CAP TODAY Pathology/Laboratory Medicine/Laboratory Management
David Wild
January 2019—Medicare hospital readmission rates are down under the Centers for Medicare and Medicaid Services readmissions reduction program, though hospitals are still paying millions in penalties, in part because new conditions are included in the calculations. Can at-home self-testing of some patients bring readmission rates down further, not only to save dollars but also to keep patients healthier and in their homes, to increase access to care, and for a better patient care experience?
That’s the question Robert Nerenz, PhD, explored in his talk at last year’s AACC annual meeting, in a session on enhancing patient care using point-of-care testing. “Atypical point-of-care testing might be able to meet some of the country’s health care challenges,” said Dr. Nerenz, assistant director of clinical chemistry at Dartmouth-Hitchcock Medical Center and assistant professor of pathology and laboratory medicine, Geisel School of Medicine at Dartmouth. Although cost savings are an important element, what interests Dr. Nerenz most about at-home testing is patient health. “Presumably,” he said, “if you’re not being admitted to the hospital, you’re doing better.”
At-home testing “is already kind of creeping into our standard of care,” he said, but “when we talk about expanding this, particularly to a fingerstick specimen, there are lots of concerns that people rightly have.”
Specimen quality is one. “We know that a fingerstick specimen is not as good as a venous specimen or arterial specimen. We know there’s tissue fluid in it, and there are a number of other concerns,” among them how accurate the value is once the specimen is applied to the instrument.
“How can we train people who don’t have a formal lab background to do this testing properly or at all the prescribed testing intervals? And does any of this matter? Is there a positive impact on patient care?”
In the first of two examples, Dr. Nerenz zeroed in on patients with congestive heart failure. A study published in JAMA (Felker GM, et al. 2017;318[8]:713–720) examined whether an NT-proBNP-guided treatment strategy improves outcomes versus usual care in high-risk patients with heart failure and reduced ejection fraction. The treatment goal in the study was to keep NT-proBNP below 1,000 pg/mL, measured in a laboratory.
The authors randomized almost 900 patients to undergo NT-proBNP-guided treatment or to receive the usual care in accordance with the guidelines, with emphasis on titration of neurohormonal therapies for HF. Serial measurement of NT-proBNP was discouraged. The NT-proBNP-guided therapy was not found to be more effective.
‘There are some ways that this [at-home testing] can go wrong . . . but, by and large, I think this has definite potential.’
—Robert Nerenz, PhD
While at-home fingerstick measurement of BNP means “stepping away from a pristine venipuncture specimen measured in a central lab toward a less perfect specimen measured on a slightly less accurate instrument,” Dr. Nerenz said, “what we gain is real-time information and more data points collected every single day.”
Generally, heart failure patients are advised to monitor their weight and symptoms. Patients in the at-home study were instructed not only to weigh themselves but also to measure their BNP each day using the Alere Heart Check system. They were asked to do so at the same time each day, before eating breakfast and before taking morning medications. Researchers examined the participants at one, three, and six months after trial outset, or at the time of study withdrawal.
Of the 107 patients monitored in the study for a median of 172 days (whose left ventricular ejection fraction was less than 40 percent), 35 had their treatment guided by daily BNP and weight values, and 34 patients had treatment guided by weight but not BNP. Thirty-eight participants had treatment blinded to both values.
“A key point in this study,” Dr. Nerenz said, “was that both BNP and weight values automatically went into a central database where researchers could then look at them.”
“And in their infinite wisdom, these authors said, ‘We know there may be some inaccuracy with the individual data points. What we really care about is the trend. So let’s look at a six-day moving average.’” Is BNP going up or down or staying the same? “By looking at the aggregate of six points,” Dr. Nerenz said, “some of that individual error will now start to normalize out. And so they asked, ‘Does the BNP trend predict decompensation?’”
Dr. Nerenz provided a look at three patients. One patient had BNP levels around <100 pg/mL until day 125, before which there were modest fluctuations from day to day but BNP was not increasing. “Presumably, that patient’s heart is not super stressed,” he said. After day 125, BNP values for this patient began to rise, and within 15 days were about 10 times higher, at which point the participant was hospitalized for acute decompensated heart failure.
