Featured Projects

Connecting black men to effective blood-pressure treatment in community barbershops

Black men have the highest rate of hypertension-related death in the United States, but are unlikely to see a doctor. Thus, community outreach is needed. 

Led by the late Dr. Ronald Victor of Cedars-Sinai, investigators developed and tested a blood-pressure control program in 52 Los Angeles County black-owned barbershops. Customers received free screenings for high blood pressure, defined as systolic blood pressure of 140 mm Hg or higher. At half of barbershops, customers got pamphlets and blood-pressure tips while they were getting their hair cut. At the remaining barbershops, customers met with pharmacists and could get treatment if their blood pressure was high. 

At the end of six months, nearly two-thirds of men who saw pharmacists lowered their readings below the threshold for high blood pressure. They had an average systolic pressure of 125.8 mm Hg; men who received only advice had an average systolic pressure of 145.4 mm Hg—too high. Investigators subsequently demonstrated the results were sustained over 12 months. A CTSA administrative supplement awarded to the UCLA CTSI in collaboration with the Vanderbilt CTSA will replicate the model in Nashville. Upon completion of that project, a tool kit will be created to provide CTSA researchers with the ability to establish barbershop research hubs locally or across the CTSA network.

References

• Victor RG, Lynch K, Li N, et al. A Cluster-Randomized Trial of Blood-Pressure Reduction in Black Barbershops. New England Journal of Medicine. 2018; DOI: 10.1056/NEJMoa1717250
• Victor RG, Blyler, CA, Li N, et al. Sustainability of Blood Pressure Reduction in Black Barbershops. Circulation. 2019; DOI:10.1161/CIRCULATIONAHA.118.038165

The impact of youth incarceration on health in adulthood

Despite compelling data on the unmet health needs of incarcerated youth, no existing studies described the longitudinal relationship between the duration of incarceration of young people and subsequent adult health outcomes. To quantify the relationship, CTSI investigators analyzed data from 14,344 adult participants in the National Longitudinal Study of Adolescent to Adult Health.

Compared with no incarceration, incarceration of less than one month predicted depressive symptoms in adulthood; incarceration of one to 12 months predicted worse general health in adulthood; and incarceration of more than one year predicted functional limitations, depressive symptoms, and suicidal thoughts in adulthood.

The study demonstrated that youth incarceration is independently associated with worse adult physical and mental health outcomes. The finding suggests an important role for pediatricians to protect youth from potentially harmful effects of incarceration and mitigate any downstream negative effects.

First author Dr. Elizabeth Barnert was supported by a CTSI KL2 award. The CTSI also provided biostatistical support.

Reference

• Barnert ES, Dudovitz R, Nelson BB, et al. How Does Incarcerating Young People Affect Adult Health Outcomes? Pediatrics. 2017;139(2):e20162624

Teleretinal diabetic retinopathy screening in primary care in the Los Angeles Safety Net

Diabetic retinopathy is the leading cause of blindness in adults of working age in the United States. Despite evidence that early detection and treatment can prevent blindness from diabetic retinopathy, a significant number of persons with diabetes in the safety net fail to receive annual screening examinations and/or sight-saving treatments due to lack of access to specialty care. Patients in the Los Angeles safety net waited eight months for diabetic retinopathy screenings from eye specialists. 

With assistance from CTSI, the Los Angeles County Department of Health Services (DHS) implemented an intervention to conduct screenings in primary care and transmit retinal images to optometrists for referrals to ophthalmologists, if necessary. The intervention eliminated the need for more than 14,000 visits to specialty eye-care professionals, increased annual rates of screening for diabetic retinopathy by 16%, and reduced wait times for screenings by 89%. 

The CTSI supported the study with pilot funds, access to the biostatistics core, research assistant support, and a health economist who assisted with data analysis, helped assure quality assurance mechanisms were sufficient, and advised on the design of a cost analysis of the intervention, which has been implemented countywide.

