During the COVID-19 pandemic, Johns Hopkins Medicine Media Relations is focused on disseminating current, accurate and useful information to the public via the media. As part of that effort, we are distributing our “COVID-19 Tip Sheet: Story Ideas from Johns Hopkins” every other Tuesday.
We also want you to continue having access to the latest Johns Hopkins Medicine research achievements and clinical advances, so we are issuing a second tip sheet covering topics not related to COVID-19 or the SARS-CoV-2 virus. “Research News Tip Sheet: Story Ideas from Johns Hopkins Medicine” alternates Tuesdays with the COVID-19 Tip Sheet.
Stories in this tip sheet associated with journal publications provide a link to the paper. Interviews with the researchers featured may be arranged by contacting the media representatives listed.
STUDY SAYS BLOOD PRESSURE READINGS ACCURATE WITH LESS THAN THREE MINUTES REST
Physicians, nurses and other health care providers traditionally been taught to let patients rest three to five minutes between blood pressure measurements. Now, researchers at Johns Hopkins Medicine have shown that this established time span may not be as medically necessary as previously believed and that shorter rest periods are just as accurate if the patient’s blood pressure reading is not elevated (greater than or equal to a systolic over diastolic reading of 140/90).
The findings were presented virtually on Sept. 10, 2020, during the American Heart Association’s Hypertension 2020 Scientific Sessions, and appear in the October 2020 issue of the journal Hypertension.
“Reducing the rest period prior to taking readings to less than three minutes could enable more patients to be screened in a shorter timeframe, which could be beneficial to medical facilities in high demand or that are understaffed because of economic reasons,” says study lead researcher Tammy Brady, M.D., Ph.D., medical director of the pediatric hypertension program at Johns Hopkins’s Children’s Center and an associate professor of pediatrics at the Johns Hopkins University School of Medicine.
In a simulated clinical setting, the Johns Hopkins Medicine team studied 113 adults ages 18 to 80 — with both normal and high blood pressure — who each received four sets of three blood pressure measurements after different rest times: zero, two and five minutes. To estimate the repeatability of these readings, the blood pressure of each participant was recorded once more at five minutes after the last measurement.
The researchers then compared the difference in average blood pressure measured after the first and second five-minute rest periods with the difference in the readings following the first five-minute rest period and the two-minute one. They also compared the difference between the measurements after the first five-minute rest period and the zero rest time.
“We were expecting to see significant differences in these average blood pressure and overall readings,” says Brady. “Instead, we discovered only marginal changes — overall, no more than a plus or minus two-point difference between the systolic blood pressures obtained after five-minute resting periods and the readings taken with rest periods of less than a minute and two minutes.”
Based on their findings, the researchers believe that a reasonable approach is measuring blood pressure after minimal to no rest, and then repeating the measurement after a five-minute rest only if the patient has an initial systolic reading of greater than or equal to 140.
DEFINITION OF PAIN UPDATED FOR FIRST TIME IN FOUR DECADES TO MAKE IT MORE INCLUSIVE
Johns Hopkins Medicine pain experts have joined the International Association for the Study of Pain (IASP) and collaborators worldwide to make a subtle but important update to the definition of “pain” for the first time in 40 years. With this change, the experts aim to make pain diagnosis and management more inclusive of all people who experience it.
“Pain is not just a sensation or symptom. It is a much more complex condition that is important to acknowledge properly to guide basic science research, patient care and public policy,” says Srinivasa Raja, M.B.B.S., professor of anesthesiology and critical care medicine at the Johns Hopkins University School of Medicine and chair of the IASP task force that created the revised description.
According to the researchers, the new pain definition — the first update since 1979 — features a key phrase (shown in boldface): “An unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage.”
The phrase is important, say the researchers, because it includes types of pain not well understood 40 years ago, such as nociplastic — where pain receptors are stimulated without evidence of the cause, such as with fibromyalgia — and neuropathic pain caused by a sensitized or maladaptive nervous system, commonly associated with chronic pain conditions such as persistent pains after surgery, nerve injuries and limb amputations (commonly called “phantom limb pain”).
