicalTrials.gov ID NCT01723332

Modifiable cardiovascular risk factors in adolescents and adults with congenital heart disease

BACKGROUND Heart murmurs are common in children and may represent congenital or acquired cardiac pathology. Auscultation is challenging and many primary-care physicians lack the skill to differentiate innocent from pathologic murmurs. We sought to determine whether computer-aided auscultation (CardioscanTM) identifies which children require referral to a cardiologist. METHODS We consecutively enrolled children aged between 0 and 17 years with a murmur, innocent or pathologic, being evaluated in a tertiary-care cardiology clinic. Children being evaluated for the first time and patients with known cardiac pathology were eligible. We excluded children who had undergone cardiac surgery previously or were unable to sit still for auscultation. CardioscanTM auscultation was performed in a quiet room with the subject in the supine position. The sensitivity and specificity of a potentially pathologic murmur designation by CardioscanTM - that is, requiring referral - was determined using echocardiography as the reference standard. RESULTS We enrolled 126 subjects (44% female) with a median age of 1.7 years, with 93 (74%) having cardiac pathology. The sensitivity and specificity of a potentially pathologic murmur determination by CardioscanTM for identification of cardiac pathology were 83.9 and 30.3%, respectively, versus 75.0 and 71.4%, respectively, when limited to subjects with a heart rate of 50-120 beats per minute. The combination of a CardioscanTM potentially pathologic murmur designation or an abnormal electrocardiogram improved sensitivity to 93.5%, with no haemodynamically significant lesions missed. CONCLUSIONS Sensitivity of CardioscanTM when interpreted in conjunction with an abnormal electrocardiogram was high, although specificity was poor. Re-evaluation of computer-aided auscultation will remain necessary as advances in this technology become available.

Investigations of the Effects of Gender, Diurnal Variation, and Age in Human Urinary Metabolomic Profiles

OBJECTIVE Individuals with congenital heart disease (CHD) may be at higher risk of acquired cardiovascular disease than the general population due to their underlying physiology and/or surgical sequelae. We sought to assess the prevalence of cardiovascular disease risk factors in youth and adults with CHD. METHODS We assessed cardiovascular health as per the Cardiovascular Health in Ambulatory Care Research Team (CANHEART) health index in patients with CHD aged 15+ years who attended cardiology outpatient clinics. Participants self-reported smoking behavior, fruit and vegetable consumption, physical activity, and whether they had diabetes and hypertension. Individual health indices were categorized into ideal/not ideal, and sum of individual health indices was categorized as poor, intermediate or ideal cardiovascular health as per CANHEART criteria. RESULTS We included n = 102 adults (35.4 ± 12.9 years, 46% female) and n = 88 youth (17.2 ±1.1 years, 41% female). Most individuals reported to be nonsmokers (88% youth vs 86% adults) and to consume ≥5 servings of fruit and vegetables per day (83% vs 85%, respectively). More adults than youth were overweight/obese (52% vs 22%, p < 0.001) though more adults than youth reported meeting age-specific physical activity guidelines (84% vs 55%, p < 0.001). According to CANHEART health index criteria, 32% of youth and 27% of adults were in ideal cardiovascular health. CONCLUSIONS A low proportion of individuals with CHD are in ideal cardiovascular health, suggesting a need to promote healthy lifestyles during adolescence and throughout adulthood in these individuals.