Browsing by Subject "Pediatrics"

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Application of Pharmacometrics to Rare Diseases
(2016-10) Ahmed, Mariam
Rare diseases affect an estimated 600–700 million people across the globe and are often chronic, progressive, degenerative, and life threatening. In United States, there are more than 7,000 known rare diseases, of which less than 5% are treatable with approximately 550 approved orphan drugs. Drug development for rare disease possesses several layers of challenges. Pharmacometrics represents an attractive tool during orphan drug development as it provides a way to integrate knowledge about the disease and its treatment in a quantitative framework. These models can be utilized to optimize clinical trial designs for evaluation of treatments under development. X-linked adrenoleukodystrophy (X-ALD) is a peroxisomal disorder, most commonly affecting boys, associated with increased very long chain fatty acids (C26:0) in all tissues, causing cerebral demyelination and adrenocortical insufficiency. Certain monounsaturated long-chain fatty acids including oleic and erucic acids, known as Lorenzo's oil (LO), lower plasma C26:0 levels. We characterized the effect of LO administration on plasma C26:0 concentrations and determined whether there is an association between plasma concentrations of erucic acid or C26:0 and the likelihood of developing brain MRI abnormalities in asymptomatic boys. Non-linear mixed effects modelling was performed on 2384 samples that were collected during an open label single arm trial. The subjects (n = 104) were administered LO daily at ~2–3 mg/ kg with a mean follow-up of 4.88 ± 2.76 years. The effect of erucic acid exposure on plasma C26:0 concentrations was characterized by an inhibitory fractional Emax model. A Weibull model was used to characterize the time-to-developing MRI abnormality. The population estimate for the fractional maximum reduction of C26:0 plasma concentrations was 0.76 (bootstrap 95% CI 0.73, 0.79). Our time-to-event analyses showed that every mg/L increase in time-weighted average of erucic acid and C26:0 plasma concentrations was, respectively, associated with a 3.7% reduction and a 753% increase in the hazard of developing MRI abnormality. However, the results were not significant (P = 0.5344, 0.1509, respectively). Congenital adrenal hyperplasia (CAH) is a form of adrenal insufficiency characterized by impaired cortisol synthesis. Replacement with oral hydrocortisone (HC) does somewhat correct the resulting over-production of adrenal androgens, but significant medical problems follow these children into adulthood. To better understand dosing requirements, population pharmacokinetics of cortisol was characterized in children with CAH. Children with CAH (n=48; median [range] age and weight were: 7.1 years [1.47-18.2 years] and 29.3 kg [10.8-80.6 kg], respectively) receiving oral HC, had 12 serum samples obtained over 6 hours starting at 0800 h. Nonlinear mixed-effect modeling assuming a one-compartment model and allometric scaling was used for data analysis. The model included information on circadian rhythm from historical data to allow simulation of 24-h profiles of cortisol. Effects of disease phenotype, formulation type, pubertal stage, and sex on cortisol disposition were examined. Clearance (CL/F) and volume of distribution (V/F) were: 21.7.(WT/70)3/4 L/h and 37.6.(WT/70) L, respectively, and a resulting half-life of 0.896 hr. The bioavailability of the suspension was comparable to tablet formulation (99.6% relative to the tablet formulation). Our model-based simulations suggest many children with CAH are exposed to prolonged periods of hypocortisolemia and hyperandrogenemia over 24 hours with current hydrocortisone dosage regimens.
Are the Kids All Right? A Look at Flourishing among School-age Children and Youth in Minnesota
(Minnesota Medical Association, 2021-01-01) So, Marvin; Lynn, Anna
Flourishing is a state characterized by positive social and behavioral functioning in children, which can be influenced by family, health care, and community factors. The National Survey of Children’s Health (NSCH) provides an opportunity to describe characteristics of the children who are—and are not yet—flourishing at the state level. Using the 2016-2017 NSCH to calculate prevalence estimates and odds ratios (ORs), this study examined parents’ perspectives on Minnesota children aged 6–17 in households, and explored select child, family, and health care correlates. The findings indicate that 41.4% of children in the state met flourishing criteria. Unadjusted ORs demonstrated differences in flourishing by child, family, and health care characteristics; after accounting for relevant covariates, parent-child connectedness, family resilience during difficult times, medical home status, and encountering adverse childhood experiences remained significantly associated with flourishing. Through highlighting factors predictive of parent-perceived flourishing, this study outlines potential insights for intervention that could accelerate child and adolescent well-being in Minnesota.
