New insights on the potential of the OSPREY trial suggested that targeted hypoglossal nerve stimulation (THN) therapy could be safe and efficacious for moderate to severe obstructive sleep apnea (OSA).

the American Thoracic Society 2020 International Conference

Obstructive sleep disorder is a condition believed to affect over 1 million people globally, with 35 million of those cases originating from the United States.

Though therapeutic options such as positive airway pressure (PAP) have been known to correct sleep disordered breathing, they are not always tolerated.

Additionally, the implications of OSA on cardiovascular and neurocognitive outcomes have raised concerns among clinicians for decades.

Meanwhile, oral appliances and surgery are optional but generally less effective strategies in combatting OSA. Thus, an unmet need for therapeutic options exists.

Previously, investigators led by Ofer Jacobowitz, MD, PhD, Co-director of Sleep at ENT and Allergy Associates in New York, suggested THN therapy could be used to treat OSA, believing in to be “a simpler approach than incumbent technology with no sensor and an easier, proximal electrode implantation”.

With the present investigation, the team intended to design a confirmatory randomized clinical trial (RCT) of THN therapy for Level 1 evidence in moderate to severe OSA. 

Jacobowitz and colleagues first reviewed primary efficacy endpoints and potential study designs from THN3, which was the RCT of HGNS in OSA to report results.

Apnea hypopnea index (AHI) response rate (RR) was prioritized as the obligatory primary outcome for regulatory approval.

As such, THN3 AHI RRs for the treatment and control groups were 52% and 20%, respectively,

The team selected a parallel-arm RCT, of which all subjects were implanted, with 2/3 are activated at Month 1 (treatment group) and 1/3 activated at Month 7 (control). 

Patients were followed for a total of 13 months, with the primary endpoint being the difference in AHI RR between Treatment and Control groups at Month 7.

Secondary endpoints included quality of life instruments such as the Epworth Sleepiness Scale; Functional Outcomes of Sleep Questionnaire, EQ- 5D, SF-6D and PROMIS sleep questionnaires, and oximetry metrics (Oxygen Desaturation Index, and the percentage of sleep time below 90% oxygen saturation). 

Notably, OSPREY followed an adaptive “Goldilocks” Bayesian design that optimized the required number of subjects with the need for high-confidence inferences from results, according to the investigators.

A maximum of 150 subjects were allowed, and simulations predicted a study power of >95% for the primary endpoint.

Interim analyses would begin once 50 patients were randomized, recurring after each 20 additional randomizations up to 150.

Predictive probabilities based on accrued results would enable detection of early success or early futility.

Investigators concluded that the OSPREY trial would be “ a unique, efficient RCT that should provide high-confidence confirmation of the safety and efficacy of THN therapy in moderate to severe OSA.”

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Investigators from this ATS session suggested THN therapy could be used to treat OSA, believing in to be “a simpler approach than incumbent technology with no sensor and an easier, proximal electrode implantation”.

OSPREY Trial Suggests THN Therapy Effective in Moderate to Severe OSA

 indicated that an as-needed, fixed-dose combination of 180 μg of albuterol and 160 μg of budesonide resulted in significantly lower risk of severe asthma exacerbation than abluterol alone in patients with uncontrolled moderate to severe asthma who were receiving a variety of inhaled glucocorticoid-containing maintenance therapies.

the American Thoracic Society 2022 International Conference

Traditionally, short-acting β2-agonist (SABA) rescue therapy will be utilized in patients whose asthma symptoms worsen. However, SABAs are not intended for addressing worsening inflammation.

Research has indicated that a fixed-dose combination of albuterol and budesonide would reduce the risk of severe asthma exacerbation when compared to albuterol alone.

Alberto Papi, MD, from the Department of Respiratory Medicine at the University of Ferrara Medical School in Italy, led a team of investigators in conducting a multinational, double-blind, phase 3 trial that evaluated the efficacy and safety of albuterol-budesonide as a rescue medication.

The investigative team enrolled adults and adolescents 12 years and older with uncontrolled moderate to severe asthma who were receiving inhaled glucocorticoid-containing maintenance therapies at the time. These therapies were continued during the trial.

Eligible patients were randomized 1:1:1 to 1 of 3 trial groups including a fixed-dose combination of albuterol at a dose of 180 μg and budesonide at a dose of 160 μg, a fixed-dose combination of albuterol at a dose of 180 μg and budesonide at a dose of 80 μg, or albuterol at a dose of 180 μg.

