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Although levodopa is considered the cornerstone treatment in Parkinson disease (PD), its long-term use may be limited by motor complications and the inability to slow neurodegeneration. Early in treatment, motor control is strong, but over time, striatal changes can cause dopamine levels to rely entirely on external sources, leading to OFF episodes. Current strategies aim to optimize dopaminergic stimulation to better mimic natural, tonic dopamine activity through pharmacologic, nonpharmacologic, adjunctive, rescue, and device-aided approaches.¹

At the recently concluded 4th Annual Advanced Therapeutics in Movement and Related Disorders (ATMRD) Congress, held by the PMD Alliance from June 27-30, 2025, movement disorder expert Cheryl Kyinn, PA-C, gave a talk about on-demand therapies that can help offer relief for OFF episodes in patients with PD and how to go about using them. In this session, Krinn, a physician assistant specializing in PD in Orange County, California, placed an emphasis on recent findings from clinical trials that documented the timing and optimal use of these medications.

In a new iteration of NeuroVoices, Kyinn discussed her clinical approach to selecting on-demand therapies for patients with PD experiencing OFF episodes. She highlighted the importance of considering comorbidities, patient preferences, and proper administration education to ensure treatment efficacy. Kyinn also underscored the advantages of therapies that bypass the gastrointestinal tract and the value of open-label data supporting options like inhaled levodopa. Additionally, she advocated for early adoption of extended-release levodopa to help reduce motor fluctuations and stressed shared decision-making to optimize patient quality of life.

NeurologyLive: How should clinicians approach determining which on-demand therapy may be best suited for a patient experiencing OFF episodes?

Cheryl Kyinn, PA-C: It’s very similar to how you would make any medication choice for a patient. The first thing is the baseline characteristics of a patient. Do they have other comorbidities? Because, let’s say, the 2 options are quite different and have different adverse effect profiles, so you want to first look at that.

For instance, if you’re doing an apomorphine subcutaneous injection, that might have a little bit more susceptibility to hypotension and nausea. If someone’s already hypotensive, like many of our patients with PD, you probably wouldn’t go for that one. But let’s say a patient has a comorbidity of COPD, you’re probably not going to go with inhaled levodopa powder, because they probably can’t inhale it. That’s 1 key factor.

Of course, you also have patient preference. Maybe patients are needle-phobic, or maybe patients honestly, they can’t get over the administration adverse effects. I think the number one thing is patient choice. First of all, I get a lot of needle-phobic patients, so that’s easy off the bat. And then again, their comorbidities as well.

What findings have maybe most influenced decision-making when it comes to on-demand treatment for PD-related off periods?

The key thing is that we know all of our oral medications run into the gastrointestinal dysfunction issues. Of course, seeing how these are delivered and that they bypass the GI tract that’s a huge thing.

I think one of the most interesting studies was the open-label study for morning akinesia. I mean, that’s huge. We don’t have a lot of stuff—actually hardly anything—that helps with that, right? I actually tell my patients, just put your first pill on your bedside, and as soon as you get up, just reach over and swallow it. But again, you have the gastrointestinal dysfunction. The study with morning akinesia was very helpful and great for us clinicians to know that there is an option for this very tough symptom that patients experience.

For the inhaled levodopa powder, I think it’s a little bit easier to use because you don’t have to do a needle. I did make a joke that it’s kind of similar to smoking but it kind of is. When I’ve seen patients do it, I’m like, it kind of looks like that. But I think the ease of use is helpful, and you see the improvement in the UPDRS score quickly, within 10 minutes. But I guess that’s the other point:, both of them show that T-max concentration within 10 to 20 minutes, and that’s a big factor in wanting to use these on-demand therapies for OFF times.

In your experience, what key factors could help with ensuring effective and consistent use of these on-demand therapies for patients?

I think education, education, education, and setting expectations. For instance, if you don’t tell a patient that they might have the cough issue with the inhaled levodopa powder, they will—when they first encounter that cough. First, they’re going to do it wrong, and they’re going to assume it’s like any other inhaler that they’ve seen like an asthma inhaler where you take a big puff and they’ll cough it all out. Not only, 1, do they have the adverse effect, 2, they’re going to cough it all out and not even get the therapeutic effect of the medication.

