Vision impairment is a pervasive problem facing nearly 2.2 billion people globally, according to the World Health Organization. But help is on the way: Neuroscientists are working at the cutting edge of technology and brain science to develop new ways for the vision impaired to navigate the world around them. At the annual meeting of the Cognitive Neuroscience Society (CNS), researchers are presenting new techniques for integrating digital haptics and sound technology to transform vision rehabilitation for both children and adults alike.

"Vision rehabilitation requires bridging fundamental research, modelling and neuroimaging methods," says Benedetta Franceschiello of the University of Lausanne, who is chairing the symposium on vision rehabilitation at CNS 2021 virtual. The new wave of devices to help the vision impaired combine these areas to deliver more personalized, democratized technological solutions. "We have cutting-edge analysis techniques, the computational power of supercomputers, the ability to record data to a level of detail that was not possible before, and the ability to create increasingly sophisticated and portable rehabilitation devices," she says.

At the same time, neuroscientists have great insight into the brain's plasticity and how the brain integrates information from multiple senses. "This field is developing at a fast rate, which is vital," says Ruxandra Tivadar of the University of Bern, "as having reduced or a lacking sensory function is an extremely grave impairment that impacts everyday function and thus the quality of life."

Tivadar is presenting new research showing how feedback from digital haptics - using the sense of touch coupled with motion - enables the visually impaired to easily learn about new objects and spaces. It's just one way researchers are leveraging all the human senses to develop new technology for vision rehabilitation.

Putting a finger on the problem

Teaching a visually impaired person how to navigate a new space is a tedious process, Tivadar says. "We need occupational therapists, we need to make tactile maps with different textures and, especially, for different places, and then we have to actually train the individual on tactile exploration before training them on the street," she explains. "Imagine future mobile phones with digital haptic feedback that allow the visually impaired to learn about new spaces instantly."

That is the future Tivadar is working toward, and with new results being presented at CNS, she and colleagues are showing it is possible, and, soon. In new unpublished research, Tivadar's team used digital haptics to represent the layout of an apartment in 2-D. Sighted participants who were blindfolded learned the layout by exploring a digital haptic rendering of the layout. They then had to actually navigate and complete tasks in the real, physical space that was previously unknown to them.

"Our data show that people learn these layouts well after only 45 minutes of training," Tivadar says. "In addition, we also see that participants have absolutely no problem in learning easy trajectories in this layout; all of our participants succeed at this task, whether previously trained or not."

The data also suggest that those participants who trained for harder navigation succeeded better than participants who were only trained on easier trajectories. "These findings imply that for really simple layouts, people need minimal training to succeed at imagining a space in their minds and then physically navigating it," Tivadar says.

Advances in big data analysis helped make this work possible. The researchers filmed the hands of 25 participants while they were exploring a haptic tablet for 8 to 10 minutes at a time. Tivadar's team then used a deep neural network to analyze the roughly 200 videos, using an algorithm that learns to track the movement of a single finger of each participant. "This enabled us to understand better how participants interact with haptics and to help further develop applications of this technology," Tivadar says. "Imagine if we can 'see' objects and spaces using one finger, what we could do by using all 10 of our fingers, or our whole palm to feel."

Tivadar's work integrating haptic data was born out of years researching sensory perception - looking not only at the sense of touch but also at auditory information. "Really, we study the ways in which people can see better using information from other senses," she says. "In neuroscience, this means looking at how the brain constructs visual images and trying to help the brain by augmenting or supplementing the information that it uses to construct these images. I think that merely the fact that we can do this is absolutely fascinating, and very promising for rehabilitation."

A sound solution for children

Millions of children globally live without sight, and their impairment can lead to manifold motor, perceptive, and social challenges. "Blind children have a lot of perceptual and social delays," says Monica Gori of the Italian Institute of Technology. "For example, sighted children learn to reach objects at 5 months. In blind children, this ability is significantly delayed and develops at one year of age. This delay produces a whole host of additional delays in movement and interaction with others that rehabilitators face every day."

A new multisensory rehabilitation device called ABBI is offering a new solution. In new work being presented at CNS, Gori and colleagues are working to identify the critical periods best suited for intervention with this device - to help blind children by 1 year of age.

Previous research had shown that the development of multisensory integration occurs late, after 8-10 years of age. "This discovery changed the way people think about the development of multisensory skills," Gori says. It provided her team the opportunity to develop an intervention that could help both visually impaired children and adults by integrating audio and motor information.

The ABBI device is a bracelet that they developed to use sound data in absence of visual data to help restore a sense of space. In a study looking at 3 months of training, visually impaired children between 6 and 15 years of age using the bracelet showed significant improvements in space representation and social skills. Those results have spurred the new follow-up study in children even younger.

"I am excited by the possibility of making early interventions and helping children develop perceptual and social skills," Gori says. "I believe that multisensory technologies, perhaps combined with sensory substitution devices, could bring significant benefits."

Gori's and Tivadar's technologies, along with the other work featured in the CNS symposium, offer glimpses of a promising future for vision rehabilitation - one not only informed by the latest in neuroscience but also driven by the need for low-cost solutions accessible to a wider population.

Says Tivadar: "We are able to do better visual rehabilitation when incorporating new technologies and using the brain's properties, such as multisensory integration and cross-modal plasticity. We need to look further into how our senses can complement or supplement each other in order to find low-cost solutions to vision rehabilitation."

