Discoveries & Impact (November 2022)

Discoveries & Impact highlights select scientific discoveries per section across the Department of Internal Medicine...

Adults Who Sleep < 6 Hrs/Night Face Higher Financial Burden & Health Risks

People who regularly sleep less than six hours each night had worse cardiovascular health and higher health expenditures, a new study has found.

The cross-sectional study, published November 10, 2022 in the journal Sleep Health, analyzed a group of nearly 9,000 employees from Baptist Health South Florida, one of the largest employers in South Florida. The majority of participants were Hispanic with the average age of 43 years.

Scientists led by Ehimen Aneni, MD, MPH, used data from a 2014 voluntary Health Risk Assessment. Overall, employees with six or more hours of sleep had better diet, physical activity, body mass index and blood pressure when compared to those who slept less than six hours. These individuals were 2-3 times more likely to achieve optimal cardiovascular health. Better sleep was also associated with lower total health expenditures, less emergency room visits, and hospitalizations compared with those who slept less than six hours.

The study was funded by grant KL2 TR001862 from the National Center for Advancing Translational Science at the National Institutes of Health.

Ehimen C. Aneni, Chukwuemeka U. Osondu, Jeffrin Joseph, Guljana Saeed, Javier Valero-Elizondo, Emir Veledar, Khurram Nasir. Habitual sleep duration and its relationship with cardiovascular health, healthcare costs, and resource utilization in a working population. Sleep Health. 2022.

Repurposing Digoxin May Be Possible for Non-Cardiac Uses

The FDA has approved digoxin to treat patients with heart failure and arrhythmia, but in the new publication from Trends in Pharmacological Sciences, researchers looked at repurposing the medication for other non-cardiac diseases.

Physicians and researchers from Yale School of Medicine, Griffin Hospital, and the VA Connecticut Healthcare System evaluated this low-cost medication for treatment of nonalcoholic fatty liver disease (NAFLD), alcohol associated liver disease (ALD), obesity, autoimmune and inflammatory diseases, cancer, and viral infections.

The authors urge further research into the drug’s characteristics to evaluate dosing and eliminate possible toxicity. Learn more in “Digoxin as an emerging therapy in non-cardiac diseases.”

Farzaneh Dashti, Fatima Jamshed, Xinshou Ouyang, Wajahat Z. Mehal, Bubu A. Banini. Digoxin as an emerging therapy in noncardiac diseases. Trends in Pharmacological Sciences. 2022.

Restrict Inflammatory Cytokines to Prevent CPI-DM

The use of checkpoint inhibitors (CPIs) in cancer care has transformed treatment, but these medications may cause some patients to develop diabetes. While this is a rare complication, the affected patients present acutely and at times, the condition is life-threatening.

In this report, researchers from across Yale School of Medicine, Columbia University Irving Medical Center, Virginia Commonwealth University School of Medicine, University of California, San Francisco, University of Utah Health Sciences Center and University of Utah School of Medicine found evidence of pancreatic inflammation, including reduction in pancreatic volume, in patients who received CPIs. They performed pre-clinical studies utilizing a mouse model and characterized changes in immune cells and pancreatic β cells leading to checkpoint inhibitor-induced diabetes. They showed that blocking inflammatory mediators in the mouse model resulted in prevention of diabetes caused by CPIs.

To learn more about their methods and analysis, read “Immune cells and their inflammatory mediators modify β cells and cause checkpoint inhibitor-induced diabetes” in JCI Insight.

Perdigoto AL, Deng S, Du KC, Kuchroo M, Burkhardt DB, Tong A, Israel G, Robert ME, Weisberg SP, Kirkiles-Smith N, Stamatouli AM, Kluger HM, Quandt Z, Young A, Yang ML, Mamula MJ, Pober JS, Anderson MS, Krishnaswamy S, Herold KC. Immune cells and their inflammatory mediators modify β cells and cause checkpoint inhibitor-induced diabetes. JCI Insight 2022, 7(17) doi: 10.1172/jci.insight.156330. PMID: 35925682.

Clinical Tools for Identifying and Treating Unhealthy Alcohol Use

Unhealthy alcohol use refers to the consumption of alcohol at a level that has caused or may cause adverse physical, psychological, or social consequences. In a recent article published in the Annals of Internal Medicine, Yale physicians review the latest evidence for the best methods of prevention, screening, diagnosis, and treatment of unhealthy alcohol use.

Although associated with clear harms, alcohol consumption is common among adults in the U.S. Healthcare professionals should aim to inform adults—and the public—on the potential harms of alcohol consumption. Special attention should be directed toward alcohol use in populations who may have greatest risk of harm, such as young adults, older adults, women, persons with marginalized identities, and individuals with certain medical conditions or taking certain medications (e.g. prescription opioids).

