Guidance from the National Lipid Association on when DNA testing becomes a priority in cardiac-risk patients.

When to Test for Genetic Dyslipidemia

HIV/AIDS researcher Dr. David Ho describes the best candidates being pursued in a new podcast.

Our Best Hope in COVID-19 Vaccines

Recent study findings demonstrate treatment with tiotropium plus olodaterol results in a lower risk escalation of factors related to 

chronic obstructive pulmonary disease (COPD)

 versus long-acting β2-agonist (LABA) plus inhaled corticosteroid in patients with the condition.

Guidelines recommend COPD maintenance treatment with a combined LAMA plus LABA therapy. Inhaled corticosteroid treatment can be added if a patient has high levels eosinophils. But COPD patients are typically prescribed LABA plus inhaled corticosteroid therapy despite such use leading to an increased risk of pneumonia. 

Investigators found there was a lower risk escalation of triple therapy, COPD exacerbations, pneumonia, and adverse outcomes in patients treated with tiotropium plus olodaterol.

Jennifer Quint, MBBS, BSc, MSc, PhD, and colleagues analyzed administrative healthcare claims and laboratory results data from the HealthCore Integrated Research Database for COPD patients initiating first treatment with tiotropium/olodaterol versus LABA/inhaled corticosteroid. The team followed patients until the discontinuation or switch of their index treatment, until the end of health plan enrollment, or 1 year after the index date.

Patients at least 40 years old with a diagnosis of COPD but not asthma were included. Those in the study had at least 1 year of medical or pharmacy health plan eligibility prior to the index date to allow identification of new users of tiotropium/olodaterol and LABA/inhaled corticosteroid, and measurement of baseline covariates.

Quint and the investigators used a Cox proportional hazard regression model to assess risk of escalation to triple therapy, COPD exacerbation, pneumonia, or an adverse outcome. Subgroup data were analyzed based on circulating eosinophil levels and exacerbation history.

Overall, 42,953 patients were included in the study population (2600 tiotropium/olodaterol; 40,353 LABA/inhaled corticosteroid. Of the patients, those taking LABA or inhaled corticosteroid were nearly three-fold as likely to have risk of escalation to triple therapy compared to tiotropium/olodaterol patients (HR, 2.9; 95% CI, 2.84-2.97 vs .54 95% CI, .46-.64).

COPD exacerbations were also more likely among LABA/inhaled corticosteroid patients (HR, 2.43; 95% CI, 2.37-2.49) compared to those taking tiotropium/olodaterol (HR, 1.63; 95% CI, 1.47-1.81). Further, pneumonia requiring hospitalization was slightly more likely to occur in LABA/inhaled corticosteroid patients compared to patients on tiotropium/olodaterol (HR, .34; 95% CI, .32-.37 vs HR, .23; 95% CI, .18-.3).

When measuring the risk of an adverse outcome, patients in the LABA/inhaled corticosteroid group were three-times as likely to have baseline eosinophils <300 cells/μL than those in the tiotropium/olodaterol group (HR, 6.38; 95% CI, 6.02-6.77 vs HR, 2.09; 95% CI, 1.55-2.82). For infrequent exacerbation history, the tiotropium/olodaterol group had a hazard ratio of 1.71 (95% CI, 1.53-1.91) compared to HR, 4.31 (95% CI, 4.21-4.4) in the LABA/inhaled corticosteroid group. Frequent exacerbation history was more common in the LABA/inhaled corticosteroid group (HR, 10.63; 95% CI, 10.36-10.9 vs 3.95; 95% CI, 3.4-4.6).

COPD maintenance therapy with tiotropium/olodaterol versus LABA/ICS: an assessment of the risk of treatment escalation and adverse outcomes in over 40,000 patients

,” was presented as part of the 2020 American Thoracic Society International Conference.

Articles

Tiotropium plus olodaterol is more effective for patients with COPD compared with LABA plus inhaled corticosteroids.

Less COPD Exacerbation Risks for Tiotropium Plus Olodaterol

The US Food and Drug Administration (FDA) has approved transcranial magnetic stimulation (TMS Therapy) for adjunct treatment in adult patients with 

TMS had previously been granted approval to MagVenture for the treatment of 

 in patients who failed to experience adequate improvement from use of antidepressant medication. The company was the first to receive FDA clearance for the 3-minute Express TMS—the shortest TMS treatment now available. 

