Department: Medicine: Clinical and Translational Research ![[clear]](close-x.png "Remove this limiter")
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1.
Abraham, Elizabeth C. M.D.
Focal Segmental Glomerulosclerosis in Children: An Emerging Epidemic and Risk Factors for Disease Recurrence in Transplants.
Degree: MS, Medicine: Clinical and Translational Research, 2011, University of Cincinnati
► The incidence of focal segmental glomerulosclerosis (FSGS), already the second leading cause…
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▼ The incidence of focal segmental glomerulosclerosis (FSGS), already the second leading cause of end stage renal disease (ESRD) in children, appears to be increasing. Moreover, post-transplant (Tx) FSGS recurrence (R) is a major problem, and there is concern that kidneys from living related donors (LRDs) are more likely to be affected by R than kidneys from deceased donors (DDs). However, prior studies have not accounted for the potentially confounding influence of race on donor type in recurrence risk. AIMS: (1) To study trends in FSGS leading to pediatric ESRD using a national database. (2) To analyze risk factors for FSGS R in the pediatric Tx recipients on a national scale. METHODS: Data from the United Network for Organ Sharing (UNOS) from 1988-2008 was analyzed for number of Tx for a primary diagnosis of FSGS in Tx recipients <21 years old. Poisson regression was used for trend analysis. Differences in trends were examined by age group, gender, race, and UNOS region. Then, UNOS data was examined in a case-control fashion for R vs. non-R in Txs for recipients ages <21years with FSGS. Multiple logistic regression analysis was used to examine the independent variables of gender, race, HLA matching, UNOS pediatric age groups and donor type (LRD vs. DD). RESULTS: Trend analysis of incident kidney Txs for FSGS over time showed a risk ratio of 1.054, or an increase in cases of 5.4% per year or 294% over 20 years (p<0.0001). Hispanic race was associated with a disproportionate increase over time. There were no significant differences in risk ratio based on UNOS pediatric age group, gender, degree of HLA mismatching or UNOS region. FSGS was reported as the cause of ESRD in 2143 pediatric Txs over 20 years. R was reported in 327 cases (15%) overall and more often in younger age groups (1-5 years: 18%, 6-10 years: 20%, 11-17 years: 15%, 18-20 years: 12%, p<0.01). In univariate analysis, males had insignificantly more Rs than females (16% vs. 14%, p=0.14), but whites had more Rs than African-Americans (19% vs. 13%, p<0.0001), and Rs occurred more often in kidneys from LRDs than DDs (17% vs. 14%, p<0.01). Using multivariate analysis, young age (p<0.005), male gender (p=0.03) and white race (p<0.0005) were identified as significant risk factors for R, while donor type became insignificant. CONCLUSIONS: This study confirms our local suspicion that FSGS as a cause of ESRD for incident pediatric kidney Txs is increasing nationally. It also shows that being male, white and very young is associated with a higher likelihood of post-Tx FSGS R. In contrast, there does not appear to be an increase in R risk in kidneys from LRDs when age, gender and ethnicity are considered, possibly because of the higher frequency of LRD Tx in whites and young children. Acknowledgements: Katarina Linden, UNOS
Advisors/Committee Members: Succop, Paul.
Subjects: Surgery
Keywords: pediatric; kidney; transplant; FSGS; recurrence; glomerulosclerosis
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2.
Aguilar, Carlos A. M.D.
"Predictors of inpatient narcotic overdose in a non-surgical population".
Degree: MS, Medicine: Clinical and Translational Research, 2012, University of Cincinnati
► Background: Medication errors are a common cause of injuries sustained in hospitals…
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▼ Background: Medication errors are a common cause of injuries sustained in hospitals and up to 6% are related to opioids. A challenging task for clinicians is to find the perfect balance between providing effective analgesia and preventing adverse events Objective: Evaluate the incidence and risk factors associated with opioid overdose in a non-surgical inpatient population. Methods: A case-control study based on information from the electronic health record following discharge from a large community hospital in Cincinnati, OH between June and December 2008. Participants were adults hospitalized on medical wards and receiving opioid therapy. Cases met clinical criteria for opioid overdose and were treated with Naloxone, while. controls were randomly selected from the same time interval. We excluded patients admitted for opioid overdose, those on patient controlled analgesia, or those in a perioperative setting including same-day outpatient procedures. Main Measures: Opioid overdose events, patient demographics, laboratory values, comorbidities, type and number of opioids used, dose in morphine equivalents and other psychotropic medications used. Results: Of a total of 19,111 patient discharges, 40 (0.21%) met the case inclusion criteria for opioid overdose. Patients with overdoses had a lower weight and were receiving higher opioid doses both prior and during the hospitalization. Hydromorphone was the opioid most frequently associated with overdose events while Hydrocodone was the least. Multivariate logistic regression analyses showed older age (OR 1.06 [95% CI 1.01 to 1.11], p= 0.012), serum creatinine (OR 1.36 [95% CI 1.07 to 1.73], p=0.011) and 24-hour total morphine equivalents received (OR 1.01 [1.00 to 1.02], p=0.002) to be most highly associated with overdose. Hydrocodone use (OR 0.12 [95% CI 0.02 to 0.69], p=0.018) was associated with a decreased risk of overdose. Conclusions: Opioid overdose events were more frequent among older patients with increased creatinine levels, receiving a high morphine equivalent dose and who were less likely to be treated with Hydrocodone. We were unable to demonstrate that prior opioid therapy, other comorbidities and concomitant use of benzodiazepines were related to an increased rate of adverse outcomes.
Advisors/Committee Members: Haynes, Erin Nicole.
Subjects: Surgery
Keywords: Opioid; Narcotic; Overdose; Inpatient; Hospitalized; Naloxone
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3.
Appleman, Stephanie S. M.D.
Bone Disease in TPN-dependent Infants and Children with Intestinal Failure.
Degree: MS, Medicine: Clinical and Translational Research, 2011, University of Cincinnati
► Total parenteral nutrition (TPN) dependent infants and children with intestinal failure (IF)…
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▼ Total parenteral nutrition (TPN) dependent infants and children with intestinal failure (IF) are at risk for reduced bone mineral content and density owing to inflammation, disturbances in the growth hormone-insulin-like growth factor (IGF)-1 axis or vitamin D and Ca metabolism, and/or aluminum toxicity. We performed a cross sectional study comparing infants and children with intestinal failure with duos of age, sex, and race matched controls. Bone mineral content (BMC) and density (BMD) of the lumbar spine was measured by dual x-ray absorptiometry, and serum cytokines, aluminum, IGF-1 and IGF-BP3, parathyroid hormone (PTH), 25(OH) Vitamin D, and 1, 25(OH)2 Vitamin D were measured. Generalized estimating equation models accounting for matching were used for comparisons. BMC and BMD were lower (15% and 12%) in IF participants than controls (p=0.0009 and p=0.004). However, group differences were attenuated (to 3% and 7%, respectfully) and did not differ (p=0.40 and p=0.07) when adjusted for length and weight. Length and weight percentiles were significantly lower in IF versus control participants (12.5% vs. 63%, p<0.0001; 29.5% vs. 54%, p=0.03). IF participants had significantly higher serum aluminum (23 vs. 7 mcg/L, p<0.0001), IGF-1 (97 vs. 64 ng/mL, p=0.04), and 25 (OH) Vitamin D concentrations (40 vs. 30 ng/mL, p=0.0005), and significantly lower IGF-BP3 (1418 vs. 1812 ng/mL, p<0.0001) and PTH concentrations (51 vs. 98 pg/mL, p=0.0002). No significant difference between IF and control participants was seen for serum cytokines (p=0.09). Additional investigation is needed to elucidate the cause of growth retardation in IF patients and its impact on bone mass and density, especially the role of IGF-1 resistance and aluminum toxicity.
Advisors/Committee Members: Succop, Paul.
Subjects: Surgery
Keywords: intestinal failure; growth; pediatric; bone mineral density; total parenteral nutrition; DXA
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4.
Babcock, Lynn M.D.
Predicting Post-Concussion Syndrome After Mild Traumatic Brain Injury in Children.
