Zackary Berger’s journal reviews—17 September 2018

Zackary Berger reviews the latest research from the top medical journals

Trial of fingolimod versus Interferon Beta-1a in pediatric multiple sclerosis

At least five percent of those with multiple sclerosis (MS) are children. Thus it came as welcome news when in 2017 the US Food and Drug Administration granted breakthrough status to a new medication developed for pediatric MS. And here, shortly afterward, is a trial sponsored, conducted, and written by Novartis showing that its medication, Gilenya (fingolimod) is more effective in preventing relapse than interferon beta-1a. The ointment is not without flies, however. The most subtle limitation, best discussed by those who are experts in pediatric MS, is that interferon beta-1a is associated with significant non response rates in children—raising the question (acknowledged by the authors) whether it is the most appropriate comparison for a randomized control trial. Further, serious adverse events were more common in the fingolimod group than the interferon group, including seizures and a variety of psychiatric effects (presumably the five-year add-on trial can help clarify these issues).

The major bone to pick? Nothing mentions here that Gilenya is available at a cool five thousand dollars for a month’s supply. It beggars belief that in 2018, with decades of discussion about pharmaceutical costs, a pharma firm can publish a study without mentioning cost. The top journals should require this.

Lethality of civilian active shooter incidents with and without semiautomatic rifles in the United States

Since the year 2000, the US Federal Bureau of Investigation has maintained a database of active shooter incidents. (Any US resident has a depressing familiarity with reports of these incidents, in which someone armed tries to kill people in a populated or enclosed area.) Researchers used the database to ask whether semiautomatic weapons (which can accept larger magazines, are designed for ease of use, and fire larger bullets) were associated with greater morbidity and mortality than other types of weapons. (The database itself does not specify the type of weapon, so the researchers made use of police or media reports to determine that information.)

The number of such incidents—248 from 2000 to 2017—is shocking, but even more are the number of wounded (898) and killed (718). Unsurprisingly, those incidents with semiautomatics involved greater numbers of casualties (though mortality rates were the same for incidents with semiautomatics or without). While a number of variables were controlled for, the authors point out that there is no national centralized database of shooting incidents to inform a potential assault weapons ban; this would be necessary to strengthen the association found in this study.

Chronic pain among suicide decedents

In the category of tragic-but-necessary databases we also find the National Violent Death Reporting System, which links data on violent deaths from police reports, medical examiners, and death certificates into a single record. Researchers from the US Centers for Disease Control and Prevention sought to estimate how many of the suicides documented in the database (from 2003 to 2014) were associated with chronic pain, and for how many of those chronic-pain-associated suicides was opiate overdose also mentioned.

Of 123,181 people older than 10 who died of suicide in that time span, 8.8% had evidence of chronic pain (this percentage increased over time during the years studied). The percentage who died of opiate overdose was low, less than 2%. These figures surprised me because they were lower than I had expected. Certainly there are many possible reasons for this: suicide can be underreported, and subgroups with higher prevalence of chronic pain (e.g. those with mental health conditions, and those who are not white) might have additional reasons for underreporting of suicide.

Suicide, chronic pain, mental health, and substances (e.g., opiates) are tightly interwoven, and a study like this can’t untangle them. But it can point to the tangle as something we should look closely at. We should also thank the CDC researchers for pursuing this unfunded work, and hope that our funding priorities align more closely with the fate of thousands who die at their own hand.

Documented pain diagnoses in adults prescribed opioids

In the same issue of the Annals of Internal Medicine, a cross-sectional survey of ambulatory visits was used to determine what percentage of opiate prescriptions were associated with a documented medical indication, and what indications were associated with such prescriptions. Out of 31,943 visits between 2006 and 2015 at which an opiate was prescribed, 5% were associated with a diagnosis of cancer-related pain, 66% with non-cancer pain, and no pain diagnosis recorded in 29% of visits. (Most common non-pain diagnoses associated with opiate prescriptions were “hypertension” and “opiate dependence,” among others.)

What does this tell us? First, not all pain diagnoses have “pain” in the name (as the authors themselves acknowledge and made an effort to address by including diabetes under pain diagnoses, since neuropathy is under-coded). Second, not all physicians code what they might or should. Third, some opiate prescriptions are filled with inertia, not after deliberation. This research raises intriguing questions, but no answers, much as pain often does.

High-sensitivity troponin in the evaluation of patients with suspected acute coronary syndrome

Medicine is not physics. Physics has adopted particle colliders of higher and higher energies to discover fundamental physical particles that are smaller and smaller, revealing new scales of fundamental scientific truths. “If medicine is a science,” reason many healthcare types, “more sensitive tests should be better.” Most thoughtful clinicians, and the authors of this study, know this is not true. Indeed, tests for troponin are more sensitive than ever before; the Universal Definition of Myocardial Infarction recommends that the 99th percentile (with different cut-offs for men and women) be used in the definition of MI. But does this increased sensitivity identify with increased specificity of those in need of treatment?