Notably, children 4 to 11 years were randomly assigned to either the lower-dose combination groups or the albuterol-only group. Among the 3132 patients included in thr trial, 97% were 12 years or older.

Papi and colleagues defined the primary endpoint as the first severe asthma exacerbation in a time-to-event analysis.

The team observed that severe asthma exacerbation was significantly lower in the higher-dose combination group, specifically by 26%, when compared to the albuterol-alone group (hazard ratio, 0.74, 95% confidence interval). (P=0.001).

Compared to the albuterol-only group, the hazard ratio in the lower-dose combination group was 0.84 (95% CI, 0.71 to 1.00) (P=0.052), and the incidence of adverse events were similar across all trial groups.

Research has indicated that a fixed-dose combination of albuterol and budesonide could better reduce the risk of severe asthma exacerbation when compared to albuterol alone.

Severe Asthma Exacerbation Risk Reduced with Combined Albuterol-Budesonide

The long pursuit of a US Food and Drug Administration (FDA) approved treatment for non-alcoholic fatty liver disease (NAFLD).

Despite no currently approved therapies for the disease, there are currently more than 400 clinical trials involving NALFD in some compacity, at least 1 stakeholder is confident there will be an approved treatment in the next calendar year.

, Sanjiv Chopra, MD, Professor of Medicine, Harvard Medical School, said he hopes a treatment for NAFLD will finally be approved in as early as 6 months from now.

And while it can be difficult to predict how the US Food and Drug Administration might react, Chopra is confident they will approve a treatment for NAFLD.

“The FDA has gotten quicker and more efficient at approving drugs,” Chopra said. “I think we will see a bunch of these drugs approved in the next 6 months.”

Chopra said even with an FDA approval, care might not be transformed overnight.

“The challenge will be are the insurance companies going to pay for it and what is the cost going to be,” he said. For some of these drugs the cost is $1,200 or $1,500 a month. That’s a lot of money and many of the people who most need it will be the ones least likely to afford it.”

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Dr. Chopra said an FDA-approved treatment for NAFLD could come in the next 6 months. 

Sanjiv Chopra, MD: Treatments for NAFLD on the Way

 was "New Drugs for the PCP: Outpatient Treatment of 

" led by Gerald Smetana, MD, Professor of Medicine, Harvard Medical School, Clinician Educator, Division of General Medicine and Primary Care, Beth Israel Deaconess Medical Center.

Smetana highlighted the key points of his presentation and went into a detailed discussion of the outpatient treatment options for the virus in an interview with 

. Every year at this conference, he talks about new drugs in primary care, but this year, Smetana decided to use his limited time on stage to focus on outpatient management of COVID-19.

"I really think it's the most important new drug advance for primary care clinicians," he said, "and in particular, I think, because many of us might be uncomfortable in that venue, and not confident in prescribing these medicines."

Smetana acknowledged that PCPs might be hesitant to prescribe monoclonals because they think these drugs are outside of their usual scope of practice, which is true, he said. However, the current position of primary care providers puts them in the role of prescribing outpatient treatments for the virus and he encouraged providers to get comfortable with monoclonal antibodies.

"We're on the front lines, we're the ones who are getting these phone calls," Smetana explained, "and we just simply don't have the time between when symptom onset occurs and patients have to be treated to get those types of subspecialty consultations."

With the emergence of various strains of COVID-19, the treatment landscape is ever-changing. And while he talks about the various monoclonal antibodies, right now, bebtelovimab is the only one that's retained an emergency use authorization (EUA) from the US Food and Drug Administration (FDA) for all variations of the virus.  

The Oral Antiviral Treatment for COVID-19

Nirmatrelvir-ritonavir (Paxlovid) is the first oral antiviral treatment of COVID-19 that's been deemed safe for the same indication as bebtelovimab--outpatients with the virus who are at risk of progression to severe disease. In addition to being safe, a primary advantage to this drug is that it's administered orally, rather than needing infusions like monoclonal antibodies. 

Smetana clarified that a few important things providers need to consider to when prescribing nirmatrelvir-ritonavir. It's crucial to be very thorough when checking for 

. Also, the adjusted dosage guidelines for patients with kidney disease must be followed. 

The treatment was approved in December and needs to be given to the patient within 5 days of symptom onset. Fortunately, nirmatrelvir-ritonavir has recently become available in commercial pharmacies and should be 

widely accessible now in most communities

"This is possible to get at local pharmacies, not just academic medical centers," he said. "It has to be given within 5 days of symptom onset, which is an important barrier. So, patients have to call us as soon as possible after testing positive. And because we do have that short window, this is why, you know, we're going to be the primary prescribers for that drug."

