(F)utility of preoperative pulmonary function testing in pectus excavatum to assess severity.

PURPOSE: The utility of pulmonary function testing (PFT) in pectus excavatum (PE) has been subject to debate. Although some evidence shows improvement from preoperative to postoperative values, the clinical significance is uncertain. A high failure-to-completion rate for operative PFT (48%) was identified in our large institutional cohort. With such a high non-completion rate, we questioned the overall utility of PFT in the preoperative assessment of PE and sought to evaluate if other measures of PE severity or cardiopulmonary function could explain this finding. METHODS: Demographics, clinical findings, and results from cardiac MRI, PFT (spirometry and plethysmography), and cardiopulmonary exercise tests (CPET) were reviewed in 270 patients with PE evaluated preoperatively between 2015 and 2018. Regression modeling was used to measure associations between PFT completion and cardiopulmonary function. RESULTS: There were no differences in demographics, symptoms, connective tissue disorders, or multiple indices of pectus severity and cardiac deformation in PFT completers versus non-completers. While regression analysis revealed higher RVEF, LVEF, and LVEF-Z scores, lower RV-ESV/BSA, LV-ESV/BSA, and LV-ESV/BSA-Z scores, and abnormal breathing reserve in PFT completers vs. non-completers, these findings were not consistent across continuous and binary analyses. CONCLUSIONS: We found that PFT completers were not significantly different from non-completers in most structural and functional measures of pectus deformity and cardiopulmonary function. Inability to complete PFT is not an indicator of pectus severity.

Cardiopulmonary Exercise Testing Provides Prognostic Information in Advanced Cystic Fibrosis Lung Disease.

Rationale: Cardiopulmonary exercise testing (CPET) provides prognostic information in cystic fibrosis (CF); however, its prognostic value for patients with advanced CF lung disease is unknown. Objectives: To determine the prognostic value of CPET on the risk of death or lung transplant (LTX) within 2 years. Methods: We retrospectively collected data from 20 CF centers in Asia, Australia, Europe, and North America on patients with a forced expiratory volume in 1 second (FEV1) ⩽ 40% predicted who performed a cycle ergometer CPET between January 2008 and December 2017. Time to death/LTX was analyzed using mixed Cox proportional hazards regression. Conditional inference trees were modeled to identify subgroups with increased risk of death/LTX. Results: In total, 174 patients (FEV1, 30.9% ± 5.8% predicted) were included. Forty-four patients (25.5%) died or underwent LTX. Cox regression analysis adjusted for age, sex, and FEV1 revealed percentage predicted peak oxygen uptake ([Formula: see text]o2peak) and peak work rate (Wpeak) as significant predictors of death/LTX: adjusted hazard ratios per each additional 10% predicted were 0.60 (95% confidence interval, 0.43-0.90; P = 0.008) and 0.60 (0.48-0.82; P < 0.001). Tree-structured regression models, including a set of 11 prognostic factors for survival, identified Wpeak to be most strongly associated with 2-year risk of death/LTX. Probability of death/LTX was 45.2% for those with a Wpeak ⩽ 49.2% predicted versus 10.9% for those with a Wpeak > 49.2% predicted (P < 0.001). Conclusions: CPET provides prognostic information in advanced CF lung disease, and Wpeak appears to be a promising marker for LTX referral and candidate selection.

Does age matter? Cardiopulmonary profiles of adolescents versus adults with pectus excavatum presenting for surgical evaluation.

PURPOSE: We sought to analyze differences in presentation and cardiopulmonary function between those referred for surgical consultation as adolescents (11-17 years) versus adults (18 + years). METHODS: Presenting symptoms, past medical history, and results from cardiac MRI (CMR), pulmonary function testing (PFT), and cardiopulmonary exercise testing (CPET) were reviewed in 329 patients evaluated preoperatively between 2015 and 2018. Adjusted regression modeling was used to measure associations between pectus indices and clinical endpoints of cardiopulmonary function. RESULTS: Our sample included 276 adolescents and 53 adults. Adults presented more frequently with chest pain (57% vs. 38%, p = 0.01), shortness of breath (76% vs. 59%, p = 0.02), palpitations (21% vs. 11%, p = 0.04), and exercise intolerance (76% vs. 59%, p = 0.02). Their Haller indices (5.2 [4.2, 7.0] vs. 4.7 [4.0, 5.7], p = 0.05) and cardiac asymmetry (1.8 [0.5] vs. 1.6 [0.5], p = 0.02) were also higher. In continuous outcome analysis, adolescents had higher FEV1/FVC on PFT and higher work on CPET (p < 0.01). CONCLUSIONS: Adults with pectus excavatum were more symptomatic than adolescents with deeper, more asymmetric deformities, decreased FEV1/FVC and exercise capacity. These findings may support earlier versus later repair to prevent age-related decline. Further studies are warranted.