Bench Testing of a Tunable Ankle-Foot Orthosis
(2023) Jiang, Tianshu
Cerebral palsy (CP) is the most common childhood motor disability and affects about 0.31% of children in the US. An ankle-foot orthosis (AFO) is commonly prescribed for children with CP to restore gait pattern and function. The properties of an AFO are primarily determined by two parameters: the neutral angle and the stiffness. There is no standard guidance for clinicians to determine what combination of parameters would maximize the function of an AFO. The Human/Machine Design Lab at the University of Minnesota is developing a tunable AFO emulator to help clinicians determine the effect of AFO with certain parameters immediately and the make more objective prescriptions of AFO. This project conducted a bench test on the latest design of this tool, and evaluated if the mechanisms to control the stiffness and the neutral angle of the emulator would work as intended. The mechanism for controlling the neutral angle worked as intended while the mechanism for stiffness was affected by the compliance of the AFO structure and the material of the prototype. A computer control system for the device all functions required.
The Blood in the Newborn Period
(1922) Lippman, Hyman Shalit
A bump on the head: Does my child need a CT image of his or her brain?
(2012-04-09) Larson, Anna
Excess Adiposity in Youth: Subclinical Cardiovascular Disease and Future Implications
(2017-07) Fyfe-Johnson, Amber
Excess adiposity remains a serious public health threat; 33% of U.S. adolescents are classified as having overweight or obesity. Adolescent obesity is associated with a 3.5 times higher lifetime risk of cardiovascular disease (CVD) mortality, thus subclinical CVD phenotypes such as carotid intima-media thickness (cIMT) have become widely accepted as relevant to earlier stages of CVD in youth. In the first manuscript, we developed a risk prediction model that predicted cIMT in middle adulthood using relevant CVD risk factors in adolescence. Longitudinal associations were observed between most CVD risk factors in adolescence and increased cIMT in middle adulthood; our risk prediction model poorly predicted cIMT in middle adulthood based on discrimination and calibration metrics. In the second manuscript, we contrasted longitudinal data from two bi-racial cohort studies by examining the association between CVD risk factors and cIMT in two distinct periods of life. Higher body mass index was associated with an increased cIMT in the younger cohort. In the older cohort, no association was present between body mass index and cIMT; higher systolic blood pressure was associated with increased cIMT. The American Heart Association set 2020 Strategic Impact Goals that defined CVD risk factors to include in the concept of ideal cardiovascular health (ICH). In the final manuscript, we examined the prevalence of ICH by adiposity level in youth, including severe obesity. We then generated a continuous ICH sample z-score, and examined the distribution of the ICH sample z-score by adiposity level in youth. Children with overweight/obesity and severe obesity had lower ICH sample z-scores than those with normal weight. Taken together, these three projects provide insight into the relationship between excess adiposity and subclinical CVD and cardiovascular health in youth. In addition, this dissertation considers metrics that have the potential to address excess adiposity prevention efforts in youth.
Extreme caregiving: an ethical analysis of narratives by parents
(2013-12) Freitag, Lisa C.
Home medical care for medically complex and intellectually disabled children is frequently prescribed by providers, but the consequences for the family of such care are rarely considered in full. It is recognized that at times the care required might become physically demanding and emotionally burdensome. However, I believe that this sort of caregiving often reaches extreme levels, making our continued reliance on family caregiving ethically problematic. This paper analyzes several novel-length narratives by parents of intellectually disabled children to look deeper into the lives effected by this complex form of home care. Building on the care ethics framework developed by Joan Tronto, I examine particularly the ways in which the parents perceive their caregiving duties and demonstrate Tronto's caregiving virtues of attentiveness, responsibility, competence and responsiveness. This work begins to theorize caregiving in a new way, revealing previously unrecognized ethical concerns raised by this sort of extreme caregiving.
Hunger in the Infant
(1917) Taylor, Rood
Interview with Alfred Michael
(University of Minnesota, 2012-04-25) Tobbell, Dominique A.; Michael, Alfred F.
