11/25/18: SKIMMING THE NEW ENGLAND JOURNAL OF MEDICINE: The Reading Can Be Rough, but It Also Can Be Fun


I look at The New England Journal of Medicine every week.

I chose the word “look,” instead of “read,” because I just look through many of the articles about clinical studies, gleaning the basics of, for example:

“CD47 Blockade by Hu5F9-G4 and Rituximab in Non-Hodgkin’s Lymphoma” (Nov. 1, 2018):

I recognize rituximab as an antibody-type of cancer drug, but I don’t know what kind of therapy Hu5FP-G4 is. If I knew somebody who had relapsed or refractory non-Hodgkin’s lymphoma, however, I would try to figure out what the article’s authors have discovered in their study of 22 patients. I would tough out the language, with my “Stedman’s Medical Dictionary” by my side.

When a disease is refractory, it is resistant to treatment, such as non-Hodgkin’s lymphoma that is refractory to rituximab. Such a cancer patient is running out of options.

Here’s another vocabulary-dense NEJM article that concerns a clinical study and drug treatment:

“Elotuzumab plus Pomalidomide and Dexamethosone for Multiple Myeloma,” Nov. 8, 2018:

This study enrolled patients with refractory multiple myeloma, a rare blood cancer, to see if the addition of elotuzumab to the other two drugs, used as their current therapy, prolonged their lives. The conclusion is that adding elotuzumab “significantly” lowers the patients’ risk of disease progression or death.

The experimental group received all three drugs, and the control group received just pomalidomide and dexamethosone. Depriving terminally ill people of a medication that might prolong their lives doesn’t seem right to me, but I’d have to read the article to find out how certain the researchers were that the control subjects would be disadvantaged. U.S. scientist-physicians are very sensitive to the ethics of such a situation.

Of the 17 authors credited in the multiple myeloma article, only one is from the United States, and it is an employee of Bristol-Myers Squibb, one of the sponsors of elotuzumab. The lead investigators are with the University of Athens. Others in this multicenter study are based in Poland, France, Japan, Canada, and Spain. I don’t know anything about the “International Conference on Harmonisation Good Clinical Practice” guidelines, which the investigators say they have observed.

Again, if I knew someone with multiple myeloma, I would slug through the article, but since I don’t, it doesn’t draw me in—right away.

Actually, you’d be surprised by how many of the NEJM’s clinical articles are accessible to medical laypeople, and do have some appeal, such as:

“Effect of Aspirin on Cardiovascular Events and Bleeding in the Healthy Elderly,” Oct. 18, 2018.”

I know healthy old people, and I plan on being a healthy old person myself one day.

This article is a report of a nearly 5-year study in Australia and the United States of community-dwelling men and women who, if white, are at least 70 years old, and, if black or Hispanic, are at least 65, and do not have cardiovascular disease, dementia, or disability. Of the 19,114 people enrolled in the study, 9,525 were randomly assigned to receive a daily dose of 100 mg. of enteric-coated aspirin, and 9,589 were randomly assigned to receive placebo.

The researchers’ conclusion is that a daily low dose of aspirin is not an effective primary prevention strategy for cardiovascular events in healthy older adults. In fact, the low-dose aspirin resulted in a “significantly higher risk of major hemorrhage” among such people. The study results show that the placebo worked just as well in lowering the risk of cardiovascular disease among healthy elderly people, as the aspirin did.

Here are other examples of NEJM’s appeal and accessibility:

*“Acceleration of BMI in Early Childhood and Risk of Sustained Obesity,” Oct. 4, 2018:

The conclusion of these German researchers, who analyzed body mass index (BMI) values over time in a population-based sample of 51,505 children, is that most children who were obese between the ages of 2 and 6 are obese in adolescence. The age of “onset of obesity” is between 2 and 6, when the most rapid weight gain occurs.

This is a study that parents might like to know more about, especially parents with children in the onset-of-obesity age group.

I set this one aside, too.

*“Changes in Prevalence of Health Care-Associated Infections in U.S. Hospitals,” Nov. 1, 2018:

This CDC-supported survey of 12,299 patients in 199 hospitals concludes that in 2015 the prevalence of health care-associated infections in U.S. hospitals was lower than the prevalence in 2011, when 4 percent of all hospitalized patients acquired a health care-associated infection. The researchers claim that a patient’s risk of acquiring a hospital infection in 2015 was 16 percent lower than it was in 2011. Conclusion: Preventive actions—starting with healthcare people washing their hands more often—are working.

I wrote extensively about hospital-acquired infections in my book, “Our Parents in Crisis: Confronting Medical Errors, Ageist Doctors, and Other Healthcare Failings,” and, frankly, I don’t trust these results. But, the truth is, I haven’t had the heart to read the article and scrutinize the researchers’ methodology: how they selected the hospitals and the patients; how they collected the data; how they analyzed the data, etc., etc. The CDC has a vested interest in showing a reduction in hospital-acquired infections. Bias might have influenced the survey’s methodology and conclusions.

The article suggests that the prevalence of surgical-site infections and urinary tract infections has declined. The CDC investigators also say that the most common health care-associated infections are pneumonia, gastrointestinal infections—mostly due to the bacteria, Clostridium difficile—and surgical-site infections.

