Renuka Tipirneni, MD, of the University of Michigan, was named the recipient of the 2020 Seema S. Sonnad Emerging Leader in Managed Care Research Award.

Congratulations to the 2020 Recipient of the Emerging Leader in Managed Care Research Award!

The Mediterranean diet, which is known to have health benefits, may help prevent rheumatoid arthritis in current or previous smoker.

Mediterranean Diet May Prevent RA in Current or Previous Smokers

Higher levels of the omega-3 fatty acid eicosapentaenoic acid (EPA) found in the blood appear to explain why icosapent ethyl drives down the risk of a cardiovascular (CV) event.

REDUCE-IT: Serum EPA Levels Hold Key to Vascepa's Dramatic CV Benefits

There are ways practices can take advantage of the delay of Oncology Care First (OCF) to continue learning from their experience in Oncology Care Model (OCM), said Mike Fazio, senior vice president of Client Services at Archway Health.

With Oncology Care First being delayed, are there ways that practices can take advantage of that delay to take what they've learned while participating in Oncology Care Model to make a smoother transition and be successful?

It's been, I think, positively received, at least from the customers that we support for OCM, that the program has been extended a year. So, that anxiety of a new model, and what that will look like is now pushed back. And so, practices can still use the data that they're getting from CMS for OCM to figure out how to refine their model, what works and what doesn't. It is still a pilot, so that pilot continues for another year.

So, using data to improve quality, which is a component of OCM, there's still time to do that. So, things like is your symptom management tool, really reducing ED [emergency department] visits and hospitalizations? You have more time to look at that and to tweak your model. Introducing palliative care early to increase hospice use at end of life—are those processes working or not? And what can you change? And the same thing with supportive therapies and in using biosimilars. So, are those taking an effect, and can we measure those results? We have more time in data to see are those changes happening and are those levers being moved so that you can address changes in the model?

So, I guess you could use the extra time to refine your model and see what's working and what isn't. So that when OCF is announced, and if it's the right program for you, you can have a better sense of what really worked in OCM. So just given the more time that you have.

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There are ways practices can take advantage of the delay of Oncology Care First (OCF) to continue learning from their experience in Oncology Care Model (OCM), said Mike Fazio, of Archway Health.

Mike Fazio Highlights How Oncology Practices Can Take Advantage of the Delay to OCF

As the only biologic on the market, dupilumab is replaced most of the more traditional treatments for atopic dermatitis, said David Pariser, MD, senior physician at Pariser Dermatology Specialists and professor at Eastern Virginia Medical School Department of Dermatology.

What do you look at when deciding to treat with the biologic compared with one of the more traditional treatment options?

Well, I do have to say now that in most people's treatment paradigm, dupilumab, the currently available biologic, has really replaced the prescription of the more traditional methotrexate, cyclosporin, mycophenolate mofetil, which work well but have a lot more side effects than dupilumab.

Methotrexate, for example, has 11 warnings in its black box safety. Dupilumab has no black box. Cyclosporin is a drug that many physicians are just not familiar with the utilization of it. And dupilumab is a medication which requires basically no laboratory follow up and which has an extremely safe safety profile, has replaced those other more traditional immunosuppressants in most people's treatment armamentarium.

How will the Janus kinase inhibitors differ from biologics?

So, the Janus kinase inhibitors, of which there are 3 at least in study now for atopic dermatitis—2 of which will be available next year—work by a completely different mechanism. They're also oral drugs which are administered and that will make a difference for some patients and prescribers, having oral therapy as opposed to an injectable one.

A big issue with the Janus kinase inhibitors, including some which are on the market now for other diseases, is that they all have black box warnings. And they all will have safety issues, which dupilumab and tralokinumab, which will be on the market at that time, will not have. So, it will be a safety versus efficacy trade off, an oral drug versus checkable drug trade off. And then of course, there's always going to be the cost and the access and what hurdles will there be in prescription?

As the only biologic on the market, dupilumab is replaced most of the more traditional treatments for atopic dermatitis, said David Pariser, MD, senior physician at Pariser Dermatology Specialists.

Dr David Pariser Outlines Future Treatment Options of Atopic Dermatitis With Biologics and JAK Inhibitors

Wayne Jonas, MD, executive director of Samueli Integrative Health Programs at H&S Ventures, discusses whether integrative health practices can be helpful in treating acute pain.

Is there a role for integrative health in acute pain?

Integrative approaches have less of a role in acute pain than they do in chronic pain. There's no question that procedures and medications for acute pain are highly effective and should be frontline. This doesn't mean that, however, they have no role. For example, a number of years ago, I was out doing a retreat with medical students and a young man dislocated his shoulder for the first time, a very painful condition. It couldn't be put back in and he needed to go to the emergency room to have it reduced and he was in considerable acute pain. And on the way to the emergency room in the hospital, I took him through some mind body and hypnosis types of techniques that helped him to relax, reduce his stress. By the time he got to the emergency room, he reported that he was in considerably less pain and more relaxed, and then, it was a lot easier to actually treat him. So, that's an example of where you can apply a mind body technique in an acute pain setting.