Degree: MS, Medicine: Clinical and Translational Research, 2012, University of Cincinnati
► Background: A cluster of cognitive, physical, emotional / behavioral and sleep problems…
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▼ Background: A cluster of cognitive, physical, emotional / behavioral and sleep problems referred to as post-concussion syndrome (PCS) occurs following mild traumatic brain injury (mild TBI) in a subset of children. Limited evidence suggests that patient and injury characteristics contribute to the development of PCS. Objective: To determine the acute predictors associated with the development of PCS in children. Methods: Retrospective analysis of a prospective observational study of children ages 5 to 18 years presenting to the Emergency Department (ED) with mild TBI. All patients had data related to the injury recorded during the initial ED visit. Telephone follow-up administration of the Rivermead Postconcussion Questionnaire was conducted at three months post injury. In a convenience sample, serum was analyzed for the biomarker S100B. Univariable and multivariable logistic regressions were performed. Results: 29% of children presenting to the ED with mild TBI developed had PCS. The most frequent PCS symptom was headache. Predictors of the development of PCS were age, headache on presentation in the ED and admission to the hospital, while controlling for other covariates. S100B levels alone did not predict development of PCS. Children who developed PCS missed, on average, 7.4 (SD 4.9) days of school. Conclusions: Children, who were older, had headache on ED presentation and required hospital admission at ED encounter, were at high risk of PCS following TBI. Interventions to identify and begin early treatment for this population may be of benefit to improve outcomes and reduce burden of disease.
Advisors/Committee Members: Haynes, Erin Nicole.
Subjects: Surgery
Keywords: mild traumatic brain injury; post-concussion syndrome; children; concussion; S100B
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5.
Bishop, Michael W. M.D.
Therapy-Related Events and Health-Related Quality of Life for Children with Leukemia and Lymphoma.
Degree: MS, Medicine: Clinical and Translational Research, 2012, University of Cincinnati
► Purpose: To identify associations between specific therapy-related events such as length of…
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▼ Purpose: To identify associations between specific therapy-related events such as length of hospitalization and neuropathic pain with health-related quality of life (HRQOL) outcomes for children with acute lymphoblastic leukemia and lymphoblastic lymphoma. Hypothesis: In children (ages 2 – 30 years) with acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma, poor health-related quality of life (HRQOL) scores as measured by the PedsQL modules during low-intensity “maintenance” therapy are significantly associated with increased care measures during the initial phases of therapy, including prolonged hospitalization and use of narcotics or neuropathic pain medications. Specific Aims: 1.To evaluate the relationship between extended hospitalization time (as defined by total days or weeks admitted, or by number of unanticipated admissions) during intensive phases of therapy, and HRQOL scores during maintenance therapy in children ages 2 years and older with ALL or lymphoblastic lymphoma. 2. To evaluate the relationship between increased supportive care for pain by use of patient-controlled analgesia (PCA), long acting oral narcotics, or the use of neuropathic pain medications during therapy, and HRQOL scores during maintenance therapy in children ages 2 years and older with ALL or lymphoblastic lymphoma. Methods: A cross-sectional single institution pilot study was performed for children with ALL or lymphoblastic lymphoma who had reached maintenance therapy or had recently completed treatment. HRQOL scores were obtained using the PedsQL 4.0 Generic Core Scales and PedsQL 3.0 Cancer Module, and retrospective chart review was performed for each patient. Results: 57 subjects were available for analysis. Multiple regression analysis found that longer total time of hospitalization correlated with poorer overall PedsQL 4.0 summary scores (p = 0.002). Age, time since the start of maintenance therapy, and the number of unscheduled hospitalizations were independently prognostic for physical scores. The use of neuropathic pain medications was strongly associated with poorer social functioning scores (OR 4.58, p = 0.03), the number of weeks hospitalized also negatively influenced social scores (OR 0.90, p = 0.04). Conclusions: Specific therapy-related events can predict changes in HRQOL outcomes for children and adolescents with ALL and lymphoblastic lymphoma. Future research should include prospective evaluations of HRQOL outcomes throughout therapy and determine what interventions may improve HRQOL outcomes.
Advisors/Committee Members: Haynes, Erin Nicole.
Subjects: Oncology
Keywords: acute lymphoblastic leukemia; lymphoblastic lymphoma; health-related quality of life; pediatric
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6.
Brady, Patrick W.
Duration of intravenous antibiotics and treatment failure in infants hospitalized with urinary tract infections.
Degree: MS, Medicine: Clinical and Translational Research, 2011, University of Cincinnati
► BACKGROUND. Urinary tract infections (UTIs) are common, and length of intravenous (IV)…
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▼ BACKGROUND. Urinary tract infections (UTIs) are common, and length of intravenous (IV) antibiotic therapy may vary in younger infants due to inadequate evidence on course necessary to prevent treatment failure. OBJECTIVE. To determine the difference between short- (=3 days) and long- (=4 days) duration IV antibiotic therapy on treatment failure in a cohort of young infants hospitalized with urinary tract infection. METHODS. We conducted a retrospective cohort study of infants less than 6 months of age hospitalized with an acute UTI between 1999 and 2004 at 24 children’s hospitals in the Pediatric Health Information System (PHIS). We characterized differences in treatment status and outcome at a patient and hospital level. Our main model adjusted for all covariates, propensity scores, and clustering by hospital to evaluate the effect of short versus long courses of IV antibiotics on treatment failure defined as readmission for UTI within 30 days. RESULTS. Of the 12,360 infants who met inclusion criteria, 240 (1.9%) experienced treatment failure. The treatment failure rate was 1.6% in children who received a short course of IV antibiotics and 2.2% in those that received a long course. Treatment course varied substantially across hospitals and with patient-level characteristics. After multivariable adjustment, including propensity scores, there was no significant association between treatment group and outcome with odds ratio for long treatment compared to short treatment of 0.90 (95% confidence interval of 0.68 to 1.19). Known presence of genitourinary abnormalities—but not age—predicted treatment failure in the final model. CONCLUSIONS. Treatment failure for infants less than 6 months hospitalized with UTI is uncommon and is not associated with duration of IV antibiotics. Treating more infants with short courses of IV antibiotics could potentially decrease the length of hospitalization without affecting the readmission rate.
Advisors/Committee Members: Haynes, Erin Nicole.
Subjects: Surgery
Keywords: urinary tract infection; children; infants; therapy; comparitive effectiveness
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7.
DeFranco, Emily A.
Placental pathologic aberrations in cases of familial idiopathic spontaneous preterm birth.
Degree: MS, Medicine: Clinical and Translational Research, 2010, University of Cincinnati
► OBJECTIVE: To test the hypothesis that placental histologic characteristics in pregnancies complicated…
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▼ OBJECTIVE: To test the hypothesis that placental histologic characteristics in pregnancies complicated by familial spontaneous preterm birth (sPTB) will differ by gestational age (GA) and reflect possible mechanisms of pathogenesis. METHODS: We conducted a prospective cohort study in women who had both an idiopathic sPTB <35 weeks and a first degree family member affected by PTB. Parturients with clinical chorioamnionitis in labor or medically indicated PTB were excluded. Placental specimens were reviewed by a single pathologist blind to GA at birth. Results were categorized with respect to the presence of maternal and/ or fetal inflammatory response (MIR, FIR). The placental findings were compared to three categories of preterm GAs: 32–35 (referent), 28–32, and <28 weeks, adjusting for statistically influential factors. RESULTS: Placental specimens were evaluated from 79 spontaneous PTBs. Inflammatory responses were found frequently: 41 (51.9%) had MIR and 28 (35.4%) had FIR. Placental inflammatory changes of maternal origin were most frequent at the earliest GAs, 85% with PTB <28 weeks [adjOR 77.5 (95% CI 5, 1213.1)], and 57% at 32-35 weeks [adjOR 6.1 (0.8, 48.5)] compared to later PTBs occuring at 32–35 weeks (22%). Inflammatory changes of fetal origin (FIR) also occurred more frequently in cases of extreme PTB, adjOR 38.4 (95% CI 2.9, 514.2). CONCLUSION: Placental inflammatory responses are common in women with familial sPTB. Maternal and fetal inflammatory responses occur most frequently in the earliest cases of PTB. This data suggests that inflammation plays an important role in the onset of parturition in cases otherwise classified as idiopathic or spontaneous in nature, especially at the earliest GAs when neonatal outcomes are the poorest.
Advisors/Committee Members: Haynes, Erin Nicole.
Subjects: Biostatistics
Keywords: prematurity; placental pathology; recurrent preterm birth; placental inflammation; preterm labor
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8.
Dorris, Kathleen.
A comparison of safety and efficacy of cytotoxic versus molecularly targeted agents in pediatric phase I solid tumor oncology trials.