The Severity of Pectus Excavatum Defect Is Associated With Impaired Cardiopulmonary Function.

BACKGROUND: Repair of pectus excavatum has cosmetic benefits, but the physiologic impact remains controversial. The aim of this study was to characterize the relationship between the degree of pectus excavatum and cardiopulmonary dysfunction seen on cardiac magnetic resonance (CMR) imaging, cardiopulmonary exercise testing (CPET), and pulmonary function testing (PFT). METHODS: A single-center analysis of CMR, CPET, and PFT was conducted. Regression models evaluated relationships between pectus indices and the clinical end points of cardiopulmonary function. RESULTS: Data from 345 CMRs, 261 CPETs, and 281 PFTs were analyzed. Patients were a mean age of 15.2 ± 4 years, and 81% were aged <18 years. The right ventricular ejection fraction (RVEF) was <0.50 in 16% of patients, left ventricular ejection fraction (LVEF) was <0.55 in 22%, RVEF Z-score was < -2 in 32%, and the LVEF Z-score was < -2 in 18%. CPET revealed 33% of patients had reduced aerobic fitness. PFT results were abnormal in 23.1% of patients. Adjusted analyses revealed the Haller index had significant (P < .05) inverse associations with RVEF and LVEF. CONCLUSIONS: The severity of pectus excavatum is associated with ventricular systolic dysfunction. Pectus excavatum impacts right and left ventricular systolic function and can also impact exercise tolerance. The Haller index and correction index may be the most useful predictors of impairment.

Ventilatory limitations are not associated with dyspnea on exertion or reduced aerobic fitness in pectus excavatum.

Exercise intolerance and chest pain are common symptoms in patients with pectus excavatum. To assess if the anatomic extent of pectus deformities determined by the correction index (CI) is associated with a pulmonary impairment at rest and during exercise we performed a retrospective review on pectus patients in our center who completed a symptom questionnaire, cardiopulmonary exercise test (CPET), pulmonary function tests (PFT), and chest magnetic resonance imaging. Of 259 patients studied, dyspnea on exertion and chest pain was reported in 64% and 41%, respectively. Peak oxygen uptake (VO2 ) was reduced in 30% and classified as mild in two-thirds. A pulmonary limitation during exercise was identified in less than 3%. Ventilatory limitations on PFT was found in 26% and classified as mild in 85%. Obstruction was the most common abnormal pattern (11%). There were no differences between patients with normal or abnormal PFT patterns for the CI, VO2, or percentage reporting dyspnea or chest pain. Scatter plots demonstrated significant but weak inverse relationships between the CI and lung volumes at rest and during exercise. Multivariable linear regression modeling evaluating predictors of VO2 demonstrated positive associations with the forced expiratory volume at one second and a negative association with the CI. We conclude that resting PFT patterns have poor correlation with the anatomic extent of the pectus defect, symptomatology or aerobic fitness. Pulmonary limitations on CPET are uncommon and lung volumes during exercise are only minimally associated with the CI.

Impact of pharmacist intervention on completion of recombinant zoster vaccine series in a community pharmacy.