Now, the out-patient procedure can be used as adjunctive to other OCD treatments that might involve pharmaceutical and behavioral therapy. Using magnetic pulses to stimulate specific areas in the brain, TMS targets its networks and deeper-lying structures that are known to be particularly affected by OCD.

The therapy was not associated with any systemic side effects.

OCD, a mental disorder characterized by obsessions and compulsions, can cause severe disruptions in one’s daily life and routines and can lead to further distress and functional impairment. Although there are currently several pharmaceutical and psychological intervention options that are available for these patients, some experience limited improvement and mitigation of symptoms. Thus, the need for greater therapeutic options becomes increasingly necessary.

“We have worked closely with brain researchers for well over 25 years, providing numerous TMS solutions to help advance the field of neuroscience – both basic and applied,” said Kerry Rome, VP of Sales for MagVenture, in a statement. “Expanding the treatment options to include other indications than major depressive disorder, such as OCD, is one more important step towards helping more adult patients improve their mental health”

MagVenture TMS Therapy can be used as adjunctive therapy to other OCD treatments. 

FDA Approves TMS Therapy to Treat OCD

 could be the next specialty to look into utilizing new deep learning technology to screen and diagnose patients with ocular disorders.

A team, led by Nihaal Mehta, MD, New England Eye Center, Tufts Medical Center, determined whether a model-to-data deep learning approach without needing to transfer any data can be applied in ophthalmology.

In the single-center cross-sectional study, the investigators examined patients with active exudative age-related macular degeneration (AMD) who underwent optical coherence tomography (OCT) at the New England Eye Center between August 2018 and February 2019.

The investigators sought main outcomes of the training of the deep learning model, using a model-to-data approach, and recognizing intraretinal fluid on OCT B-scans.

The model-to-data approach was taken by freezing the model parameters from a prior study where a deep learning model was trained to segment IRF on Heidelberg Spectralis OCT B-scans.

The model parameters, retraining code, data preprocessing, and code for evaluation were packaged from the University of Washington and transferred using GitHub.

The model was training with a learning curve Dice coefficient greater than 80% using 400 OCT B-scans from 128 patients, 69 of which were female. The mean age of the patient population was 77.5 years old.

The scan protocol consisted of 512 A-scans per B-scan and 128 B-scans per volume, while the spectral-domain OCT system has an 840 nm central wavelength, as well as 68 000 A-scans per second, an A-scan depth of 2.0 mm, an axial resolution of 5 μm, and a transverse resolution of 15 μm.

The investigators compared the model with manual human grading of IRF pockets and found no statistically significant difference in Dice coefficients or intersection over union scores (

“A model-to-data approach to deep learning was demonstrated for the first time, to our knowledge, in ophthalmology,” the authors wrote. “Using this approach, the performance of the deep learning model was trained and showed no statistically significant difference in quantifying the intraretinal fluid pockets in OCT compared with human manual grading. Such a paradigm has the potential to more easily facilitate large-scale and multicenter deep learning studies.”

While more deep learning tools are being used in virtually every medical specialty, there remains concerns regarding data privacy, security, and sharing. However, by using a model-to-data approach, the model itself can be transferred rather than the data, circumventing many of the existing challenges.

This technique has been tried in other specialties, but has not yet been attempted in ophthalmology. However, this technology could be transformative in the space due to ophthalmology’s dependence on outpatient ancillary testing.

Machine learning and deep learning have already been applied in ophthalmology in a variety of contexts and to a range of clinical conditions, ranging from diabetic retinopathy, age-related macular degeneration,

 and glaucomato, Stargardt disease, and post–small incision lenticule extraction surgical outcomes.

Model-to-Data Approach for Deep Learning in Optical Coherence Tomography Intraretinal Fluid Segmentation

In a comparison with manual human grading, investigators find machine learning model produced no statically significant differences in Dice coefficients. 

Deep Learning Could Transform Ophthalmology

A new study finds significant disparities between heart team recommendations and those of original treating interventional cardiologists for patients with 

multivessel coronary artery disease (CAD)

The study, led by Michael Tsang, MD, MSc, and colleagues and funded by the Hamilton Health Sciences New Investigator Fund, consisted of a cross-sectional study to determine the extent of differences in multivessel CAD treatment decisions between heart teams and original treating interventional cardiologists. Their findings also indicated that in cases when both group opinions differed, the heart team tended to have a greater frequency of internal discordance.The investigators noted that it is currently unclear whether heart team reviews generally lead to improved clinical outcomes, yet the results of this study indicate that it may be necessary to identify which patients would benefit from such an approach.