Degree: MS, Medicine: Clinical and Translational Research, 2012, University of Cincinnati
► Background: Prior reviews of phase I pediatric oncology trials involving primarily cytotoxic…
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▼ Background: Prior reviews of phase I pediatric oncology trials involving primarily cytotoxic agents have reported objective response rates (ORR) and toxic death rates (TDR) of 7.9-9.6% and 0.5%, respectively. These data may not reflect safety and efficacy in phase I trials of molecularly targeted drugs, which are usually cytostatic. Methods: A systematic review of pediatric phase I oncology trials in patients with refractory solid tumors published from 1990 to 2010 was performed. Publications were identified through a PubMed query for “phase I,” “pediatric” and “cancer” search terms. The published reports were evaluated for patient characteristics, toxicity information and response numbers. Results: Eighty-nine phase I pediatric solid tumor clinical trials enrolling 2623 children were identified. Thirty trials investigated 26 molecularly targeted drugs; 59 trials evaluated 37 cytotoxic agents. A meta-analysis demonstrated that the ORR is significantly higher with cytotoxic drugs (0.068 vs 0.026 per study subject; p<0.001). On the contrary, the pooled estimate of the SDR is similar for cytotoxic versus molecularly targeted drugs (0.201 vs. 0.211 per study subject; p=0.796). The pooled estimate of the DLT rate is higher with cytotoxic drugs (0.3229 vs 0.2402 per study subject; p=0.0807, marginally significant). The hematologic grade 3-4 toxicity episode rate is significantly higher with cytotoxic drugs (0.4798 vs. 0.2043 per course of therapy; p=0.0035); however, the overall and non-hematologic grade 3-4 toxicities occur at similar rates for cytotoxic and molecularly targeted drugs. Conclusions: In phase I pediatric solid tumor trials, ORR were significantly higher for cytotoxic versus molecularly targeted agents. SDR were similar in molecularly targeted and cytotoxic drug trials. Although TDR were similar in both groups, patients treated with cytotoxic agents were more likely to experience a DLT or hematologic grade 3-4 toxicity than those patients receiving molecularly targeted drugs. These observations should help to guide future phase I/II pediatric oncology clinical trial designs for novel molecularly targeted drugs.
Advisors/Committee Members: Haynes, Erin Nicole.
Subjects: Surgery
Keywords: pediatric oncology; solid tumor
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9.
Dykes, Dana Michelle Hines.
Evaluating the use of a new radiographic tool to identify high-risk pediatric Crohn's Disease patients.
Degree: MS, Medicine: Clinical and Translational Research, 2012, University of Cincinnati
► Background. Patients with Crohn’s Disease (CD) and elevated levels of Granulocyte-Macrophage Colony-Stimulating…
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▼ Background. Patients with Crohn’s Disease (CD) and elevated levels of Granulocyte-Macrophage Colony-Stimulating Factor auto-antibodies (GM-CSF Ab) are twice as likely to develop stricturing and penetrating behavior requiring surgery. Detection of small bowel lesions such as luminal narrowing with the highly sensitive techniques Computed Tomography and Magnetic Resonance Enterography (CT-E and MR-E) may identify patients prior to developing strictures requiring surgery. Objective. To determine whether CD patients with high GM-CSF Ab (more than 1.6 mcg/mL) have a higher prevalence of luminal narrowing and complicated disease behavior on CT-E or MR-E. Methods. A single center, two-phase, cross-sectional study of pediatric patients undergoing both enterography and GM-CSF Ab levels. For the retrospective arm 51 patients with CD were included for analysis, and for the prospective arm, 120 pediatric patients scheduled for CT-E or MR-E. Exams were evaluated for presence or absence of luminal narrowing, stricture (fixed luminal narrowing combined with pre-stenotic dilation and/or fecalization of the proximal small bowel), abscess, or fistulae. Patients underwent GM-CSF Ab testing if no previous value was available. Continuous variables were analyzed using t-test and dichotomous variables using Fisher’s exact test. Results. Of the 51 retrospective and 65 prospective CD patients, the median GM-CSF Ab was elevated with median (IQR) of 2.35 (0.6, 7.4) mcg/mL and 2.0 (0.5, 6.1) mcg/mL compared with the non-CD healthy/disease control median of 0.6mcg/mL (0.3,1.3), p=0.009. A previously identified cut-off of 1.6 mcg/mL was used for high vs low antibody for the CD patients. Among CD patients, race, age, and duration of disease were not different by antibody status within each cohort. Duration of disease was longer for the retrospective cohort with an average of 3.5 (3.0) years compared with the prospective patients with an average 2.2 (3.2) years, p=0.009. The retrospective cohort averaged 21 (6) months of follow-up compared with the prospective 8 (4) months, p=0.02. Paris criteria were not different for age at diagnosis for either cohort. High GM-CSF Ab was associated with an increased prevalence of ileal disease (L1/L3 vs L2) with p<0.005 for both cohorts. Stricturing and/or penetrating behavior was more prevalent in high GM-CSF Ab patients, but this difference was significant only for the prospective cohort, p=0.024. On enterography examination, luminal narrowing was more prevalent for both retrospective and prospective cohorts with p=0.047 and p=0.004. Stricture prevalence was increased for high GM-CSF Ab patients in both cohorts with p=0.05 and 0.01, but there was no difference in penetrating disease outcomes. Of five patients with isolated luminal narrowing at the time of enterography who have progressed to develop stricture, all had high GM-CSF Ab and four also had luminal narrowing on enterography. Conclusion. Pediatric CD patients with high GM-CSF Ab levels have a higher prevalence of luminal narrowing and strictures and on enterography. Luminal narrowing may progress to stricturing in high risk individuals. Prospective evaluation will be necessary to further evaluate this correlation and to determine whether early infliximab use might reduce progression to stricturing disease and surgery.
Advisors/Committee Members: Haynes, Erin Nicole.
Subjects: Surgery
Keywords: Granulocyte-Macrophage Colony Stimulating Factor; Crohn's Disease; enterography; pediatric; radiology; stricture
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10.
Fitzgerald, Sarah E. M.D.
A Meta-Analysis of the Diagnostic Performance of Procalcitonin in the Diagnosis of Serious Bacterial Infection in Pediatric Febrile Neutropenia.
Degree: MS, Medicine: Clinical and Translational Research, 2012, University of Cincinnati
► Background: Continued advancements and intensification of chemotherapy regimens have enhanced outcomes for…
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▼ Background: Continued advancements and intensification of chemotherapy regimens have enhanced outcomes for children with cancer. With more aggressive therapy, however, infection rates due to immune system suppression have increased1. Although progress in supportive care strategies has improved management of such infections2, infection remains a major cause of morbidity and mortality among pediatric oncology patients3. Serious bacterial infections often present non-specifically with only fever and neutropenia; however, infection represents only one etiology of fever and neutropenia. Objective: Identification of a biomarker to more quickly diagnose serious infection in fever and neutropenia episodes would be advantageous. Prior small studies suggest that procalcitonin may be a feasible and reliable marker for bacterial infection in febrile neutropenic pediatric patients. Because the implementation of such a biomarker would be significant to pediatric oncology practice, stronger evidence is required before the assay can be meaningfully, reliably, and safely applied to patient care. Design/Methods: We conducted a systematic review and meta-analysis of the literature regarding the use of procalcitonin as a marker of serious infection in neutropenic febrile children. We searched several electronic databases that included records from 1966 to July 2011 using the keyword “procalcitonin†alone and in combination with several terms related to our topic. Results: The ten selected studies included 591 pediatric oncology patients with a total of 1161 febrile episodes. Regression analysis and the random effects model were used to estimate the common effect size for each measure of diagnostic performance for procalcitonin: pooled odds ratio was 39.29, with 95% confidence interval (12.61, 122.4); sensitivity was 0.709, or 70.9%, with p<0.0001 and 95% confidence interval (0.357, 1.06); specificity was 0.826, or 82.6%, with p<0.0001 and 95% confidence interval (0.629, 1.02). Conclusions: Procalcitonin is an appropriate candidate biomarker for serious bacterial infection in pediatric oncology fever and neutropenia patients, given that the odds of having an elevated procalcitonin assay and a serious bacterial infection are 39.29 times higher than the odds of having an elevated procalcitonin assay in the absence of serious bacterial infection. Furthermore, this meta-analysis produced evidence of modest to good sensitivity and better specificity with values of 71% and 83%, respectively. References: 1. Finberg R. and Talcott J., New England Journal of Medicine, 1999. 2. Rubnitz J., Lensing S., Zhou Y., et al, Cancer, 2004. 3. Slats A., Egeler R., Van Der Does-van den Berg A., et al, Leukemia, 2005.
Advisors/Committee Members: Haynes, Erin Nicole.
Subjects: Oncology
Keywords: procalcitonin; fever and neutropenia; pediatric oncology; biomarker
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11.
