INDIANAPOLIS — LOINC, the world's most commonly used universal code system for identifying medical test results, observations and other clinical measurements, has announced the inaugural recipients of the LOINC Award for Distinguished Contributions. The new award honors individuals whose work advances the interoperability that ensures that medical data can be recorded, electronically exchanged and ultimately used to improve health — when and where needed.

J. Gilbert Hill, M.D., Ph.D., of Canada and Cindy Johns, MSA of the United States were presented with the award at the annual LOINC meeting in June. Both are long-time active members of the LOINC participant community.

Hill, who worked at the Hospital for Sick Children in Toronto as director of the Clinical Biochemistry Service for 30 years, then as consultant to the electronic Child Health Network (eCHN) for 20 years, is an internationally respected scientist who, working with Canada Health Infoway, has influenced terminology standardization and the employment of LOINC for lab tests across Canada for over a decade.

Johns, a senior information technology specialist for LabCorp with responsibility for maintaining LabCorp's LOINC database, has presented LOINC courses throughout the medical laboratory industry. Three years ago she was recognized at the American Society for Clinical Pathologists with a Lifetime Achievement Award and currently serves on the organization's Board of Directors.

In addition to hospital systems, clinical laboratories, health information exchanges and other private and quasi-private sector entities, LOINC users include ministries and departments of health around the world. U.S. government agencies in the LOINC community include the National Library of Medicine, the departments of Veterans Affairs and Defense, the Indian Health Service, the National Cancer Institute and the Centers for Disease Control and Prevention.

LOINC is used in 172 countries and is available in Chinese, Dutch, Estonian, French, German, Greek, Italian, Korean, Portuguese, Russian, Spanish, and Turkish in addition to English.

LOINC traces its roots to the mid-1990s when Regenstrief Institute investigators, using their extensive experience with electronic medical records, developed the Indiana Network for Patient Care, the nation's first citywide health information exchange. They found they could receive data from various INPC-member institutions but that the clinical content was difficult to interpret because each used a different code for the same test or observation. A blood sugar result at one institution might be called a blood glucose score at another and something different at a third facility. It was as if the computer system was receiving messages in Vulcan, Klingon and Ferengi when all it had been programmed to understand was English.

To solve the problem the Regenstrief researcher-clinicians, led by Clement McDonald, M.D., developed the lingua franca they called LOINC, short for Logical Observation Identifiers Names and Codes. The Regenstrief Institute is the owner, developer, and overall steward for LOINC.

"Today, LOINC is the most accepted and used international standard of names and codes for medical results, observations and other clinical measurements in the world," said Regenstrief Institute investigator Daniel Vreeman, DPT. "Thanks to dedicated people like Gil Hill and Cindy Johns we are constantly expanding both in terms of codes and users with the ultimate goal of improving human health."

Vreeman serves as associate director for terminology services in the Center for Biomedical Informatics at the Regenstrief Institute.

With support from the National Library of Medicine, the Regenstrief Institute and other organizations, LOINC is an open, freely available standard. Updates to LOINC are issued twice annually.

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INDIANAPOLIS — The National Institutes of Health has awarded grants totaling more than $1 million to two researchers in the School of Health and Rehabilitation Sciences at Indiana University-Purdue University Indianapolis to study the effects of exercise on health conditions affecting millions of Americans.

Keith Avin, assistant professor of physical therapy, received a $674,186 grant to study the effects of aerobic and resistance exercise and myostatin inhibition on the prevention or reduction of skeletal muscle loss in animals with chronic kidney disease.

The study's findings could advance efforts to help many of the 20 million Americans with chronic kidney disease suffering muscle loss, muscle weakness and reduced mobility.

"Chronic kidney disease is considered an accelerated aging model," Avin said. "If you compare someone who is 50 years old and has end-stage renal disease, their muscles look like those of an 80-year-old."

There is little known about the mechanism behind skeletal muscle loss associated with chronic kidney disease or what exercise can do to help patients with that disease improve the condition of their muscles. Avin's study is designed to shed light on the latter.

"The goal is to see if exercise can mitigate the progression of the disease, providing prevention and treatment along the continuum of care," Avin said.

One of the aims of the study is to compare the effects of high-intensity versus low-intensity exercise to see if they are different, he said.

"A lot of people see exercise as just something you do, and the more you do, the better," Avin said. But with exercise, like any other drug, dosage matters: "If we're already looking at a system under stress, as is the case with someone with chronic kidney disease, and we tell patients to engage in high-intensity exercise, we may be doing more harm than good," he said.

Avin will determine what dose of exercise is best for the study animals as a prelude to determining correct exercise dosages for humans.

The study will also examine whether exercise or drugs influence myostatin levels in patients with chronic kidney disease. Myostatin is a natural protein produced within the body that inhibits muscle growth.

