-
1دورية أكاديمية
المؤلفون: McGeachie, Michael J, Yates, Katherine P, Zhou, Xiaobo, Guo, Feng, Sternberg, Alice L, Van Natta, Mark L, Wise, Robert A, Szefler, Stanley J, Sharma, Sunita, Kho, Alvin T, Cho, Michael H, Croteau-Chonka, Damien C, Castaldi, Peter J, Jain, Gaurav, Sanyal, Amartya, Zhan, Ye, Lajoie, Bryan R, Dekker, Job, Stamatoyannopoulos, John, Covar, Ronina A, Zeiger, Robert S, Adkinson, N Franklin, Williams, Paul V, Kelly, H William, Grasemann, Hartmut, Vonk, Judith M, Koppelman, Gerard H, Postma, Dirkje S, Raby, Benjamin A, Houston, Isaac, Lu, Quan, Fuhlbrigge, Anne L, Tantisira, Kelan G, Silverman, Edwin K, Tonascia, James, Strunk, Robert C, Weiss, Scott T
المصدر: Am J Respir Crit Care Med ; ISSN:1535-4970 ; Volume:194 ; Issue:12
مصطلحات موضوعية: CSMD3, asthma, chronic obstructive pulmonary disease, genome-wide association studies, longitudinal lung function patterns
الوصف: Patterns of longitudinal lung function growth and decline in childhood asthma have been shown to be important in determining risk for future respiratory ailments including chronic airway obstruction and chronic obstructive pulmonary disease.
العلاقة: https://doi.org/10.1164/rccm.201602-0250OCTest; https://pubmed.ncbi.nlm.nih.gov/27367781Test; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5215031Test/
الإتاحة: https://doi.org/10.1164/rccm.201602-0250OCTest
https://pubmed.ncbi.nlm.nih.gov/27367781Test
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5215031Test/ -
2دورية أكاديمية
المؤلفون: Covar, Ronina A, Strunk, Robert, Zeiger, Robert S, Wilson, Laura A, Liu, Andrew H, Weiss, Scott, Tonascia, James, Spahn, Joseph D, Szefler, Stanley J
المصدر: J Allergy Clin Immunol ; ISSN:1097-6825 ; Volume:125 ; Issue:2
الوصف: The course of mild to moderate persistent asthma in children is not clearly established.
العلاقة: https://doi.org/10.1016/j.jaci.2009.10.037Test; https://pubmed.ncbi.nlm.nih.gov/20159245Test; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2844768Test/
الإتاحة: https://doi.org/10.1016/j.jaci.2009.10.037Test
https://pubmed.ncbi.nlm.nih.gov/20159245Test
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2844768Test/ -
3رسالة جامعية
المؤلفون: Salazar Osuna, Jose H
المساهمون: Tonascia, James, Segev, Dorry, Frank, Steven, Haut, Elliot
مصطلحات موضوعية: blood transfusion, clinical decision support, benchmarking, packed red blood cell, provider order entry
الوصف: In recent years, the use of blood products has come under increased scrutiny in an effort to optimize the use of medical resources. We assembled a working group and developed a set of evidence based recommendations for red blood cell (RBC) transfusions at the Johns Hopkins Bloomberg Children’s Center (JHBCC). Before implementing the guidelines, we began our studies by using a national surgical dataset to develop regression models that allow for benchmarking of transfusion practices in surgical patients between hospitals (Chapter 1). We then characterized the allocation of RBC to specific high-risk surgeries and found that more than half of the transfusions in children’s surgery are associated to only two procedures: spinal fusion for arthrodesis and craniectomy for craniosynostosis (Chapter 2). Once our guidelines were finalized, we embedded them into a clinical decision support (CDS) logic within our computerized provider ordering system. This intervention reminded providers of the evidence-based guidelines when attempting to transfuse outside of recommended thresholds. We analyzed the effect of the CDS mechanism by comparing incidence rates of transfusion (Chapter 3). We used a zero-inflated negative binomial regression model to adjust for covariates while using historical controls. The CDS intervention was associated with a decrease of blood transfusions in patients >3 months of age (IRR 0.818, p<0.001) but not in patients <3 months (IRR 0.972, p=0.739). The ascertainment of pre and post-transfusion hemoglobin values during the year of the intervention allowed us to investigate adherence to the newly created JHBCC guidelines (Chapter 4). From 1955 transfusions, 41.6% were compliant with institutional recommendations (46.7% in patients <3 months and 35.1% in patients >3 months). Lastly, we studied the different approaches that hospital units have in relation to volume of RBC ordered. While there are differences in comorbidity profiles of patients between hospitals units, we found that similar ...