Dr. Gerald Smetana encourages PCPs to familiarize themselves with the outpatient drug options for managing COVID-19 because of the limited treatment window for administration.  

Gerald Smetana, MD: Outpatient COVID-19 Treatment Relies on Primary Care Providers

Doctors have been fighting misinformation regarding 

Whether it is about the safety of vaccines, the efficacy of treatments, or the overall threat of the actual disease, combating some of these misconceptions and purposeful misinformation attempts can be a full time job on it’s own.

, Tara Vijayan, MD, assistant professor of medicine in the Division of Infectious Diseases and medical director of antimicrobial stewardship at the David Geffen School of Medicine at UCLA, spoke about the role of primary care physicians in fighting those misconceptions.

“It’s hard to counter misinformation with a lot of information because I think it can be overwhelming,” she said. “But I think it’s really bringing it back to the patient and trying to get patients to really think about their own social network in a meaningful way can really build that trust.”

Vijayan said there are also misconceptions over clinical trials.

“I think maybe there are some ideas about what is actually being measured,” Vijayan said. “I’ve seen a little bit of chatter of this idea that they are keeping this information from us. I certainly think vaccine misinformation is often misrepresented.”

Dr. Tara Vijayan talks about how primary care physicians can be best combat misinformation. 

Tara Vijayan, MD: Doctors Fighting Misinformation

, the Anaheim Convention Center Ballroom CDE filled with physicians who have always wondered, "what conditions is cannabis really useful for?" or, "what does it work for?"

There may not be a simple answer to these questions, however, they were addressed in the "Curbside Consults" session on top questions from primary care providers (PCPs) about marijuana, led by Timothy Fong, Md, Professor of Psychiatry, Co-Director, UCLA Gambling Studies Program, David Geffen School of Medicine at UCLA, Director, UCLA Addiction Psychiatry Fellowship, David Geffen School of Medicine at UCLA.

Fong gave further insight on the topic in an interview with 

, saying that the overall reception to marijuana has drastically shifted in the US within the last decade and as a result, there's been an increase in research. 

There are currently a few medical conditions in which the US Food and Drug Administration (FDA) have approved medications that come from cannabis or cannabinoids. However, the only medication that's derived CBD from the plant itself is cannabidiol (Epidiolex), which treats intractable seizures in infants and young children, he explained. 

Other treatments like dronibanol (Marinol) are synthetic and, like cannabidiol, unlikely to be used in a primary care setting, Fond said, since they're indicated by the FDA for anorexia associated with weight loss in patients with acquired immune deficiency syndrome (AIDS), and for nausea and vomiting associated with chemotherapy in patients with cancer and who have inadequate response to conventional antiemetic treatments. 

What about the cannabis that's available in dispensaries? What about the cannabis that's available on the street? What about the cannabis that people borrow from their friends? Can those be effective for medical conditions? These are some of the common questions that PCPs and patients ask Fong, so he spoke about some of the risks and benefits of this type of thinking and the current landscape.

"Right now, we know that through cannabis research over the last 25 years, there are only a few conditions to which we think cannabis is really, really helpful for right now, in addition to chemotherapy-induced nausea and vomiting, chronic pain, muscle spasticity for multiple sclerosis (MS)," he explained, "those are the ones that we know that cannabis is probably helpful for--all the other conditions which people come into offices for, insomnia, depression, gaining weight, anxiety management, PTSD--unfortunately, the science right now does not support the use of cannabis for those conditions."

How to Answer Patient Questions about Marijuana

From a therapeutic perspective, cannabis is incredibly interesting, according to Fong, because the active ingredient goes beyond THC. There are hundreds of different chemical compounds, or cannabinoids, in any cannabis plant, and there's not enough research examining it.

"When patients come in asking about cannabis, it definitely is our duty as physicians to explain the risks and benefits of cannabis," he explained, "the side effects of cannabis, and to what medical conditions we know, scientifically, it's useful for."

"For patients," Fong continued, "we also had to explain to them that it's much more important and better practice of medicine for us to be using standard approved medical treatments for that condition."

Expert psychiatrist Dr. Timothy Fong explains the complexity of using marijuana as treatment in a primary care setting and shares advice on how to address it with patients.

Timothy Fong, MD: Is Cannabis Useful in Primary Care?

Americans were plagued by sedimentary lifestyles well before the 

Teenagers opting for video games rather than sports, office workers logging long hours without a break, and other unwinding with television is having a negative impact on the health of many.