Research shows that certain types of nondrug approaches can be useful in acute setting. For example, [patients with] acute back pain and back strain and semi-acute back strain, respond very favorably to manipulation, and that can be brought into the treatment. Acupuncture has been shown to be helpful both in acute and chronic pain and in fact, the Department of Defense has trained almost all their providers in something called battlefield acupuncture, which is a simple 5-point ear technique that they're actually using on the battlefield for acute pain and in the clinic for chronic pain. So, yes, there is a role but it needs to be integrated with standard medical treatment.

 Dr Wayne Jonas Discusses Integrative Health for Acute Pain

A recent review examined treatment options for aplastic anemia (AA), a hematopoietic stem cell disorder marked by pancytopenia and hypocellular bone marrow.

The degree of pancytopenia (when all 3 types of blood cells have low counts) determines the severity of AA, which has high mortality in the worst forms of the disease.

Although different causes of AA may be considered, such as environmental or genetic, most cases of AA are immune-mediated.

For a few decades, hematopoietic stem cell transplantation (HSCT) and immunosuppressive therapy (IST) have changed AA outcomes by improving marrow function and pancytopenia.

Outcomes with either HSCT or IST are similar, and the choice depends on patient age, availability of a histocompatible donor, comorbidities, and patient preference.

Allogeneic HSCT is generally preferred in patients younger than 40, while IST is typically seen in patients older than 40.

While standard IST produces a hematologic response rate of 60% to 70%, about one-third of patients eventually relapse, and 10% to 15% can develop cytogenetic abnormalities.

The introduction of eltrombopag, a thrombopoietin receptor agonist, improved severe AA outcomes as both second-line and first-line therapy combined with IST.

Eltrombopag, initially approved in 2008, received FDA breakthrough treatment designation in 2014 for patients with aplastic anemia for which immunosuppression has not been successful and was approved for that indication in 2018

As a single agent, eltrombopag in doses up to 150 mg daily improved cytopenias in 40% to 50% in those who failed initial IST.

Combined with IST as upfront therapy, eltrombopag achieved an overall response of about 90% and complete responses of about 50%, higher than observed with IST alone (about 65% and 10%, respectively).

The majority of patients were alive after a median follow-up of 18 months.

The action of eltrombopag continues to be confirmed in other studies involving longer follow-up times and real-word data in different combinations and doses. In addition, understanding which patients would benefit from eltrombopag through biomarkers would be useful.

Another thrombopoietin receptor agonist in AA, romiplostim, is performing similarly, suggesting a class effect, and the author said more discoveries about how these drugs can be optimized are expected.

Scheinberg P. Novel therapeutic choices in immune aplastic anemia.

. Published online September 10, 2020. doi: 10.12688/f1000research.22214.1

Articles

Severe aplastic anemia used to have few options and mortality was high, but a new class of drugs offers some hope.


Review Examines New Options for Patients With Aplastic Anemia

Magnetic resonance imaging (MRI) of high-risk plaque characteristics have identified cerebrovascular events prospectively in asymptomatic patients, but, despite this progress it remains uncertain whether measures of MRI plaque characteristics are associated with cardiovascular disease events independent of plaque burden at the population level.

, looked to determine whether measures of plaque characteristics through use of MRI are independently associated with cardiovascular disease events, when adjusted for carotid artery (CA) wall thickness, in an asymptomatic community-based cohort.

Between January 2004 and December 2005, the study enrolled 1256 men and women with CA intima media thickness of roughly the 68th percentile or higher. All participants were imaged on 1.5-T MRI systems with a 4-element phased-array carotid coil and standard MRI protocols. Measures of MRI CA plaque burden included total carotid wall volume, maximum carotid wall thickness, lumen and wall area, normalized wall index, and maximum stenosis.

Cardiovascular disease events were defined by the authors as the composite of incident coronary heart disease events or incident ischemic strokes. These events included definite or probable myocardial infarction, coronary heart disease death, and the occurrence of a coronary artery bypass surgery or angioplasty during follow-up.

Of the 1256 participants enrolled, 701 (55.8%) were women. CA plaques in participants with incident cardiovascular disease events (172 [13.7%]) compared with those without (1084 [86.3%]) had a higher normalized wall index (median interquartile range [IQR], 0.48 [0.36-0.62] vs 0.43 [0.34-0.55]; 

= .001), maximum CA wall thickness (median [IQR], 2.22 [1.37-3.52] mm vs 1.96 [1.29-2.85] mm; 

= .01), maximum CA stenosis (median [IQR], 5% [0%-22%] vs 0% [0%-13%]; 

< .001), and when present, a larger lipid core volume (median [IQR], 0.05 [0.02-0.11] mL vs 0.03 [0.01-0.07] mL; 

The occurrence of a lipid core was independently associated with incident cardiovascular disease events when adjusted for traditional cardiovascular disease risk factors and maximum CA wall thickness (HR, 2.48; 95% CI, 1.36-4.51; 

= .003), however, the presence of calcification was not.