The symposium "New Frontiers and technologies in Vision Rehabilitation" is taking place at 2pmET on Tuesday, March 16, 2021 as part of the CNS 2021 Virtual, from March 13-16.

CNS is committed to the development of mind and brain research aimed at investigating the psychological, computational, and neuroscientific bases of cognition. Since its founding in 1994, the Society has been dedicated to bringing its 2,000 members worldwide the latest research to facilitate public, professional, and scientific discourse.

Source: EurekAlert!

Patients with osteoarthritis-related pain were shown to benefit from cognitive behavioral therapy for insomnia (CBT-I) via telephone, in which the treatment significantly improved sleep and fatigue after 12 months, with pain temporarily relieved as well.

Cognitive behavioral therapy for insomnia (CBT-I) was shown to improve sleep and fatigue among patients with osteoarthritis-related pain, according to study findings published this week in JAMA Internal Medicine.

Insomnia is a common comorbidity in older adults alongside other chronic conditions. Notably, more than half of patients with osteoarthritis, which affects 50% of older adults, report symptoms of disturbed sleep.

“Insomnia and chronic pain have reciprocal effects, each initiating, maintaining, and exacerbating one another,” noted the study authors

Recently, CBT-I has emerged as an effective therapeutic intervention for people with comorbid conditions and was recommended for use in recent clinical practice guidelines issued by the American Academy of Sleep Medicine. More noteworthy amid the pandemic, CBT-I delivered via telemedicine was found to be noninferior to in-person delivery in managing severity of insomnia and improving daytime functioning.

As the first large randomized trial to assess CBT-I delivered via telephone among older adults with comorbid moderate to severe insomnia and chronic osteoarthritis pain, the Osteoarthritis and Therapy for Sleep study compared the efficacy of the remote therapy with education-only control (EOC) in 327 participants 60 years and older from Kaiser Permanente Washington (mean [SD] age, 70.2 [6.8] years; 244 [74.6%] women).

The study was conducted from September 2016 to December 2018, with participants undergoing six 20- to 30-minute telephone sessions (n = 163) or EOC (n = 164) over 8 weeks. Participants were double screened 3 weeks apart for moderate to severe insomnia and osteoarthritis pain symptoms, and were blindly assessed for the primary outcome of Insomnia Severity Index (ISI) score at baseline, 2 months posttreatment, and at 12-month follow-up.

In addition to the ISI, secondary outcomes included pain (Brief Pain Inventory-short form), depression (8-item Patient Health Questionnaire), and fatigue (Flinders Fatigue Scale).

“Participants submitted daily diaries and received group-specific educational materials,” explained study authors. “The CBT-I instruction included sleep restriction, stimulus control, sleep hygiene, cognitive restructuring, and homework. The EOC group received information about sleep and osteoarthritis.”

Among the 282 participants who provided follow-up ISI data, total 2-month posttreatment ISI scores exhibited a significant adjusted mean between-group difference of −3.5 points between the CBT-I group and the EOC group (95% CI, −4.4 to −2.6 points; P < .001), which was sustained at 12-month follow-up (adjusted mean difference, −3.0 points; 95% CI, −4.1 to −2.0 points; P < .001).

Additionally, at 12-month follow-up, 56.3% of participants receiving CBT-I remained in remission (ISI score ≤ 7), compared with 25.8% of those receiving EOC.

Secondary outcome measures indicated:

Participants of the CBT-I group exhibited significant reductions in fatigue compared with the EOC group at 2 months post-treatment (mean between-group difference, −2.0 points; 95% CI, −3.1 to −0.9 points; P = .001) and 12-month follow-up (mean between-group difference, −1.8 points; 95% CI, −3.1 to −0.6 points; P = .003)

Posttreatment significant differences were observed for pain after 2 months, but these differences were not sustained at 12-month follow-up

“Telephone CBT-I was effective in improving sleep, fatigue, and, to a lesser degree, pain among older adults with comorbid insomnia and osteoarthritis pain in a large statewide health plan,” concluded study authors. “Results support provision of telephone CBT-I as an accessible, individualized, effective, and scalable insomnia treatment.”

Reference

McCurry SM, Zhu W, Korff MV, et al. Effect of telephone cognitive behavioral therapy for insomnia in older adults with osteoarthritis pain. JAMA Intern Med. Published online February 22, 2021. doi:10.1001/jamainternmed.2020.9049

Source: AJMC

A pilot study assessing the use of telemedicine in patient-reported responses to adult ADHD treatment showed a notable sensitivity to the impact of therapy changes on symptoms and patient functioning.

In new data presented at The American Professional Society of ADHD and Related Disorders (APSARD) 2021 Annual Conference, investigators from Massachusetts General Hospital reported outcomes from an online survey-based assessment of adults with ADHD asked to gauge real-time response to psychopharmacology.

They observed a likely correlation to patient sensitivity and mobile ADHD symptom monitoring following changes in treatment status.

The Shire and Takeda-supported trial, presented by author Craig Surman, MD, included 90-plus patients aged 18-80 who self-identified a taking stimulant therapy for ADHD. Participants recorded their demographic information, medication use history and patterns, and their symptoms associated with ADHD.

Surman and colleagues used mobile phone surveys and messaging systems from RedCAP to remotely monitor patients. Their hypothesis was that personalized surveys via mobile messaging could be sensitive to ADHD-specific therapy effects.

“Technology opens the possibility of using measurements by mobile messaging to inform clinical care,” they wrote. “We know that ADHD symptoms respond rapidly to some forms of psychopharmacology as measured on well-validated rating scales. In clinical practice, individuals may find particular symptoms easier to recognize and report on than others.”