Then when the pandemic is added in with gym closures and social opportunities cancelled, the health of many suffered greatly.

One such disease that individuals with a sedimentary lifestyle are prone to is 

non-alcoholic fatty liver disease (NAFLD)

, Sanjiv Chopra, MD, Professor of Medicine, Harvard Medical School, that the pandemic had a profound impact on an already growing liver disease problem.

Chopra also said alcoholic hepatitis rates increased during the pandemic.

“People were drinking more, perhaps because they were stressed and had access to alcohol,” he said. “They were not exercising, eating comfort food, and stressed.”

However, for many of these liver disease simple lifestyle fixes could make a large difference.

Chopra said even losing a little weight makes a profound impact on the risk of NAFLD. Other tips include regularly drinking coffee, vitamin D supplementation, and taking regular walk breaks at work when possible to avoid sitting for long stretches at a time.

Alcohol use increased during the COVID-19 pandemic, leading to an increase in alcoholic hepatitis.

Sanjiv Chopra, MD: Liver Disease During the COVID-19 Pandemic

Drug scarcity are a major problem in medicine that was only exacerbated during the 

In fact, during the height of the pandemic when new and effective drugs to combat the virus were produced, drug scarcity involving these drugs was a huge issue.

With more and more patients being hospitalized with COVID-19, particularly in inner cities and minority communities, there was a need to disperse the drugs in a fair and equitable way.

, Tara Vijayan, MD, assistant professor of medicine in the Division of Infectious Diseases and medical director of antimicrobial stewardship at the David Geffen School of Medicine at UCLA, explained some of the issues with drug scarcity and how exactly primary care physicians can combat this issue.

“This is an ongoing issue, not just with novel therapeutics, but with drugs that we’ve had for a long, long time,” Vijayan said. “Drug scarcity is going to be an ongoing issue and really prioritizing individuals who are at the highest risk is really important, both highest risk for progression and highest risk for exposure by virtue of being in certain communities that have lower access to certain resources.”

However, Vijayan did say that it has come a long way in this area and changes are beginning to take hold.

Vijayan recently gave a keynote address during 

High-risk individuals should be targeted when drug scarcity comes into play.

Tara Vijayan, MD: Combating Drug Scarcity

There are many things that can be said about the overall health of Americans, but really for many everyday life is littered with health problems.

With obesity and diabetes rates increasing in recent years, the rates for 

And this increase in disease rates can be seen in patients of all ages, from as young as 3 to senior citizens.

This increase is also coupled with the fact that there is not currently a treatment approved by the US Food and Drug Administration (FDA).

But there are ways to prevent or reduce the odds of NAFLD and help could be on the way.

, Sanjiv Chopra, MD, Professor of Medicin, Harvard Medical School, said losing weight and drinking 2-3 cups of coffee daily could help reduce the risk of NAFLD.

But the current state of affairs is not good.

“We have 3 year old’s in our country with fatty liver,” Chopra said. “We have 16 year old’s with liver scaring, we have 28-30 year old’s getting a liver transplant. It’s a sad commentary on what’s happened to us with our lifestyle.”

And while there is a push for a healthier overall lifestyle, there also may be finally a treatment coming for NAFLD.

Chopra said there is currently 452 clinical trials involving the disease and an FDA-approved drug could come by the end of the year.

NAFLD is currently the most prevalent liver disease in the US.

Sanjiv Chopra, MD: How to Treat NAFLD

 pandemic, clinicians might be finally confortable with the treatment options outside of the obvious benefits of vaccinations.

Treatments like monoclonal antibodies and paxlovid have shown much promising in reducing mortality for hospitalized patients with COVID-19.

 in Anaheim, Tara Vijayan, MD, assistant professor of medicine in the Division of Infectious Diseases and medical director of antimicrobial stewardship at the David Geffen School of Medicine at UCLA, talked about some of the novel COVID-19 treatments and the associated problems with drug scarcity in the midst of a global pandemic.

, Vijayan explained how it is crucial to target certain high-risk populations with these patients that could have an overall public health impact during the pandemic.

Overall, Vijayan said she is comfortable with certain aspects of treatments, including having options to reduce hospitalizations and mortality. However, there needs to be more attention paid to treatment as a form of prevention in addition to the vaccine.

She also said the current antivirals are difficult to scale for those types of outcomes.

Finally, Vijayan talked about the role the pharmacist in COVID-19 drug stewardship.

There remains a need to develop more antivirals that can be easily scaled up for COVID-19.

Tara Vijayan, MD: Targeting the Right Population for COVID-19 Treatments

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