Garza, Jose M.
Evaluation of acid suppression medications, symptoms and type of feeding in infants suspected of gastroesophageal reflux utilizing pH-impedance monitoring.
Degree: MS, Medicine: Clinical and Translational Research, 2010, University of Cincinnati
► Introduction: Gatroesophageal reflux (GER) occurs more frequently in infants compared to older…
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▼ Introduction: Gatroesophageal reflux (GER) occurs more frequently in infants compared to older children. Reflux episodes in most infants are considered to be physiologic. Yet many infants are diagnosed with gastroesophageal reflux disease (GERD) and empirically treated with acid suppression medications due to non-specific symptoms. Methods: Combined pH-multichannel intraluminal impedance (pH-MII) studies were retrospectively reviewed in 186 infants. We evaluated GER characteristics to compare those infants on ranitidine, lansoprazole and no medications; investigated if the method of feeding (oral, nasogastric or gastrostomy) is associated with GER, and by using logistic regression and negative binomial distribution we evaluated which symptoms are associated with GER. Results: There was no difference in the total number of reflux events or number of proximal reflux events between the medication groups. Infants receiving lansoprazole had significantly fewer number of acid reflux events (p<0.0001), but there was no difference in the number of acid reflux events between infants receiving ranitidine or those on no acid suppression medication. A total of 4159 symptoms were recorded during the studies; 1504 (36 %) were associated with a reflux event and only 369 (9%) were associated with an acid reflux event. When total number of reflux episodes and events are taken into consideration, acid reflux episodes are as likely to be associated with a symptom as non acid events (p=0.66). The NG fed group had less total reflux episodes when compared to the PO fed group (p=0.012) and no difference was seen when compared to the GT fed group (p=0.64). In the NG tube fed group there was no difference the number of total (p=0.84), proximal (p=0.29) or acid (p=0.31) reflux events between those infants fed NG continuously and those fed by NG bolus Conclusion: Most of the attributable of GERD in infants such as cough, gagging, pain and desaturation are less likely to be associated with a reflux event and have very poor symptom correlation to reflux. In those patients for which an association exists, non-acid episodes are as likely to cause symptoms as acid reflux episodes. If the symptoms are still suspected to be due to GERD, a combined pH-impedance study may be indicated before putting the infant on long-term acid suppression therapy.
Advisors/Committee Members: Haynes, Erin Nicole.
Subjects: Surgery
Keywords: impedance; gastroesophageal reflux; infants; acid reflux
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12.
Grossoehme, Daniel H.
Cognitive Reframing and Adherence Motivation: Using Spirituality After an Adult CF Diagnosis.
Degree: MS, Medicine: Clinical and Translational Research, 2012, University of Cincinnati
► Introduction: Diagnosis and living with a chronic illness is a significant life…
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▼ Introduction: Diagnosis and living with a chronic illness is a significant life stressor and the majority of Americans utilize spirituality to cope. Numerous studies demonstrate links between spiritual coping and health outcomes. We hypothesized that persons diagnosed with cystic fibrosis (CF) as adults would use spirituality to cope and influence day-to-day disease management. Methods: Semi-structured interviews were completed and analyzed using grounded theory methodology. A theoretical model centered on a core dimension with supporting themes was developed. Results: Twelve adults participated (n=10 female); mean age=47 (sd=13); mean age at diagnosis=40 (15). The sample represents 48% of those eligible and the point at which interpretive sufficiency was reached with the data. Persons with late-life CF diagnoses used spirituality to make meaning of their diagnosis, understanding themselves in a collaborative partnership with their pulmonologist and God. Supporting themes were: i) God's intervention depended on treatment adherence; and ii) spiritual meaning was constructed through positively reframing their experience. Discussion: Spirituality is a clinically relevant aspect of care of patients diagnosed with CF as adults. Adults diagnosed later in life with CF relate their spiritual beliefs to their CF and to the physical care of their bodies. The constructed meaning differed from that of adult parents of children diagnosed with CF. Meaning was empowering; for late-life diagnosed adults, the diagnosis itself was empowering whereas adult parents constructed a spiritual meaning. Late-life diagnosed adults focus on personal responsibility for their health. Clinical and research implications are presented.
Advisors/Committee Members: Succop, Paul.
Subjects: Health Sciences
Keywords: Cystic fibrosis; Adult; spirituality; religion; adherence; grounded theory
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13.
Hooper, David K.
The Impact of CYP3A5 Genotype on the Interaction Between Tacrolimus and Intravenous Nicardipine in Kidney Transplant Recipients.
Degree: MS, Medicine: Clinical and Translational Research, 2010, University of Cincinnati
► Tacrolimus (TAC) is prescribed for immunosuppression in the majority of solid organ…
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▼ Tacrolimus (TAC) is prescribed for immunosuppression in the majority of solid organ transplant recipients, yet overexposure can cause acute and chronic kidney injury. Continuous intravenous nicardipine (CIVN) for the treatment of post-transplant hypertension inhibits TAC metabolism by cytochrome P450 (CYP) 3A4. We hypothesized that CIVN in TAC-treated patients would lead to TAC overexposure in patients who genetically lack the alternative pathway for TAC metabolism, CYP3A5. We compared maximum 12-hour TAC trough (MaxC0) and dose-adjusted MaxC0 in 12 cases treated with CIVN immediately following kidney transplantation with 26 controls who were not treated with CIVN. CYP3A5 genotype was determined for all cases. The eight cases who do not express CYP3A5 (CYP3A5*3/*3) had higher median MaxC0 (24.3 ng/ml) than the four cases who do express CYP3A5 (CYP3A5*1/*1) (13.9 ng/ml, p=0.28) and the 26 controls (14.6 ng/ml, p=0.003). Time to MaxC0 was half as long in CYP3A5*3/*3 cases than in the other two groups combined (36 vs. 72 hours, p=0.002) and significantly more scheduled TAC doses were held per patient (1.75 vs. 0.4, p=0.007). Dose-adjusted MaxC0 was likewise higher for CYP3A5*3/*3 cases than the two other groups combined (p=0.02). Six of eight (75%) CYP3A5*3/*3 cases had potentially toxic MaxC0 (> 20 ng/ml) compared to none of four CYP3A5*1/*1 cases and three of 26 (11.5%) controls (p<0.001, CYP3A5*3/*3 cases vs. all others). Thus CYP3A5 nonexpressors who are treated with CIVN are at increased risk for TAC levels in the toxic range. Well designed clinical studies should be carried out to further characterize the clinical implications of this interaction.
Advisors/Committee Members: Succop, Paul.
Subjects: Surgery
Keywords: Tacrolimus; Kidney Transplant; Nicardipine; Cytochrome P450; Pharmacogenetics
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14.
Kanakatti Shankar, Roopa.
Association of Glycemia with Cystatin C in Youth with Diabetes.
Degree: MS, Medicine: Clinical and Translational Research, 2012, University of Cincinnati
► Abstract Objective: Serum cystatin C (cysC) is proposed as a biomarker of…
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▼ Abstract Objective: Serum cystatin C (cysC) is proposed as a biomarker of early renal dysfunction and cardiovascular disease in adults with diabetes. Potential factors affecting cysC in youth with diabetes are unknown. We sought to establish the distribution of cysC in youth with diabetes and determine the influence of measures of glycemia on cysC. Hypothesis: CysC will correlate negatively with fasting serum glucose (FSG) and hemoglobinA1c (A1c) in youth with type 1 and type 2 diabetes. Aim 1: Describe the distribution of cysC in youth with type 1 and type 2 diabetes Aim 2: Determine the influence of FSG and A1c on cysC after adjusting for known determinants such as age, gender, race/ethnicity and other cardiovascular risk factors. Methods: The study population consisted of 959 participants in the SEARCH for Diabetes in Youth study with 825 ‘type 1’, 127 ‘type 2’ and 7 ‘other’ diabetes, all of less than 5 years duration. Linear regression models were fitted for type 1 and type 2 diabetes to study the contribution of FSG and A1c to variability in cysC after adjusting for age, gender, race/ethnicity, duration of diabetes, body mass index Z-score, systolic and diastolic blood pressure Z-scores, urine albumin/creatinine ratio, total cholesterol, HDL cholesterol and triglycerides. Results: Serum cysC showed no deviation from normality (mean 0.75mg/L, SD 0.12). In type 1 diabetes, FSG and A1c were significantly negatively associated with cysC. In type 2 diabetes, FSG but not the A1c was significantly negatively associated with cysC. FSG explained 2.7% and 5.3% of variability in the models for type 1 and type 2 diabetes. Conclusions: Acute glycemic control is associated with cysC in both type 1 and type 2 diabetes while chronic glycemic control, measured by A1c is associated with cysC in type 1 but not type 2 diabetes. Glycemic control must be accounted for, in the interpretation of cysC measures in youth with diabetes.