Same thing with apomorphine. I think if you set the precedent that, yes, there’s a possibility you can have hypotension and nausea, especially because there’s no current antiemetic therapy that we can give to counter that, at least if they know about it and it happens. They’re not going to be completely caught off guard and then just choose to discontinue either of the medications.

Setting good expectations, educating the patient on what could happen, and letting them know that if it happens, it’s okay it’s not going to be permanent. It’s going to be very short and brief and mild to moderate, I guess, based off of clinical trials. You’ll get over it, and if you don’t like it, then you don’t have to do it again. That’s the first part of it. And luckily, the companies also I think send nurses to the patient’s home to educate them about that as well, and to help them administer their first couple of doses. So hopefully there’s that continuity of care.

What clinical signs would prompt you to consider switching a patient with PD to a different levodopa formulation?

Honestly, I think from the get-go, based off all the clinical data that we have now, the preference is showing that ER formulations are much preferred. All the data suggests that, unfortunately, even though IR levodopa is great and cheap and effective, long-term use of this volatile pulsing of the medication is going to cause issues over time.

We definitely see that with our patients who’ve had long-standing PD where we feed into the motor fluctuations. I think presenting patients with that data, if we can, we should start them on an ER formulation. But let’s say they are on an IR formulation then, when they start experiencing these motor fluctuations because we know it’s a question of when, not a question of if that, for sure, is a reason. If accessibility wasn’t an issue and cost wasn’t an issue, for sure, as soon as they start experiencing motor fluctuations, we should switch to an ER formulation if possible.

How do you go about the decision-making process with the patient for treatment?

I always try to tell my patients when we’re together, I’m here to provide you with the information, and I will guide you on what I think might work best for you but ultimately, they’re in the driver’s seat. It’s a full-on conversation that we’re having. It’s not a one-sided, “I tell you what to do” situation. I’ll even tell patients, “I’m not your mom—I can’t make you do anything,” It’s all up to you. This is your life, the life that you’re living. But it is an open discussion between clinical provider and patient. And I tell them, we’re trying to optimize your quality of life. And the decision-making process is 2-fold. I provide information, and then we, together, pick what’s best for your life, what fits into your lifestyle, with the ultimate goal of improving quality of life.

Transcript edited for clarity. Click here for more coverage of ATMRD 2025.

REFERENCES
1. Masood N, Jimenez-Shahed J. Effective Management of “OFF” Episodes in Parkinson’s Disease: Emerging Treatment Strategies and Unmet Clinical Needs. Neuropsychiatr Dis Treat. 2023;19:247-266. Published 2023 Jan 25. doi:10.2147/NDT.S273121
2. Kyinn, C. Conquering Off Episodes With On-Demand Therapies. Presented at: ATMRD; June 27-30, 2025; Washington, DC.

The patient: A 77-year-old man in China

The symptoms: Seven hours before being admitted to a hospital, the patient developed shortness of breath, abdominal pain and “obvious” abdominal distension, meaning his belly appeared very bloated and stretched out, doctors wrote in a report of the case. He’d had trouble urinating and defecating for about four days, and one week prior to admission, he’d been given antiviral and pain-relieving medicines for a case of shingles that was affecting his lower back, around the sacrum, or the base of the spine.

In an interview with HT Lifestyle, Dr Sharmila Tulpule, orthopaedic surgeon, regenerative medicine specialist, and founder and director of Orthobiologix Biotech Pvt Ltd, said that osteoarthritis, long thought of as a ‘wear-and-tear’ disease, has become incredibly complex, especially for women.

The prevalence of osteoarthritis, a type of joint disorder that occurs due to cartilage breakdown in the joints, is expected to increase with ageing populations and rising rates of obesity and injuries. By understanding the causes, symptoms, and treatment options for OA, you can take steps to manage the condition and improve your quality of life. 

According to Dr Tulpule, below are the factors concerning osteoarthritis in women:

Hormonal changes and menopause

● Estrogen decline during menopause accelerates cartilage degradation, increasing OA risk.

● Hormone replacement therapy (HRT) may offer some benefits but requires careful consideration due to potential risks.