Investigators used the Weiss Functional Impairment Rating Scale (WFIRS) and the Adult ADHD Self Report Scale v1.1 (ASRS) to gauge patient-reported therapy effects.

Participants identified medication-sensitive items, and received such items as queries during selected time periods in the morning and evening. From this, investigators inferred “on” and “off” medication statuses for analyses.

In their outcome, the research observed that data confirmed self-reported ADHD symptom severity discriminated “on” versus “off” stimulant therapy status.

Investigators also noted sensitivity thresholds for symptom reporting, as well as reporting patters: within-day and between-day differences.

“Mobile monitoring of ADHD symptoms and functional impact is likely sensitive to changes in treatment status,” they concluded. “Future research may validate the clinical utility of using personalized self-reported mobile-messaged items in treatment optimization.”

The study, “Sensitivity of Electronic Patient Reported Outcome Measures to Medication Effects in Adult ADHD – A Pilot Study,” was presented at APSARD 2021.

Source: HCP Live

Video visits, temperature sensors and wearables can replace the need for clinic visits. The pandemic has only accelerated this process – and shown the need to innovate infrastructure and make investments.

At Geisinger in Pennsylvania, a pilot program to bring care to the homes of older patients with complex healthcare needs has shown a 35% reduction in visits to the emergency department visits, a 40% drop in hospital admissions and an average annual savings of nearly $8,000 per patient. The future will see chronic disease being managed more from homes and physicians' offices than in a hospital setting.

Chronically ill patients may not always require visiting the hospital frequently if their follow-ups and routine checkups can be managed remotely. Especially in times of a pandemic, they are better off staying at home.

However, that should not affect their care. Given today’s technological advancement in healthcare, most follow-ups can be well managed remotely. While nothing can beat an in-person experience, physicians can check in on them digitally, through remote patient monitoring tools or video consults.

Technology is rapidly changing the bedside examination. Video visits, infrared temperature sensors, mobile health, and wearables replace the need for clinic visits. While remote patient monitoring and telehealth have been on the radar for a few years now, defined workflows and processes around it are continually evolving to improve the care delivery experience. The pandemic has only accelerated this process and the need to innovate better infrastructure and device investments.

Infrastructure to manage chronic diseases remotely

Technology components that can help better organize chronic care management remotely include:

• Devices and Sensors: Medical devices and sensors help a physician measure the vitals and other patient parameters. For example, as a patient walks into the clinic, a physician notices his gait. The technology equivalent of this can be gait recognition sensors using mobile accelerometers. Similarly, sensors for measuring blood pressure, temperature, glucometers, pulse oximeters, and respiratory rate sensors, all integrated with mobile applications, can be used to monitor patients remotely. Many healthcare facilities and smaller clinics offer remote monitoring devices or kits, as per a patient’s need.

• Platforms: Platforms are required to aggregate data and facilitate communication between patients, physicians, and caregivers. These platforms are HIPAA compliant and offer integration with devices and EMRs.

• Integration with EMR: While EMRs are part of the technology infrastructure in any health system, integrating wearable data from devices into the EMR can help physicians maintain data continuity with the initial in-person visit recorded in the EMR. Facilities and providers can choose to reduce the noise created by large volumes of data from personal devices by requesting data at specified intervals only. With EMRs offering healthcare-standard APIs (such as FHIR) for integration, patients need to select devices with integration capabilities using healthcare standards.

• Data analytics for risk stratification and decision support: Devices and sensors can generate vast amounts of data stored in big data repositories. Algorithms on top of this data can help in risk stratification, prediction, and improving outreach. AI techniques like machine learning, cognitive computing, and deep learning can play a critical role in identifying chronic diseases using predictive modeling techniques.

Preferred functionalities to manage remote care

Type 2 diabetes, coronary artery disease, atrial fibrillation, chronic obstructive pulmonary disease, congestive heart failure, stroke, and chronic wounds are seven diseases where technology has been used to manage care for patients with promising results.

These diseases impact at least half of the adult population globally and account for over 80% healthcare costs. Current care delivery for these chronic diseases is reactive. For proactive management of care, patient data at regular intervals is needed to provide real-time feedback and motivate patients to adapt to healthy behavioral changes.

Chronic disease management needs a holistic approach focused on lifestyle changes and behavior modifications. It uses technology to gather data from wearables and adds AI and analytics to drive outcomes. While there are not many stand-alone solutions specifically for managing chronic diseases, it is important to make sure that these technology solutions or applications have the following functionalities:

1. The ability to group patients: Data from an EMR can help group patients by disease conditions, risk factors, comorbidities, age, and active medications. Such groupings help provide valuable information for sending alerts, reminders, and prescription refills to patients suffering from chronic diseases.

2. The ability to engage patients: Often, chronic diseases are due to health risk behaviors such as physical inactivity, incorrect nutrition, tobacco use, and excess alcohol consumption. Engaging patients throughout their healthcare journey can help achieve desired outcomes in chronic disease management. "Tell me and I forget, teach me and I may remember, involve me and I learn" (Benjamin Franklin). Improvement in behavior patterns can ensure continuous reminders, alerts, and engaging patients to track behavior patterns, diet, and lifestyle goals to improve health. A two-way communication flow from the patient to the care provider team and vice versa should be a necessary feature.

3. The ability to integrate remote patient monitoring devices: IoT devices and wearables integrated with the EMR workflows can allow caregivers to provide advice at the point of care. Vital data points captured with wearables, smartphone apps, and home monitoring devices are used in between follow up visits to provide interim care and advice in chronic disease management.