Dr. Alfred Michael begins his interview with a reflection on his childhood and education in Philadelphia and his interests in medicine and pediatrics. He describes his decision to move to the University of Minnesota in order to work with Dr. Robert A. Good. He then discusses all of the following in relation to his research: working with Robert Vernier; changes in technology and methodology related to testing the kidney; his graduate work in biochemistry; specialization in medical research; work on transplantation and dialysis with John Najarian and Carl Kjellstrand; kidney research at the University; the expansion of and coverage for dialysis; and his time in Copenhagen. Dr. Michael then describes Dr. John Anderson’s tenure as department chair and his own tenure as dean, during which he made efforts to create a major children’s hospital facility in combination with the University. He also reflects on the larger context of changes in healthcare structures in the period, particularly the emergence of HMOs and Minnesota’s role in the development of HMOs, and town/gown relations in the Twin Cities. Dr. Michael then discusses Robert Howard and David Brown’s tenures as dean of the Medical School and issues with private practice and finances at the University. Turning to administrative matters, Dr. Michael describes his work with Win Wallin; William Brody’s tenure as provost of the AHC; and the growth of the administrative power of the AHC. He then elaborates on the creation of University of Minnesota Clinical Associates and University of Minnesota Physicians; the sale of University Hospital to Fairview; divisions of responsibility and administration within the AHC; relations between different schools in the AHC; and the investigation of John Najarian in connection with Antilymphocyte Globulin (ALG). He concludes with reflections on the balance of research, teaching, and clinical work; his moves into administrative positions; his work on various boards; his work with the Legislature; and the Medical School’s standing.
Interview with Arnold Anderson
(University of Minnesota, 2010-02-02) Tobbell, Dominique A.; Anderson, Arnold
Arnold Anderson begins by discussing his background, including his education and why he became a physician. He discusses his experiences as a medical student at the University of Minnesota, as an intern at San Diego County Hospital, in the army as a pediatrician, and as a pediatric fellow at the Mayo Clinic. He describes setting up his group practice and establishing the Park Nicollet Clinic and the development and building of the Minneapolis Children’s hospital. He discusses pediatric medicine, the University of Minnesota Medical School, the UMN Medical School’s relationship with private practitioners, Internal Medicine at the UMN, the Department of Pediatrics at the UMN, the relationship between the Mayo Clinic and the UMN Medical School, the relationship between the UMN Medical School and Twin Cities hospitals, and relations between departments at the UMN Medical School. He discusses the Teenage Medical Center, Human Ecology, physician fees, academic medicine, and principles of management and leadership. He talks about Robert Howard, Irvine McQuarrie, John Anderson, Robert Good, and Richard Magraw.
Interview with Barbara Leonard
(University of Minnesota, 2011-10-20) Tobbell, Dominique A.; Leonard, Barbara
Dr. Barbara Leonard begins her interview by discussing her education and her interest in public health nursing. In particular, she describes her early experiences with vaccination and her clinical rotations in college. She then reflects on her work toward a master’s degree in public health at the University of Minnesota, including her coursework, mentors, the creation of the Public Health Nurse Practitioner Program, and the changes to and restructuring of nursing programs in the School of Public Health. She also discusses the following: the impact of the Rajender Consent Decree, relations between the School of Public Health and the School of Nursing; curriculum reform within the School of Nursing; the positioning of nursing programs within the School of Public Health; the favorable economic position of the health sciences in the 1960s and 1970s; and knowledge and skills-based competition among healthcare professionals. The interview then turns toward the following topics: Lee Stauffer as dean of the School of Public Health; transitions in the scope of public health regarding prevention and healthcare delivery; relations among divisions within the School of Public Health; the leadership of Alma Sparrow; her pursuit of a Ph.D. in Healthcare Administration; and her interests in maternal and child health and particularly children with chronic disease.
Interview with Carl A. Osborne
(University of Minnesota, 2011-10-17) Tobbell, Dominique A.; Osborne, Carl A.