Myostatin levels often go up in older people and in those with a disease, Avin said. The researchers want to see if exercise, which has previously been shown to influence myostatin levels, or a drug can reduce myostatin levels and have a beneficial effect on muscle.

For a different study, William Thompson, assistant professor of physical therapy, received a $462,400 grant to examine how exercise directs bone marrow stem cells to become bone cells and prevents them from developing into fat cells, thereby strengthening bones and offsetting the deleterious effects of conditions such as osteoporosis.

Stem cells in bone marrow are able to become several different types of cells, including bone cells or fat cells, Thompson said.

"There are a lot of cues that direct the fate of these stem cells, helping them decide what type of cell they will eventually become," he said. "One of those cues is mechanical loading, which is the force exerted through your body during exercise. Such forces promote bone formation."

What the cells eventually become is important, because fat cells don't contribute to the strength of bones while bone cells do, Thompson said.

"The big picture is to understand how mechanical loading during exercise helps direct more of these cells to become bone cells and fewer to become fat cells," he said. "When people get up and move, it helps bias those cells, providing the necessary mechanical cues to say, all right, I need to turn into a bone cell and not into a fat cell."

These studies are being conducted in collaboration with Dr. Janet Rubin, a professor of endocrinology at the University of North Carolina School of Medicine, as well as Fred Pavalko, a professor of cellular and integrative physiology at the Indiana University School of Medicine.

The work will examine how molecules within these stem cells move within the cell to get where they need to be to turn mechanical force signals into biochemical responses, thereby promoting bone formation, Thompson said.

"Our goal is to understand which molecules are involved in this process, which would then enable the design of exercise or pharmacological interventions to target these pathways," he said. "Once you identify the targets, it's possible to select which exercise regimens would be best to initiate intercellular signaling cascades to elicit anabolic responses."

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INDIANAPOLIS – Many testicular cancer survivors experience hearing loss after cisplatin-based chemotherapy, according to researchers at Indiana University.

The researchers, led by Lois B. Travis, M.D., Sc.D., the Lawrence H. Einhorn Professor of Cancer Research at the IU School of Medicine and a researcher at the Indiana University Melvin and Bren Simon Cancer Center, studied for the first time the cumulative effects of cisplatin-based chemotherapy on hearing levels in testicular cancer survivors through comprehensive audiometry measurements. They found that increasing doses of cisplatin were associated with increased hearing loss at most of the tested frequencies, involving 4, 6, 8, 10, and 12 kHz.

The research was published online June 27 in the Journal of Clinical Oncology.

"In addition to hearing loss, about 40 percent of patients also experienced tinnitus (ringing-in-the-ears), which was significantly correlated with reduced hearing," Dr. Travis, also director of the cancer center's Survivorship Research Program, said.

Although this study was conducted in patients with testicular cancer, the authors point out that the general conclusions are likely applicable to patients with other types of adult-onset cancers that are commonly treated with cisplatin. They indicate that it will be important to follow patients given cisplatin-based chemotherapy long-term to better understand the extent to which the natural aging process may further add to hearing deficits, as it does in the general population.

"The results show the importance of comprehensive hearing assessments, preferably, both before and after treatments," Dr. Travis said. "Our findings suggest that health care providers should, at a minimum, annually query patients who have received cisplatin-based chemotherapy about their hearing status, consulting with audiologists as indicated. Patients should also be urged to avoid noise exposure, drugs having adverse effects on hearing, and other factors that may further damage hearing."

Co-first author Robert Frisina, Ph.D., added: "We are the first to show definitively that in a significant number of the cancer survivors, they have hearing loss above and beyond age-related hearing loss. They were of different ages –20s to 60s — so this was a new analysis." Dr. Frisina is a professor in the Department of Chemical and Biomedical Engineering, director of the Biomedical Engineering Program, and director of the Global Center for Hearing and Speech Research at the University of South Florida. He designed the auditory portion of the study.

Platinum-based cisplatin is one of the most commonly used drugs in medical oncology that also has toxic effects on the inner ear. Despite its use for more than 40 years, knowledge about the effects of cumulative cisplatin dose on hearing loss in survivors of adult-onset cancer has remained limited.

The researchers found that every 100 mg/m2 increase in cumulative dose of cisplatin resulted in a 3.2 dB impairment in hearing. The researchers also found high blood pressure was significantly related to hearing loss in these patients, even when cisplatin dose was taken into account. Thus, they emphasized the importance of high blood pressure control.

The researchers pointed out that because alterations in the highly successful testicular cancer regimens are unlikely for patients with advanced disease, their results underscore the importance of ongoing research aimed at the identification of genetic variants associated with cisplatin-related ototoxicity. An ultimate goal is to use the genetic results to develop effective agents that will protect the ear during the administration of cisplatin. For patients treated with cisplatin-based regimens for other types of cancer, it might also influence a physician to offer an alternative to those patients found to be genetically susceptible to the ototoxic effects of cisplatin after carefully weighing the risks and benefits of alternative treatments.

