Check out “What’s New in Research” to find out about discoveries and advancements from Brigham researchers. This month, we feature new research from Brigham researchers on fall prevention cost savings, pulmonary arterial hypertension, rare cells that play a role in multiple sclerosis and more.  

Evidence-Based Fall Prevention Program Reduced Both Harm and Costs

Despite the large number of patient falls at hospitals, there are few large-scale studies to quantify the cost savings of intervention programs. The Fall TIPS (Tailoring Interventions for Patient Safety) Program is an evidence-based fall prevention effort implemented in 33 medical and surgical units across 8 hospitals. Investigators at the Brigham used electronic health record data from a large cohort of 900,635 patients to determine the average total cost of a fall. Using 7,858 non-injurious falls and 2,317 injurious ones they calculated that a fall costs $62,521 (with $35,365 in direct costs) and that injury was not a significant predictor of increased costs. Given that falls are expensive in terms of both human suffering and healthcare costs, the authors then conducted an economic analysis of Fall TIPS. The program was implemented for all adults hospitalized from 2013 to 2019 in healthcare systems in New York and Boston. They found that the intervention program was associated with $22 million in savings at eight study sites across the five-year study period.

“Through a series of clinical trials, the Fall TIPS program has demonstrated reductions in falls and fall-related injuries, and this study indicates that the Fall TIPS program is also cost effective,” said corresponding author Patricia C. Dykes, PhD, RN, FAAN, FACMI, from the Brigham’s Center for Patient Safety, Research, and Practice in the Department of General Internal Medicine. “Our findings suggest that policies which incentivize organizations to implement evidence-based strategies which reduce the incidence of all falls may be effective in reducing both harm and costs.”

Read more in JAMA Health Forum.

Investigators Capture a “Molecular Snapshot” to Illuminate the Origins of Pulmonary Arterial Hypertension

Bradley Maron

Bradley Wertheim

Pulmonary arterial hypertension (PAH) is a rare and incurable disease of the lung arteries that causes early death. In PAH, excess scar tissue and thickening of lung blood vessels occur as the result of increased cell “biomass.” These changes obstruct blood flow and are detrimental to the heart, but until now the basic features of biomass in PAH were not known. A team led by investigators at Brigham and Women’s Hospital (BWH), a founding member of the Mass General Brigham healthcare system, in collaboration with Matthew Steinhauser, MD, a metabolism and cell imaging expert at the University of Pittsburg, and investigators at the University of Vienna, set out to better understand the origins of arterial biomass in PAH. Using an animal model of PAH, the team applied network medicine and advanced molecular imaging tools to identify chemical building blocks that are taken up by arterial cells and ultimately contribute to blood vessel obstruction. Using multi-isotope imaging mass spectrometry (MIMS) under the guidance of Steinhauser and Christelle Guillermier, PhD, at BWH, the researchers could pinpoint the location and abundance of key contributors to biomass, including the amino acid proline and the sugar molecule glucose. Using MIMS, the team visualized proline and glucose tracers injected into the bloodstream of an animal model of PAH. They saw that the molecules were used by arterial cells of the lung to build excess scar tissue (including the protein collagen), which contributed to blood vessel obstruction.

“Our study describes the world’s first use of multi-isotope imaging mass spectrometry (MIMS) in the study of lung disease,” said Bradley Wertheim, MD, of the Brigham’s Division of Pulmonary and Critical Medicine. “MIMS is a powerful microscopy tool that produces a ‘molecular snapshot’ that can provide information down to the resolution of a single cell.”

“These findings suggest that the uptake and metabolism of protein precursors may be fundamental to PAH biology.  Closer investigation of proline and glucose in human PAH may uncover opportunities to inhibit biomass formation, prevent obstruction of lung arteries, and decrease the chance of heart failure for PAH patients,” said co-senior author Bradley Maron, MD, of the Brigham’s Division of Cardiovascular Medicine.

Read more in JCI Insight.

Researchers Develop a Tool to Investigate Rare, Previously Inaccessible Cells that Play a Key Role in Multiple Sclerosis

Francisco Quintana

Rare cell types can have an undue influence on human health. Previous research has suggested that a subset of astrocytes—star-shaped cells in the brain and spinal cord—may be responsible for multiple sclerosis (MS), a disease in which the immune system attacks the covering that protects nerves. But finding these rare cells is no easy task—to pinpoint them, investigators need to identify unique surface markers that can distinguish these culprit cells from others. Single-cell RNA sequencing can help find them, even in the absence of distinguishing surface marker, but this technique can become extremely expensive. To address this problem, a team led by investigators from the Brigham developed FIND-seq, which combines nucleic acid cytometry, microfluidics, and droplet sorting to isolate and analyze rare cells of interest based on the expression of mRNA biomarkers detected by digital droplet PCR. Using this method, the team analyzed in great detail a population of astrocytes that drives central nervous system inflammation and neurodegeneration. When used in combination with other tools, FIND-seq identified signaling pathways controlled by the mineralocorticoid receptor NR3C2 and the nuclear receptor corepressor 2 that play important roles in the development of pathogenic astrocytes in mice and humans. In another study, researchers used FIND-seq to identify mechanisms used by HIV to “hide” in immune cells in patients treated with anti-retroviral therapies.

“These findings identify novel targets for therapeutic intervention in neurologic diseases such as MS,” said corresponding author Francisco Quintana, PhD, of the BWH Department of Neurology. The team is working to develop novel small molecules which could be used to target this pathway therapeutically.

Read more about FIND-Seq in a paper in Nature and about its application for the study of HIV in a companion paper published in the same issue.