The authors found that in asymptomatic participants, the presence of a CA lipid core on MRI is associated with incident cardiovascular disease independent of maximum CA wall thickness. Furthermore, the authors noted that when present, noninvasive MRI carotid plaque characteristics improved risk prediction of incident cardiovascular disease events.

Brunner G, Virai S, Sun W, et al. Associations between carotid artery plaque burden, plaque characteristics, and cardiovascular events. Published online November 18, 2020. 

It remains unclear whether measures of magnetic resonance imaging plaque characteristics are associated with cardiovascular disease events independent of plaque burden at the population level.

Carotid Artery Lipid Core Associated With CVD, Independent of Artery Wall Thickness

A small study of hospitalized patients with chronic obstructive pulmonary disease (COPD) and asthma in Sweden found that more than a quarter of them do not use their inhalers properly and struggle with treatment adherence.

All inhalers, whether they are metered dose inhalers (MDIs) or dry powder inhalers (DPIs), require multiple steps in order for the user to adequately receive the right dose of medication. If steps are performed incorrectly or if important ones are overlooked, some or all of the drug may not reach the lungs. Incorrect technique can lead to a poorer prognosis for patients with COPD and asthma, a higher risk of hospitalization, and can increase the costs of disease management.

Additionally, previous research has found that a higher risk of morbidity and mortality are associated with nonadherence to inhaled medications for people with COPD.

For the study, researchers invited 38 patients who were admitted to the orthopedic, geriatric, and medical wards at the Umeå University Hospital in October, November, and December 2018 and prescribed inhaled medications prior to admission. After some patients declined to participate and some were excluded, 23 were included in the final analysis. The majority were women with a mean age of 65 and the average number of medications they were taking was 7.2.

Participants who accepted the invitation were observed by the hospital pharmacist using a placebo inhaler to determine poor inhaler technique as assessed by a checklist for each inhaler and by a definition of critical errors.

Overall nonadherence to medication was determined using the Medication Adherence Report Scale (MARS)-5, a validated scale where participants rate how much they agree with 5 general statements about their adherence (forgetting the dose, altering the dose, stopping the dose, deciding to miss a dose, or taking less than instructed).

, showed that 26.1% (6) of the 23 patients had 1 or more critical errors when using an inhaler and 30.4% (7) reported themselves as having issues being adherent with drug medication.

Out of 34 observations (29 DPIs and 5 MDIs) in 23 participants, 14 critical errors in technique were seen, and 6 (26.1%) participants had 1 or more critical errors. The 2 most common critical errors, referring to inhaler charging and positioning as well as inhaling/breathing errors, each accounted for 5 out of the 14 errors detected. 

Other critical errors were incorrect lip and teeth placement around the inhaler mouthpiece (2 out of 14).

For each inhaler type, critical errors were observed for 10 out of 29 observations for DPIs and 4 out of 5 observations for MDIs. Two of the critical errors for MDIs were related to breathing.

The most common error in inhaler technique was not checking if there were any available doses in the inhaler before usage. However, investigators said that this may have been because participants were aware that they were using a placebo inhaler and may have assumed that a dose was available.

The researchers also found that patients with poor inhaler technique had a higher number of regularly prescribed medications than people who had no technique errors, and they were also older than those with no errors in technique. In addition, of those who were self-reported to be nonadherent to treatment, 29.5% performed critical errors in inhaler treatment.

The study had a number of limitations and the investigators urged caution in interpreting the results. The small sample size of participants means that the results may be over or understated and that they may not apply to a larger population of hospitalized patients. In addition, the patients were not recruited from respiratory units; if they had, the results might have been different. Moreover, given that the patients were hospitalized, they may not have been feeling well during the time or observation, or for privacy reasons, may not have answered the MARS-5 as fully as they would have otherwise. However, the investigators said that the results could serve “as a pilot to a larger study” and that they were in line with already published literature.

Investigators said that the results showed that interventions to improve inhaler technique and adherence medications are needed going forward.

Elander A, Gustagsson M. Inhaler technique and self-reported adherence to medications among hospitalized people with asthma and COPD. 

. October 14 2020;7(4):317-323. doi: 10.1007/s40801-020-00210-x.

A study on patients who use inhalers found that interventions to improve inhaler techniques and drug adherence are needed.

Study Finds High Rate of Errors in Inhaler Technique and Treatment Nonadherence for COPD

 gene dropped precipitously between 2008 and 2018, according to 

 pathogenic variants help to inform the treatment and prevention of related cancers, with positive findings indicating higher risk, but changing testing criteria likely mean fewer women know these results. The present study investigated the impact of these changes.

