What’s New in Research: April 2022
Medication Abortion Pills Safe for Early Use in Patients Even if Ectopic Pregnancy Has Not Been Ruled Out
The medication combination of mifepristone and misoprostol, referred to as “abortion pills,” is highly effective for early abortion and early pregnancy loss. Typically, when patients have not yet had an intrauterine pregnancy confirmed by ultrasonogram, they are followed with serial blood tests (hCG) and a repeat ultrasonogram to ‘rule out’ ectopic pregnancy — a life threatening condition in which a fertilized egg has implanted outside the uterus and will not be viable. In a retrospective cohort study, researchers from the Brigham and Planned Parenthood compared the safety and efficacy of immediately starting the medication combination after a person has a positive pregnancy test versus waiting to initiate treatment until a diagnosis of ectopic pregnancy has been ruled out. The researchers found that administering the pills as early as possible could be done safely and could also help the patient determine if their pregnancy was an ectopic pregnancy or not faster than if they had waited for an ultrasonogram. Researchers found no evidence of an increase in the rates of serious adverse events, emergency department visits, or nonadherence with follow-up. However, the team did see a higher failure rate for the pills when given early, meaning that patients with an undesired pregnancy who are treated early may need to re-initiate a medical abortion.
“This study should encourage clinicians to shift clinical practice to meet the demand of patients and facilitate an approach of ‘the sooner, the better,’ which is what many patients want,” said corresponding author Alisa Goldberg, MD, MPH, of the Department of Obstetrics and Gynecology. “Our data suggest that there is no reason to mandate that patients with pregnancies of unknown location delay initiating abortion to first obtain a definitive diagnosis. In contrast, there is diagnostic and therapeutic benefit to administering abortion medications to patients with undesired pregnancy of unknown location.”
Read more in Obstetrics & Gynecology.
Researchers Identify Reliable Measures of Racial Inequities in Quality of Oncology Care
Researchers from the Brigham who studied care provided to more than one million Medicare beneficiaries being treated with chemotherapy for cancer found that on average and in most practices, Black patients had higher rates of chemotherapy-related emergency department (ED) visits and hospitalizations than white patients, suggesting that quality of oncology care may be worse for Black patients. Using data from more than 4,800 medical oncology practices across the U.S., the researchers tested whether they could reliably assess differences across oncology practices to better inform practice profiling or payment. They found that they could estimate reliable differences in ED visits and hospitalizations for Black versus white patients who received care at about 10 percent of practices, but these practices treated more than half of patients with cancer, and about two-thirds of all Black patients with cancer. The authors describe these measures as having potential for identifying higher- and lower-equity practices.
“There is robust literature that Black patients are more likely than white patients to be treated in emergency departments and to be hospitalized. At least some of these differences are related to structural racism and social determinants of health, including poverty, insufficient housing, and low-wage jobs without paid time off during daytime hours for office visits,” said author Nancy Keating, MD, of the Division of General Medicine and Primary Care. “We found that there was substantial variability in Black-white differences across practices, suggesting that care in some practices is more equitable, at least on these measures, than in others. In future work, we hope to provide feedback to practices on their performance in hopes of improving both quality and equity concurrently.”
Read more in Health Affairs.
Epigenetic Study Provides New Insights into the Origins of Glioma
MicroRNA-10b (miR-10b) is a regulatory molecule that is silenced in normal cells of the brain but becomes abundant in more than 90 percent of high-grade gliomas. Glioblastomas (GBM) — the highest grade of glioma — appear to be addicted to this microRNA: without it, cancer cells die. In a new study, Brigham investigators examined derepression of miR-10b to uncover the mechanism by which the microRNA gets turned back on in GBM. The researchers found that miR-10b as well as several HOXD genes were commonly activated in gliomas, despite a lack of locus amplification or common mutations. The team performed a detailed epigenetic analysis of normal and cancer cells and tissues and found a new mechanism that involves topologic reorganization of chromatin and implicates two long-non-coding RNAs. One of these molecules, an enhancer RNA, was sufficient to turn miR-10b and multiple HOXD genes back on to promote cancer growth; inactivating the molecule in glioma cells reduced glioma viability.
“Our work provides new insights into the question of glioma origin,” said corresponding author Anna Krichevsky, PhD, of the Department of Neurology. “Our study identifies a new regulatory layer that may drive the genesis of high-grade gliomas, implies the unique vulnerability of tumor-initiating cells and points to new RNA- targeted strategies for glioma therapy.”
Read more in Molecular Cell.
Unexpected Melatonin Increase During Daytime Sleep May Provide Novel Insight into Circadian Rhythm Disorders Among Shift Workers
Melatonin, a hormone known to regulate the sleep-wake cycle and a critical biomarker in clinical sleep research, is commonly thought to rise at night and fall during the circadian day and may provide novel insights into sleep disorders seen in shift workers. Light at night is known to acutely suppress melatonin secretion; however, darkness is not known to increase the levels of circulating melatonin. Although a modest increase in melatonin levels has been observed sporadically during daytime sleep in a few prior studies in healthy participants, the findings have received little attention. To further investigate if there is an unknown mechanism underlying the regulation of melatonin secretion, researchers at the Brigham conducted a highly controlled simulated night shift protocol with 12-hour inverted behavioral/environmental cycles in 14 healthy participants. Researchers discovered a reproducible secondary melatonin peak during daytime sleep episodes in the circadian day following overnight shifts. The authors note that the findings challenge the current understanding of melatonin secretion, specifically the physiological mechanisms controlling the process. They also found that this daytime melatonin rise correlated with an increase in the 24-h circulating glucose and insulin concentrations. Furthermore, the authors acknowledge that additional research is needed to clarify the drivers of the unexpected daytime melatonin secretion.