Advisors/Committee Members: Haynes, Erin Nicole.
Subjects: Surgery
Keywords: Cystatin C; Type 1 diabetes; Type 2 diabetes; Glycemia
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15.
Kerrey, Benjamin T.
Rapid sequence intubation for pediatric emergency patients: higher frequency of failed attempts and adverse effects by video review.
Degree: MS, Medicine: Clinical and Translational Research, 2011, University of Cincinnati
► Background and objective: Rapid sequence intubation (RSI), or the delivery of sedative…
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▼ Background and objective: Rapid sequence intubation (RSI), or the delivery of sedative and paralytic medications in rapid succession, is the reference standard for definitive airway management in emergency medicine. RSI is thought to be an effective and safe procedure for the majority of emergency department (ED) patients, but published research is limited for RSI in pediatric emergency patients. Our study's objective was, using video review, to estimate the true frequency of first attempt success and adverse effects of RSI for children intubated in a pediatric ED. Methods: We conducted an observational study of a 12-month sample of patients managed in the ED of a tertiary care pediatric institution. All children undergoing RSI in the ED were eligible. Video review was the primary source for all data, where possible. Three investigators independently collected data from a third of subject video and medical records. The primary outcome measure was the number of patients successfully intubated on the first attempt at laryngoscopy. The secondary outcome was the number of patients with at least one adverse effect during RSI, including episodes of physiologic deterioration. We collected additional data elements from the RSI process and intubating providers, including physician type and time data. The unit of analysis was the patient. We analyzed first attempt success by intubating physician type and conducted an analysis of inter-rater reliability for 10% of subjects, whose videos were reviewed independently by a second investigator. Results: We obtained complete records for 114 of 123 (93%) children who underwent RSI from March 2009 through April 2010. Median age was 2.4 years (IQR 0.4, 10.1) and 78% were medical (non-trauma) resuscitations. The first attempt at laryngoscopy was successful for 59 subjects (52%, 95% CI 43%, 61%); 30 required three or more attempts for successful intubation, with a maximum of 9 attempts. RSI was ultimately successful for all 114 subjects, and no subject required a surgical airway. Seventy subjects (61%, 95% CI 52%, 70%) suffered at least one adverse effect during RSI. Thirty-eight patients (33%) had at least one episode of oxyhemoglobin desaturation (<90%). Two patients required CPR for physiologic deterioration and loss of pulses during RSI; both had return of spontaneous circulation after successful intubation on the third attempt and survived to hospital discharge. No study subject died in the ED; 5 died during hospitalization. The median duration of the RSI process (first RSI sedative to insertion of final ETT) was 3.2 minutes (1.9, 7.5). First attempt success varied by physician type, with pediatric residents successful on 35% of first attempts (n = 48) and attending level providers successful on 89% of first attempts (n = 18; p < 0.001 for difference). After controlling for patient age and other covariates, attending providers were 10 times more likely to be successful on the first attempt that all trainees combined. Conclusions: Video review revealed that first attempt failure and adverse effects were much more common than previously reported. Video review uniquely allowed a detailed description of the RSI process.
Advisors/Committee Members: Haynes, Erin Nicole.
Subjects: Surgery
Keywords: intubation; RSI; emergency department; children
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16.
Kinder, Brent W. M.D.
Clinical Predictors of Survival in Lymphangioleiomyomatosis.
Degree: MS, Medicine: Clinical and Translational Research, 2011, University of Cincinnati
► RATIONALE: Lymphangioleiomyomatosis (LAM) is a rare, progressive, cystic lung disease that almost…
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▼ RATIONALE: Lymphangioleiomyomatosis (LAM) is a rare, progressive, cystic lung disease that almost exclusively affects women. Prognostic information in LAM has been limited by heterogeneous study methodology. OBJECTIVES: We sought to establish which clinical characteristics are associated with survival and to determine cause of death in patients with LAM. METHODS: The LAM Foundation maintains a population-based registry of self-identified LAM patients who completed a questionnaire with demographic and clinical data at enrollment. Vital status was obtained on all participants. Cox proportional hazard analysis evaluated the association of demographic and clinical features with survival. RESULTS: Among the 401 subjects, there were 50 deaths and 55 lung transplantations during a median of 10 years of observation time. The estimated median survival time for LAM patients in the US is 29 years from symptom onset and 23 years from diagnosis. Age at diagnosis (HR per decade 0.80, CI 0.64-0.99, p=0.04), supplemental oxygen use (HR 3.13, CI 1.90-5.18, p<0.001), and reported weight loss (HR 1.93, CI 1.23-3.04, p=0.004) were strong independent predictors of time to death or transplant. Neither mode of presentation, history of pregnancy, nor hormonal treatment was found to be associated with survival after adjustment for covariates. Among decedents, the most common cause of death was respiratory failure. CONCLUSIONS: Median survival in a population-based cohort of patients with LAM in the United States is longer than previously estimated. Demographic and clinical predictors are useful for prognostic determination. Patients with LAM frequently die from complications directly related to their lung disease.
Advisors/Committee Members: Haynes, Erin Nicole.
Subjects: Surgery
Keywords: Lymphangioleiomyomatosis; epidemiology; Survival
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17.
Kurowski, Brad G.
Executive Dysfunction after Moderate and Severe Pediatric Traumatic Brain Injury Predicts Clinical Dysfunction on the Child and Adolescent Functional Assessment Scale.
Degree: MS, Medicine: Clinical and Translational Research, 2012, University of Cincinnati
► Objective: To identify neurobehavioral and neurocognitive predictors of impaired behavioral functioning after…
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▼ Objective: To identify neurobehavioral and neurocognitive predictors of impaired behavioral functioning after adolescent traumatic brain injury (TBI). Design: Multicenter cross-sectional study. Setting: Outpatient. Participants: 132 primary caregivers and children age 12-17 years who sustained a moderate or severe TBI within the past 1-6 months. Primary Measures: Self and parent ratings of executive function (EF), tests of memory and processing speed (PS), and a structured clinical interview of behavioral functioning. Analysis: Logistic regression was used to examine associations of behavioral functioning with ratings of EF and tests of memory and PS. Results: Caregiver ratings of problems in EF were associated with global behavioral functional impairment (OR 1.11 [95% CI: 1.05, 1.17], p<0.01) as well as impairments in the domains of school (OR 1.09 [95% CI: 1.04, 1.15], p <0.01), home (OR 1.10 [95% CI: 1.04, 1.16], p<0.01), community (OR = 1.13 [95% CI: 1.04, 1.22], p = 0.01), behavior towards others (OR = 1.13 [95% CI: 1.07, 1.20], p<0.01), and moods and emotions (OR =1.06 [95% CI: 1.01, 1.11], p=0.02). Slower PS (OR 0.97 [95% CI: 0.95, 1.00], p = 0.03) and lower memory scores (OR 0.96 [95% CI: 0.93, 1.00], p=0.03) were also associated with global behavioral impairment. Conclusions: Caregiver ratings of EF and measures of PS and memory are associated with behavioral impairment after adolescent TBI. Understanding the ability of neuropsychological measures to predict clinical impairment will potentially help hone assessment batteries and focus treatments where they are needed most.
Advisors/Committee Members: Dietrich, Kim.
Subjects: Surgery
Keywords: Traumatic brain injury; adolescent; executive function; memory; processing speed
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18.
Laskin, Benjamin L.
Cost-Effectiveness of Screening Strategies for Latent Tuberculosis in Pediatric Idiopathic Nephrotic Syndrome.
Degree: MS, Medicine: Clinical and Translational Research, 2011, University of Cincinnati
► Introduction: Current guidelines differ on screening for latent tuberculosis (LTB) infection prior…
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▼ Introduction: Current guidelines differ on screening for latent tuberculosis (LTB) infection prior to starting immunosuppressive therapy. We developed a Markov state-transition model to determine the most “cost-effective” screening strategy prior to initiating steroid treatment in a 5 year old with newly diagnosed idiopathic nephrotic syndrome. Methods: Using data from the published literature, universal purified protein derivative (PPD) testing was compared with targeted screening using a risk-factor questionnaire. A secondary model also included testing with the newer interferon gamma release assays (IGRAs), requiring only a single visit and having greater specificity than the PPD. Results: At an LTB prevalence of 1.1%, universal PPD testing was more costly and less effective than other strategies. Instead, we found that a targeted strategy using a simple risk assessment questionnaire to determine who should receive a PPD cost roughly $44,000 per quality-adjusted life year (QALY) gained compared to a no screening strategy. Conversely, at an LTB prevalence >12.8%, universal PPD became “cost-effective” compared to targeted screening. In the secondary model, targeted screening with a questionnaire followed by IGRA testing was the preferred strategy. Conclusion: Patients who live in areas with a higher prevalence of LTB will likely benefit from universal PPD testing. Once IGRA testing is approved in children, it may become a component of “cost-effective” screening options.