At the outset of the study, the investigators selected 245 out of 771 screened patients who met specific criteria for multivessel CAD, which they defined as stenosis of 70% or more in 3 epicardial vessels, stenosis of at least 1.5 mm in their branches, or stenosis in 2 epicardial coronary vessels with involvement of the proximal left anterior descending artery.

The recruitment process included an interview and treatment recommendation from an original treating interventional cardiologist.

Another 60 patients from their database with similar distribution of original treatment recommendations were retrospectively added to the data for analysis.

The investigators constructed 8 three-member heart teams, each consisting of 1 interventional cardiologist, 1 cardiovascular surgeon, and 1 noninvasive cardiologist. Each member was blind to their other team members and their decisions, so as to mitigate any social influences on decision-making, and decisions were made asynchronously and independently. Members were able to view the other decisions only after their independent recommendations were submitted—a change in decisions was then allowed.

Of the 245 selected patients, the teams evaluated 237 cases through a virtual heart team interface. Each team received 6 randomized sets of 5 cases. The investigators determined the heart team recommendation to be either the unanimous or majority decision.

The 3 recommendations considered among the original treating interventional cardiologists and heart teams were coronary artery bypass grafting (CABG), percutaneous coronary intervention, and medical therapy.

Results showed that 71 differences (30.3%; 95% CI, 24.5-36.7) occurred between both types of recommenders.

Tsang and colleagues used the Cohen x statistic to determine the overall agreement between both treatment cases. A paired analysis between original treatment decision and heart team decisions showed an x coefficient of .478 (95% CI, 0.336 - 0.540, 

 = .006), which indicates moderate agreement.

Further analysis revealed that agreement between the heart team decision and original treatment agreement was often associated with a unanimous recommendation among the heart team (109 of 163 cases [66.9%]), compared with discordance between both recommendations (28 of 71 cases [39.4%], 

The heart team interventional cardiologist often agreed with the original testing cardiologist when both decisions were concordant with each other (138 of 163 cases [84.7%]) versus when both original treatment and heart team treatment disagreed with each other (14 of 71 cases [19.7], 

Tsang and team have noted the implications of such conflicting treatment decisions, especially in uncertain multivessel CAD cases.

“If use of the heart team approach were found to be associated with improvements in outcomes, selection of these cases a priori would likely require a scoring tool that uses common clinical characteristics (eg, age, frailty, cognitive dysfunction, and SYNTAX score) to quantify the therapeutic dilemma,” they wrote. “Because multivessel CAD accounts for approximately 25% to 60% of patients with CAD, such a tool would have wide applicability.”

Heart Team vs Interventional Cardiologist Recommendations for Multivessel Coronary Artery Disease

In a cross-sectional study among CAD patients, investigators found that 30.3% of heart team treatment recommendations diverged from original consultation. 

Heart Team Recommendations Conflict with Original CAD Treatment

) pandemic is novel in its absolute effect on healthcare, in patients, and on society as whole. It is an unprecedented outbreak in size, scale, and speed, and has resulted in entirely unique measures of response and discourse in a matter of months.

But it does ring a bell for some epidemiologists—not the entire virus, but parts of its characteristics, most difficult questions, its ultimate effect on patients, likens to other outbreaks.

Last week, HIV/AIDS research pioneer David Ho, MD, joined 

 and the American Lung Association (ALA) on Lungcast, to discuss the up-to-date burden of COVID-19, and what future optimal response would look like—from vaccines to public health practices. Being a world-leading virology expert, Ho also made note of a trio of past viruses in which he sees similarities, and stark differences, within COVID-19.

Of course, COVID-19 manifests as a SARS-CoV-2 infection in patients, burdening individuals through mostly symptomatic effects on their upper respiratory system—similar to the SARS outbreak of 2003.

But both viruses have been more diverse and unpredictable in pathophysiology. Ho noted that clinicians have consistently observed renal failure, cardiac events, hepatic disease, and central nervous system manifestations in SARS-CoV-2-infected adults, as well as multi-inflammatory syndromes in children. On a lesser scale, such was the case in some SARS patients.

“There’s just so much we don’t know, and why that only small minorities are susceptible to complications,” Ho explained. “We’ve seen a bit of that from SARS, but SARS was in magnitude dwarfed by the current one. The clinical manifestations were not so clearly delineated.”