The revised definition also is more inclusive of people who cannot express their pain in words. According to Raja, the previous definition used the word “described,” which excludes non-verbal behaviors to indicate pain in animals and certain vulnerable individuals.
“Changing this language enables physicians to adequately account for pain in disempowered and neglected populations such as children, the elderly and people with disabilities,” he says.
The updated definition can ultimately have an impact on access to health care, if adopted by insurance providers. A 2016 survey by the U.S. Centers for Disease Control and Prevention estimates that 20.4% of U.S. adults live with chronic pain and approximately 20 million reported that pain limits the ability to accomplish tasks in their work and daily life.
“When pain affects peoples’ function, psyche and their social well-being, it needs to be recognized by insurance carriers that dictate who gets care and what aspects of their multidisciplinary care are reimbursed,” says Raja.
Overall, the IASP task force says the revised definition has provided a starting point to integrate more evidence-based and holistic pain management into medical and mental health care.
“Pain cannot be simplified to a 0 to 10 scale. Assessments instead need to look at the whole person, accounting for the cognitive, psychological and social factors that are critical to treating pain,” says Raja.
SHORTER TREATMENT TIME NEEDED TO PREVENT HEPATITIS C IN KIDNEY TRANSPLANT RECIPIENTS
In a 2018 clinical trial, researchers at Johns Hopkins Medicine demonstrated that a 12-week prophylactic course of direct-acting antivirals (DAAs) — drugs that destroy the hepatitis C virus (HCV) by targeting specific steps in its life cycle — could keep HCV-negative patients virus free after they received kidneys from deceased donors who had HCV. In a new follow-up study, the researchers improved on their past success and showed that the same protection can be achieved in a third of the time without losing effectiveness or putting the recipient at greater risk of HCV infection.
According to statistics from the U.S. Department of Health and Human Services, nearly 100,000 Americans with kidney failure, also known as end-stage renal disease, are awaiting donor organs. Unfortunately, as reported by the U.S. Centers for Disease Control and Prevention, nearly 9,000 of these patients drop off the waiting list each year, succumbing to death or deteriorating in health so much that transplantation is no longer possible.
Making matters worse, says the National Institute of Diabetes and Digestive and Kidney Diseases, the need for donor kidneys is rising 8% per year. However, their availability has not grown to match.
“Kidneys from deceased donors with HCV are increasingly available, yet hundreds are discarded annually because they have traditionally only been given to the small number of recipients who also had the virus,” says study senior author Niraj Desai, M.D., surgical director of the Johns Hopkins kidney and pancreas transplant program, and assistant professor of surgery at the Johns Hopkins University School of Medicine. “Our previous trial showed it’s possible to make these donor organs acceptable for HCV-negative recipients, but the timing and duration of the DAA therapy wasn’t clear until now.”
In their clinical trial known as Renal Transplants in Hepatitis C Negative Recipients with RNA Positive Donors (REHANNA), Desai and his colleagues gave HCV-negative kidney transplant candidates a four-week course of two DAAs, glecaprevir and pibrentasvir. In the 2018 trial, 10 transplant candidates received two other DAAs, grazoprevir and elbasvir (with or without a third drug, sofosbuvir), to protect them against HCV from the donated kidneys. However, a 12-week course of treatment was needed.
Throughout most of the four-week therapy period in the new study — and more importantly, at the 12-week mark after the prophylactic treatment ended — all 10 patients were HCV free. They have all remained this way since receiving their deceased HCV-positive donor kidneys, along with showing no related adverse events such as organ rejection or liver problems.
“Although our study population was small, the trial does provide a strong proof-of-concept that transplantation of HCV-positive deceased donor kidneys to HCV-negative recipients can be successful with just four weeks of DAA prophylaxis,” says study lead author Christine Durand, M.D., associate professor of medicine at the Johns Hopkins University School of Medicine. “These results support adding kidneys with HCV into the overall donor pool to shorten the transplant waiting time for seriously ill patients who would not previously have had them as an option.”
