Diagnosing concussion with a blood test?

- Jennifer Middleton, MD, MPH

The Food and Drug Administration (FDA) reported last week that it had approved a new blood test to help diagnose mild traumatic brain injury (mTBI or "concussion") called the Banyan Brain Trauma Indicator. The test measures two proteins, UCH-L1 and GFAP, that are released by the brain into the bloodstream within 12 hours of injury. The FDA press release includes discussion regarding this test's potential to reduce the number of CT scans patients with suspected mTBI receive. The study cited by the FDA to approve this test, however, has not yet been published for physicians to review.

A 2012 AFP article reviewing "Current Concepts in Concussion: Evaluation and Management" describes the difficulties in making a concussion diagnosis:

Concussion can be difficult to recognize, complicated by the lack of a universal definition. Additionally, there are no direct objective measures for diagnosis or recovery, no treatments with well-documented effectiveness, and limited empiric prospective data to guide return-to-play decisions.

The article reviews the high incidence of mTBI in the United States (estimated to be between 1.6-3.8 million injuries annually) and cites that over 1 million of these patients are evaluated in US emergency departments every year. Many of these patients get CT scans of their brain to rule out serious intracranial processes despite the existence of guidelines like the New Orleans criteria that discourage CT scans in patients without headache, vomiting, intoxication, amnesia, seizure, or visible trauma. Using serum biomakers to reduce the use of CT scans in suspect mTBI patients would save patients from unnecessary radiation exposure; this radiation exposure may increase risk for future cancers, especially in patients who receive multiple scans over their lifetimes. An AFP Journal Club article author from 2010 is quoted as saying, "After I have told a patient or parent that a head CT is the equivalent of 100 to 200 chest radiographs, you'd be surprised how many say they really don't need or want the test."

Prior studies regarding the utility of UCH-L1 and GFAP to diagnose concussion have had mixed findings. A previous study examining the use of these 2 proteins along with a 3rd not mentioned in the Banyan Brian Trauma Indicator found decent sensitivity for detecting mTBI but poor specificity; a positive test result was suggestive of mTBI, but a negative test result did not reliably rule it out. A systematic review of these biomarkers' utility from last year was less enthusiastic, finding "insufficient evidence" that these tests are "ready for clinical application."

While the FDA's desire to make this test available as quickly as possible is admirable, not sharing the data that led to its approval makes it challenging for physicians to use it. As with most medical diagnostic tests, the results of the Banyan Brain Trauma Indicator will not merely be "yes" or "no," and understanding the chances of a false positive (or negative) along with the positive (or negative) predictive value will be important for physicians to apply it thoughtfully. Hopefully more information will be forthcoming from the FDA soon, and hopefully, too, the study they cite will be available for our scrutiny as well. In the meantime, here are some mTBI resources from AFP for your review.

Enthusiasm should not outweigh evidence on vitamin D

- Kenny Lin, MD, MPJH

In 2005, Dr. Mark Ebell authored an AFP editorial on the rise and fall of vitamin E, subtitled "lessons in patient-oriented evidence." Observational studies associated lower vitamin E levels with coronary artery disease, leading many physicians to recommend that patients take vitamin E supplements for cardiovascular protection. 19 randomized, controlled trials later, the verdict was in: vitamin E supplementation actually increased all-cause deaths. Dr. Ebell viewed the "vitamin E saga" as an instructive cautionary tale:

It is important to remember that biochemical theory does not equal clinical benefit. Improvements in disease-oriented outcomes, such as free-radical activity, are no substitute for patient-oriented outcomes, such as all-cause mortality. Sometimes our enthusiasm for unproven treatments may harm our patients.

Physicians and patients, it turns out, were already turning to testing and treatment with another vitamin that was a marker of chronic health conditions in observational studies: vitamin D. Between 2000 and 2010, the volume of serum 25-hydroxyvitamin D levels in Medicare patients increased 83-fold, and by 2014, 4 out of 10 adults 70 years or older reported taking a daily vitamin D supplement of at least 1,000 IU, and nearly 7 percent of adults over 60 were taking more than 4,000 IUs daily, a level that the National Academy of Medicine considers to be potentially toxic.

Unfortunately, the vitamin D saga has much in common with the vitamin E saga. According to a review article in the February 15th issue of AFP by Drs. Michael LeFevre and Nicholas LeFevre, vitamin D supplementation in community-dwelling adults has not demonstrated any benefits for ischemic heart disease, cerebrovascular disease, or cancer in clinical trials. The U.S. Preventive Services Task Force and the American Academy of Family Physicians concluded that there is inadequate evidence that supplements improve psychosocial or physical functioning in persons with lower vitamin D levels.