4. The ability to aggregate data from other hospital information systems: These could be data aggregated from multiple sources, including labs, pharmacy, sensors, and valuable clinical-decision support (CDS) to track patient information to manage chronic diseases proactively.

Population health management experts recommend closing gaps in care in high-risk populations for better health outcomes. Mobile applications, customer relationship management applications, patient portals, and patient education platforms are part of the technology infrastructure to engage patients.

Integrating technology to improve access, affordability

The CDC runs several structured intervention programs to manage chronic diseases. The National Diabetes Prevention Program and Chronic Disease Self-Management Program (CDSMP) is one such program with the CDC's necessary resources. The National Diabetes Prevention Program, for example, provides good economic value and could save an estimated $1,146 per participant for in-person classes and $618 for online classes over five years.

Many of these programs are now being run online using video visits for interaction and wearable devices to capture vital data.

Successful programs like Livongo offer connected glucometers, support from health coaches, and unlimited strips for diabetes management. Livongo’s success in the chronic disease management space can be attributed to its B2B partners, including employers, insurances, associations, and other providers.

Integrating technology for chronic disease management needs planning for functionality, processes, and leadership policies in place for it to be successful and improve overall health outcomes. As more and more wearable devices are coming into the market, planning chronic devices' management is getting more affordable and convenient.

To summarize, a technology solution for chronic disease management should include these capabilities:

• The ability to ientify the population eligible for intervention

• Communication with multidisciplinary teams that may include physicians, pharmacists, nurses, dieticians, and psychologists

• Algorithms for risk identification and stratification

• Patient education platforms

• Video visits

• Outcomes evaluation

• Tracking and monitoring the program

• Security and Compliance

As healthcare systems move towards value-based care, creating the shift towards remote monitoring of chronically ill needs to happen.

Source: Healthcare IT News

This burgeoning industry has been propelled to the forefront of medicine with the onset of the Covid-19 pandemic, which shined a light on the need for innovative treatment options that can be used at home from your phone or tablet

In medicine, we’re getting real-time experience with what many believed was an inevitable but potentially distant future – fully digital treatments.

In what may have sounded like a futuristic scenario mere months ago, doctors today can prescribe a video game treatment for their patients. Children with ADHD are now “playing” their medicine thanks to an emerging category of medicine – digital therapeutics (DTx). In June 2020, the industry experienced a watershed moment when the U.S. Food and Drug Administration (FDA) cleared the first-ever prescription video game. At the end of 2020, a mobile sleep app received FDA clearance to treat nightmares caused by Post Traumatic Stress Disorder (PTSD). These and other recent milestones in creative and innovative products are paving the way for a new pillar of medicine. Patients and doctors are already recognizing the value of DTx on the market. And with increased awareness of and experience with these unique treatments, we can expect a massive increase in demand.

This burgeoning industry has been propelled to the forefront of medicine with the onset of the Covid-19 pandemic, which shined a light on the need for innovative treatment options that can be used at home from your phone or tablet. DTx not only meet that need, but importantly they meet the new expectations of patients: control, flexibility, and seamless integration.

Why did Covid-19 alter the path for DTx acceptance and adoption, and how will it position the industry to grow in 2021?

Acceleration driven by Covid-19

Consumer expectations of always-on access and tech-savvy solutions have transformed the leisure, retail, and finance industries among others – but medicine is one area people begrudgingly accept as “the way it has to be.” However, the pandemic massively accelerated expectations around the most critical aspects of people’s lives, inciting a more tech-forward approach to medicine. The broad and lasting shift in patient expectations can be attributed to two specific drivers:

1. Covid-19 demanded convenience and accessibility of digital health; DTx perfectly fit: When the pandemic hit, digital healthcare went from novel to necessary. Covid-19 moved healthcare from the doctor’s office to the living room with many patients opting into digital healthcare solutions, such as telemedicine or ordering prescription refills online. This inherently increased acceptance of digital health and introduced people to a simplified experience that demonstrated healthcare efficiency is possible.

This demand for quicker and easier approaches to healthcare isn’t going away. Once consumers get a taste of efficiency, they’ll continue to demand it. Just look to Amazon’s decision to integrate pharmaceutical delivery into its rapid home delivery revolution. Patients are asking how to most efficiently access their medicine.

But DTx offer more than just rapid access; they meet patients on their own terms and engage them in their care. DTx are accessed from anywhere, personalized and automatically adaptable, and rich with data to foster meaningful conversations with the patient, caregiver, and providers. In that way, DTx are a key new therapeutic pillar answering an important and futuristic question in medicine: How is my treatment tailored for me and my life?

2. Long overdue attention on mental health: Not only has the pandemic increased mental health challenges across the population, it uncovered an enormous need for new treatment options. One representative example in ADHD: 90% of pediatric patients are on medication and 45% are receiving behavioral therapy; and yet, 80% are unsatisfied with their treatment or want more options. And that was before families were faced with remote schooling, limited in-person behavioral services, and the general added stress of a national pandemic and alteration of daily life. [This is based on a 2017 Akili market research.]

These data tell an important story. Drugs and therapy, while critical to the treatment of symptoms of many diseases and disorders, are often not the complete answer. DTx can be a missing piece of the puzzle, providing a new effective tool that can work in tandem with other treatment options. And importantly, DTx can deliver technologies designed to impact brain and mental processes in entirely new ways through new physiological mechanisms.