A chief finding was the greater likelihood of a BRCA-positive result among women who were non-Hispanic Black (adjusted odds ratio [aOR], 1.52; 95% CI, 1.04-2.22), living in the West (aOR, 2.67; 95% CI, 1.63-4.49) or South (aOR, 1.80; 95% CI, 1.14-2.86) regions of the United States, and living in areas with few college graduates (aOR, 1.54; 95% CI, 1.10-2.17), as well as those 

 a personal history of breast or ovarian cancer (aOR, 1.30; 95% CI, 1.12-1.50).

“The current study evaluates how the rate of documented positive results for 

 testing changed over time and also evaluates the association between clinical and demographic characteristics and positive test results among US women 65 years of age or older,” the authors noted.

The study population of 5533 women, with a mean age of 68.1 (95% CI, 67.9-68.4) years, were culled from Optum’s Claims-Clinical data set. All received 

test results between January 1, 2008, and March 31, 2018. The primary outcome was percentage change in positive 

results and how that was affected by race/ethnicity, region of residence, income, educational level, and personal history of breast or ovarian cancer.

results: from 85.7% (36/42) in 2008 to 55.6 (140/252) in 2018, for an annual percentage change (APC) of –2.55 (95% CI, –3.45 to –1.64)

results for women with breast or ovarian cancer: from 83.3% (20/24) in 2008 to 61.6% (61/99) in 2018, for an APC of –3.17

results for women without breast or ovarian cancer: from 87.5% (21/24) in 2008 to 48.4% (74/153) in 2018, for an APC of –2.49

Drops in positive findings were also soon over the 10-year period in the Midwest and Northeast regions, while in the West they increased.

During the study period, most of the women tested were non-Hispanic White (84.6%, n = 4679) and from the Midwest (34.6%; n = 1915). The Optum database their data came from represents more than 91 million lives across all states, and race/ethnicity were self-reported.

“The significantly decreasing rate of positive 

 test results is evident among women 65 years of age or older, which may be partly explained by loosening of testing criteria during the evaluated time range,” they concluded. “However, socioeconomic and regional disparities were identified and persisted in testing use.”

Future studies should investigate their findings compared with those of women younger than 65, the authors recommended.

Fangjian G, School M, Fuchs EL, Wong R, Yong-Fang K, Berenson AB. Trends in positive 

test results among older women in the United States, 2008-2018. JAMA Netw Open. Published online November 5, 2020. doi:10.1001/jamanetworkopen.2020.24358

Among older women with and without breast and ovarian cancers, testing for the BRCA gene dropped precipitously between 2008 and 2018.

10-Year BRCA Testing Decreases, Study Shows 

If green light therapy were proven to be effective for migraine, it would be hugely important, said Frank Porreca, PhD, professor of pharmacology and anesthesiology at the University of Arizona 

and a member of the Department of Collaborative Research at Mayo Clinic in Arizona.

Preliminary data have been released on light exposure therapy as a low-cost, non-invasive treatment option for individuals with migraine. What are your thoughts on this therapy?

This is actually a very, very exciting area of research. There were really 2 independent laboratories that were pursuing this. One was the laboratory of Rami Burstein and colleagues at Harvard. Rami had investigated the underlying basis for photophobia. This is the hypersensitivity of patients with migraine to light. He was able to investigate the effects of different colors of light and found that green light was actually less aversive than other colors of light, and actually saw that some of his patients actually showed an improvement in pain with the green light. That was quite an amazing discovery. At the same time, at the University of Arizona, one of our clinicians, Mohab Ibrahim, had independently begun studies of the effects of green light on pain. He was exposing rodents with pain, different pain models, to green light, and showed that green light actually was producing pain relieving effects. Just recently, Mohab published in 

, a paper where he did an assessment of patient self-report with migraine where they underwent green light therapy or white light therapy for some period of time, sort of a crossover study. They filled in questionnaires. What he showed was that the green light, it was 2 hours of green light per evening for some period of weeks, actually produced a decrease in the frequency of their migraines and the intensity of their migraines and beneficial effects from a number of different points of view.


I think that, first of all, that outcome has to be validated in a much more rigorous study. Hopefully, that will occur. Then secondly, if the outcome is shown to be true, then what is the mechanism by which green light can produce improvements in migraine, or in other kinds of pain? We don't know that. Mohab had shown that it depends on the visual system. If you put contact lenses on rodents and expose them to the green light, the green light has no beneficial action, so it is dependent upon input to the visual system. But then what is the consequence of that? How does that translate into improvements in responses to pain? This is something that we don't know.
The reason that this I think is important is that it's highly translatable. Humans can experience green light therapy themselves quite easily. We have all kinds of therapies that we can use for the treatment of disease states in humans. These include pharmaceutical therapies, for example. All of these have some level of side effects. But the side effect profile of something like green light is almost non-existent. I mean, as far as we can tell, there is no downside of green light therapy. If this were proven to be effective, then it would be hugely important because pretty much anybody can do it without any significant risk of any deleterious outcomes. I think it's exciting and it's just emerging. I'd love to see where this goes. I think the groups from Dr. Burstein and Dr. Ibrahim are driving this question forward and it's very exciting to see where this will lead.