Dr. Carl Osborne begins with his upbringing, educational background, and childhood relationships with animals. He earned his DVM at Purdue University and took a tenure-track position at the University of Minnesota while he pursued his PhD with a research focus in the urinary tract. He discusses his early years in the Department of Veterinary Medicine, including W. T. S. Thorp’s tenure as dean. He also recounts the relationship of the department to the state legislature in working with large animals and the political influence of the rural population of the state. He describes the potential for retrenchment of the Vet School that occurred in 1988. In reflecting on his time as a researcher, clinician, and teacher, Dr. Osborne shares his philosophies on life, teaching, and veterinary medicine. He describes the leadership changes within and the politics of the school, exploring some of the conflicts that arose over the course of his career. In discussing changing leadership, Dr. Osborne also comments on his own leadership roles. He then describes the internal and external relationships of the vet school, in aligning itself with the Academic Health Center and establishing reciprocity with the University of Wisconsin. Dr. Osborne returns to discussions of leadership within the school in describing the tenures of deans Sidney Ewing, David Thawley, and Bob Dunlop. In returning to his role within the department as clinician, researcher, and teacher, Dr. Osborne again shares his philosophy of veterinary medicine.
Interview with David Brown
(University of Minnesota, 2012-05-09) Tobbell, Dominique A.; Brown, David M.
David Brown begins by describing his childhood and education in Illinois. He discusses his experience attending medical school in the 1960s and his decision to join the University of Minnesota’s Department of Pediatrics. He describes his experiences with Ellis Benson and others with whom he worked in the Department. He discusses the role of women in laboratory medicine and his work in comparative endocrinology. He explains the differences in the administrations of several different deans of the Medical School and the School’s changing relationship with the University (and later, Fairview) Hospital. He describes some of the issues of town/gown in Minneapolis and in Minnesota at large, especially related to pediatric medicine. He describes his decision to become an administrator and his own tenure as Dean of the Medical School, the development of the Masonic Cancer Center, and the University’s ALG scandal. He concludes with his retirement and his discovery of a passion for art.
Interview with Frank Cerra
(University of Minnesota, 2014-07-31) Cerra, Frank B.; Tobbell, Dominique
Dr. Frank Cerra begins part one of his interview by describing his undergraduate education at SUNY Binghamton, his medical education at Northwestern University Medical School, and his residency at SUNY Buffalo. He then describes his recruitment to the University of Minnesota, his early goals, and his growing administrative roles. He describes the leadership implications of investigations into Antilymphocyte Globulin (ALG) on the Medical School and the merging of University Hospital with Fairview Health Services. He then discusses the following topics: his interest in surgery; the culture of the University of Minnesota’s Department of Surgery; his work with the pharmaceutical industry and the College of Pharmacy; his work developing a critical care program at the University; and his relationships with the hospital directors, hospital nursing, and the School of Nursing. In part of two his interview, Dr. Cerra intersperses reflections on finances and relations among different levels of administration in the University, the AHC, and University Hospital. He also discusses the following topics: his relationship with Neal Gault; strategic and long-range planning; the goals of the AHC; the formation of University of Minnesota Physicians; the establishment of the Biomedical Ethics Center (later the Center for Bioethics) and the Masonic Cancer Center; the investigations into ALG and Dr. John Najarian; the establishment of the Center for Drug Design; William Brody as Provost of the AHC and issues surrounding faculty tenure; and the establishment of the Institute for Health Informatics. In part three of his interview, Dr. Cerra expands on the decision to merge University Hospital with Fairview Health Services, particularly focusing on logistics, culture, and reception. He also discusses failed attempts to create a unified children’s hospital in the Twin Cities. He then reflects on the following topics: the major challenges and achievements of his tenure as senior vice president; the merging of the positions of Senior Vice President of Health Sciences and Dean of the Medical School; the creation of the Clinical and Translational Science Institute and the Biomedical Discovery District; and the medical device industry in Minnesota. He concludes by describing the University of Minnesota and Mayo Clinic partnership in research.