OBJECTIVES: The objectives of this study were to analyze the impact a pharmacist phone call has played on patients completing the 2-dose shingles vaccine series and to explore the effect that patient cost has on the second dose administration. METHODS: A retrospective cohort study design was used to evaluate whether patients who had a pharmacist phone call intervention were more likely to return for their second recombinant zoster vaccine (RZV) dose than patients who did not have a pharmacist phone call intervention. In addition, the impact of immunization cost on series completion was analyzed. The study evaluated the SHINGRIX call lists from 10 randomly selected pharmacies within a large pharmacy chain. The percentage of patients who received the call intervention and their second RZV dose was compared with the percentage of patients who did not receive the intervention yet returned for their second dose of RZV. A chi-square test of independence analyzed the relationship between the 2 variables. An odds ratio (OR) was calculated to determine the relationship between payment data and second dose return status. RESULTS: The relationship between pharmacists' phone calls and patients' return for the second dose vaccination was statistically significant (P < 0.05). Based on payment data, the relationship between the cost of the first dose to the patient and the second dose vaccination was not statistically significant (OR 0.6703; 95% CI 0.4153-1.082). CONCLUSION: A higher percentage of patients received their second RZV dose if they spoke with a pharmacist. Based on the results of this study, a pharmacist's intervention may affect completion rates of the RZV series more than cost.

The chest wall gender divide: females have better cardiopulmonary function and exercise tolerance despite worse deformity in pectus excavatum.

PURPOSE: Pectus excavatum (PE) is a chest wall deformity of variable severity and symptomatology. Existing female-specific literature highlights breast asymmetry and cosmetic reconstruction. We sought to evaluate gender differences in cardiopulmonary function. METHODS: Cardiac MRIs, pulmonary function tests (PFTs), and cardiopulmonary exercise tests (CPETs) were reviewed in 345 patients undergoing preoperative evaluation for PE. Regression modeling was used to evaluate associations between gender and clinical endpoints of cardiopulmonary function. RESULTS: Mean age was 15.2 years, 19% were female, 98% were white. Pectus indices included median Haller Index (HI) of 4.8, mean depression index (DI) of 0.63, correction index (CI) of 33.6%, and Cardiac Compression Index (CCI) of 2.79. Cardiac assessment revealed decreased right and left ventricular ejection fraction (RVEF, LVEF) in 16% and 22% of patients, respectively. PFTs and CPETs were abnormal in ~ 30% of patients. While females had deeper PE deformities-represented by higher pectus indices-they had superior function with higher RVEF, LVEF Z-scores, FEV1, VO2 max, O2 pulse, work, and breathing reserve (p < 0.05). CONCLUSION: Despite worse PE deformity and symptomatology, females had a better cardiopulmonary function and exercise tolerance than males. Further research is needed to assess the precise mechanisms of this phenomenon and postoperative outcomes in this population.

Relationship between exercise capacity and glucose tolerance in cystic fibrosis.

BACKGROUND: Improved exercise capacity (EC) and normal glucose tolerance (NGT) are independently associated with favorable outcomes in CF, however, little information on this relationship exists in patients with CF. METHODS: Cardiopulmonary exercise tests, oral glucose tolerance tests (OGTT), and HbA1c values measured within a 12-month period were evaluated on 83 pediatric patients diagnosed with CF. Patients were categorized as having NGT, abnormal glucose tolerance (AGT), or CF-related diabetes (CFRD). RESULTS: EC decreased as severity of glucose intolerance increased across NGT, AGT, and CFRD groups (P = 0.02). Compared to patients with NGT, patients with CFRD had lower peak VO2 mL/kg/min (33.0 ± 7.3 vs 41.3 ± 9.4, P = 0.01), lower VO2 % (81 ± 20 vs 93 ± 17, P = 0.03), and higher HbA1c (6.9 ± 1.7 vs 5.4 ± 0.4, P < 0.01). There was a positive association with age and FEV1 % with EC in the 17 patients with CFRD. In the 66 patients without diabetes, peak EC was positively associated with FEV1 % and negatively associated with age, fasting insulin, and insulin 120 min. After accounting for age and FEV1 %, multivariate analyses indicated that insulin and glucose values at 120 min predicted EC. CONCLUSIONS: These data provide evidence that poor glucose tolerance is associated with lower EC in pediatric patients with CF. There was a significant relationship between glucose and insulin values obtained by OGTT with EC in a sample of non-diabetic patients with preserved lung function. Future studies are warranted to confirm these findings and investigate the potential role of exercise in the management or prevention of CFRD.

Results of a Prospective Study Evaluating a Noninvasive Method of Hemoglobin Adjustment for Determining the Diffusing Capacity of the Lung.

