Medical Bulletin 09/ October/ 2024

Among the 7.8 million women with breast cancer worldwide, at least 33% to 44% are affected by lymphatic pain. Breast cancer survivors usually suffer lymphatic pain in the ipsilateral body or upper limb, and pharmacological approaches are not effective for lymphatic pain.

In a recent publication in Women and Children Nursing, a group of researchers from the United States and Spain further deepened our understanding of this particular type of pain through evidence-based knowledge and insights into precision assessment and therapeutic behavioral intervention.

“Historically, the concept of cancer-related pain has been used to study chronic pain associated with cancer or cancer treatment. Cancer-related pain refers to persistent pain that continues more than three months after active cancer treatment,” says lead author, Jeanna Qiu, a MD-PhD student at Harvard Medical School. “Conventional research on chronic cancer pain focuses on occurrence and severity of general bodily pain in any body location. This approach has not been able to distinguish different types of pain after cancer treatment, such as lymphatic pain due to fluid accumulation and inflammation, general bodily pain, postmastectomy pain, chemotherapy-induced peripheral neuropathy, or arthralgias related to hormonal treatments.”

Hence, opportunities are missed when it comes to investigating the underlying physiological and psychosocial mechanisms of different types of pain and develop efficacious pain treatments.

To that end, the team provided evidence for the etiology of lymphatic pain, conducted objective and subjective assessment of lymphatic pain, and further offered evidence for the effective behavioral interventions to promote lymph flow and reduce inflammation for lymphatic pain.

According to co-first author Mei Fu, at Dorothy and Dale Thompson Missouri Endowed Professor in Nursing and Associate Dean for Research at University of Missouri-Kansas City School of Nursing and Health Studies, the study provided much needed knowledge regarding precision assessment that enables clinicians to distinguish different types of pain.

“Detailed evidence also underscored the effectiveness of behavioral interventions to promote lymph flow, such as The-Optimal-Lymph-Flow program,” says Fu. “The comprehensive knowledge and evidence in this study can be directly applied to clinical practice to reduce lymphatic pain in women treated for breast cancer to reduce lymphatic pain.”

Reference: Jeanna Mary Qiu, Mei Rosemary Fu, Catherine S. Finlayson, Charles P. Tilley, Rubén Martín Payo, Stephanie Korth, Howard L. Kremer, Cynthia L. Russell Lippincott, Lymphatic pain in breast cancer survivors: An overview of the current evidence and recommendations, Women and Children Nursing, Volume 2, Issue 2, 2024, Pages 33-38, ISSN 2949-7515, https://doi.org/10.1016/j.wcn.2024.04.001.

The current study employed a mathematical model of men’s and women’s metabolisms, showed that men’s metabolisms respond better on average to a meal laden with high carbohydrates like oats and grains after fasting for several hours, while women are better served by a meal with a higher percentage of fat, such as omelettes and avocados.

“Lifestyle is a big factor in our overall health,” said Stéphanie Abo, an Applied Mathematics PhD candidate and the lead author of the study. “We live busy lives, so it’s important to understand how seemingly inconsequential decisions, such as what to have for breakfast, can affect our health and energy levels. Whether attempting to lose weight, maintain weight, or just keep up your energy, understanding your diet’s impact on your metabolism is important.”

The study builds on an existing gap in research on sex differences in how men and women process fat. “We often have less research data on women’s bodies than on men’s bodies,” said Anita Layton, a professor of Applied Mathematics and Canada 150 Research Chair in Mathematical Biology and Medicine.

“By building mathematical models based on the data we do have, we can test lots of hypotheses quickly and tweak experiments in ways that would be impractical with human subjects.”

“Since women have more body fat on average than men, you would think that they would burn less fat for energy, but they don’t,” said Layton. “The results of the model suggest that women store more fat immediately after a meal but also burn more fat during a fast.”

Going forward, the researchers hope to build more complex versions of their metabolism models and extend beyond the consideration of biological sex by incorporating an individual’s weight, age, or stage in the menstrual cycle.

Reference: Stéphanie M.C. Abo, Anita T. Layton, Modeling sex-specific whole-body metabolic responses to feeding and fasting, Computers in Biology and Medicine, Volume 181, 2024, 109024, ISSN 0010-4825, https://doi.org/10.1016/j.compbiomed.2024.109024.

A study led by Johns Hopkins Medicine researchers concludes that commonly used ways of positioning the patient's arm during blood pressure (BP) screenings can substantially overestimate test results and may lead to a misdiagnosis of hypertension.

In a report on the study, published in JAMA Internal Medicine, investigators examined the effects of three different arm positions: an arm supported on a desk, arm supported on a lap, and an unsupported arm hanging at the patient's side. Researchers found that lap support overestimated systolic pressure (the top number in a BP reading) by nearly 4 mmHg, and an unsupported arm hanging at the side overestimated systolic pressure by nearly 7 mmHg.

The findings confirm that arm position makes a "huge difference" when it comes to an accurate blood pressure measurement, says Tammy Brady, M.D., Ph.D., vice chair for clinical research in the Department of Pediatrics at the Johns Hopkins University School of Medicine, medical director of the pediatric hypertension program at Johns Hopkins Children's Center, deputy director of the Welch Center for Prevention, Epidemiology, and Clinical Research and senior author of the study. And they underscore the importance of adhering to clinical guidelines calling for firm support on a desk or other surface when measuring blood pressure, the investigators add.