Interview with John Kersey
(University of Minnesota, 2011-05-09) Tobbell, Dominique A.; Kersey, John
John Kersey begins by describing his background, including his education and why he went into medicine. He describes his experiences during his residencies, being appointed a Medical School faculty member, and as a faculty member. He discusses faculty and research at the UMN Medical School while he was a student, the reorganization of the Health Sciences in 1970, the effort to establish a children’s hospital in Minneapolis in the 1960s, relations between UMN faculty pediatricians and community pediatricians, teaching, Homecare for the Dying Child Program, and hospitalists. He talks extensively about cancer research and treatment work, touching on topics including his own research and other work, funding and the NIH, clinical research versus laboratory research, informed consent and medical ethics, cancer research in the 1970s, the development of medical and pediatric oncology and chemotherapy, bone marrow transplantation, cancer research funding, the bone marrow transplantation program, nurses who worked on cancer treatment, the Masonic Center in the 1970s, the Cancer Coordinating Committee, the development of organ transplantation treatments, the Comprehensive Cancer Center in the 1980s, the Cancer Detection Center, ALG, experimental treatments, and clinical research. He talks about James Dawson, Mead Cavert, and Robert Good.
Interview with John P. Delaney
(University of Minnesota, 2012-03-27) Tobbell, Dominique A.; Delaney, John P.
Dr. John Delaney begins by describing his education at Notre Dame and the University of Minnesota. He discusses his perception Harold S. Diehl as Dean of the Medical School, C. Walton Lillehei’s surgical innovations, and Dr. Owen Wangensteen’s tenure as chief of surgery during Delaney’s time in the medical school. He also describes University Hospital administrator Ray Amberg and his assistant Gertrude Gilman. He discusses the changing fee system in hospitals in the mid 1960s. Delaney describes the cardiac program at the University of Minnesota in the 1950s and 1960s. He discusses his early research interest in bleeding from the stomach and his clinical specialization in gastrointestinal surgery. He describes changes in the Department of Surgery when John Najarian took over for Owen Wangensteen as chief. He recounts his experiences with Robert Howard as dean of the medical colleges, particularly his role in the faculty practice plan. He also discusses surgical nurses and the increasing emphasis on patient satisfaction with hospital care to receive full reimbursement for services. Delaney discusses the reorganization of the health sciences at the University of Minnesota, town/gown issues with Twin Cities practitioners, and competing medical school plans in Saint Paul and at Saint Thomas. He also discusses his later focus on surgical oncology and working with B.J. Kennedy and Seymour Levitt. Finally, he describes the ALG scandal.
Interview with John S. Najarian
(University of Minnesota, 2011-09-27) Tobbell, Dominique A.; Najarian, John S.
Dr. John Najarian begins part one of his interview with a reflection on where he was born and raised and how he became interested in medicine. He then discusses his time in the U.S. Air Force, his interest in transplantation, the research he conducted under the mentorship of Frank Dixon and Joe Feldman, his decision to return to surgical work, his time at UCSF, and his move to the University of Minnesota. Dr. Najarian then reviews his time at the University of Minnesota, covering all of the following topics: his efforts to increase the number of surgical patients and work with surgeons in the community; relations with administrators at University Hospital; the continued training of academic surgeons; relations between different departments within the Medical School; cultural differences across the United States; the organ transplantation program at the University; ethical issues in transplantation; Robert Good’s work on bone marrow transplantation; transsexual surgery at the University; the faculty practice plan and income in the Medical School; the impact of Medicare and Medicaid; the health manpower shortage and problems with manpower distribution; and efforts to recruit minority and female surgeons. Dr. Najarian begins part two of his interview by reviewing collaborations with different schools and departments across the University and the differences between the University of Minnesota and the University of California-San Francisco. He comments on his experiences as the College of Medical Sciences reorganized as the Academic Health Center and relations with the state legislature. Dr. Najarian then discusses the following topics: changes to the hospital’s Board of Governors; space and staffing issues; the expansion of the hospital in the late 1970s and 1980s; and the sale of University Hospital to Fairview. Dr. Najarian spends a considerable portion of the interview reflecting on the development of Minnesota antilymphocyte globulin (ALG) and the legal problems he faced with the FDA and the University surrounding its sale. In the remainder of the interview, Dr. Najarian discusses the following topics: the leadership of Lyle French and Neal Vanselow; the impact of the National Organ Transplant Act of 1984; transplants conducted in pediatric patients and Jamie Fisk’s successful liver transplant at eleven months old; and changes in surgical technologies. He concludes his interview with reflections on the legacy of Dr. Owen Wangensteen and other figures important to the history of the AHC.
Interview with Karlind T. Moller
(University of Minnesota, 2013-04-26) Klaffke, Lauren E.; Moller, Karlind T.