In a randomized trial in Scotland, implementing a high-sensitivity assay for troponin (as well as sex-specific thresholds) did identify more patients with myocardial injury (reclassifying one in six), but only a third had type 1 myocardial infarction (the type of MI due to thrombus). The incidence of cardiovascular death or recurrent MI at one year showed no change with use of the high-sensitivity versus the conventional assay. If the assay is high-sensitivity, but no more specific, and outcomes are not improved, should it be routinely used?

As a side note, I was fascinated by the finding that 30-40% of patients diagnosed with MI with the high-sensitivity or conventional assay had a normal ECG. Are there ways to increase the sensitivity of that old standby while retaining its usefulness?

Intensification of older adults’ outpatient blood pressure treatment at hospital discharge

The more attention is paid to inpatient blood pressures, the more pressure there is to do something about them. Many is the intern or nurse who has had to figure out what to do about an elevated blood pressure at 2am, and the patient who has been woken up from sleep.

Researchers at the US Veterans Administration Health System, thus, asked: who gets their blood pressure medications intensified on discharge? More than half of these, it turns out, had well controlled blood pressure before admission. Not just that, but intensification of blood pressure treatment on discharge did not bear any relation to whether patients had diagnoses for which such intensification might be useful (e.g., myocardial infarction or heart failure); conversely, such intensification was no less likely to happen in patients with contraindications (e.g., metastatic cancer or dementia). No rhyme or reason? Despite the limitations of such a complicated study, one is left with the conclusion that there are many reasons for blood pressure to be transiently elevated in the hospital (pain, anxiety, delirium) and we should think before intensifying treatment on discharge, since benefits might be questionable and harms are real (though the risk/benefit balance must be answered in a future study). In short: in medicine, numbers can mislead.

Effectiveness of a therapeutic Tai Ji Quan intervention vs a multimodal exercise intervention to prevent falls among older adults at high risk of falling

A trial in Oregon randomized 670 participants at high risk of falls (mostly white people with an average age in their 70s) to tai ji quan (TJQ, also romanized as tai chi), versus a multi-modal exercise intervention (MME) or stretching exercises. The participants were included if they had fallen at least once in the preceding twelve months or were identified by their provider as having poor mobility. (There were additional criteria excluding those who already participated in vigorous exercises or were too medically or cognitively compromised to participate.) The tai ji quan intervention, marketed by a consulting firm led by the study’s first author, consisted of 60-minute sessions twice weekly for 24 weeks. Chinese drum roll.

It worked! At six months, the TJQ participants had 31% fewer falls than the MME group. (A number needed to treat just above three is nothing to sneeze at.) Are these patients like yours? Can they do tai chi for six months? Where is it provided in your area and who is paying for it? What happens after six months? Perhaps we can stay tuned for future studies, or interventions by you or other enterprising readers.

Patient-reported experiences of dialysis care within a national pay-for-performance system

I have a Spanish-speaking patient who went to a dialysis center that treated him poorly. They didn’t have enough staff, and no one spoke Spanish. I tried calling them to complain, but apparently my patient complained to them in person, and now they treat him a lot better.

Dialysis, of course, can be stressful and draining at the best of times as a procedure in itself. But the quality of centers can significantly vary, a new study tells us. I admit that I have been suspicious of the usefulness of CAHPS (patient-satisfaction data from the US Centers for Medicaid and Medicare Services) to drive change. But this study was only made possible by surveys administered by dialysis centers to be in compliance with Medicare requirements. 59% of dialysis centers (2,939) reported ICH-CAHPS scores in 2015-6, the period analyzed. (Some dialysis centers not reporting scores did not have enough patients to be required to report, though not all of them, and one suspects that the non-reporting centers differed in other important ways.)

Which centers had higher scores, and which had lower ones? (Close this tab for a minute and write down your guesses.) Quoting the paper itself is most efficient: “Facilities in the top 50th percentile of mean facility ICH-CAHPS scores cared for more white and Asian and older patients [….] those with private group insurance, and higher incomes.” Lower scoring facilities had more black or Native American patients, fewer nurses, and were more likely to be for-profit.

Also, facilities with higher proportions of Hispanic and Asian patients received lower scores on communication -which my patient mentioned above could have testified to. There is economic and social inequity, and patients likely not to speak English are underserved. Will quality scores help make Medicare for dialysis patients equitable, or will it require a broader systems change?

Zackary Berger, is an associate professor at Johns Hopkins School of Medicine in the division of general internal medicine, and core faculty in the Johns Hopkins Berman Institute of Bioethics, both in Baltimore, Maryland. Zackary’s research focuses on shared decision making, patient-centered care, and health justice. He is also a practising physician at a free health clinic for undocumented, predominantly Spanish-speaking, immigrants.

Competing interests: None declared