Advisors/Committee Members: Succop, Paul.
Subjects: Surgery
Keywords: pediatrics; nephrotic syndrome; tuberculosis; cost-effectiveness; screening; immunosuppression
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19.
Levinson, Courtney M.D.
Social-Emotional Problems Among Low Income Preschool-Aged Children and Potential Factors Affecting Early Intervention.
Degree: MS, Medicine: Clinical and Translational Research, 2011, University of Cincinnati
► Background: Preschool-aged children with social-emotional (SE) problems (e.g., behavior problems, delayed social…
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▼ Background: Preschool-aged children with social-emotional (SE) problems (e.g., behavior problems, delayed social competencies) are at high risk for later psychopathology. To develop protocols for addressing SE development in primary care, a better understanding is needed of the scope of the problem and parental attitudes toward potential interventions. Objectives: To estimate prevalence of SE problems among preschool-aged children in a low-income clinical population, to explore correlates of SE problems, and to assess families’ receptivity to referrals to services that promote health SE development. Methods: 254 parents of 3- and 4-year-old children at two primary care clinics completed a standardized screen for SE problems (Ages and Stages Questionnaire: Social-Emotional (ASQ:SE)). Additional questions addressed childcare arrangements, parental depressive symptoms, and attitudes toward preschool and behavioral health referrals. Descriptive and chi-squared statistics and logistic regression were used to analyze the data. Results: The sample was 91% Medicaid. 24% (95% CI 16.5-31.5%) of children screened positive for SE problems. 27% of parents screened positive for depression. 99% of parents reported they “would welcome” or “would not mind” a referral to preschool. Among parents of children who screened positive for SE problems, 79% reported they would welcome or would not mind a referral to a counselor or psychologist; only 16% had been referred previously. Conclusions: One in four low-income preschool-aged children screens positive for SE problems, and most parents are amenable to referrals to preschool or early childhood mental health. This represents an opportunity for improvement in primary prevention and early intervention.
Advisors/Committee Members: Haynes, Erin Nicole.
Subjects: Surgery
Keywords: social-emotional; behavior; ASQ:SE; early childhood mental health; preschool; screening
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20.
Lo, Megan M.
Increased Adiponectin is Associated with Left Ventricular Mass Index in Pediatric Chronic Kidney Disease.
Degree: MS, Medicine: Clinical and Translational Research, 2011, University of Cincinnati
► Introduction: Chronic kidney disease (CKD) is associated with significantly increased risk of…
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▼ Introduction: Chronic kidney disease (CKD) is associated with significantly increased risk of cardiovascular morbidity and mortality. In the general population, adiponectin, a hormone produced by adipocytes with effects on insulin sensitivity, is associated with improved cardiovascular health. In chronic kidney disease, however, adiponectin levels are higher than in the general population despite increased cardiovascular risk. The current analysis determines adiponectin levels in association with left ventricular mass index (LVMI), an earlier indicator of cardiovascular risk. Methods: A cross-sectional analysis was undertaken using blood samples and clinical data from the Chronic Kidney Disease in Kids cohort. Adiponectin was measured using ELISA. Associations between adiponectin, additional cofactors, and LVMI were tested by univariate analysis. Factors with p<0.2 were entered into multivariable models using multiple methods. Results: Contrary to the general population, increased adiponectin was associated with increased LVMI, but this relationship was not significant until race was taken into effect. In non-African-American subjects, there was a positive relationship after adjusting for age, systolic blood pressure, and body mass index. In African-Americans, there was a non-significant negative relationship. Conclusions: In pediatric CKD, adiponectin may be differentially associated with increasing LVMI according to race. This relationship was significant after adjusting for common predictors of LVMI.
Advisors/Committee Members: Succop, Paul.
Subjects: Surgery
Keywords: adiponectin; left ventricular mass index; pediatric; chronic kidney disease
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21.
Mackey, Jason S.
Unruptured Intracranial Aneurysms in the FIA and ISUIA Cohorts: Differences in Multiplicity and Location.
Degree: MS, Medicine: Clinical and Translational Research, 2011, University of Cincinnati
► Background and Purpose: Familial predisposition is an important non-modifiable risk factor for…
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▼ Background and Purpose: Familial predisposition is an important non-modifiable risk factor for the formation and rupture of intracranial aneurysms (IAs), though the data regarding the characteristics of familial IAs are currently limited. We sought to more fully describe familial IAs and compare their characteristics with a large cohort of non-familial IAs. Methods: The Familial Intracranial Aneurysm (FIA) Study is a multicenter international study whose goal is to identify genetic and other risk factors for formation and rupture of IAs in a highly enriched population. We compared subject demographics, IA location, and multiplicity in the FIA Study cohort with the International Study of Unruptured Intracranial Aneurysms (ISUIA) cohort. To improve comparability, we excluded all ISUIA subjects with a family history of IAs or subarachnoid hemorrhage, as well as all subjects in both cohorts who had a ruptured IA prior to study entry. Results: Of 983 subjects enrolled in the FIA Study with definite or probable phenotypes for IA, 511 met inclusion criteria for this analysis. Of the 4059 subjects in the ISUIA study, 983 had a previous IA rupture and 657 of the remainder had a positive family history, leaving 2419 subjects in the analysis. Multiplicity was more common in familial than nonfamilial subjects (35.6% vs. 27.9%, P=.0005). FIA subjects also had a slightly higher proportion of MCA IAs (28.6% vs. 24.9%), while ISUIA subjects had a higher proportion of PComm IAs (13.7% vs. 8.2%, P=.016). Conclusions: Subjects with a strong familial predisposition are more likely to have multiple IAs and an IA in the MCA territory than subjects without a family history of IAs. Heritable structural vulnerability is a possible explanation for these findings; this emphasizes the importance of ongoing investigations into the underlying genetic mechanisms of IA formation.
Advisors/Committee Members: Haynes, Erin Nicole.
Subjects: Surgery
Keywords: familial; aneurysms; genetics
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22.
Madueme, Peace C.
Predictors of Exaggerated Exerise-Induced Systolic Blood Pressures in Young Patients After Coarctation Repair.
Degree: MS, Medicine: Clinical and Translational Research, 2012, University of Cincinnati
► Background: In normotensive subjects, an exaggerated blood pressure response to exercise is…
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▼ Background: In normotensive subjects, an exaggerated blood pressure response to exercise is associated with the development of resting hypertension. We sought to 1) determine the prevalence of elevated blood pressures during exercise in post-operative coarctation patients with normal resting blood pressure and 2) investigate associations with exercise induced hypertension in this population. Method: 38 subjects status post end to end anastomosis repair and resting normotension were prospectively enrolled. All patients underwent anthropometric and blood pressure measurements, echocardiographic evaluation of function, arterial stiffness assessment by pulse wave velocity and a graded exercise test. An abnormal response was defined as a maximum systolic blood pressure greater than the 95th percentile of published normal values. Correlation analyses and stepwise regression analyses were performed. Results: Mean age was 12.7 years, 79% male. Mean resting systolic blood pressure was 111.3 mmHg, mean exercise systolic blood pressure was 178.1 mmHg. The prevalence of a systolic blood pressure greater than the 95th percentile was 16.7%. In multivariate analysis, exercise systolic blood pressure index was associated with body mass index, age, aortic valve annulus, shortening fraction and pulse wave velocity (R2 = 0.79, p = 0.0009). Estimates of ventricular filling and indexed left ventricular mass were elevated. Conclusions: There is a risk of elevated systolic blood pressure during exercise in normotensive patients after coarctation repair. Resting blood pressures are useful but not sufficient. Echocardiography demonstrated abnormalities suggestive of a chronic cardiac burden despite resting normotension. Regular imaging may be necessary to improve long term outcomes. New paradigms for the continued follow-up of these patients are necessary.
Advisors/Committee Members: Haynes, Erin Nicole.
Subjects: Surgery
Keywords: Coarctation; Hypertension; Exercise; Pulse wave velocity; Ambulatory Blood Pressure; End to end resection
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23.