If green light therapy were proven to be effective for migraine, it would be hugely important, said Frank Porreca, PhD, professor of pharmacology and anesthesiology at the University of Arizona and a member of the Department of Collaborative Research at Mayo Clinic in Arizona.

Dr Frank Porreca Shares His Thoughts on Green Light Therapy for Migraine

Low-frequency transcranial stimulation of the pre-supplementary motor area was found to delay the onset and reduce severity of levodopa-induced dyskinesia in patients with 

 (PD), according to study findings published in 

, long-term usage of the commonly used dopamine therapy levodopa has been associated with 

, which is characterized by involuntary and uncontrollable movements. As researchers explain, prior analyses utilizing pharmacodynamic functional MRI (fMRI) exhibited that the intake of levodopa triggers an excessive activation of the pre-supplementary motor area in patients with PD with peak-of-dose dyskinesia.

They sought to examine whether the abnormal responsiveness of the pre-supplementary motor area to levodopa may signal a stimulation target for treating dyskinesia. In the pre-registered, interventional study, researchers recruited a gender-balanced group of 17 patients with PD with peak-of-dose dyskinesia who received 30 minutes of robot-assisted repetitive transcranial magnetic stimulation after they had paused their anti-Parkinson medication.

Participants were applied real-repetitive transcranial magnetic stimulation at 100% or sham-repetitive transcranial magnetic stimulation at 30% of individual resting corticomotor threshold of left first dorsal interosseous muscle on separate days in counterbalanced order.

After undergoing repetitive transcranial magnetic stimulation, patients were then administered 200 mg of oral levodopa and underwent fMRI to map brain activity, while additionally performing a visually cued go/no-go task.

“Patients were positioned in the MRI scanner and task-related brain activity was mapped with fMRI until the emergence of dyskinesia,” explain the study authors. “If patients did not develop choreiform dyskinesia within four cycles of task- and resting-state-fMRI the session was stopped.”

Prior to the stimulation and immediately after the scanning session, patients were assessed clinically for symptoms of PD, via 

part 3 of the Unified Parkinson Disease Rating Scale

 (UDysRS). “The assessment was video recorded for subsequent blinded scoring of the UPDRS-III (except rigidity) and the objective part of the UDysRS,” wrote the researchers.

After completion of the blinded video assessment, it was revealed that real-repetitive transcranial magnetic stimulation delayed the onset of dyskinesia and reduced its severity when compared with sham-repetitive transcranial magnetic stimulation.

Moreover, individual improvement in dyskinesia severity was indicated to scale linearly with the modulatory effect of real-repetitive transcranial magnetic stimulation on task-related activation in the pre-supplementary motor area. Stimulation-induced delay in dyskinesia onset was also found to correlate positively with the induced electric field strength in the pre-supplementary motor area.

“Our results provide converging evidence that the levodopa-triggered increase in pre-supplementary motor area activity plays a causal role in the pathophysiology of peak-of-dose dyskinesia and constitutes a promising cortical target for brain stimulation therapy,” concluded the study authors.


Lohse A, Meder D, Nielsen S, et al. Low-frequency transcranial stimulation of pre-supplementary motor area alleviates levodopa-induced dyskinesia in Parkinson disease: a randomized cross-over trial. 

. Published online September 18, 2020. doi:10.1093/braincomms/fcaa147

Low-frequency transcranial stimulation of the pre-supplementary motor area was found to delay the onset and reduce severity of levodopa-induced dyskinesia in patients with Parkinson disease.

What Can Alleviate Levodopa-Induced Dyskinesia in Parkinson Disease?

Intermittent hypoxia sensitizes control centers in the brain, the result being exaggerated responses to even a minor change in breathing, noted Krishna M. Sundar, MD, clinical professor, Pulmonary Division, Department of Medicine, and medical director, Sleep-Wake Center, University of Utah.

How do the physiologies for obstructive and central sleep apnea overlap?

They overlap quite a bit, because each time there is a lack of the respiratory generator rhythm, which drives a breath, there is a pause in breathing because of a central apnea. So with each breath, it's not really that the diaphragm contracts and opens up the lung, the area has to be opened up also. So again, if there is no impulse to breathe, there is a tendency for the airway to narrow. A central sleep apnea can actually lead to airway collapse and obstruction. So that's one simplistic explanation.