Obesity and metabolic factors

● Obesity is a significant risk factor for OA, particularly in weight-bearing joints like the knees.

● Excess weight increases joint stress and systemic inflammation, exacerbating OA symptoms.

● Even modest weight loss can reduce OA risk and improve joint function.

Physical activity and joint health

● Regular, moderate physical activity strengthens muscles around joints, enhancing mobility and reducing pain.

● Conversely, sedentary lifestyles contribute to joint stiffness and muscle weakness.

Mental health and quality of life

● OA can lead to depression and anxiety, particularly in women, affecting overall well-being.

● Addressing mental health is crucial for effective OA management and improving quality of life.

What to know about regenerative therapies

Dr Tulpule said, “Regenerative therapies offer a more holistic approach by addressing the underlying causes of OA rather than merely alleviating symptoms. They are particularly beneficial for women seeking alternatives to invasive surgeries and medications.”

According to Dr Tulpule, stem cell therapy holds promise as a regenerative treatment for knee osteoarthritis, offering potential benefits in pain reduction and functional improvement. 

Explaining platelet-rich plasma (PRP) therapy, Dr Tulpule said it utilises growth factors from the patient’s own blood to stimulate tissue repair and reduce inflammation. “Studies indicate that PRP can provide longer-term pain relief and functional improvement compared to traditional treatments like hyaluronic acid (HA) injections,” she said.

Dr Tulpule added that gold-induced cytokine therapy is a novel regenerative treatment that involves incubating the patient’s own blood with gold particles, enhancing the anti-inflammatory and reparative properties of platelets. Studies have shown that it can lead to significant improvements in pain and function in patients with knee OA, with minimal adverse effects, she said.

Management and prevention

“For women, osteoarthritis is not just a joint issue — it intertwines with hormonal health, body weight, lifestyle, mental wellness, and occupational context,” Dr Tulpule said. 

According to her, a nuanced approach means:

1. Advocating early detection especially during menopause.

2. Promoting preventive strategies combining diet, weight management, and exercise.

3. Considering hormone-based therapies for symptomatic relief when appropriate.

4. Supporting women’s mental health alongside physical care.

5. Raising community awareness on how everyday activities shape OA risk.

Dr Tulpule concluded, “By addressing the unique facets of OA in women, clinicians can shift from reactive interventions to proactive, personalised care. This not only delays disease progression, but preserves mobility, dignity, and quality of life for millions of women worldwide.”

Note to readers: This article is for informational purposes only and not a substitute for professional medical advice. Always seek the advice of your doctor with any questions about a medical condition.

NEED TO KNOW

• A man in his 50s has been hospitalized in critical condition after contracting the Australian bat lyssavirus (ABLV) in New South Wales, Australia

• This is the first confirmed case of the virus in the state and fourth overall in Australia, NSW Health announced

• NSW Health Protection director Keira Glasgow called this case “a very tragic situation” in a statement following the diagnosis

A man is in critical condition after contracting a rare bat virus in Australia.

The first confirmed case of Australian bat lyssavirus (ABLV) has been reported in the state of New South Wales, involving a man in his 50s. He fell ill after being “bitten by a bat several months ago,” New South Wales Health announced in a release on Wednesday, July 2.

“This is a very tragic situation. The man had been bitten by a bat several months ago and received treatment following the injury,” said NSW Health Protection director Keira Glasgow. “Further investigation is underway to understand whether other exposures or factors played a role in his illness.”

ABLV is closely related to the rabies virus and is found in flying foxes, fruit bats and microbats. It is transmitted by bites from bats to humans, causing a potentially fatal illness that affects the central nervous system, according to NSW Health. The symptoms are flu-like, including a fever, headache and fatigue, which can develop into delirium, paralysis and death.

In 2024, 118 people required medical assessment after being bitten or scratched by bats. ABLV was first identified in 1996 and there have since been four confirmed cases in Australia, NSW Health reported.

NSW Heath is urging Australians not to handle or touch any bats after the first confirmed case of ABLV in the state in order to prevent the spread of the virus, as there is currently no cure.

“It is incredibly rare for the virus to transmit to humans, but once symptoms of lyssavirus start in people who are scratched or bitten by an infected bat, sadly there is no effective treatment,” said Glasgow, per the release.