Advancement will still require clearing hurdles

Despite the proven success of some DTx solutions in clinical trials and growing awareness among consumers, the industry still needs to stretch the minds of many, including physicians and insurance providers. Realizing the full potential of DTx to transform the patient experience requires imagination and creativity, areas in which traditional medicine has been, rightfully, more conservative. The establishment of clinical trial data and regulatory successes for prescription products remain key for credibility, and now the products themselves must inspire confidence.

Early pioneering DTx represented innovative expansions of traditional medicine approaches, supporting existing treatments and digitizing medical processes and behavioral therapy. As the industry evolves, we’re seeing a second generation of products driven by new mechanisms that only technology can deploy. This gradual evolution is well-designed to shift traditional mindsets and pave the way for other DTx companies to follow, using technology to do what traditional medicine cannot.

The next frontier for DTx companies will be securing buy-in from insurance providers. We’ve already seen innovative leaders dip their toes in the water of offering DTx to members – in July 2020, UnitedHealth Group piloted a digital therapeutic designed to improve the health of patients with type 2 diabetes, and some of the earliest prescription digital therapeutics are gaining important early coverage decisions. As more providers engage broadly in digital health offerings, expect a boom of more insurance companies looking to validate digital therapeutics to support their members’ health, especially in mental and cognitive health. It’s just a matter of time before their members demand it, and providers slow to adopt will be left behind.

DTx in 2021 and beyond

In the wake of COVID-19, people are not only showing a willingness to accept DTx as valuable treatments for various conditions but beginning to demand it. Much like their favorite consumer app or game, digital medicine is becoming a source of comfort and relief, putting people in control of their treatment in a time when there are so many unknowns surrounding their health.

Computer scientist Roy Amara once observed, “we tend to overestimate the effect of a technology in the short run and underestimate the effect in the long run.” As is often the case with products positioned for exponential growth, initial adoption of DTx has taken time. While development has been well underway for the last decade, the payoff is just now being seen and ubiquity will happen rapidly.

It took the urgency and sense of purpose associated with Covid-19 to mobilize digital transformation within health care. Will people again accept driving to a doctor’s office and sitting in a waiting room when they’ve experienced the efficiency and comfort of an appointment via video call from their home? Will they continue to visit the pharmacy, when they can have medications proactively shipped to them at the right time?

Technology is disrupting healthcare to bring a better experience to patients, and there will be lasting changes. In the next year, doctors will more regularly turn to DTx treatments alongside traditional medication for conditions like substance abuse, ADHD and sleeplessness. How long will it be before physicians and their patients start routinely asking for and expecting digital treatment options for other mental, physical and cognitive conditions?

The beauty of DTx products is that, at their core, they give people control of their care, adapt to them, and integrate into their lives. As consumer mindsets continue to shift in 2021, so will their demand for easily accessible, personalized and enjoyable medicine. As inefficiency in medicine becomes a thing of the past, let’s embrace the future that has arrived. The experience of medicine can, in fact, be wonderful.

Source: MedCityNews

The introduction of world-leading standards for digital mental health services in Australia is set to be a game-changer for the nation at a time when the delivery of high-quality mental health care has never been more important.

The announcement today of new National Safety and Quality Digital Mental Health (NSQDMH) Standards by the Australian Commission on Safety and Quality in Health Care (the Commission) has been embraced by the mental health sector and consumer and carer advocates.

The NSQDMH Standards will support the delivery of high quality and safe care including counselling, treatment and peer-to-peer support services via telephone, videoconferencing, websites, SMS, webchat and mobile apps. They encompass mental health, suicide prevention and alcohol and other drug services.

With one in five adults and one in seven adolescents experiencing a common mental health disorder each year in Australia – combined with unprecedented demand for digital delivery of mental health services this year – there are tangible benefits in being able to access safe and effective care on digital platforms.

The coronavirus outbreak has amplified the scale of mental health issues and research has shown it has adversely impacted Australia’s mental wellbeing. Three quarters (78%) of Australians reported in April this year that their mental health had been impacted and more than one million Australians had sought help from mental health services.

Dr Peggy Brown AO, the Commission’s Senior Clinical Advisor who led the development of the NSQDMH Standards, said they were recognised as an important leap forward by service providers, clinicians and end users.

“It is more important than ever for Australians to have ready access to high-quality digital mental health services,” she said. “The standards will engender more trust and confidence among consumers, carers and clinicians in Australia’s digital mental health services. Service providers will also benefit from having a quality framework to improve their delivery of digital mental health care.

“The Commission has consulted widely on the digital mental health standards to consider all perspectives. Given the rapid transition to digital services as part of the pandemic response, there is a compelling case to ensure the standards are swiftly adopted by service providers, which will benefit so many Australians,” said Dr Brown.

Within the framework, there are three core NSQDMH Standards: 1) clinical and technical governance; 2) partnering with consumers; and 3) the model of care, which includes communicating for safety and recognising and responding to acute deterioration. Not all recommended actions within each standard will apply to every service provider.

The Commission has worked closely with consumers, carers, health professionals, digital mental health service providers, academics, experts, and government and peak body representatives to shape the NSQDMH Standards. The draft standards received a strong response when they were put out for national public consultation from February to May this year.

Source: Mirage News

Could telehealth help paralyzed stroke victims recover their motor skills faster than they would working directly with a physical therapist?