Lawrence Einhorn, M.D., Indiana University Distinguished Professor, Livestrong Foundation Professor of Oncology at the IU School of Medicine, and a physician scientist at the IU Simon Cancer Center, also was an author of the study.

In 1974, Dr. Einhorn tested cisplatin with two additional drugs that were effective in killing testis cancer cells. The combination became the cure for this once deadly disease. The results of this three-drug regimen were stunning. Tumors dissolved within days. Subsequent clinical research directed by Dr. Einhorn minimized the extremely toxic side effects of treatment; shortened the duration of two years of therapy to nine to 12 weeks; and established a model for a curable tumor, which has served as a research roadmap for generations of oncologists.

The researchers studied 488 men enrolled in the Platinum Study, which is open at the IU Simon Cancer Center and seven other cancer centers in the United States and Canada. The aim of the study is to gain new information that can benefit future testicular cancer patients and other patients treated with cisplatin-based chemotherapy.

The study was funded by a grant from the National Cancer Institute (R01CA157823).

Other authors included M. Eileen Dolan of the University of Chicago; Steven E. Lipshultz of Wayne State University School of Medicine; Shirin Ardeshir-Rouhani-Fard and Patrick Monahan of the IU Simon Cancer Center; Eileen M. Johnson and Sophie D. Fossa of Oslo University Hospital, Oslo, Norway; Amy Budnick and Darren R. Feldman of Memorial Sloan-Kettering Cancer Center; Clair J. Beard of Dana-Farber Cancer Institute; David J. Vaughn of the University of Pennsylvania; Robert Hamilton of Princess Margaret Cancer Centre; Howard D. Sesso of Brigham and Women’s Hospital; Chunkit Fung and Sarah L. Kerns of J.P. Wilmot Cancer Institute; and Heather Wheeler of Loyola University.

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INDIANAPOLIS — A new grant to the Indiana University Center for Aging Research from the National Institute on Aging funds the first study to assess the potential benefits and harms to family members of early dementia screening of older adults.

The Effects on Families of older adults Experiencing Cognitive Testing (EFECT) study is linked to the Indiana University CHOICE trial, a ground-breaking randomized controlled study assessing the harms and benefits of screening for dementia, compared to no screening for dementia, among 4,000 older adults cared for in typical primary care practices.

"EFECT is the first study to investigate if the benefits for family members — who may likely evolve into caregivers — of early dementia screening of seemingly cognitively healthy older adults outweigh the harms," said IU Center for Aging Research and Regenstrief Institute scientist Nicole Fowler, Ph.D, who leads the new study. "Our results will directly inform optimal care for older adults at risk of dementia as well as impacting the lives of the spouses, daughters, sons, and other family members who face the daunting task of caring for a loved one with dementia.

"We will measure family members’ knowledge of the screening event and potential caregiver preparedness in terms of the ability to plan for future care needs and accessing community and long-term care support. We will also be able to assess if early identification of dementia by screening harms family members by inducing anxiety or depression."

Dr. Fowler, an implementation scientist with the IU Center for Health Innovation and Implementation Science — a part of the Indiana Clinical and Translational Science Institute, reported in 2012 and 2015 studies that more than half of older adults are willing to be screened for dementia in primary care.

The aims of the EFECT study include evaluating the impact of dementia screening on family members’ health-related quality of life and well-being and the impact of dementia screening on family members’ mood and anxiety. The researchers are also assessing the impact of dementia screening on family members’ caregiving preparedness and caregiving self-efficacy.

Currently about half of patients with dementia in the U.S. are undiagnosed. It is not known whether dementia screening better prepares family members for the practical, physical, and emotional realities of caregiving or impacts their well-being and health-related quality of life.

The United States Preventive Services Task Force has stressed the need for research on links between dementia screening and patient or family caregiver outcomes given the tremendous burden of dementia on family caregivers.

There are an estimated 5.4 million adults with Alzheimer’s disease or related dementias and 11 million dementia caregivers in the United States. By 2050, it is estimated that those numbers will rise to 13.8 and 27 million, respectively.

"Delaying a diagnosis of dementia has the potential to impact the family member’s behaviors toward the patient and their perceived role," said Dr. Fowler. "For example, it may perpetuate the belief that changes in cognition are part of ‘normal aging’ which have been shown to aggravate family caregivers’ stress, burden, and sense of isolation, which, in turn, may impact the health of caregivers and their ability to access important services."

NIA has awarded $126,000 to support EFECT in conjunction with CHOICE, which has received $2.65 million in NIA funding through 2017.

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