The other thing is that in obstructive sleep apnea, we have a phenomenon called intermittent hypoxia, because oxygen levels keep fluctuating each time [the airway closes, reopens] when the patient wakes up, and then [closes] again as they drift into deep sleep. So this fluctuating oxygen levels sensitizes the control centers in the carotid body in the brain. And that can lead to something called an exaggerated response to any minor change in breathing, which may also cause some instability of breathing. Any instability of breathing at night, indeed, the more central apneas. So obstructive sleep apnea can lead to more central apneas, and central apneas lead to obstructive sleep apnea.

Again, practitioners need to understand what is driving what and what are the factors which [are] driving central sleep apnea in the [patients].

Intermittent hypoxia sensitizes control centers in the brain, noted Krishna M. Sundar, MD, clinical professor, Pulmonary Division, Department of Medicine, and medical director, Sleep-Wake Center, University of Utah.

Dr Krishna Sundar: Obstructive Sleep Apnea Can Lead to Central Sleep Apnea and Vice Versa

 since 2019 and has a BA in philosophy and journalism & professional writing from The College of New Jersey. 

Among patients with glaucoma, diffuse macular damage was associated with diminished facial recognition and contrast sensitivity (CS), according to results of a cohort 

. The findings suggest evaluation of macular optical coherence tomography (OCT) and 10-2 

 field (VF) and resultant detection of diffuse macular damage may help minimize glaucoma-related visual disability, the researchers wrote.

Facial recognition is a complex visual task that relies on central visual function and CS. Because it is vital for social interaction and forming relationships, any impairment to facial recognition negatively impacts quality of life.

“Because CS is a clinical measure of macular function and is critical to successful facial recognition, it may be an important component to the association of macular damage with impairment of facial recognition,” the authors hypothesized.

Focal or diffuse patterns of macular damage are differentiated by comparing abnormal regions on the 10-2 VF with corresponding regions on retinal ganglion cell (RGC) and retinal nerve fiber layer (RNFL) probability maps. However, it is unclear how each type of macular damage contributes to visual disability.

To evaluate the association of the pattern of glaucomatous macular damage with CS and facial recognition, and to gain a better understanding of the relative contribution of focal and diffuse macular damage in visual disability, the researchers carried out a prospective cohort study.

A total of 72 patients who presented at the Department of Ophthalmology at Columbia University Irving Medical Center in New York between March and April 2019 were included in the analysis. All participants had a diagnosis of primary open-angle glaucoma in 1 or both eyes, as determined by a glaucoma specialist, and underwent a comprehensive ophthalmologic exam. Spectral-domain OCT (SD-OCT) images were also acquired while VF testing was performed with the Humphrey Field Analyzer II.

“The SD-OCT RNFL and RGC+ and 10-2 VF data were examined for the presence of corresponding regions of macular damage on VF and OCT probability maps to classify eyes as having focal, diffuse, or mixed macular damage.”

Of the 72 participants, 49 (68%) were White, 41 (57%) were female, and the mean (SD) age was 67 (11.6) years. At baseline, of the 72 better-seeing eyes, 44 (61%) had macular damage, 22 (50%) had focal damage, 15 (34%) had diffuse damage, and 7 (16%) had mixed focal and diffuse damage. Among the 72 worse-seeing eyes, “63 eyes (88%) had macular damage and 9 (12.5%) did not. Of 63 eyes with macular damage, 26 (41%) had focal damage, 19 (30%) had diffuse damage, and 18 (29%) had mixed focal and diffuse damage.”

Eyes with diffuse damage had greater contrast impairment compared with eyes with focal damage (β = −0.5; 95% CI, −0.6 to −0.4; 

 < .001) after adjusting for 10-2 VF mean deviation (MD), 24-2 VF MD, age, presence of an early cataract, and number of drops

Cambridge Face Memory Test scores were significantly lower in patients with diffuse rather than focal macular damage, regardless of eye (better-seeing eye: β = 10.0; 95% CI, 2.0-18.2; 

 = .001; worse-seeing eye: β = 5.5; 95% CI, 0.8-10.0; 

Relative risk of facial disability was greater for patients with diffuse but not focal macular damage in the better-seeing eye (relative risk, 86.2; 95% CI, 2.7-2783.3; 

Overall, the results suggest diffuse macular damage is disproportionately associated with both CS and facial recognition impairments as opposed to a focal pattern of damage.

“Although diffuse damage may be more difficult to identify than focal damage, it is an important determinant of visual function and should prompt early and aggressive intervention. Therefore, careful evaluation of the macular OCT and 10-2 VF and resultant early detection of diffuse macular damage is critical to minimize glaucoma-related visual disability,” the researchers concluded.

Hirji SH, Hood DC, Liebmann JM, Blumberg DM. Association of patterns of glaucomatous macular damage with contrast sensitivity and facial recognition in patients with glaucoma. 