Yes, claims a new study that found patients who had participated in at least 12 weeks of at-home rehabilitation with live video consultations ("telerehabilitation") scored higher in testing of the recovery of their motor skills than those who had 12 weeks of in-person rehabilitation.

Study authors, including Chuancheng Ren from Fudan University in Shanghai, China, reported that the convenience of rehabilitating at home may have helped study participants stick to their programs. That may have helped them recover their motor skills better than those who had conventional rehab.

"I'm not surprised that they could see similar effects of therapy with patients using telemedicine as they would via in person," said Dr. Andrew Southerland, an associate professor of neurology and public health sciences at University of Virginia Health, in Charlottesville, Va. "Extrapolating that same technology and line of thinking to rehabilitation makes sense."

Telemedicine for a lot of patients is a way to receive care in the home in situations where they otherwise would need to get in their car, travel, and possibly walk up and down stairs. That can be very strenuous for patients, said Southerland, who was not involved with the new study. It's possible they would be more receptive and able to perform the rehabilitation in a home environment.

"I think that's one possible reason why something like this could potentially work better or help patients more," he added. "I still think that's perhaps an open question about whether telerehabilitation is truly better versus just simply being equivalent to what they could receive by in-person rehabilitation."

In the study, the researchers analyzed the cases of 52 patients in China, half of whom completed home-based telerehabilitation while the other half were in a conventional outpatient group. For both groups, each session included 60 minutes of occupational and physical therapy, plus 20 minutes of a therapy called electromyography-triggered neuromuscular stimulation. The patients had each been admitted to Shanghai Fifth People's Hospital, affiliated with Fudan University, between July 2017 and January 2019.

The patients participated in motor function and brain assessments before the start of the study, once they completed rehab, and again three months later. The investigators found that participants who did in-home rehabilitation received higher scores in motor skills than those who did their therapy in a more conventional setting.

One limitation of the study was that there was not a "control group" receiving no rehabilitation, the authors noted. If there had been, the researchers would have been able to estimate the amount of recovery that occurs naturally.

A challenge of telemedicine for rehab is ensuring that the patient is physically able to do the rehab techniques. Having a caregiver or family member in the home to help is critical to their success, Southerland said.

And doctors still need a nurse or a technician at the bedside to help walk the patient through the neurological exam with telerehabilitation, Southerland noted.

Dr. Sheital Bavishi is an assistant professor in the department of physical medicine and rehabilitation at Ohio State University's Wexner Medical Center, in Columbus. She said that studies show that early rehabilitation after a stroke brings greater improvement for the patient.

"Quality of life is enhanced if post-stroke patients have more functional abilities to manage their [activities of daily living] and have a greater independence," Bavishi said.

It's possible that home-based rehab may work better for some patients because they are being taught exercises in their home environment, which can make compliance better, she said. In a clinic, they're using equipment available in the clinic, while at home they're adapting the exercises to what they have.

"Rehabilitation is most effective when it is patient-centered," Bavishi said. "Therefore, some patients may have greater benefit in conventional rehab than home-based rehab."

Bavishi thinks that studies that show success in telerehabilitation or experiences with telemedicine during the pandemic may lead to more telemedicine in the future.

"This is very exciting for us as physiatrists because our patients with disabilities will get greater access to care," Bavishi said. "The health care disparities and access to care will decrease with more telehealth options." (A physiatrist is a physical medicine and rehabilitation physician.)

The pandemic has accelerated the understanding and acceptance of telemedicine as a platform to care for patients, Southerland said.

"Probably more important to the expansion and sustainability of telemedicine is really to emphasize with our lawmakers and our policy makers the importance of reimbursement pathways and regulatory environments that incentivize folks to perform telemedicine services, and that's also true for telerehabilitation," Southerland said.

Source: U.S. News

More than half of young adults at risk for alcohol-related harm report symptoms of insomnia. Cognitive behavioral therapy (CBT) is one of the first-line treatments for insomnia, but it's never been tested on young adults who are actively drinking. Researchers from the University of Missouri School of Medicine conducted a pilot study to evaluate CBT's effect on young adult binge drinkers with insomnia to determine if this treatment can improve their sleep and potentially affect alcohol use outcomes.

"The potential for insomnia treatment to influence alcohol-related consequences has significant implications for the prevention and treatment of alcohol use among young adults," said Mary Beth Miller, PhD, assistant professor of clinical psychiatry at the MU School of Medicine. "Given the stigma associated with mental health issues and addiction, it's crucial to identify other forms of treatment that either influence alcohol outcomes or open the door to alcohol-related treatment."

Miller tested CBT in a pilot study of 56 people between 18 and 30 years old who reported at least one binge-drinking episode in the past month. Binge drinking was defined as four or more drinks in one occasion. Participants were randomly assigned to either five weekly sessions of CBT -- a behavioral therapy program that focuses on changing patterns of thinking and behavior -- or a single session on sleep hygiene, which focuses on creating optimal sleeping conditions and establishing a bedtime routine. The CBT session topics included sleep hygiene, sleep restriction, relaxation techniques, behavioral experiments, insomnia prevention discussions and sleep diary use. All participants wore wrist devices to objectively measure sleep and completed subjective daily sleep and drinking surveys.

Results showed CBT participants reported a 56% reduction in insomnia severity, compared to a 32% reduction in symptoms for those who completed only the sleep hygiene session. The CBT participants also showed moderate improvement in objectively assessed sleep efficiency after treatment compared to the sleep hygiene participants. Both groups reduced their drinks per week and alcohol-related consequences after treatment. However, CBT participants reported greater improvements in insomnia, which in turn were associated with reductions in alcohol-related problems.