The NSW Health director advises that if anyone is bitten or scratched by a bat to seek urgent medical assessment.

“You will need to wash the wound thoroughly for 15 minutes right away with soap and water and apply an antiseptic with anti-virus action, such as betadine, and allow it to dry,” said Glasgow. “You will then require treatment with rabies immunoglobulin and rabies vaccine.”

NSW Health said that if a bat appears to be in distress, injured or trapped “do not try to rescue it [and] instead, contact trained experts WIRES or your local wildlife rescue group.”

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This update comes as twenty new bat viruses have been discovered in China, posing serious risk to humans.

According to a study published by the Public Library of Science (PLOS), researchers tested ten different species of 142 bats in China’s Yunnan province and discovered 20 new viruses, a new species of bacteria and a new type of parasite.

Two of the viruses are similar to the deadly Hendra and Nipah viruses, the former of which causes a rare, flu-like reaction that can be fatal in humans and horses, according to the World Health Organization.

Read the original article on People

Prevention and preparedness play central roles in global health security, with the EU’s Health Emergency Preparedness and Response Authority (DG HERA) now working with third-country governments to strengthen cooperation on medical countermeasures for preparedness and response to serious cross-border public health threats. The recently published WHO Pandemic Agreement also represents a significant step forward in strengthening the global health architecture to better address future pandemics.

While timely access to critical medical resources, such as vaccines, therapeutics, and diagnostics often take centre stage in preparedness discussions, a crucial dimension remains underappreciated: animal health. Yet, history tells us that this is precisely where the next global health emergency may begin.

The term “Disease X” a kind of placeholder name adopted by the WHO in 2018 refers to an unknown pathogen with the potential to cause a serious international epidemic or pandemic. Although Disease X is hypothetical, the concept is very real, and one fact is consistently reaffirmed by scientific evidence: pandemics predominantly originate in animals. Zoonotic pathogens (those that can jump from animals to humans) are the likeliest culprits for future pandemics, as SARS, MERS, Ebola, avian influenza, and mostly recently, COVID-19, have all been linked to animal origins. This reality places animal health systems on the front line of prevention, long before the first human case emerges.

The WHO Pandemic Agreement reflects a notable shift toward integrated approaches that span across sectors. A few articles within the text touch on the need to reduce risks of interspecies transmission, strengthen surveillance, and promote the One Health approach, a framework that recognises the interconnectedness of human, animal, and environmental health. The animal health sector is uniquely positioned to play a central role in helping to turn these ambitions into concrete outcomes.

Tackling disease outbreaks in livestock and wildlife at their source prevents them from spreading to other animals, and more importantly to people.

Animal health professionals, including veterinarians, epidemiologists, researchers, and medicines manufacturers, are already deeply engaged in surveillance, prevention, and management of animal disease outbreaks. But continued threats from infectious diseases and evolving pathogens influencing disease distribution and severity have reinforced the need for robust surveillance, early warning systems, and preparedness planning. A recent report from the World Organisation for Animal Health (WOAH) shares some key facts on how animal health impacts human health:

• Animal diseases are migrating into previously unaffected areas and half (47%) of these diseases have zoonotic potential.
• Between 2005 and 2023 68% of the notifications to WOAH for emerging diseases were considered to have zoonotic potential.
• Outbreaks of bird flu in mammals more than doubled in 2024 compared to 2023, increasing the risk of further spread and transmission to people.

Tackling disease outbreaks in livestock and wildlife at their source prevents them from spreading to other animals, and more importantly to people. Moreover, taking bird flu as an example, aside from the devastating loss of poultry, HPAI (highly pathogenic avian influenza) is causing unprecedented mass die-offs in wild-bird populations. This can seriously disrupt ecosystems and threaten biodiversity. And, although in this case the risk of human infection remains low, the more animals are affected, the greater the possibility for the virus to jump from mammal to mammal, and potentially also to people.

It’s clear that decreasing the burden of animal diseases will mitigate the risk of zoonotic disease transmission. Preparedness actions must begin before a pathogen reaches human populations, so investing in disease surveillance, vaccine development, and healthcare infrastructure for animals is not a luxury but a necessity.