In an accompanying editorial, I argued that the harms of routine screening and supplementation with vitamin D outweigh the benefits, especially when the costs of testing (more than $300 million annually in Medicare alone) are considered:

It is time for clinicians and patients to curb our enthusiasm for vitamin D screening and supplementation. Strategies to decrease unnecessary testing could include distributing the patient handout on vitamin D tests created by Consumer Reports for the Choosing Wisely campaign and implementing clinical decision support for ordering laboratory tests. ... Family physicians should also counsel patients on the recommended dietary allowance for vitamin D (600 IU per day in adults 70 years and younger, and 800 IU per day in adults older than 70 years), and discourage most patients from using supplements, especially in dosages near or above the tolerable upper limit of 4,000 IU per day.

Treating and preventing disease with dietary fiber

- Jennifer Middleton, MD, MPH

The current issue of AFP includes a review article on Hemorrhoids: Diagnosis and Treatment Options that discusses the roles fiber intake has both in contributing to hemorrhoids (when too low) and treating them (when appropriately increased). The authors recommend that patients with hemorrhoids increase their fiber intake to 25-35 grams per day and provide a link to a handout listing high fiber foods. As a high fiber diet can also help prevent and treat hyperlipidemia, constipation, and diverticulosis, family physicians should be proficient in discussing this important digestive component with patients.

Adequate daily fiber intake may protect against the development of hyperlipidemia. Children with chronic constipation consume less fiber than their peers with normal bowel patterns. Inadequate fiber intake is associated with the development of diverticulosis, which can put patients at risk for diverticulitis.

Increasing dietary fiber can modestly reduce LDL levels, improve constipation, and, along with exercise and weight loss if indicated, reduce the risk of recurrent diverticulitis. (Of note, a Cochrane meta-analysis found no role for using fiber supplementation to improve symptoms of irritable bowel syndrome.) Increasing fiber by increasing consumption of high-fiber whole foods, and not with fiber product supplementation, provides the most benefit.

Most Americans consume less than half of those recommended 25-35 grams of fiber daily, though many are trying to increase their consumption by choosing more fruits, vegetables, and whole grain products. Unfortunately, many products marketed as "whole grain" in the United States contain very little fiber. We should counsel patients to look beyond claims about whole grain content and examine food labels to choose products with a minimum of 3 grams of fiber per serving. Advising patients, also, to gradually increase their fiber intake may help them minimize the unpleasantness of bloating and excess flatulence that can accompany a rapid change in fiber consumption. Patients may find nutrition tracking apps such as My Diet Coach, reviewed in the current issue of Family Practice Management, to be useful in monitoring their daily fiber intake. Other apps such as (Fooducate and Shopwell) can help patients make more informed choices at the grocery store.

Providing specific advice in the context of motivational interviewing increases our patients' likelihood of success at making any behavioral modification stick; there's an AFP By Topic on Health Maintenance and Counseling as well as an AFP By Topic on Nutrition if you'd like to read more. What resources have you found useful to help patients increase their daily fiber intake?

The changing of the guard: from Dr. Siwek to Dr. Sexton

- Kenny Lin, MD, MPH

The February 1 issue of AFP marked the first time since 1988 that a family physician other than Dr. Jay Siwek was serving as the journal's editor-in-chief. Dr. Siwek, who bade farewell to readers in a poignant, memory-filled editorial in the January 15 issue, will stay on as editor emeritus. This month, Dr. Siwek introduced his successor, longtime associate editor Dr. Sumi Makkar Sexton. You can read about Dr. Sexton's extensive qualifications and experience in Dr. Siwek's latest piece, and learn about her plans for the future of AFP, which include making journal content more usable at the point of care, in her introductory editorial.

It has been my good fortune to know Jay and Sumi for the past 14 years, since I arrived at Georgetown University School of Medicine as AFP's medical editing fellow in the summer of 2004. Both played critical roles in my development as a family physician and medical editor, during and after my one-year fellowship. It was Jay, in his previous capacity as Chair of Georgetown's Department of Family Medicine, who hired me as a junior faculty member and supported each of my subsequent promotions to assistant, associate, and full professor. After I left the department for several years to work as a medical officer at the Agency for Healthcare Research and Quality and earn a master's degree in public health, it was Jay who convinced me to return and deploy my new skills to direct the department's health policy fellowship and eventually take on other leadership and teaching positions in population health.

On the other hand, it was Sumi, as the editor of Tips from Other Journals (an AFP department that ended in 2013) who continued to hone my writing and evidence-based medicine skills for years after my fellowship ended. Under her supervision, from 2005 to 2010 I wrote more than 60 summaries of primary care-relevant research studies for AFP. And after my first post-fellowship clinical position unexpectedly fell through, it was Sumi who hired me to see patients at her thriving practice, Premier Primary Care Physicians, which was an early adopter of innovations such as electronic medical records and advanced-access scheduling.

As AFP's new deputy editor, I have worked closely with Sumi and Jay for the past several months to support their changing of the guard at editor-in-chief, and I look forward to many more years of collaborating with them both. Moving on from Dr. Siwek to Dr. Sexton is an important transition, but the best-read journal in primary care won't miss a beat.