Adding to the confusion of interpreting the drivers of multi-organ burden in severe COVID-19 patients is the fact that previous coronaviruses have been observed to simply affect the airways—nothing more.

Perhaps everyone’s favorite likening of the most common COVID-19 symptoms: fever, dry cough, shortness of breath, etc. Indeed, some of the earliest public health messages around COVID-19 was that symptoms alike a severe case of the flu could indicate possible COVID-19 infection.

Though that message has been misconstrued to many laypeople believing the overall effect of COVID-19 is nothing worse than the flu—despite very conflicting mortality rate comparisons and burden on various systems of the body—the connection Ho sees between the two simply has to do with future vaccination.

According to the US Centers for Disease Control and Prevention (CDC), 

 and 62.6% of children were covered for flu vaccination in the 2018-19 season. This, combined with the growing anti-vaccination rhetoric in the nation, complicates the matter of introducing rapidly-developed COVID-19 vaccine candidates to the population in the coming months.

“There’s a lot of misinformation being circulated,” Ho said. “We need to do our very best to counter that effort.”

As one of the earliest clinical witnesses to AIDS and a globally-heralded researcher of HIV pharmacotherapy, Ho likely sees the previously most famous epidemic in much of his virologic work.

But some of it obvious: though COVID-19 is an acute disease versus the chronic nature of HIV, both are outbreaks which were surrounded by shrouds of public denial, inattention, and clinical confusion as to how they could be treated.

HIV was a “mysterious illness” at the time of its discovery, Ho said, and it remained so for several years. Though the causative agent of COVID-19 was quickly identified and sequenced, it shares in the HIV outbreak that many mostly ineffective antiviral therapies are being assessed for any benefit in severe patients.

“I would say there were at least 3-4 dozen drugs that were put forward as potential treatments or cures for HIV; none of that panned out,” Ho said. “In this instance, we went through the same. We have so many drugs being tested—drugs that were developed for other purposes.”

While some including hydroxychloroquine have recurred in national debate over its limited to no value in COVID-19 treatment, other antivirals including remdesivir have been expedited to emergency use—despite playing a minute role in a very select population of hospitalized patients with COVID-19.

It echoes Ho’s experiences in the early years of HIV: whatever could help, would help.

“While it may help a few patients get out of the hospital a little sooner, we’re still searching for more effective agents,” Ho said about remdesivir. “All of that, from HIV, is reflected in SARS-CoV-2.”

Unfortunately, the greatest bridge Ho sees between early HIV and COVID-19 is in the fate of its first fatal patients. In his words:

“The HIV patients, early on, were dying alone. Because of stigma, discrimination, and unjustified fear, they were shunned by friends and family. And of course, early on, we had no therapies. They were dying in large numbers in the hospital, largely alone. And in my experiences in the past few months, the SARS-CoV-2 severe cases were dying alone—not because there was no support, but because of the isolation required. And that’s really registered with me, thinking about the early days of HIV.”

At the same time, he sees the innovations and breakthroughs that came in HIV care—massive steps in diagnostics and treatment that he played a major hand in progressing—as a foundation by which COVID-19 research and development has been built upon.

And fortunately, that characteristic of COVID-19—the work toward combating it—is unlike any other in both speed and size.

David Ho, MD, likens and contrasts the pandemic to 3 other viral outbreaks and their respective responses.

What COVID-19 Shares in Common with Other Viruses

Videos

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Benralizumab Safe, Effective for Asthma Patients

An expert in Alzheimer disease describes some of the struggles dementia patients might be going through during the COVID-19 pandemic.

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New data shows an adherence to troponin testing could complement optimized care.

High-Sensitivity Troponin Testing Could Identify Stratified ASCVD Risk

National Health Center Week kicks off on August 9.

COVID-19 Only Adding to the Challenges Health Centers Face

Dupilumab significantly reduces exacerbation rates in patients with asthma compared to standard of care.

Dupilumab Reduces Asthma Exacerbation Rates

In a study presented virtually at ATS 2020, investigators find 15 mg of the study drug resulted in a 43% decrease in FeNO.

GDC-0214 Well-Tolerated for Patients with Mild Asthma

A new case study  assesses biopsy and autopsy tissues to characterize pathological patterns in suspected EVALI cases .

Autopsies, Biopsies Link Lung Injuries to E-Cigarette Use  

Investigators found a 22% reduction in clinical decline at the 78-week cutoff in the intent to treat population in EMERGE who received high-dose aducanumab, with a similar reduction seen in the opportunity to complete population. 

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