وصف الملف: application/pdf; application/vnd.openxmlformats-officedocument.wordprocessingml.document
-
4رسالة جامعية
المؤلفون: DiBrito, Sandra R
المساهمون: Tonascia, James A, Segev, Dorry L, Garonzik-Wang, Jacqueline, Dodson, Jennifer L, Higgins, Robert SD
مصطلحات موضوعية: transplant recipients, acute care surgery
الوصف: With improved medical and surgical care, kidney transplant recipients (KTR) are living longer than ever before. When KTR require acute care (AC) surgery for non-transplant issues, it is unclear who should manage this unique population and what specific risks KTR face during the course of surgical care. To elucidate surgeon perspectives on acute care surgical management of transplant recipients, we designed and nationally administered a survey to transplant and AC surgeons. We then investigated the differences in mortality, morbidity, length of stay (LOS) and cost between KTR and non-transplant recipients (non-KTR) undergoing appendectomy, cholecystectomy and colorectal resection as a retrospective cohort study using data from the National Inpatient Sample and adjusting for patient and hospital level factors. There were 230 survey participants who were AC surgeons (response rate 14%) and 204 from transplant surgeons (response rate 20%). Both AC and transplant surgeons (78% and 100%) agreed that KTR care would be better at transplant centers, and that KTR requiring urgent surgery should be transferred to a transplant center if possible (80.2% and 87.2%). However, AC surgeons with more years of practice were less likely to transfer KTR to a transplant center (p = 0.03). In the national cohort study of appendectomy, complications were similar among KTR and non-KTR, while LOS and costs were greater for KTR (LOS ratio:1.31 95%CI 1.19-1.45; cost ratio: 1.17 95% CI 1.11-1.26). For cholecystectomy, KTR had higher mortality (2.7% vs 1.2%, p<0.001), morbidity (18.8% vs 13.9%, p<0.001; aOR 1.30 95%CI 1.12-1.51), LOS and costs (LOS ratio:1.23 95% CI 1.17-1.28; cost ratio:1.17 95%CI 1.08-1.31). For colorectal resection, KTR had higher mortality (11.1 vs 4.3%, p <0.001; aOR: 3.59 95%CI 2.68-4.81), morbidity (38.5 vs 31.5%, p =0.001; aOR: 1.30 95% CI 1.08-1.56), LOS and costs (LOS ratio: 1.53 95%CI 1.42-1.65; cost ratio: 1.54 95%CI 1.42-1.63). Both AC and transplant surgeons recommend managing KTR at transplant ...
وصف الملف: application/pdf
-
5رسالة جامعيةCardiovascular safety of dipeptidyl peptidase-4 inhibitors in patients with type 2 diabetes mellitus
المؤلفون: Baksh, Sheriza Naseema
المساهمون: Tonascia, James, Ehrhardt, Stephan, Alexander, George C, Burke, Thomas A, Kalyani, Rita R
مصطلحات موضوعية: Dipeptidyl peptidase-IV inhibitors, drug-related side effects and adverse reactions, heart failure, pharmacovigilance, pharmacoepidemiology
الوصف: Objective: The proposed study will examine the association between the dipeptidyl peptidase-4 inhibitors (DPP-4i) drug class and the risk of major adverse cardiovascular events (MACE) in patients with diabetes. Methods: In the surveillance portion of this dissertation, we utilized the Food and Drug Administration’s Adverse Events Reporting System (FAERS) to conduct a Bayesian disproportionality analysis on reports for MACE associated with DPP-4i, to assess the association of DPP-4i with a cardiovascular subset of reports to the full database. These associations were quantified using the posterior distribution of the empirical Bayes lower bound (EB05) of the relative reporting ratio, among high- and low- risk populations. Next for the longitudinal analyses, we conducted retrospective, time to first MACE analyses of data from Truven Marketscan Commercial Claims and Encounters to compare new users of DPP-4i versus sulfonylurea and DPP-4i versus metformin. This association was measured using propensity score weighted Cox proportional hazards models, adjusted for baseline demographics, comorbidities, and concomitant medications. Propensity score weights, based on baseline clinical characteristics and concomitant medications, were calculated using a generalized boosted logistic regression model. This analysis was repeated in both individuals with established cardiovascular and/or kidney disease (high-risk cohort), as well as in individuals without these medical conditions (low-risk cohort). Results: In the surveillance study, there was a safety signal for heart failure with linagliptin (EB05=2,782.47) and saxagliptin (EB05=2.40), myocardial infarction with alogliptin (EB05=290.11), and cerebral infarction with sitagliptin (EB05=2.80) in the cardiovascular subset of reports. Eight of fourteen possible MACE events had a percent positive agreement ≥50% for a drug-event safety signal in both the cardiovascular subset and the full dataset. Overall, the cardiovascular subset elicited 11 more safety signals for DPP-4i than ...