While weight rose along with BNP values in the period immediately preceding heart failure, it also increased between days 80 and 100 and between days 20 to 40 with no corresponding increases in BNP and no need for hospitalization or clinic visits. “So at least in this particular patient, it appears that BNP is a more specific predictor of decompensation than is weight gain,” Dr. Nerenz said.
A second patient had BNP values steadily decline from greater than 500 pg/mL at baseline until day 40, when they began to rise, and the patient was ultimately hospitalized on day 65 for acute decompensated heart failure. “In this patient, there was a slightly different pattern but the same basic take-home message.” Although values in weight gain and BNP “pretty much parallel each other” during the period before hospitalization, “if we go all the way back to day zero [up until] day 30, BNP is trending down while weight is trending up. So again weight appears to be a slightly misleading, or at least a nonspecific, indicator,” he said.
The third patient’s BNP values were elevated at the start and declined steadily over the first 60 days of monitoring, falling from greater than 1,000 pg/mL and stabilizing at less than 100 pg/mL, but body weight rose steadily during the same period. This patient did not experience acute decompensated heart failure or require IV diuretics during the monitoring period but was hospitalized for vasovagal syncope.
In sum, a univariate analysis found that every 2.7-fold increase in the natural log of the six-day moving average of BNP leading up to the time of hospitalization or cardiovascular death was associated with a 2.2-fold increase in the risk of such an event (hazard ratio 2.2; 95 percent CI 1.48–3.34).
“If we look at the univariate models, the hazard ratio indicates weight gain is actually a stronger predictor of poor outcomes than BNP, but the 95 percent confidence interval is very wide,” Dr. Nerenz noted (HR 3.22; 95 percent CI 0.97–10.71). “We really don’t know. It could be a very poor predictor with a hazard ratio less than one, all the way up to a very strong predictor with a hazard ratio of 10.7.”
However, in a multivariate analysis, the authors found the six-day moving average of BNP, when adjusted for the patient’s initial BNP value, was a stronger predictor of a primary event than weight gain with a narrower confidence interval (HR 3.27; 95 percent CI 1.84–5.83).
They concluded that BNP home testing is feasible and that in this patient group, “given adequate training,” Dr. Nerenz said, individuals can perform home BNP testing. “And, relative to weight gain, the adjusted natural log of the six-day moving average seemed to be a stronger predictor of poor outcomes.”
Research is needed to determine the most accurate alert criteria for this patient population, Dr. Nerenz said. “If we’re going to use this to intervene in patients and be more aggressive with their treatment to prevent hospitalization, what are the cues that stimulate us to do that?” And the critical question: Are outcomes better? “That’s the next step that’s required for at-home BNP measurement,” he said.
Dr. Nerenz moved to a different patient group: kidney transplant recipients. A study conducted at Leiden University Medical Center in the Netherlands looked at at-home monitoring for these patients. It examined whether transitioning creatinine and blood pressure testing into the home can lead to earlier detection of rejection, reduce the number of outpatient visits, and “make patients more active players in their care,” Dr. Nerenz said (Van Lint C, et al. J Med Internet Res. 2017;19[9]:e316).Participants were asked to monitor their creatinine levels daily for four weeks, every other day in weeks five to nine, twice weekly in weeks 10 to 15, and weekly from week 16 onward for the duration of the one-year study. They used the Nova Biomedical StatSensor Xpress-i Creatinine Meter and were given a blood pressure self-monitoring device. They were instructed in how to use the devices, how to manually register their creatinine values in an online system that physicians could also access, and how to respond to feedback from the system. Fifty-eight patients were supplied with devices; four never performed any measurement.
To provide feedback to patients, the system compared the most recent creatinine value to the mean of the five previous values. If the registered value was less than 15 percent higher than the mean of the five previous values, patients were given a “green light” and asked to continue with their current testing schedule. If the value was 16 to 20 percent higher, they were given an “orange light” and asked to repeat their measurement, and if the value was more than 20 percent higher, they were advised to seek care.