The study was the first to evaluate the effect of a system-level intervention on improving access to eye care and definitive treatment for diabetic retinopathy in an urban medically underserved, or safety net, population. With standardization and oversight, primary care-based teleretinal diabetic retinopathy screening programs have the potential to maximize access and efficiency in the safety net, where the need for such programs is most critical.

Reference

• Daskivich LP, Vasquez C, Martinez C, Tseng C, Mangione CM. Implementation and Evaluation of a Large-Scale Teleretinal Diabetic Retinopathy Screening Program in the Los Angeles County Department of Health Services. JAMA Intern Med. 2017;177(5):642–649. doi:10.1001/jamainternmed.2017.0204

Utilizing machine learning to predict clinical deterioration

Critically ill patients are vulnerable to septic shock, cardiac arrest, pulmonary failure and other life-threatening complications that require their timely transfer from a hospital’s general medicine floor to the ICU. However, clinical monitoring systems produce many false alarms, resulting in alarm fatigue and delays in transferring deteriorating patients to the ICU.

By applying machine learning techniques to information from the electronic heath records (EHR) of more than 6,000 patients admitted to Ronald Reagan UCLA Medical Center, investigators developed an improved method for assessing risk that produces more accurate and timely alarms. Importantly, the model takes into account the individual characteristics of each patient, allowing for a personalized risk assessment. The new risk-scoring model promises to speed transfers to the ICU, conferring huge clinical and social benefits on critically ill patients. Next steps include real-time monitoring of critically ill patients to determine the model’s clinical impact.

Reference

• Alaa AM, Yoon J, Hu S, et al.  Personalized Risk Scoring for Critical Care Prognosis Using Mixtures of Gaussian Processes. IEEE Transactions on Biomedical Engineering. 2018; DOIi: 10.1109/TBME.2017.2698602

FDA approval of larotrectinib, a targeted, tissue-agnostic cancer drug

CTSI's clinical research infrastructure supported a multisite study that led to the FDA approval of larotrectinib, a drug that targets specific genetic mutations found in a variety of cancers. The UCLA lead was Noah Federman, medical director of CTRC and director of the UCLA Jonsson Comprehensive Cancer Center's Pediatric and Soft Tissue Sarcoma Program. CTSI support was invaluable in study activation and successful conduct of the trial.

At the Connective Tissue Oncology Society Meeting in Rome, Dr. Federman provided results on 120 patients with various types of cancers, including common cancers like lung and colon and rare cancers like soft tissue sarcomas. At one year, 81 percent of patients responded to the drug. In bone and soft tissue sarcoma, the response rate was an unprecedented 93 percent. Among them was "Little Linda," who at age one month became the youngest person to enter the trial. When she arrived at UCLA, Linda's tumor, a rare childhood cancer known as infantile fibrosarcoma, took up 50 percent of her scalp. Within days of treatment, the tumor began to shrink. Today, Little Linda is an active toddler. 

Reference

• Drilon A, Laetsch T, Kummar S, et al. Efficacy of Lartrectinib in TRK Fusion-Positive Cancers in Adults and Children. New England Journal of Medicine. 2018; DOI: 10.1056/NEJMoa1714448

A novel target for detecting and treating early-stage lung cancer

A team led by CTSI KL2 scholar Claudio Scafoglio has identified a protein lung cancer cells need to use glucose, which is essential for tumor growth and survival. The finding suggests that the protein, the sodium-dependent glucose transporter 2 (SGLT2), is a novel biomarker that doctors may one day use to detect lung cancer early, when tumors are small and  easier to treat. The senior author on the paper, UCLA Associate Professor David Shackelford, is Dr. Scafoglio's mentor and a former KL2 scholar. Thus, the research also demonstrates a "daisy chain" approach to translational science training, in which the KL2 program produces scientific leaders who, in turn, train new KL2 scholars.