"The results of this study indicate that insomnia treatment may improve alcohol-related problems, and therefore, may be an ideal first step toward treatment among binge-drinking young adults with insomnia," Miller said.

Miller believes the data collected in this study warrants a larger sample size study looking at alcohol-related problems as a primary outcome. She plans to determine if insomnia treatment improves executive function and the ability to regulate emotions, which in turn might decrease risk for alcohol-related problems.

Source: Science Daily

Digital cognitive behavioral therapy for insomnia reduced Insomnia Severity Index scores and resulted in remission of insomnia for some patients, according to findings published in The Lancet Digital Health.

“Although several large-scale randomized controlled trials have shown the efficacy of digital cognitive behavioral therapy for insomnia (dCBT-I), there is a need to validate widespread dissemination of dCBT-I using recommended key outcomes for insomnia,” the researchers wrote. “To address crucial knowledge gaps regarding dCBT-I, we did [a randomized controlled trial] using a fully automated screening and intervention program among adults recruited from the general population in Norway.”

Øystein Vedaa, PhD, of the Norwegian Institute of Public Health, Voss District Psychiatric Hospital and St Olavs University Hospital, all in Norway, and colleagues performed a parallel-group, superiority trial comparing dCBT-I with online patient education about sleep. The interventions, which were available through a website at no cost to participants, included automated screening, informed consent and randomization processes, in addition to outcome evaluations. The researchers recruited adult patients aged greater than 18 years with regular internet access who scored 12 or higher on the Insomnia Severity Index (ISI).

Vedaa and colleagues randomly assigned patients 1:1 to dCBT-I, which included six core interactive sessions completed over 9 weeks, or to patient education; the latter served as the control group. The dCBT-I group addressed the primary topics that are discussed in face-to-face CBT-I including sleep restriction, stimulus control, cognitive restructuring, sleep hygiene and relapse prevention. The patient education website included fixed information about the rate, causes and effects of insomnia, associated symptoms, when to see a health professional and basic lifestyle, environmental and behavioral recommendations about improving sleep (ie, sleep hygiene education). Change in ISI score from baseline to follow-up at 9 weeks served as the primary outcome, which the researchers evaluated in the intent-to-treat population.

The researchers enrolled 5,349 individuals in the online screening process between Feb. 26, 2016, and July 1, 2018. Of those patients, Vedaa and colleagues randomly assigned 1,721 to receive dCBT-I (868) or patient education (853). At the 9-week follow-up point, 584 (67%) participants in the dCBT-I group and 534 (63%) participants in the patient education group finished the ISI evaluation.

Participants in the dCBT-I group experienced a significantly greater decrease in ISI scores from baseline (mean score, 19.2 at baseline to 10.4 at 9-week follow-up) than those in the patient education group (mean score, 19.6 at baseline to 15.2 at 9-week follow-up; estimated mean difference, –4.7; 95% CI, –5.4 to –4.1). Compared with patient education, the number of sessions needed with dCBT-I was 2.7 (95% CI, 2.4-3.2) to achieve treatment response (defined as an ISI score reduction of 8) and 3.2 (95% CI, 2.8-3.8) to achieve insomnia remission (ISI score <8).

Vedaa and colleagues found that the dCBT-I group reported greater improvements in most secondary measures compared with the patient education group. Individuals in the dCBT-I group were significantly less likely to be using sleep medications at follow-up compared with the patient education group, with the decrease in the rate of sleep medication use from baseline to follow-up estimated to be approximately 16 percentage points for dCBT-I and 10 percentage points for patient education (OR = 0.49; 95% CI, 0.23-0.74).

The dCBT-I group also demonstrated a significantly greater decrease in fatigue according to the Chalder Fatigue Questionnaire scores (between-group effect sizes, –0•4; 95% CI, –0•53 to –0•27). The researchers observed no differences between the groups regarding total sleep time or perceived physical health according to the SF-12 physical health score. Vedaa and colleagues also observed no adverse events.

“This study is one of the largest [randomized controlled trials] to date to examine the efficacy of fully automated dCBT-I in a community-based sample of adults with high levels of insomnia. It is also the largest [randomized controlled trial] to evaluate efficacy with the recommended standard outcomes for insomnia (ie, changes in ISI ratings and sleep–wake patterns as assessed using sleep diaries),” the researchers wrote. “Overall, our findings support those obtained in previous high-quality trials on the effects of fully automated dCBT-I for individuals with insomnia.”

Source: Healio

While virtual medical and rehabilitation appointments seemed novel when COVID-19 first appeared, they now seem to be part of the new norm and might be paving the way to the future.

A recent review paper, co-authored by Brodie Sakakibara with the Centre for Chronic Disease Prevention and Management (CCDPM) has determined that virtual appointments, in the form of telerehabilitation, also work for people recovering from a stroke.

After a stroke, a client is provided with a therapy program to help re-gain loss of skills or motion--this can range from speech and memory, strength, balance and endurance. While not initially introduced for disease outbreaks, Sakakibara a UBCO assistant professor says research shows remote therapy can be effective during stroke recovery.

“Telerehabilitation has been promoted as a more efficient means of delivering rehabilitation services to stroke patients while also providing care options to those unable to attend conventional therapy. These services can be provided to remote locations through information and communication technologies and can be accessed by patients in their homes." - Brodie Sakakibara, UBCO Assistant Professor

To learn how effective telerehabilitation can be, six different clinical trials--examining stroke telerehabilitation programs--were launched across Canada as part of a Heart and Stroke Foundation initiative. People recovering from a stroke were provided with interventions ranging from lifestyle coaching to memory, speech skills and physical-exercise training.