Malatesta Muncher, Rossana.
Early cardiac dysfunction in pediatric patients on maintenance dialysis and post kidney transplant.
Degree: MS, Medicine: Clinical and Translational Research, 2012, University of Cincinnati
► Background: Young patients with advanced chronic kidney disease (CKD) frequently develop left…
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▼ Background: Young patients with advanced chronic kidney disease (CKD) frequently develop left ventricular (LV) hypertrophy. The extent of hypertrophy that is maladaptive and results in cardiac dysfunction is unknown. Systolic function, routinely determined by ejection fraction (EF), is usually preserved in these young patients. However, a decrease in EF represents an advanced cardiac dysfunction. We utilized Cardiac Magnetic Resonance (CMR) and 31P MR spectroscopy (MRS) to assess markers of early cardiac dysfunction in children and young adults with CKD. Methods: Twenty patients, 10 on dialysis and 10 post-transplant (mean age 16.9±2.8y, range 11-22y, 10 males) had CMR and 31P MRS. The outcomes were: 1) Peak left ventricular myocardial circumferential strain (Ecc), 2) Myocardial T2 relaxation time and full width at half maximum (FWHM) of T2 distribution to quantify T2 heterogeneity, 3) PCr/ATP as a measure of muscle energy metabolism. Healthy controls were used to compare cardiac structure and function. Results: All patients had normal EF. Nine (45%) (6 on dialysis and 3 post-transplant) had low Ecc. Ecc was significantly lower in dialysis patients versus post-transplant, p<0.0001. Ecc was inversely correlated with LV mass index (LVMI), r= -0.47, p=0.04. Patients had higher T2 (p=0.056) and FWHM of T2 (p=0.01) than controls. T2 levels were positively correlated with LVMI (r=0.46, p=0.04). PCr/ATP was lower in subjects than in controls (p=0.02). No significant difference in T2, FWHM or PCr/ATP ratio was found between transplant and dialysis subjects. Conclusion: Young patients with advanced CKD and normal EF have early cardiac changes. Association of these myocardial abnormalities with increased LVMI suggests development of maladaptive cardiac hypertrophy.
Advisors/Committee Members: Succop, Paul.
Subjects: Statistics
Keywords: Cardiac MRI; Children; Chronic Kidney Disease; Dialysis; Transplant
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24.
Merhar, Stephanie L. M.D.
Pharmacokinetics of levetiracetam in neonates with seizures.
Degree: MS, Medicine: Clinical and Translational Research, 2011, University of Cincinnati
► Objective: To evaluate the pharmacokinetics and adverse events of intravenous levetiracetam in…
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▼ Objective: To evaluate the pharmacokinetics and adverse events of intravenous levetiracetam in treating newborns with seizures. Study design: This was a prospective, open-label observational pharmacokinetic study in neonates = 32 weeks gestational age and = 30 days of age with seizures persisting despite treatment with phenobarbital. A loading dose of intravenous levetiracetam was given as per the prescribing physician, followed by additional doses based on clinical response. Blood samples were prospectively collected and analyzed for levetiracetam concentrations. Vital signs were monitored during levetiracetam treatment, and safety and efficacy data were collected. Results: Eighteen patients (median 39 weeks gestation and 2 postnatal days) were included. Initial loading doses ranged from 14.3-39.9 mg/kg. Median (range) clearance, volume of distribution, and elimination half-life were 1.2 ml/min/kg (0.5-2.9), 0.89 L/kg (0.4-1.3), and 8.9 hours (3.2-13.3), respectively. No adverse events related to levetiracetam were observed. Nine out of 18 patients required additional loading doses of levetiracetam to control their seizures. Conclusions: LEV clearance was lower, volume of distribution larger, and half life longer in neonates as compared to older children. Given the increased volume of distribution and lower clearance in neonates, we recommend a loading dose of at least 30 mg/kg, followed by maintenance dosing every 8-12 hours.
Advisors/Committee Members: Succop, Paul.
Subjects: Surgery
Keywords: levetiracetam; seizure; neonate; antiepileptic; pharmacokinetics
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25.
Mina, Rina M.D.
Effectiveness of Dexamethasone Iontophoresis for Temporomandibular Joint Involvement in Juvenile Idiopathic Arthritis.
Degree: MS, Medicine: Clinical and Translational Research, 2011, University of Cincinnati
► Objective: Temporomandibular joint (TMJ) involvement is common in Juvenile Idiopathic Arthritis (JIA).…
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▼ Objective: Temporomandibular joint (TMJ) involvement is common in Juvenile Idiopathic Arthritis (JIA). Dexamethasone iontophoresis (DIP) uses low-grade electric currents for transdermal dexamethasone delivery into deeper anatomic structures. The purpose of this study was to assess the safety and effectiveness of DIP for the treatment of TMJ involvement in JIA, and to delineate variables that are associated with improvement after DIP. Methods: Medical records of all JIA patients who underwent DIP for TMJ involvement at a larger tertiary pediatric rheumatology center from 1997 to 2011 were reviewed. DIP was performed using a standard protocol. The effectiveness of DIP was assessed by comparing the maximal inter-incisor opening (MIOTMJ) and the maximal lateral excursion (MLETMJ) before and after treatment. Results: Twenty-eight patients (ages 2- 21 years) who received an average of eight DIP treatment sessions per involved TMJ were included in the analysis. Statistically significant improvement in the median MIOTMJ (p< 0.0001) was observed in 68%. The median MLETMJ (p= 0.001) improved in 69%, and resolution of TMJ pain occurred in 73% of the patients who had TMJ pain at baseline. Side effects of DIP were transient site erythema (86%), skin blister (4%), and metallic taste (4%). Improvement in TMJ range of motion from DIP is associated with lower MIOTMJ, lower MLETMJ, and absence of TMJ crepitus at baseline. Conclusion: In this pilot study DIP appeared to be an effective and safe initial treatment of TMJ involvement in JIA, especially among patients with decreased TMJ measurements. Prospective controlled studies are needed.
Advisors/Committee Members: Haynes, Erin Nicole.
Subjects: Surgery
Keywords: temporomandibular joint; juvenile idiopathic arthritis; dexamethasone iontophoresis
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26.
Moncrief, Terri M. M.D.
Single-parenthood, Psychosocial Stressors and Child Asthma Morbidity.
Degree: MS, Medicine: Clinical and Translational Research, 2012, University of Cincinnati
► Background: Single-parenthood has been associated with increased asthma prevalence, but studies have…
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▼ Background: Single-parenthood has been associated with increased asthma prevalence, but studies have not addressed its effect on asthma-related morbidity among children. Objective: To characterize whether single-parenthood is associated with repeat pediatric asthma-related healthcare use and to examine characteristics of single-parent families that may explain this relationship. Hypothesis: Pediatric patients hospitalized with asthma or wheezing who come from homes with married parents will be at increased odds of a repeat asthma-related hospitalization or emergency room (ER) visit within 12 months of an index admission than children from homes with single-parents. Specific Aim 1: Identify single-parenthood as a novel risk factor for repeat asthma-related hospitalization or ER visit within 12 months of an index admission in a cohort of pediatric patients admitted for asthma or wheezing. Specific Aim 2: Examine characteristics of single-parent homes, including household income, psychological distress, ratio of children to adults in the home, and child's time spent outside the home that may contribute to the increased risk of repeat asthma-related admission/ER visit in a cohort of pediatric patients admitted for asthma or wheezing. Methods: We analyzed a prospective cohort of 601 children aged 1-16 years admitted for asthma or wheezing. The primary outcome was an asthma-related admission or emergency room visit within 12 months of the index admission. Caregiver marital status was assessed along with psychosocial strain variables: household income, psychological distress, ratio of children to adults in the home, and child's time spent outside the home. Results: Forty-percent returned to the hospital for asthma within 12 months. Fifty-nine percent of caregivers described themselves as single-parents. Compared to children of married parents, children of single-parents were more likely to return to the hospital (43% vs. 34%, p=0.04). Children from homes with income <$60,000 were more likely to return than children from homes with income =$60,000 (44% vs. 27%, p=0.009). An increased ratio of in-home children to adults was associated with an increased rate of reutilization (p=0.002). Single-parenthood was significantly associated with each strain variable. Adjusted analyses suggest independent contributions of single-parenthood, income, and psychological distress to reutilization. Conclusion: Among children admitted for asthma or wheezing, those from single-parent homes were 50% more likely to return to the hospital within 12 months. This relationship may result from lower income and increased psychological distress in single-parent homes.
Advisors/Committee Members: Haynes, Erin Nicole.