Karlind Moller begins his interview with a reflection on his upbringing and early education. He then discusses how he came to the field of speech pathology and particularly, speech pathology in relation to the cleft palate, relating his experiences in the Cleft Palate Clinic and at the National Institute for Dental Research. He emphasizes the interdisciplinary nature of the Cleft Palate Clinic. He also discusses his experiences publishing with the University of Minnesota Press, his committee work, particularly his work on the Admissions Committee and Minority Student Committee, his work with out-of-state patients, the work of the Cleft Palate Clinic in consulting on treatment, and the completion of the building of the Dental School facilities in the 1970s. Dr. Moller then reflects on his cleft palate work in Guatemala, funding for the Cleft Palate Clinic, the relationship between the Dental School and the Department of Communication Disorders, the Cleft Palate Clinic team, and issues with the state legislature and speech pathologist licensing. He also discusses his teaching, work with dental hygienists, the culture of the Dental School, Dr. Erwin Schaeffer’s tenure as dean, the relationship of the Cleft Palate Clinic with other schools in the AHC, the tenures of Dr. Richard Oliver and Richard Elzay as deans, the threatened closure of the Dental School in 1988, retrenchment, work with the state legislature and the insurance industry over cleft palate correction, the vice presidents for the AHC in the 1990s, and the tenure of Dr. Michael Till as dean. He concludes by discussing additional figures of importance in the Dental School’s history.
Interview with Paul Quie
(University of Minnesota, 2011-03-21) Tobbell, Dominique A.; Quie, Paul
Paul Quie begins by discussing his background, including his childhood, why he went into medicine, his education, and being drafted into the Navy. He discusses his experiences as a student at Yale Medical School, as an intern at the Minneapolis General Hospital, as a pediatrician in the Navy, and doing research at the Rockefeller Institute in New York in the early 1960s. He describes medical developments in the 1950s; the environment in the UMN Medical School in the 1950s; the American Legion professorship; his research; collaboration between Pediatrics, Medicine, and Surgery in the 1960s; the UMN Pediatrics Department; the College of Medical Sciences deans; the faculty practice issue and Robert Howard; leadership at the UMN health sciences; the strict full-time model in Pediatrics in the 1960s; the relationship between the UMN and private practitioners in Minneapolis and St. Paul; the effort to establish a second medical school in the Twin Cities; and the establishment of the Department of Family Practice at UMN. He also discusses medical specialization in the US; the establishment of the Children’s Hospital; the medical school curriculum revisions in the 1960s; the reorganization of the health sciences in the 1960s; the Korea Project; the Program in Human Sexuality; the pediatric infectious diseases program at Red Lake at the Indian Reservation; the transsexuality program in the late 1960s and early 1970s; the appointment of Konald Prem as chair of the Department of Obstetrics and Genecology in 1976; retrenchments in the early 1980s; the NIH; the early history of HIV/AIDS; the Center for Bioethics; and the Rural Physician Associate Program. He talks about Lewis Thomas; Irvine McQuarrie; John Anderson; Harold Diehl; Robert Howard; Neal Gault; Lyle French; John Westerman; Richard Chilgren; his brother, Al Quie; and Jack Verby.
Interview with Robert Ulstrom
(University of Minnesota, 2010-02-18) Tobbell, Dominique A.; Ulstrom, Robert
Robert Ulstrom begins the interview by describing his background, including his education, his service in the US Army, and why he became a pediatrician. He reflects on his mentor Irvine McQuarrie, and his colleagues John Anderson, Robert Howard, and Lyle French. He discusses his experiences in University of Minnesota Medical School, his move to UCLA, his return to the University of Minnesota in the mid-1950s, and his work as associate dean in the College of Medical Sciences. Other topics discussed include, his research, the private practice issue, relations with affiliated hospitals and their faculty after the expansion of the Medical School class size in the 1960s, the curriculum revision in the 1960s, the attempt to establish a medical school in St. Paul, the establishment of the Department of Family Practice, tensions between private practice physicians and Medical School physicians, the effort to establish a Minneapolis children’s hospital in the 1960s, tensions between Minneapolis and St. Paul physicians, the reorganization of the health sciences into the Academic Health Center in 1970, the Mayo Clinic and the Mayo School of Medicine.

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