. Published online November 5, 2020. doi:10.1001/jamaophthalmol.2020.4749

Among patients with glaucoma, diffuse rather than focal glaucomatous macular damage was associated with diminished facial recognition and contrast sensitivity, according to results of a cohort study published in JAMA Ophthalmology. 

Diffuse Macular Damage Linked to Diminished Facial Recognition, Contrast Sensitivity

Intravenous (IV) iron reduced rehospitalization risk among patients hospitalized with acute 

 (HF) and low iron, according to research presented at the American Heart Association’s 

In patients with HF, iron deficiency (ID) is common and is associated with reduced exercise capacity, poor quality of life, and increased risk of hospitalization and death. However, IV ferric carboxymaltose (FCM) has been shown to improve physical performance and quality of life in stable patients with HF.

To test if IV FCM administered to patients with iron deficiency admitted for acute HF is superior to placebo, researchers conducted a multicenter, randomized (1:1) double-blind trial. The 

 included 1108 patients from 121 centers across 15 countries. Average participant age was 71 years, and the majority (56%) were male. The cohort had an average ejection fraction of 33%.

ID was defined as serum ferritin less than 100 ng/mL, or serum ferritin 100 to 299 ng/mL and transferrin saturation (TSAT) less than 20%. Participants received between 500 and 2000 mg of FCM or placebo during the repletion phase, or up to postdischarge week 6. Dosing regimens were based on weight and hemoglobin level. At weeks 12 and/or 24, during the maintenance phase, patients received 500 mg of FCM or placebo only if ID persisted.

The study’s primary end point was a composite of recurrent HF hospitalizations and cardiovascular death up to 52 weeks after randomization. Secondary end points included total HF hospitalizations, cardiovascular death, time to first HF or cardiovascular death, and days lost due to HF hospitalizations or CV death.

Overall, 558 patients received IV FCM and 550 received placebo. Those who received FCM had significantly fewer hospital readmissions due to HF compared with those who received the placebo.

293 primary events (57.2 per 100 patient-years) occurred in the FCM group and 372 (72.5 per 100 patient-years) occurred in the placebo group (rate ratio [RR], 0.79; 95% CI, 0.62-1.01; 

370 total cardiovascular hospitalizations and cardiovascular deaths occurred in the FCM group and 451 occurred in the placebo group (RR, 0.80; 95% CI, 0.64-1.00; 

There was no difference in cardiovascular death between the 2 groups (77 [14%] of 558 in the FCM group vs 78 [14%] in the placebo group; HR, 0.96; 95% CI, 0.70-1.32; 

217 total HF hospitalizations occurred in the FCM group and 294 occurred in the placebo group (RR, 0.74; 95% CI, 0.58-0.94; 

The composite of first HF hospitalization or cardiovascular death occurred in 181 (32%) patients in the FCM group and 209 (38%) in the placebo group (HR, 0.80; 95% CI, 0.66-0.98; 

Fewer days were lost due to HF hospitalizations and cardiovascular death for patients assigned to the treatment compared with placebo (369 days per 100 patient-years vs 548 days per 100 patient-years; RR, 0.67; 95% CI, 0.47-0.97; 

When it comes to safety, 45% of patients in the treatment group experienced serious adverse events compared with 52% of those in the placebo group. The most common adverse events reported included cardiac disorders, infections, diarrhea and constipation. The study found no apparent effect on the risk of cardiovascular death.

“This is the first study demonstrating the benefits of iron supplementation initiated in stabilized patients hospitalized for acute [HF], and only two doses were needed in the vast majority of patients,” 

 Piotr Ponikowski, MD, the study’s lead author.

“Health care professionals should screen patients with [HF] for the presence of [ID], and [IV] iron should be considered for those with [ID] and ejection fraction of 50% or lower.”

Ponikowski P, Kirwan B, Anker SD, et al. Ferric carboxymaltose for iron deficiency at discharge after acute heart failure: a multicenter, double-blind, randomized, controlled trial. 

. Published online November 13, 2020. doi:10.1016/S0140-6736(20)32339-4

Intravenous (IV) iron reduced rehospitalization risk among patients hospitalized with acute heart failure (HF) and low iron, according to research presented at the American Heart Association’s Scientific Sessions 2020. 

IV Iron Reduces Risk of Rehospitalization Among Iron-Deficient Patients With HF

 referenced a study published in the January 2020 issue of 

Using Applied Machine Learning to Predict Healthcare Utilization Based on Socioeconomic Determinants of Care

,” exhibited the possibility in generating a highly accurate model to predict inpatient and emergency department utilization using data on socioeconomic determinants of care.

 spotlighted a study published in the February 2013 issue of 

Impact of Oral Nutritional Supplementation on Hospital Outcomes

,” found through an instrumental variables regression analysis that inpatient oral nutritional supplement use decreased length of stay, episode cost, and 30-day readmission probability.

Coverage of our peer-reviewed research and news reporting in the health care and mainstream press.