“We were certainly surprised to observe an increase in melatonin during daytime sleep that was positively associated with the change in glucose and insulin levels and hypothesize that the suprachiasmatic nucleus neuronal network or a direct effect of sleep may explain this unanticipated phenomenon,” said lead author Jingyi Qian, PhD, of the Division of Sleep and Circadian Disorders. “We are eager to continue investigating the underlying mechanisms of this process to provide novel insights to the medical community on the organization of the human circadian system, circadian rhythm disorders and the consequences for these changes in melatonin regulation for glucose control and increased diabetes risk commonly seen in shift workers,” said senior author Frank A.J.L. Scheer, PhD, Director of the Medical Chronobiology Program at the Brigham and Women’s Hospital.
Read more in the Journal of Pineal Research.
Circadian Misalignment Can Alter Oral Microbiota
Circadian misalignment refers to the misalignment between the central circadian “clock” and daily behavioral and environmental cycles, such as sleep/wake, fasting/eating, and dark/light cycles. This has been shown to have negative effects on cardiovascular and metabolic health. A randomized clinical trial from Brigham’s Division of Sleep and Circadian Disorders included six healthy participants (two women) between the ages of 18-35 with no prior sleep issues. The study included a 14-day highly controlled circadian laboratory protocol that included a baseline (pre-circadian misalignment) constant routine protocol (i.e., constant wakefulness, body posture, and dim light conditions; hourly identical snacks; no time cues), then four “days” under circadian misalignment and lastly a second constant routine protocol to assess the after-effects of circadian misalignment on endogenous circadian rhythms. During both constant routines, microbiota assessments were performed on saliva samples collected every four hours. The researchers found circadian misalignment significantly altered the oral microbiota landscape and altered specific functional pathways associated with metabolic control and immunity.
“Contemporary lifestyle leads to a myriad of behaviors and environments that are at odds with our internal circadian rhythms. This misalignment is often experienced by shift workers and frequent flyers,” said Sarah Chellappa, MD, PhD, and Frank A.J.L. Scheer, PhD, of the Brigham’s Division of Sleep and Circadian Disorders. “In the long-term, frequent exposure to circadian misalignment might result in a microbiota-driven heightened proinflammatory state with ramifications for health and disease.”
Read more in The FASEB Journal.
Across Specialties, Female Physicians Spend More Time on Electronic Health Records than Men
A new retrospective study from the Brigham’s Department of Medicine analyzed how the time spent working on Electronic Health Records (EHR) differs between male and female physicians in ambulatory services. While previous studies have analyzed gender-based EHR differences among primary care physicians (PCPs), this analysis of 318 physicians included about 54 percent PCPs, with the rest being medical and surgical specialists. The results show that, on average, female physicians spent 5.81 hours per day on the EHR compared to male physicians, who spend an average of 5.23 hours per day on the EHR. Both male and female physicians were found to put in EHR time outside of work; however, female physicians were spending 0.91 hours on the EHR outside of work, compared to 0.75 EHR hours from their male counterparts. Lastly, female physicians spent an average of 2.03 hours on clinical documentation, whereas male physicians spent an average 1.67 hours.
“These differences persisted after accounting for hours worked, physician specialty, and other characteristics, despite female physicians caring for slightly fewer patients on average,” said Lisa Rotenstein, MD, MBA, of the Brigham’s Department of Medicine. “Our findings provide a potential mechanism for the gender gap in burnout, which has implications for workforce mental health and physician retention. They suggest that women physicians may benefit from policy changes, workflows, and technologies that reduce documentation burden, including scribes, team documentation and artificial intelligence-powered solutions.”
Read more in JAMA Network Open.
Manometry Device Inspired by Quipu Provides Cost-Effective Method for GI Diagnosis
In the United States, $130 billion is spent every year on gastrointestinal (GI) disorders, with over 50 million outpatient clinic visits for GI problems. Manometry measurements, used to diagnose GI motility disorders, require instrumentation which are costly, bulky and require maintenance. Researchers from the Brigham’s Division of Gastroenterology, in collaboration with engineers from the Massachusetts Institute of Technology, have developed a new device to diagnose these disorders which follows the design of a quipu, an ancient Inca device used to store and convey information. The key design element to quipu is its colorful threads tied in intricate knots. This new device keeps this composition, using knotted piezoresistive pressure sensors to achieve performance similar to traditional GI manometry devices. Through experimentation, the researchers were able to find knotting configurations to optimize the collection of sensory information. Furthermore, the novel tool, which resembles a catheter, is both low cost and easy to manufacture.
“The quipu-inspired liquid metal-enabled pressure transducer, or QUILT, provides significant sensitivity through the incorporation of knots which also provide spatial location of the pressure source which can be critical in the diagnosis of dysmotility,” said Carlo Giovanni Traverso, MD, PhD, of the Brigham’s Division of Gastroenterology. “This easy-to-assemble, low-cost, and disposable catheter could address manometry challenges and allow expanded use in regions with limited medical resources.”
Read more in Nature Biomedical Engineering.