Despite their importance, animal health systems often face chronic underfunding. This leaves significant gaps in pandemic preparedness planning, particularly in developing countries where disease emergence risks are high and surveillance capacity is limited. For example, a key vulnerability globally is the inadequate number of trained veterinarians, and Europe is not a stranger to this phenomenon either. An insufficient vet-to-livestock ratio not only means less prevention of zoonotic diseases, but it also means less effective surveillance and a higher likelihood of diseases crossing borders.

The path to pandemic prevention runs not only through our hospitals and laboratories, but also through the world’s ecosystems, our farms, food markets, and veterinary clinics.

By directing greater resources and political attention toward animal health, promoting the development of joint training programmes for the workforce at the human-animal-environment interface, and developing integrated disease surveillance systems the global community can close these gaps and better protect itself from future disease emergencies, while also creating more resilient health systems overall.

The WHO Pandemic Agreement offers a framework to facilitate this shift, as its emphasis on international cooperation, technology transfer, and capacity-building opens the door to greater collaboration between human and animal health sectors. One of the key challenges ahead lies in making sure these ideas are not only endorsed on paper but implemented in practice, which means ensuring that veterinary services are embedded within European and national pandemic preparedness plans and that animal vaccines producers are consulted before a disease outbreak reaches crisis scenario. DG HERA and the EU Preparedness Union Strategy published earlier this year set a good basis for addressing emerging health threats, but the role for animal health is not clearly defined, nor mentioned in the latter.   

It is important that decision-makers understand the value of One Health action, i.e. involving all the health sectors. preventive action over reactive measures, while also fostering a regular dialogue between the public and private sectors, including Chief Veterinary Officers, to ensure strategies are informed by real-world experience and scientific expertise.

The path to pandemic prevention runs not only through our hospitals and laboratories, but also through the world’s ecosystems, our farms, food markets, and veterinary clinics. Ultimately, the global health community must recognise that animal health is public health and that by enhancing animal health systems today, we can reduce the risks and impacts of tomorrow’s pandemics.

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Dry eye is top of mind for optometrists year-round, but Prevent Blindness has declared July as Dry Eye Month in hopes to raise awareness among the public and the eye care industry. To support this, Prevent Blindness has created a variety of free dry eye resources: a dedicated webpage about the etiology and treatment of dry eye, fact sheets and social media graphics in both English and Spanish for distribution, and how-to videos about how to apply eye drops and other tips and tricks for dry eye relief. For the fifth year in a row, OCuSOFT is partnering with Prevent Blindness in support of Dry Eye Month.¹

“A number of treatment options are available for dry eye that can help address symptoms and save sight,” Jeff Todd, president and CEO of Prevent Blindness, said in a press release. “We invite everyone to check out our free dry eye resources and make an appointment with an eye doctor to find out what type of treatment is best for them.”

The National Eye Institute reports nearly 16.4 million Americans live with dry eye.² Here are some risk factors for dry eye that eye care providers see regularly in their chairs:

• Being over 50 years old
• Hormonal changes or medications that impact hormone levels
• History of refractive eye surgery (such as LASIK)
• Eyelid inflammation (blepharitis)
• Environmental factors, including allergies, smoke exposure, or dry climates
• Wearing contact lenses
• Poor makeup hygiene practices
• Medical conditions like rheumatoid arthritis, rosacea, Sjögren’s syndrome, and other autoimmune diseases
• Reduced blink rate, often due to prolonged screen use or certain neurological conditions like Parkinson’s disease
• Eyelid disorders that prevent complete eyelid closure
• Excessive use of digital devices, including computers, tablets, and smartphones
• Certain medicines that may decrease tear production, including antihistamines, decongestants, hormone replacement therapy, antidepressants, high blood pressure medications, birth control, acne prescriptions, and Parkinson disease therapies

To learn more about Prevent Blindness’s dry eye resources, visit their website. You can download printouts in both English and Spanish, and view patient educational videos. Additionally, there are interviews about dry eye with April Jasper, OD, FAAO, and Stephanie Jones Marioneaux, MD.