وصف الملف: application/pdf
-
6رسالة جامعية
المؤلفون: Limketkai, Berkeley Nguyen
المساهمون: Tonascia, James A, Brant, Steven R, Hendrix, Craig W, Adkinson, N. Franklin
مصطلحات موضوعية: inflammatory bowel disease, Crohn's disease, ulcerative colitis, vitamin D
الوصف: Vitamin D has traditionally been known for its role in bone metabolism, but more recently been implicated in immune function. Emerging evidence has further suggested that vitamin D may be involved in inflammatory bowel disease (IBD) pathogenesis and activity. Studies found lower vitamin D levels among IBD patients, particularly in the setting of increased disease activity, implying that vitamin D influenced IBD. However, interpretation of these findings is challenged by the concept of reverse causation, where intestinal inflammation is already known to reduce vitamin D levels. These studies have therefore not established vitamin D deficiency as a cause or effect of IBD in humans. The principal objective of this thesis was to clarify the causal role of vitamin D in IBD pathogenesis and severity, while employing diverse methodologic approaches to overcome the issue of reverse causation. The first study was a case-control comparison of vitamin D levels from sera that were prospectively collected before and around the time of diagnosis of Crohn’s disease (CD). This longitudinal analysis permitted the evaluation of vitamin D levels as precursors to CD pathogenesis, while reducing interference by reverse causation. Vitamin D levels were similar between cases and controls prior to diagnosis, but significantly lower among cases around the time of diagnosis. The second study was an ecologic study that evaluated the association of ultraviolet (UV) exposure – a surrogate marker of vitamin D that was not influenced by IBD – and IBD hospitalization severity. Low UV exposures were associated with increased rates of hospitalization, prolonged hospitalization, and need for bowel surgeries. The third study was a systematic review of randomized trials that evaluated the effect of vitamin D supplementation on IBD activity. Randomization in these trials would have theoretically permitted assessment of the effect of vitamin D on IBD independent of disease activity. The meta-analysis of 4 studies with 12-month follow-up showed a ...
وصف الملف: application/pdf
-
7رسالة جامعية
المؤلفون: King, Elizabeth A.
المساهمون: Tonascia, James A., Segev, Dorry L., Dodson, Jennifer L., Diener-West, Marie
مصطلحات موضوعية: Transplantation, Readmission
الوصف: In the United States, 30% of kidney transplant (KT) recipients experience early hospital readmission (EHR), or readmission within 30 days of discharge following transplantation. Known predictors of EHR include older age, African American race, comorbidity, and increased length of stay, and EHR is associated with inferior patient and graft survival. To broaden our understanding of EHR in transplantation, we began with a prospective cohort study of EHR among KT recipients at Johns Hopkins Hospital. We used granular clinical data to characterize clinical scenarios leading to EHR. We also explored the association between EHR and novel predictors, including cognitive function, physical function, and socioeconomic factors. Next, we used national data to further explore novel predictors of EHR and to determine whether the risk of adverse outcomes associated with EHR varies over time. We used County Health Rankings and U.S. Census data to quantify the association between EHR and social determinants of health. We then estimated the association between EHR and adverse outcomes for two distinct time periods: during the EHR hospitalization and post-EHR. Finally, we used national data to develop a risk prediction model for EHR following simultaneous pancreas-kidney (SPK) transplantation and to quantify the association between EHR and post-SPK outcomes. At our center, we found that a high number of KT recipients are readmitted directly to the hospital without prior evaluation by a healthcare provider. Using national data, we found that living in a high-risk community increases the risk of EHR, but socioeconomic status was not associated with EHR. Following SPK, we found that 55% of recipient experience EHR. EHR following SPK was associated with younger recipient age, African American donor, and length of stay. We also found that EHR, following both KT and SPK, was most strongly associated with graft loss and mortality during the readmission hospitalization, but also portends a lasting, albeit attenuated, risk ...
وصف الملف: application/pdf
-
8رسالة جامعية
المؤلفون: Bembea, Melania
المساهمون: Tonascia, James A., Diener-West, Marie, Pronovost, Peter J., Everett, Allen D.