MYSTERY MOLECULE UNMASKED: NEWLY IDENTIFIED PROTEIN SAVES THE AIRWAY FROM DISTRESS
In the respiratory system, when the airway becomes irritated by small particles, infections or other invaders, the body’s immune system is signaled to attack. Once the immune system is primed, it sends white blood cells called eosinophils and mast cells to the affected area to immediately begin to fight.
The weapons of choice for these immune cells are chemical compounds, such as histamine and cytokines, that cause the airway to become inflamed. Past research showed that eosinophils and mast cells possess a special type of protein on their surface, known as Siglec-8, which uniquely fits and locks onto a second, and previously unknown, glycoprotein. When this mysterious molecule and Siglec-8 are bonded, the inflammatory response dies down.
Johns Hopkins Medicine researchers, led by Ronald Schnaar, Ph.D., professor of pharmacology at the Johns Hopkins University School of Medicine, found the mystery glycoprotein using mass spectroscopy. Called DMBT1S8, the molecule is an isoform, or nearly identical twin, of a known protein, DMBT1, that is believed to play a role in defending the respiratory tract’s mucosal cells. DMBT1S8 remained hidden until now because of its close likeness to DMBT1.
Newly formed DMBT1 is processed in a pancake-like structure called a Golgi body within a human cell. The Golgi body, which acts as the cell’s postal system, delivers proteins and lipids to various locations. Like Clark Kent turning into Superman as it goes through the Golgi body, DMBT1 transforms into DMBT1S8 before leaving the submucosal gland to meet eosinophils and mast cells in the respiratory tract. There, the binding of DMBT1S8 to Siglec-8 halts inflammation and saves the airway from distress.
Based on their study results, the researchers suggest that targeting the newly identified molecule may one day lead to treatments for inflammatory respiratory conditions such as asthma.
STUDY TIES CHRONIC ITCH TO SLEEP LOSS AND POSSIBLE SIGNAL OF INCREASED HEART DISEASE RISK
Many people suffer from a skin disorder known as chronic pruritic dermatosis, commonly referred to as “chronic itch.” Recent research has suggested that chronic itch may be at the root of other related medical conditions, including sleep disturbances. Now, Johns Hopkins Medicine researchers have gone a step further, providing more evidence that the connection between chronic itch and sleep problems exists, and that these patients may be at greater risk for cardiac disease as indicated by elevated levels of a circulating protein sometimes used to predict heart problems.
Chronic itch has been associated in previous studies with multiple sleep disturbances, including repeated nighttime and early morning awakenings. The resulting loss of quality slumber may lead to fatigue, anxiety and even depression, all of which have lasting and negative overall health impacts.
In its investigation, the Johns Hopkins Medicine team studied 5,560 U.S. adults. Background data on the participants were obtained from the 2005–2006 edition of the National Health and Nutrition Examination Survey (NHANES), a federal database tracking the health and nutritional status of adults and children in the United States over long periods of time. NHANES findings are used to determine the prevalence of major diseases and risk factors for those illnesses.
Participants were surveyed for their current social and demographic status, as well as updates on their medical history and health behaviors. Physical exams were conducted and laboratory specimens, including blood and urine, were taken.
The study results confirmed the link between sleep disturbances and chronic itch, showing that pruritic dermatosis was associated with trouble falling asleep one to five times per month, waking during the night or too early in the morning, leg jerks and cramps while sleeping, and the impacts of fatigue (such as feeling overly sleepy during the day and having difficulty with memory).
The Johns Hopkins Medicine experts also found that these disturbances were more likely in those with elevated blood levels of C-reactive protein (CRP). Produced by the liver, CRP is sent into the bloodstream in response to inflammation. It has been used as a blood test to predict cardiovascular disease when other biomarkers, primarily low-density lipoprotein (LDL) cholesterol, are at normal levels.
“CRP levels were 52.8% higher among chronic pruritic dermatosis patients reporting trouble sleeping compared to those who did not,” says Shawn Kwatra, M.D., assistant professor of dermatology at the Johns Hopkins University School of Medicine. “This suggests that along with the reduction in quality of life brought on by chronic itch, these patients also may have heightened cardiometabolic risk.”
Kwatra adds “that while chronic pain is well recognized in the medical community, many patients with chronic itch quietly suffer because there are no approved therapies for the condition.”