RATIONALE: Measurement of the diffusing capacity of the lung for carbon monoxide (DlCO) is significantly influenced by the pulmonary capillary blood volume. Consequently, measurements require adjustment for blood hemoglobin concentration (DlCOadj) to allow meaningful clinical interpretation. Noninvasive point-of-care devices that measure hemoglobin transcutaneously provide immediate values for hemoglobin that may be useful in pulmonary function laboratories for determining DlCOadj. OBJECTIVES: To test the hypothesis that DlCOadj determinations obtained with a commercially available device for noninvasive, point-of-care measurement of blood hemoglobin concentrations are not significantly different from determinations obtained using hemoglobin concentrations measured conventionally in venous blood samples. METHODS: In a prospective open trial, hemoglobin measurements were obtained with the Pronto-7 spot check pulse CO-oximeter (Massimo, Irvine, CA) and by venipuncture for 205 patients referred for DlCO testing at Cincinnati Children's Hospital. Hemoglobin and DlCOadj measurements were compared between the two methods, using Student paired t tests and Bland-Altman plots. To assess variability, the differences in DlCOadj between the two methods were also compared by a modification of the current standard for acceptable within-session variability for DlCO. Clinical interpretation for individual DlCO tests based on DlCOadj values obtained from the two methods were compared statistically using Kendall's coefficient of concordance to determine whether the Pronto-7 altered the classification of the severity of DlCO defects. MEASUREMENTS AND MAIN RESULTS: Measurements of hemoglobin concentration by the Pronto-7 analyzer were significantly lower than those obtained from venipuncture blood samples (13.1 ± 1.8 vs. 13.4 ± 2.0; P = 0.01). However, there were no differences for DlCOadj between both methods (23.6 ± 7.7 vs. 23.7 ± 7.5 ml/min/mm Hg; P = 0.42). There was strong correlation between the Pronto-7 and venipuncture DlCOadj values (r = 0.99, P < 0.0001). Variability between the two methods was low for DlCOadj, with a bias of -0.07. More than 96% of tests met acceptable within-session variability. There was no significant difference in the clinical interpretation of the DlCO test based on DlCOadj values recovered from both methods (Kendall's coefficient, 0.96). CONCLUSIONS: Noninvasive measurement of hemoglobin for determination of DlCOadj was accurate and provided acceptable within-session variability. The results obtained noninvasively did not alter clinical interpretation of test results compared with venipuncture. These findings support noninvasive point-of-care devices as an alternative to venipuncture for determining hemoglobin to measure DlCOadj in most patients.

Review of the therapeutic uses of liraglutide.

BACKGROUND: Glucagon-like peptide (GLP-1) is a neuroendocrine hormone that increases blood glucose and is a drug target for treatment of type 2 diabetes. Liraglutide, a subcutaneous, once-daily GLP-1 agonist, is approved for the treatment of type 2 diabetes in the United States and Europe. It also has been studied for weight loss. OBJECTIVE: The purpose of this article is to review all of the relevant literature on the chemistry, pharmacology, pharmacokinetics, metabolism, clinical trials, safety, drug interactions, cost, and place in therapy of liraglutide. METHODS: Literature searches of MEDLINE between 1969 and September 2010, International Pharmaceutical Abstracts between 1970 and September 2010, American Diabetes Association Meeting abstracts (2008-2010), and European Association for the Study of Diabetes abstracts (2008-2010) were performed using liraglutide, Victoza, and NN2211 as key terms. RESULTS: Thirteen randomized controlled trials were identified and summarized. Liraglutide has been shown to increase glucose-dependent insulin release by 34% to 118% and reduce postprandial glucagon levels by 20%. Studies showed that liraglutide, as monotherapy and in combination with glimepiride, metformin, and/or rosiglitazone, lowers glycosylated hemoglobin (HbA(1c)) between 0.84% and 1.5%. Transient nausea was reported by 7% to 40% of subjects. Severe hypoglycemia-glucose <55 mg/dL-was observed by 2.5% of subjects in 1 trial. CONCLUSION: Liraglutide safely and effectively reduces HbA(1c) in patients with type 2 diabetes. The most recent American Diabetes Association guidelines recommended a GLP-1 agonist along with metformin as a second-tier therapy for type 2 diabetes. Although the American Association of Clinical Endocrinologists/American College of Endocrinologists' guidelines recommended it for first-line monotherapy in patients with HbA(1c) between 6.5% and 7.5% and with metformin if HbA(1c) is between 7.6% and 8.5%, liraglutide should be considered for patients who cannot tolerate first-line agents or if an additional agent is needed to help reach target HbA(1c) goals.