Subjects: Epidemiology
Keywords: single-parent; child; asthma; psychosocial; income
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27.
Nehus, Edward J.
Correlates of Resistin in Children with Chronic Kidney Disease: The CKiD Cohort.
Degree: MS, Medicine: Clinical and Translational Research, 2011, University of Cincinnati
► Resistin, a 12.5 kDa protein, is produced by inflammatory cells and is…
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▼ Resistin, a 12.5 kDa protein, is produced by inflammatory cells and is elevated in patients with chronic kidney disease (CKD). While resistin was initially thought to mediate insulin resistance, more recent attention has focused on its role in inflammation and cardiovascular disease. This cross-sectional study analyzes the association of serum resistin with clinical and demographic parameters in the CKiD cohort, a large cohort of pediatric patients with stage II-IV CKD. In univariate analyses, serum resistin levels correlated negatively with glomerular filtration rate (GFR, p < 0.01). Increased serum resistin levels were associated with elevation of inflammatory cytokines, including interleukin-6 (IL-6, p < 0.01), interleukin-10 (p < 0.01), and tumor necrosis factor-a (p < 0.01). Resistin was not associated with insulin resistance (p = 0.13) as assessed by the homeostasis model assessment of insulin resistance (HOMA-IR), although it was positively correlated with serum triglycerides (p < 0.01) and negatively correlated with high-density lipoprotein cholesterol (p < 0.01). In multivariate analysis, only GFR, IL-6, pubertal status, and HOMA-IR were significantly associated with serum resistin. HOMA-IR, however, was negatively correlated with serum resistin. This was an unexpected finding that demonstrated an association of serum resistin levels with improved insulin sensitivity. IL-6 was strongly associated with resistin in multivariate analysis, suggesting that resistin is involved in the inflammatory milieu present in CKD and therefore may represent a novel risk factor for cardiovascular disease. Future prospective data will be needed to evaluate the predictive value of resistin in cardiovascular morbidity in children with CKD.
Advisors/Committee Members: Succop, Paul.
Subjects: Surgery
Keywords: chronic kidney disease; cardiovascular disease; inflammation; pediatrics
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28.
Newman, Nicholas C.
Traffic Related Air Pollution Exposure in the First Year of Life and Hyperactivity at Age Seven in a High Risk Atopic Birth Cohort.
Degree: MS, Medicine: Clinical and Translational Research, 2011, University of Cincinnati
► Objective: The purpose of this study is to explore the association between…
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▼ Objective: The purpose of this study is to explore the association between attention deficit hyperactivity disorder (ADHD) symptoms and exposure to traffic related air pollution (TRAP) in children at risk for atopic disease. Methods: A cross sectional analysis assessing exposure to TRAP and ADHD symptoms was conducted utilizing seven-year-old children who were participants in a longitudinal birth cohort. They were recruited from a mid-sized metropolitan area with a mix of rural, suburban, and urban areas. Enrollment in the Cincinnati Childhood Allergy and Air Pollution Study (CCAAPS) cohort required at least one parent with atopy and birth residence either <400m or >1500m from a major highway or bus route. Exposure to TRAP was modeled using data from 27 air monitoring stations over the first year of life using land-use regression modeling. ADHD symptoms were measured using the Hyperactivity, Inattention, Aggression, Conduct Problems, and Atypicality T scores from the Behavioral Assessment System for Children 2nd Edition, Parent Rating Scale (BASC-2). Results: At age seven, 18.4% of children were reported to have hyperactive behaviors in the “at risk” range (T score > 59), 19.3% had inattentive behaviors, 15.7% had aggressive behaviors, 14.1% had conduct problems, and 14.3% had atypical behaviors. In analysis adjusting for cigarette exposure, maternal education, rhinitis, and habitual snoring, the children with the highest tertile of TRAP exposure during their first year of life had significantly more hyperactive behaviors than children exposed to lower amounts of TRAP (aOR=1.68 [1.02, 2.74]). After stratifying by race, black children who had high TRAP exposure had significantly higher aggressive behaviors than children exposed to lower amounts of TRAP (aOR=4.19 [1.08, 21.58]). Conclusions: Higher exposure to TRAP is associated with hyperactive behaviors in children at risk for atopy. Black race modifies the association between TRAP exposure and aggressive behaviors.
Advisors/Committee Members: Dietrich, Kim.
Subjects: Environmental Health
Keywords: traffic emissions; attention deficit-hyperactivity disorder; epidemiology
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29.
Ngamprasertwong, Pornswan.
Impact of Maternal Hypotension during Fetoscopic Surgery on Fetal Survival.
Degree: MS, Medicine: Clinical and Translational Research, 2012, University of Cincinnati
► Background: Twin-twin transfusion syndrome (TTTS), a serious complication of monozygotic twin pregnancy…
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▼ Background: Twin-twin transfusion syndrome (TTTS), a serious complication of monozygotic twin pregnancy is characterized by abnormal vascular anastomosis and imbalance of blood flow between fetuses. Selective fetoscopic laser photocoagulation (SFLP) is the standard method of treatment of this condition. Maternal medical therapy with nifedipine has been demonstrated to improve fetal survival after SFLP. However, a common side effect of nifedipine is hypotension. Maternal hypotension is also the most common intraoperative complication from epidural anesthesia, a common anesthetic method for SFLP. Method: To access the impact of intraoperative maternal hypotension on fetal survival rate, we conducted a retrospective cohort study in 404 pregnant patients undergoing SFLP at Cincinnati Children's hospital between April 2004 and July 2010. The independent variable is maternal nifedipine. The primary dependent (outcome) variables are intraoperative maternal hypotension, acute fetal survival rate and survival rate at birth. This association was stratified by severity of TTTS categorized by Cincinnati Staging. Result: The incidence of intraoperative maternal hypotension in our study is 53.8%. There was no significant difference in the incidence of intraoperative maternal hypotension when patients received preoperative nifedipine (55.3% vs. 51.24%). However, patients who developed intraoperative hypotension received significantly more vasopressors (8.03 vs 3.71 units, p <0.001) and intravenous fluids (150.2 vs 105.5 ml, p<0.001). Preoperative nifedipine improved acute fetal survival and recipient survival rate at birth, while higher doses vasopressors and intravenous fluids needed to manage intraoperative maternal hypotension had no effect of fetal survival. Conclusion: Intraoperative maternal hypotension during SFLP has no effect on acute fetal survival rate and survival rate at birth. Preoperative nifedipine does not increase incidence of intraoperative maternal hypotension.
Advisors/Committee Members: Haynes, Erin Nicole.
Subjects: Surgery
Keywords: fetoscopic surgery; maternal hypotension; fetal survival; nifedipine; epidural block
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30.
Nylund, Cade McCoy.
Clostridium difficile associated disease in hospitalized children in the United States.
Degree: MS, Medicine: Clinical and Translational Research, 2010, University of Cincinnati
► Background: Clostridium difficile associated disease (CDAD) can lead to prolonged hospital course,…
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▼ Background: Clostridium difficile associated disease (CDAD) can lead to prolonged hospital course, colectomy and death. In previous epidemiological studies there is evidence that the national rate and severity of CDAD are increasing. Little is known about the risks and impact of CDAD in children. Objective: To evaluate epidemiology, and risk factors of CDAD in hospitalized children in the United States Design: The Healthcare Cost and Utilization Project Kids’ Inpatient Database (KID) was utilized to design a retrospective cohort study of hospitalized children in the United States over four time periods:1997, 2000, 2003, and 2006. Outcome measures: Trends in national cases of CDAD. Severity was measured by length of stay, hospital costs, colectomy rate and case fatality rate. Results: The total discharges were 10,495,728 and those with CDAD were 21,274 over the four time periods. There was an increasing trend in CDAD (p<.0001).There was no trend in length of stay, colectomy rate or case fatality rate associated with CDAD over the four time periods. CDAD in children is associated with an increased risk of death, colectomy, longer length of stay and higher charges. Multivariate logistic regression results evaluating risk comorbid diagnoses associated with CDAD demonstrate a high risk in inflammatory bowel disease, odd ratio (95% CI) of 11.42 (10.16-12.83) and other comorbid diagnoses associated with immunosuppression, or with antibiotic administration. Conclusion: There is an increasing trend of hospitalized children with CDAD. In contrast to adults, there is no increasing trend in the severity of CDAD in children. Children with certain medical conditions including IBD, immunosupression, or conditions requiring antibiotic administration are at high risk of CDAD.
Advisors/Committee Members: Rao, Marepalli.
Subjects: Epidemiology
Keywords: clostridium difficile; pediatric; children
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