The latest clinical practice guidelines from the American Heart Association emphasize several key steps for an accurate measurement -- including appropriate cuff size, back support, feet flat on the floor with legs uncrossed, and an appropriate arm position, in which the middle of an adjustable BP cuff is positioned at mid-heart level on an arm supported on a desk or table.

Despite these recommendations, the researchers say BP is too often measured with patients seated on an exam table without any, or inadequate, arm support. In some cases, a clinician holds the arm, or the patient holds an arm in their lap. In the new Johns Hopkins study, the researchers recruited 133 adult participants (78% Black, 52% female) between Aug. 9, 2022, and June 1, 2023. Study participants, who ranged from age 18 to 80, were sorted at random into one of six possible groups that differed by order of the three seated arm positions. Measurements were taken during a single visit between 9 a.m. and 6 p.m. Before BP measures were taken, all participants first emptied their bladders and then walked for two minutes to mimic a typical clinical scenario in which people walk into a clinic or office before screening takes place. They then underwent a five-minute, seated rest period with their backs and feet supported. Each person, wearing an upper arm BP cuff selected and sized based on their upper arm size, had three sets of triplicate measurements taken with a digital blood pressure device 30 seconds apart.

Upon completion of each set of three measurements, the cuff was removed, participants walked for two minutes and rested for five minutes. In the same visit, they then underwent a fourth set of triplicate measurements with their arm supported on a desk, a set used to account for well-known variations in BP readings.

Researchers found that BP measurements obtained with arm positions frequently used in clinical practice -- an arm on the lap or unsupported at the side -- were markedly higher than those obtained when the arm was supported on a desk, the standard, recommended arm position. Supporting the arm on the lap overestimated systolic BP -- the top number of a reading, or the force of blood flow when pumped out of the heart, by 3.9 mmHg and diastolic blood pressure -- the bottom number, or the pressure in the arteries when the heart rests between beats, by 4.0 mmHg. An unsupported arm at the side overestimated systolic by 6.5 mmHg and diastolic by 4.4 mmHg.

The longstanding epidemic of severe pediatric depression is a significant public health concern, with only one third of the affected population receiving any mental health care. A new systematic review suggests that FDA-issued warnings about antidepressant use, intended to increase monitoring of suicidal thoughts among youth, have led instead to unintentional harm.

The study was led by the Harvard Pilgrim Health Care Institute with collaborators from the University of Pennsylvania, London School of Economics and Political Science, Northeastern University, Drexel University, and The University of Sydney.

The findings are published in the October issue of Health Affairs.

Since 2003, the FDA has advised that antidepressants might be linked to suicidal thoughts and behaviors in young people. These warnings, upgraded to a Black-Box Warning (the most serious level of warning) in 2005 for those under 18 and an expansion in 2007 to include young adults up to the age of 24, were intended to encourage physician vigilance in monitoring patients for suicidal thoughts and behaviors. However, experts say evidence shows they resulted in a decline in pediatric mental health.

The study team screened a total of 1,841 research reports published about the warnings spanning the period between January 1, 2003 and October 31, 2022. Of these, 34 measured the outcomes of the warnings, 11 of which met well-recognized research design criteria. These 11 reports included studies measuring abrupt changes in outcome trends following the October 2003 FDA advisory and/or January 2005 Black-Box Warnings.

The review found that fewer than 5% of pediatric patients were monitored in accordance with FDA’s recommended contact schedule recommendations following the advisory. This low rate remained unchanged from the rate prior to the warnings. Zero studies documented improvements in mental health care or declines in suicide attempts or suicides after the warnings went into effect.

Four studies, including a total of over 12 million patients, reported substantial reductions in doctor visits for depression and depression diagnoses. Most studies showed increasing use of antidepressants in the years before the FDA Advisory, followed by abrupt, sustained reductions in use after the warnings. Seven studies showed the relative reduction in antidepressant treatment and use ranging from 20% to 50%. Three studies showed increases in psychotropic drug poisonings (a proxy for suicide attempts) and suicide deaths among pediatric patients. While young adults from age 18 to 24 were not included in the studies of younger pediatric patients, the effects of these warnings “spilled over” to young adults who frequently experienced declines in mental health care and increases in suicides.

Because it is unlikely that any one outside factor can account for the multiple sudden and parallel effects on depression care, suicidal behavior, and deaths by suicide, the authors suggest that allowing the warnings to stand may contribute to the continuing pediatric mental health crisis.

“The sudden, simultaneous, and sweeping effects of these warnings––the reduction in depression treatment and increase in suicide––are documented across 14 years of strong research. The consistency in observed harms and absence of observed benefits after the Black-Box Warnings indicate this is not a coincidence,” adds Dr. Soumerai, Harvard Medical School professor of population medicine at the Harvard Pilgrim Health Care Institute “We recommend that the FDA consider incorporating the Black-Box Warnings into the list of routine warnings that pose fewer health risks, or potentially removing the warnings altogether.”

Reference: Intended And Unintended Outcomes After FDA Pediatric Antidepressant Warnings: A Systematic Review Stephen B. Soumerai, Ross Koppel, Huseyin Naci, Jeanne M. Madden, Andra Fry, Alyssa Halbisen, Jesenia Angeles, Jonah Koppel, Rachelle Rubin, and Christine Y. Lu Health Affairs 2024 43