In addition, patients often go without the proper screening and subsequent care for unhealthy alcohol use. It is recommended that standardized approaches with validated instruments are incorporated into practice settings and that screening in all patients for unhealthy alcohol use is made routine.

Patients who have a negative screening result should be guided towards lower-risk alcohol use or abstinence. Those with a positive screening for unhealthy alcohol use require further assessment to determine their level of risk, from at-risk alcohol use to alcohol use disorders, in order to guide the next treatment steps. It is important to utilize the range of different treatment options, including brief interventions, psychosocial modalities, and medications.

To read the full article, go to Annals of Internal Medicine.

Donroe JH, Edelman EJ. Alcohol Use. Ann Intern Med 2022;10:ITC145-1TC160.

New Findings on Telehealth Inpatient Palliative Care During Peak COVID-19 Pandemic

Before COVID-19, inpatient palliative care services were largely delivered in person. During the pandemic, demand for inpatient palliative care surged at the same time the pandemic ushered in a new era of telehealth. In the face of mounting restrictions on in-person encounters, the result was a rapid and widespread rise in the use of telehealth-delivered palliative care (TPC) services in the inpatient setting.

A team of Yale researchers sought to characterize the quality of TPC during the first 4-month peak of the pandemic, comparing it to care delivered during two other time periods: in-person palliative care two months prior to COVID-19 and during a post-peak, 2-month period when the majority of inpatient palliative care returned to in-person delivery.

The researchers found that palliative care consultations during peak COVID-19 occurred more frequently for discussions of goals of care or for referrals to hospice when compared to pre-COVID-19 consultations. Across all three time periods, the researchers found no differences in key quality metrics including the assessment of patients’ social needs, family burden, or goals of care. Despite major challenges in the early COVID-19 era, TPC served as a way to provide high-quality inpatient palliative care during this time.

Learn more in “Quality of Telehealth-Delivered Inpatient Palliative Care During the Early COVID-19 Pandemic.”

Ann A. Soliman, Kathleen M. Akgün, Jane Coffee, Jennifer Kapo, Laura J. Morrison, Elizabeth Hopkinson, Dena Schulman-Green, Shelli L. Feder. Quality of Telehealth-Delivered Inpatient Palliative Care During the Early COVID-19 Pandemic. Journal of Pain and Symptom Management. 2022.

Peripheral Blood Flow Involvement Correlates with Bone Marrow Involvement in PTCL

Peripheral T-cell Lymphoma (PTCL) is a rare, aggressive form of non-Hodgkin’s lymphoma that often stops responding to treatment. PTCL is categorized by their molecular features. Due to the diversity of PTCL, there is limited data available for treatments and disease course.

Clinicians at Yale School of Medicine and University of Miami School of Medicine performed a retrospective study using Epic records of flow cytometry lab results from Yale New Haven Hospital. Of the patient population looked at, 102 patients had flow cytometry available at diagnosis. They found that 27% of patients had peripheral blood involvement by flow cytometry, which correlated to bone marrow involvement.

To learn more about patient demographic information such as race, age, disease diagnosis, stage, first line treatment, and more, read “Peripheral Blood Involvement at Staging in Patients With Aggressive Peripheral T-Cell Lymphoma.”

Avery J, Chandhok N, Rainey C, Torres R, Huntington S, Isufi I, Seropian S, Xu ML, Foss F. Peripheral Blood Involvement at Staging in Patients With Aggressive Peripheral T-Cell Lymphoma. Clinical Lymphoma, Myeloma & Leukemia 2022, 22(9): 680-689. doi: 10.1016/j.clml.2022.04.019. PMID: 35568635.

Amidst War in Ukraine, Yale Experts Collaborate with Ukrainian Stakeholders to Ensure HIV Prevention

Opioid agonist therapies (OAT) with methadone or buprenorphine are the most effective treatment for opioid use disorder and are especially effective in preventing HIV amidst Ukraine's intertwined opioid and HIV epidemics. A recent article published in The Lancet Psychiatry traces how experts are collaborating to provide OAT during war.

Experts have adapted the Network for the Improvement of Addiction Treatment (NIATx) model for the Ukrainian context since 2014. With regional addiction treatment experts in Ukraine, the NIATx model has been used to overcome barriers to OAT scale-up and solve real-time problems with policy changes, the COVID-19 pandemic, and now during war.

Ukraine’s Public Health Center has been responsible for ensuring adequate supply of OAT. Meanwhile, OAT scale-up has been guided by non-governmental organizations like the Alliance for Public Health in collaboration with Yale University, using NIATx weekly coaching to respond to sudden changes during the war. Experts have successfully addressed medication shortages, heightened security concerns in conflict regions, and barriers to enrolling new patients whose risk increased due to the stressors of war.