I’ve set this article aside to read, too.

Believe it or not, there are entertaining articles in The New England Journal, many of them published in a section titled “Perspective.” It is in “Perspective” that physicians contribute first-person essays and advocate for change. (E.g., “What We Can Do About Maternal Mortality—And How to Do It Quickly,” Nov. 1, 2018.) Like people in every other walk of life, physicians enjoy writing about their experiences and ideas, too, sharing what they have learned, felt, and believe.

“Becoming a Caregiver—Lessons from My Dad,” by Dr. Audrey M. Provenzano of the Massachusetts General Hospital Chelsea Health Center, is an essay that elicits understanding and empathy from many of us. It begins:

“When I imagined this moment, I always thought that it would crush me. Dad stared at me and then back at the social worker. She stood in the doorway, smiling expectantly. She asked again, more loudly than necessary: ‘Can you introduce me, Paul?’ She’d just started work at the nursing home, and I hadn’t met her yet. . . .

“‘Yes, yes, this is . . . ’ Dad trailed off. . . .

“‘This is, this is my sister Jean,’ he offered, blinking at me.

“‘No, no, Dad,’ I said quietly, taking his hand. ‘It’s me, Audrey, your daughter.’”

The beauty of Provenzano’s memoir is that the lessons she learns from her father occur after he fails to recognize her, when their visits have “a new rhythm.” She finds love, peace, value, and meaning in their interactions, even though they no longer have high-level cognitive content.

When her father dies, peacefully and comfortably, Provenzano unexpectedly feels a “harsh, raw anger” erupting from “somewhere” within her. She misses being a caregiver.

Another recent reassuring contribution to the NEJM Perspective section was:

“The Name of the Dog” (Oct. 4, 2018), by Dr. Taimur Safder, of Baylor University Medical Center in Dallas.

Like Provenzano, Safder opens with a telltale anecdote that is set on a day and time that many physicians remember: their first day of residency.

Nervous and over-prepared with much of the wrong equipment—including copies of studies, which did not impress his attending physician—Safder is “brought up short” by the attending with a question that “kept replaying in my mind.” As he relates:

“During morning rounds, I had presented a patient who was admitted for chest pain after walking his dog. My attending had asked: ‘What was the name of his dog?’

“I was stumped. Worse, I didn’t know why we needed to know. Nowhere in the books or the studies I’d read had a dog’s name contributed to the differential [diagnosis]. But the attending took us back to the patient’s bedside and asked.

“‘Rocky,’ the patient said. And there followed a brief conversation that was more colorful than any other I’d had with a patient that day. It led to a transformation I did not fully appreciate at the time: there was an actual person behind that hospital-issued gown.”

Later, Safder learns the value of showing his patients that there is a person inside the white lab coat, too.

My absolute favorite feature of the NEJM, which is owned and published by the Massachusetts Medical Society, is called “Case Records of the Massachusetts General Hospital.” The Mass General, as you undoubtedly know, is affiliated with the Harvard Medical School, and Harvard is still the premier place for medical education.

Each Mass General case that a physician presents is typically a “whatdunnit?” A diagnostic puzzle. The case report provides diagnostic clues in the form of history and physical exam results, progression of symptoms, various lab tests and imaging, etc., and involves a roundtable discussion among physicians that culminates in a “final diagnosis.”

Being naturally inclined toward sleuthing, puzzling, and analyzing, I love reading these reports, even though I don’t have a medical degree. I try to deduce what’s going on or, at least, what’s not going on.

Some of the cases are not that mysterious. “Case 35-2018: A 68-Year-Old Woman with Back Pain and a Remote History of Breast Cancer” (Nov. 15, 2018) concludes with a diagnosis of metastatic breast cancer: “Hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer of the lobular type, with ESR1 mutations,” to be precise.

“Case 34-2018: A 58-Year-Old Woman with Paresthesia and Weakness of the Left Foot and Abdominal Wall” (Nov. 8, 2018) is first seen in the outpatient neurology of the Mass General because of hypoesthesia (numbness), paresthesia (tingling or prickling), and weakness. She had been well until 10 weeks before this presentation, when back pain developed between her shoulder blades.

The timing in this case report is a bit unclear—did Harvard neurology drop the ball?—but what is clear is that the woman’s symptoms progress: The numbness spreads to her hands and fingers and her genital area; the muscles of her abdomen and chest weaken; urinary incontinence develops, then fecal incontinence. She is unable to rise from a supine (lying on her back) position. Eventually, she is seen in the emergency department at the Mass General and admitted.

The medical roundtable considers a number of causes of “polyradiculopathy” (multifocal diseased nerves) and finally settles on Lyme meningoradiculitis.

Lyme disease! Early and disseminated.

The woman is treated with three weeks of intravenous ceftriaxone, which is a broad-spectrum antibiotic. Four months after the initiation of her treatment, she is seen in a hospital clinic and has improved considerably, but she still has some residual damage, affecting her walk and her ability to get up. I would like to know what has happened to her since.

In my next blog, I’ll share with you a NEJM case record that presents physicians with political and social issues, not a diagnostic puzzle. It actually gave me some insight into a friend’s suicide. As edifying as I found some of the analysis, the outcome in the case left me wondering: “How did that happen?”

Ann, 11/25/18


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