مصطلحات موضوعية: extracorporeal membrane oxygenation, ECMO
الوصف: Extracorporeal membrane oxygenation (ECMO) is a life-saving technique of cardiopulmonary bypass employed in intensive care units since 1976.1 ECMO is used in >1,000 children each year for cardiopulmonary failure refractory to maximal medical management, when chances of mortality exceed 80%.2 However, ECMO patients are at high risk for neurologic injury due to cannulation of large neck vessels, systemic anticoagulation and altered cerebrovascular dynamics. As many as 28%-52% of patients have abnormal neuroimaging findings during ECMO,3-8 and poor neurologic outcomes have been reported in 10% to 60% of survivors.7, 9, 10 The work presented in this thesis is organized around monitoring for coagulopathy, a risk factor for neurologic injury during ECMO, and monitoring for neurologic injury during ECMO by using plasma brain injury biomarkers. The overarching goal of our research program is to improve clinical care of ECMO patients to mitigate risk factors leading to acute neurologic injury and subsequent poor neurodevelopmental outcomes of these critically ill children.
وصف الملف: application/pdf
-
9رسالة جامعية
المؤلفون: Shillcutt, Samuel Dedman
المساهمون: Tonascia, James A., Sorkin, Alan, Holtgrave, David R., Winch, Peter J., Rao, Krishna D.
مصطلحات موضوعية: Diarrhea, zinc, oral rehydration salts, cost-effectiveness, economic evaluation
الوصف: Problem: Diarrhea is the third leading killer of young children, with India bearing the largest national burden. Effective and low-cost treatment is available through oral rehydration salts and zinc supplementation, and trial based literature suggests that these interventions are cost-effective. However, coverage of these interventions remains low, and strategies are being developed for scaling them up. It is less certain whether this health systems strategy is cost-effective at scale, or what economic impact it will have on caregivers. This dissertation evaluates the Diarrhea Alleviation through Zinc and ORS Treatment (DAZT) program in rural Gujarat India in terms of impact on caregiver costs, cost-effectiveness, and cost-effectiveness of different bundles of diarrhea and pneumonia prevention and treatment interventions. Methods: The influence of factors on the odds and amount of economic costs to caregivers was evaluated with a two part model. Due to the non-randomized study design, a net-benefit regression approach was used to evaluate cost-effectiveness while controlling for covariates. Cost-effectiveness of bundled services was evaluated with a mathematical model using probabilistic sensitivity analysis to evaluate uncertainty, and the Lives Saved Tool to project the number of deaths averted over five years. Results: The DAZT program was not associated with a change in odds of incurring an economic cost, although was associated with a $2.12 lower amount spent controlling for covariates. While a 14% to 11% reduction in diarrhea prevalence was observed, it is difficult to infer causality due to study design limitations. Estimates of cost-effectiveness were highly dependent on covariates included, never achieving 95% certainty in the fully specified model. The cost-effectiveness of the program bundled with other services was favorable relative to a ceiling ratio of per capita Gross National Income. Conclusions: It is inconclusive whether the DAZT intervention is a good investment in rural Gujarat based on its ...
وصف الملف: application/pdf
-
10رسالة جامعية
المؤلفون: Orandi, Babak John
المساهمون: Tonascia, James A., Segev, Dorry L., Montgomery, Robert A., Dodson, Jennifer L., Desai, Niraj M.
مصطلحات موضوعية: HLA-incompatible kidney transplantation, antibody-mediated rejection
الوصف: Survival for dialysis patients is dismal. They have an adjusted mortality rate 6.5-7.9 times higher than the general population. Kidney transplant (KT) recipients enjoy significant survival and quality of life advantages compared to remaining dialysis-dependent (1-5). Unfortunately, kidney demand far exceeds supply, with over 90,000 on the wait list (5). Highly sensitized patients constitute an increasingly large part of the wait list (6). Advancements in desensitization have allowed for KT across previously insurmountable immunological barriers; however, incompatible live donor kidney transplantation (ILDKT) is in its nascency and the literature is limited by single-center data, small sample sizes, and publication bias. ILDKT risks are generally considered to be higher than for compatible KT, but these risks have never been quantified precisely. Chapter 2 does precisely this using primary data collected from 22 U.S. transplant centers, constituting the largest cohort of ILDKT patients in existence. ILDKT risks are not limited to recipients. The federal government provides strict oversight of transplant outcomes. Chapter 2 quantifies the regulatory risk centers assume when they transplant immunologically high-risk patients. IKT patients are also at elevated risk of antibody-mediated rejection (AMR), which mediates much of the graft loss in ILDKT. Chapter 3 details the formation of the world's largest cohort of AMR patients, defined using strict clinical, pathological, and immunologic criteria, and quantification of the risk of graft loss associated with AMR by transplant type. There exists an uncommon, but virulent phenotype of AMR in ILDKT patients that is rapid in onset, severe in the graft dysfunction it causes, difficult to treat, and immediately graft-threatening without prompt action. Chapter 4 describes these patients in detail and compares the early rescue rate and impact of the severe AMR episode on the development of transplant glomerulopathy between salvage modalities, offering novel insight into the ...
وصف الملف: application/pdf