Despite an initial reduction in OAT patients, Ukraine rallied through NIATx to create collaborations between governmental and non-governmental OAT clinics, provide same-day access to treatment, and expand take-home dosing. Innovative practices emerged to respond to conflict and internally displaced persons, paving the way for sites throughout the country to adopt these effective strategies. Learn more in “Collaborative learning and response to opioid misuse and HIV prevention in Ukraine during war.”

Altice FL, Bromberg DJ, Klepikov A, Barzilay EJ, Islam Z, Dvoriak S, Farnum SO, Madden LM. Collaborative learning and response to opioid misuse and HIV prevention in Ukraine during war. The Lancet Psychiatry 2022;11:852-854.

Adolescent and Young Adult Cancer Patients Are Living Longer; Physicians Want to Help Them Cope

The number of adolescent and young adult cancer survivors is increasing as more treatments become available, leading physicians to strive to better understand their concerns. Researchers from three academic institutions including Yale School of Medicine conducted a study that reviewed postings from the American Cancer Society Cancer Survivors Network, an online, publicly available forum.

The posts from adolescent and young adult cancer survivors, their family and friends in the "Young Cancer Survivors" discussion board from January 2010 to October 2020 were systematically assessed using a previously published cancer survivorship care framework. The researchers found that psychosocial issues were a top concern for adolescent and young adult cancer survivors, their family and friends. Read more in Journal of Cancer Survivorship.

Smith A, Fogarasi M, Lustberg MB, Nekhlyudov L. Perspectives of adolescent and young adult cancer survivors: review of community-based discussion boards. Journal Of Cancer Survivorship : Research And Practice 2022, 16(5): 1079-1089. doi: 10.1007/s11764-021-01098-4. PMID: 34471949.

Is Taking Blood Pressure Medication at Bedtime More Effective Than Morning Dosing?

Antihypertensive drug therapy is one of the most efficient medical interventions for preventing disability and death globally. Most of the evidence supporting its benefits has been derived from outcome trials with morning dosing of medications. Accumulating evidence suggests an adverse prognosis associated with night-time hypertension, non-dipping blood pressure (BP) profile and morning BP surge, with increased incidence of cardiovascular events during the first few morning hours.

“These observations provide justification for complete 24-hour BP control as being the primary goal of antihypertensive treatment,” authors of a consensus document report in the Journal of Hypertension. A position paper by the International Society of Hypertension reviewed the published evidence to provide consensus recommendations for clinical practice. Read the paper in the Journal of Hypertension.

Stergiou, George; Brunström, Mattias; MacDonald, Thomas; Kyriakoulis, Konstantinos G.; Bursztyn, Michael; Khan, Nadia; Bakris, George; Kollias, Anastasios; Menti, Ariadni; Muntner, Paul; Orias, Marcelo; Poulter, Neil; Shimbo, Daichi; Williams, Bryan; Adeoye, Abiodun Moshood; Damasceno, Albertino; Korostovtseva, Lyudmila; Li, Yan; Muxfeldt, Elizabeth; Zhang, Yuqing; Mancia, Giuseppe; Kreutz, Reinhold; Tomaszewski, Maciejt. Bedtime dosing of antihypertensive medications: systematic review and consensus statement: International Society of Hypertension position paper endorsed by World Hypertension League and European Society of Hypertension. Journal of Hypertension: October 2022 - Volume 40 - Issue 10 - p 1847-1858 doi: 10.1097/HJH.0000000000003240

Minority Children Disproportionately Affected by Food Allergies

Yale researchers reviewed current literature regarding health disparities in in the prevalence, diagnosis, and management of pediatric food allergy and discuss possible interventions in a review article in Annals of Allergy, Asthma & Immunology. Their sources included PubMed and Google Scholar.

Their review revealed that an overall prevalence of food allergy appears to be increasing, and disproportionately affecting minority groups. “Racial and socioeconomic disparities are evident across all aspects of food allergy care: diagnosis, prevention, acute management,” such as access to epinephrine autoinjectors, visits to emergency department, and long-term management through oral immunotherapy,” the authors wrote. https://pubmed.ncbi.nlm.nih.gov/35476967/

Tepler E, Wong KH, Soffer GK. Health disparities in pediatric food allergy. Annals Of Allergy, Asthma & Immunology : Official Publication Of The American College Of Allergy, Asthma, & Immunology 2022, 129(4): 417-423. doi: 10.1016/j.anai.2022.04.022. PMID: 35476967.