References

1. Prevent Blindness Provides a Variety of Free Dry Eye Educational Resources including a dedicated Webpage, Fact Sheets and Graphics in English and Spanish, Expert Interviews and Informative Videos. Prevent Blindness. Press release. Published June 25, 2025. Accessed June 30, 2025. https://preventblindness.org/dry-eye-month-2025/

2. Dry eye. National Eye Institute. Last updated February 18, 2025. Accessed June 30, 2025. https://www.nei.nih.gov/learn-about-eye-health/eye-conditions-and-diseases/dry-eye

A new AI model is much better than doctors at identifying patients likely to experience cardiac arrest.

The linchpin is the system’s ability to analyze long-underused heart imaging, alongside a full spectrum of medical records, to reveal previously hidden information about a patient’s heart health.

The federally funded work, led by Johns Hopkins University researchers, could save many lives and also spare many people unnecessary medical interventions, including the implantation of unneeded defibrillators.

“Currently we have patients dying in the prime of their life because they aren’t protected and others who are putting up with defibrillators for the rest of their lives with no benefit,” said senior author Natalia Trayanova, a researcher focused on using artificial intelligence in cardiology. “We have the ability to predict with very high accuracy whether a patient is at very high risk for sudden cardiac death or not.”

The findings are published today in Nature Cardiovascular Research.

Hypertrophic cardiomyopathy is one of the most common inherited heart diseases, affecting one in every 200 to 500 individuals worldwide, and is a leading cause of sudden cardiac death in young people and athletes.

Many patients with hypertrophic cardiomyopathy will live normal lives, but a percentage are at significant increased risk for sudden cardiac death. It’s been nearly impossible for doctors to determine who those patients are.

Current clinical guidelines used by doctors across the United States and Europe to identify the patients most at risk for fatal heart attacks have about a 50% chance of identifying the right patients, “not much better than throwing dice,” Trayanova says.

The team’s model significantly outperformed clinical guidelines across all demographics.

Multimodal AI for ventricular Arrhythmia Risk Stratification (MAARS), predicts individual patients’ risk for sudden cardiac death by analyzing a variety of medical data and records, and, for the first time, exploring all the information contained in the contrast-enhanced MRI images of the patient’s heart.

People with hypertrophic cardiomyopathy develop fibrosis, or scarring, across their heart and it’s the scarring that elevates their risk of sudden cardiac death. While doctors haven’t been able to make sense of the raw MRI images, the AI model zeroed right in on the critical scarring patterns.

“People have not used deep learning on those images,” Trayanova said. “We are able to extract this hidden information in the images that is not usually accounted for.”

The team tested the model against real patients treated with the traditional clinical guidelines at Johns Hopkins Hospital and Sanger Heart & Vascular Institute in North Carolina.

Compared to the clinical guidelines that were accurate about half the time, the AI model was 89% accurate across all patients and, critically, 93% accurate for people 40 to 60 years old, the population among hypertrophic cardiomyopathy patients most at-risk for sudden cardiac death.

The AI model also can describe why patients are high risk so that doctors can tailor a medical plan to fit their specific needs.

“Our study demonstrates that the AI model significantly enhances our ability to predict those at highest risk compared to our current algorithms and thus has the power to transform clinical care,” says co-author Jonathan Chrispin, a Johns Hopkins cardiologist.

In 2022, Trayanova’s team created a different multi-modal AI model that offered personalized survival assessment for patients with infarcts, predicting if and when someone would die of cardiac arrest.

The team plans to further test the new model on more patients and expand the new algorithm to use with other types of heart diseases, including cardiac sarcoidosis and arrhythmogenic right ventricular cardiomyopathy.

Authors include Changxin Lai, Minglang Yin, Eugene G. Kholmovski, Dan M. Popescu, Edem Binka, Stefan L. Zimmerman, Allison G. Hays, all of Johns Hopkins; Dai-Yin Lu and M. Roselle Abraham of the Hypertrophic Cardiomyopathy Center of Excellence at University of California San Francisco; and Erica Scherer and Dermot M. Phelan of Atrium Health.

The work was supported by National Institutes of Health grants R01HL166759, R01HL174440, R35HL1431598, and a Leducq Foundation grant.