Wide variability in physical activity environments and weather-related outdoor play policies in child care centers within a single county of Ohio.

OBJECTIVES: To examine the variability of physical activity environments and outdoor play policies in child care centers and to determine whether this variability is associated with the demographic characteristics of the child care centers surveyed. DESIGN: Early Learning Environments Physical Activity and Nutrition Telephone Survey. SETTING: Child care centers in Hamilton County (greater Cincinnati area), Ohio, during the period from 2008 to 2009. PARTICIPANTS: Directors of all 185 licensed full-time child care centers in Hamilton County. OUTCOME MEASURES: Descriptive measures of playground and indoor physical activity environments and weather-related outdoor play policies. RESULTS: Of 185 eligible child care centers, 162 (88%) responded to our survey. Of the 162 centers that responded, 151 (93%) reported an on-site playground, but slightly more than half reported that their playgrounds were large, that they were at least one-third covered in shade, or that they had a variety of portable play equipment. Only half reported having a dedicated indoor gross motor room where children could be active during inclement weather. Only 32 centers (20%) allowed children to go outside in temperatures below 32°F (0°C), and 70 centers (43%) reported allowing children outdoors during light rain. A higher percentage of children receiving tuition assistance was associated with lower quality physical activity facilities and stricter weather-related practices. National accreditation was associated with more physical activity-promoting practices. CONCLUSION: We found considerable variability in the indoor and outdoor physical activity environments offered by child care centers within a single county of Ohio. Depending on the outdoor play policy and options for indoor physical activity of a child care center, children's opportunities for physical activity can be curtailed as a result of subfreezing temperatures or light rain. Policy changes and education of parents and teachers may be needed to ensure that children have ample opportunity for daily physical activity.

Effect of elimination games on physical activity and psychosocial responses in children.

BACKGROUND: This study evaluated the effect of elimination and nonelimination games on objectively measured physical activity and psychosocial responses in children. METHODS: A total of 29 children in grades 4 to 6 (65.5% male; 10.5 +/- 1.0 years old) wore an accelerometer while participating in 2 elimination and 2 nonelimination games. Activity counts were collected using a 30-second epoch and converted to METs to determine minutes spent in sedentary behavior and light, moderate, vigorous, and moderate-to-vigorous physical activity. Self-efficacy, enjoyment, and peer-victimization were assessed on 4 occasions (before and after 2 elimination and 2 nonelimination games). RESULTS: Overall, girls spent more time in sedentary behavior compared with boys. Children engaged in significantly more moderate-to-vigorous physical activity during nonelimination games compared with elimination games. Furthermore, children significantly increased self-efficacy after playing both game sessions. A significant interaction between type of game and time of measurement in the prediction of enjoyment showed that enjoyment modestly increased after elimination games and slightly decreased after nonelimination games. There were no differences in peer-victimization. CONCLUSION: This study provides preliminary evidence that nonelimination games provide more moderate-to-vigorous physical activity compared with elimination games, but elimination games may be more enjoyable.

Impact of a diabetes certificate program on PharmD students' knowledge and skills.

OBJECTIVES: To determine the impact of a pregraduation diabetes certificate program on PharmD students' knowledge and skills. METHODS: A comprehensive elective in diabetes was created and implemented in the third-professional year of the PharmD curriculum. A nonrandomized, single-blinded, controlled, 2-year study was conducted to determine the impact of the elective. Written and oral examinations were administered to the participants and students in a control group. RESULTS: The certificate students' (N = 25) and control students' (N = 12) average oral examination grades were 88.5% +/- 13.4% and 89.5% +/- 15.8%, respectively (p = 0.58). The certificate students' average grade on the counseling section of the oral examination was 9% higher than that of the students in the control group (p = 0.01). The certificate students' and control students' grades on the written examination were 80.9 +/- 11.1% and 61.1 +/- 17.4% (p = 0.0062), respectively. CONCLUSIONS: A diabetes certificate program improved students' knowledge of diabetes disease state management and patient education skills compared to students who did not take the elective.