In Dr. Scafoglio's experiment, mice with human cancer cells were injected with radioactive tracers to hone in on the SGLT2 protein. Then scientists used positon-emission tomography (PET) imaging to measure the activity of SGLT2. Next, they gave the mice canagliflozin, an FDA-approved diabetes drug that blocks the SGLT2 protein, reducing the cancer's glucose supply. The drug slowed the growth of early-stage lung cancer and improved survival in the mice. Dr. Scafoglio, an assistant professor at UCLA, said the next step for his research would be clinical studies of SGLT2-specific PET imaging in early-stage lung cancer patients, followed by trials testing SGLT2-blocking drugs for lung cancer treatment – and, potentially, disease prevention. 

Reference

• Scafoglio C, Villegas B, Abdelhady G, et al. Sodium Glucose Transporter 2 is a Diagnostic and Therapeutic Target for Early-Stage Lung Adenocarcinoma. Science Translational Medicine. 2018; DOI: 10.1126/scitranslmed.aat5933

Behavioral deficits and cholinergic pathway abnormalities in male Sanfilippo B mice

Sanfilippo B syndrome is a devastating neurological disorder of childhood. It is caused by an enzyme deficiency that leads to an accumulation of heparan sulfate throughout the body and brain. Affected children experience progressive neurological deterioration and early death. The purpose of this experiment was to evaluate the neurobehavior of Sanfilippo B mice using methods that would be best suited for preclinical development of brain-directed therapies. 

The study found reduced fearfulness in Sanfilippo B mice, as evidenced by increased time spent in the center of an open field, reduced stretch attend postures in the elevated plus maze, and decreased reluctance to approach a novel mouse during the social interaction test. The behaviors occurred early in the disease, before hearing and vision loss are expected. Work by others showed that behavioral abnormalities in Sanfilippo children with the phenotypically-similar type A include reduced fearfulness. Additionally, reduced acetylcholinesterase activity was detected in the brain of Sanfilippo B mice, a deficiency also found in adult-onset dementias.

The experiment was supported by a core voucher award to Dr. Patricia Dickson. The results suggest that male Sanfilippo B mice display neurobehavioral deficits at a relatively early age, and that as in adult dementias, they may display deficits in cholinergic pathways. Preliminary data from this study was used to support a successful application for a $1.57-million R01 award from NIH.

Reference

• Kan S, Le SQ, Bui QD, et al. Behavioral deficits and cholinergic pathway abnormalities in male Sanfilippo B mice. Behavioral Brain Research. 2016;312:265-271. doi:10.1016/j.bbr.2016.06.023

A novel approach for creating functional muscle cells in the laboratory from stem cells

Duchenne muscular dystrophy is a progressive muscle-wasting disease, caused by an absence of dystrophin, a protein that helps keep muscle cells intact. The first symptoms are usually seen between 3 and 5 years of age and worsen over time. 

In their search for a cell therapy, scientists have tried to direct human pluripotent stem cells to generate skeletal muscle stem cells that function appropriately and regenerate mature dystrophin-producing muscle fibers. But these efforts have failed because they produced only immature cells.

By analyzing human development, however, CTSI-supported researchers found a fetal skeletal muscle cell that is extraordinarily regenerative. They further discovered that the cell matured only when a signaling pathway called TGF beta was turned off.

Working in a mouse model of Duchenne, researchers took cells from mice and reprogrammed them to become pluripotent stem cells. The researchers then removed the genetic mutation that causes Duchenne using the gene editing technology. Skeletal muscle cells were isolated and then injected into mice at the same time a TGF beta inhibitor was administered. 

The study was the first to demonstrate that functional muscle cells can be created in a laboratory and restore dystrophin in animal models of Duchenne (depicted in accompanying image). The research was supported by a Team Science Award to PI Dr. April Pyle from the CTSI and the Center for Duchenne Muscular Dystrophy at UCLA.

Reference

• Hicks MR, Hiserodt J, Paras K, et al. ERBB3 and NGFR mark a distinct skeletal muscle progenitor cell in human development and hPSCs. Nature Cell Biology. 20, 46-57 (2018) doi:10.1038/s41556-017-0010-2