AJMC® in the Press, November 27, 2020

's parent company, MJH Life Sciences, since 2011. She has an MA in business and economic reporting from New York University.

Combination therapy plays a central role in treating pulmonary arterial hypertension (PAH), and 2 abstracts presented at the CHEST annual meeting highlighted real-world treatment patterns.

 the researchers used the combined OPsumit Users (OPUS) Registry and OPsumit Historical Users cohort (OrPHeUS) to assess treatment pattern changes over time to manage PAH, comparing patients who initiated macitentan before the 2015 European Society of Cardiology (ESC)/European Respiratory Society (ERS) guidelines (pre-GL) and after the guidelines (post GL). OPUS is a prospective, multicenter, observational drug registry, and OrPHeUS is a multicenter medical chart review.

Of the 4428 total patients, 2318 (52%) initiated macitetan pre-GL and 2110 (48%) initiated the therapy post GL. Although median age and proportion of patients who were female were similar between the pre- and post-GL groups, patients in the post-GL group were far more likely to have been diagnosed in the previous 6 months (52% vs 39%) and had a much shorter median time from diagnosis (5.2 months vs 12.5 months).

The proportion of patients receiving macitetan as a mono, double, or triple therapy remained largely the same. In the pre-GL group, 41% of patients initiated macitentan as a monotherapy, 45% as double therapy, and 14% as a triple therapy. In the post-GL group, 41% initiated macitentan as a monotherapy, 47% as a double therapy, and 13% as a triple therapy.

“The majority of patients initiating macitentan received combination therapy at baseline and 6 months postbaseline across all years reported,” the authors concluded. “However, these proportions remained relatively constant over time, despite recommendations for increased use of combination therapy in the 2015 ESC/ERS PAH GL.”

In the second abstract, the researchers reviewed the OPUS registry to evaluate patients with PAH receiving triple combination therapy.

 They described the demographics, patient characteristics, treatment patterns, outcomes, and safety for patients with PAH receiving triple combination therapy of macitentan plus a phosphodiesterase type 5 inhibitor (PDE5i) and a prostacyclin pathway agent.

A total of 404 patients with PAH in the OPUS registry received triple therapy at any point, with 51 patients (12.6%) receiving triple therapy as initial treatment and 353 patients (87.4%) receiving it as sequential treatment. The median time from diagnosis to initiation of triple therapy was 22.7 months.

Half (49.9%) of the patients received triple therapy for ≥ 2 years and 63.4% received triple therapy for 1 year or more. The majority (76.2%) of patients reported at least 1 adverse event and 45.8% of patients stopped triple therapy because they discontinued at least 1 of the drugs: 39 (9.7%) patients discontinued all 3; 10 (2.5%) discontinued 2; 26 (6.4%) discontinued the PDE5i only; 42 (10.4%) discontinued the prostacyclin pathway agent; and 68 (16.8%) discontinued macitentan.

1. Chin K, Channick R, McLaughlin V, et al. Treatment patterns in pulmonary arterial hypertension: changes in clinical practice over time using real-world evidence from the combined OPUS/OrPHeUS data sets. Presented at: CHEST Annual Meeting 2020; October 18-21. https://journal.chestnet.org/article/S0012-3692(20)34063-0/fulltext

2. McConnell J, Chin K, Kim N, et al. Experience with macitentan triple combination therapy in pulmonary arterial hypertension: real-world evidence from the OPUS registry. Presented at: CHEST Annual Meeting 2020; October 18-21. https://linkinghub.elsevier.com/retrieve/pii/S0012369220340812

Real-World Data of Combination Therapy With Macitentan to Treat PAH

Clinicians must talk to their patients, because it may help to uncover possible gaps in their medication access, which can be helpful to addressing overall medication persistence and care engagement, stressed Milena Murray, PharmD, MSc, BCIDP, AAHIVP, associate professor at Midwestern University Chicago College of Pharmacy, who practices at Northwestern Medicine's Infectious Disease Center in Chicago.

How can managed care professionals collaborate with clinicians to ensure persons living with or at risk of HIV remain engaged in their care?

We know that there's literature showing that attending clinic appointments is associated with medication persistence. So medication persistence is filling every month, being adherent over a span of time. And this type of question could be added into just the general questions, such as shipping information, if they're coming from a mail order pharmacy, or just even at the point of dispense, [such as asking], “Oh, when's your next follow-up appointment?” And if somebody hasn't been there in over a year or it's coming up on a year to get that appointment scheduled, specialty pharmacies are really able to get this information from the electronic medical record. So for example, if I'm looking and trying to refill a prescription, I might, you know, say, “Oh, gosh, this patient hasn't been here in however many months,” or the last note said, “Follow up in 3 months,” and it's been more than that now.

Clinicians must make sure patients are engaged in their care, stressed Milena Murray, PharmD, MSc, BCIDP, AAHIVP, associate professor at Midwestern University College of Pharmacy.