"Researchers from each of the six trials came together to write a review paper describing their experiences conducting a telerehabilitation study, and to report on the facilitators and barriers to the implementation of telerehab services within a research context," says Sakakibara.

Going forward with telerehabilitation as a new reality, Sakakibara says the study authors determined there are important lessons learned from each of the six trials. Most notably, the efficacy and cost of telerehabilitation is similar to that of traditional face-to-face management. He also notes patients mostly reported satisfaction with the telerehabilitation when therapists were trained appropriately, and when there was some social interaction. Overall, clinicians prefer face-to-face interactions but will use telerehabilitation when face-to-face is not feasible.

And finally, since seniors are a key target group for stroke rehabilitation--as stroke is associated with aging--the technology needs to be easy to use and suit the needs of the end users.

"The older adult of today, in terms of technology comfort and use, is different than the older adult of tomorrow," he says. "While there might be some hesitation of current older adults using technology to receive health and rehab services, the older adult of tomorrow likely is very comfortable using technology. This represents a large opportunity to develop and establish the telehealth/rehabilitation model of care."

Sakakibara notes COVID-19 has amplified the necessity for telehealth and telerehabilitation for many Canadians--especially those in remote areas or for the estimated 70 per cent of stroke victims who are no longer able to drive.

"Prior to the outbreak, telehealth/rehabilitation was highly recommended in Canadian stroke professional guidelines, but was underused," he says. "Now in response to COVID-19, the use of telerehabilitation has been accelerated to the forefront. Once these programs are implemented in practice, it'll be part of the norm, even when the outbreak is over. It is important that we develop and study telerehabilitation programs to ensure the programs are effective and benefit the patients."

Source: News Medical

Nearly 50 percent of women say they get PMS, with symptoms including bloating, headaches and moodiness. Here’s how to get rid of period bloating. INTIMINA’s gynecologist Dr Shree Datta reveals exactly how to tackle premenstrual symptoms, from period bloating to headaches.

Dr Datta said: “National guidelines estimate that 40 percent of women experience PMS symptoms, with around five percent having severe symptoms.

“As you can see, it includes a whole range of symptoms and their severity varies from person to person.

“If you think you suffer from PMS keep a diary of your symptoms over two periods, in relation to your menstrual cycle and note down any appetite and sleep changes.

“Make sure you get things reviewed by your Gynaecologist early; things that we will consider include the supplements mentioned above, exercise, and of course, review your diet.

“We'll work with your cycle, looking at how long your symptoms last, and whether they affect your lifestyle.

"We will consider these in conjunction with medications such as the pill, or other interventions such as cognitive behaviour therapy.”

What is PMS?

Dr Datta explained the main players in menstruation are the ovaries, hypothalamus, and pituitary gland.

She said: “Together, these heavy hitters dictate the production and secretion of reproductive hormones.”

The first day of bleeding is the start of your “cycle”.

About 14 days after that is when ovulation occurs and you enter the luteal phase. Usually about two weeks after your period - although this can vary.

PMS comes in the luteal phase of your cycle, which is usually about two weeks after your period, but this can vary from person to person.

Dr Datta said: “When an egg released during ovulation goes unfertilised, progesterone levels begin to fall.

“This powerful hormone controls a lot in your body, including chemicals in the brain such as serotonin.

“A drop in this so-called ‘happy chemical’ is a contributing factor in the emotional swings that can come before your period.

“Progesterone also aids in relaxation and sleep. So when levels of it drop, you may feel anxious and irritable.

“On the other hand, high levels of estrogen, sometimes called ‘estrogen dominance’, can increase symptoms of PMS.

“For the most part, the two main theories around PMS, revolve around sensitivities to progesterone and progestins, along with the neurotransmitter (Serotonin and GABA) theory.”

How to get rid of period bloating, headaches and mood swings

Change your diet

That’s right, you need to change what you eat to improve your symptoms.

Dr Datta said: “Many of the things we eat on a daily basis can have a significant impact on PMS symptoms.

“Sneaky things like sugar, caffeine, and alcohol can all negatively affect your hormonal levels.

“Cutting these out, or limiting them may improve your symptoms.

“If you eat meat and other animal products, be sure to choose ones made from animals not treated with hormones.

“This may seem like common sense, but added hormones to your food means added hormones to your body.

“Stick to the basics here. Whole foods, organic preferred, with lots of fruits and veggies.

“Fiber is also crucial to your body’s ability to process estrogen.”

The food you eat not only impacts your hormones but also your overall mood.

Exercise

Even though it’s the last thing you want to do when you are due on your period, you need to exercise.

Dr Datta said: “When it comes to PMS, it matters what you do throughout your whole cycle, not just while you’re feeling uncomfortable.

“Regular exercise and movement can help improve symptoms of PMS before they even start.”

Working out all month round will reduce symptoms, so get on that yoga mat or head out for a run ahead of time.

Regulate hormones

One of the reasons so many people are experiencing symptoms related to high levels of estrogen is because of lifestyle and environmental factors.

Dr Datta explained if you watch the chemicals you are using, you could regulate your hormone levels.

She said: “Certain chemicals in plastics, cosmetics, cleaning products, and plenty of other things we use in our daily lives, have high levels of BPA, and other compounds that negatively affect our hormone levels.

“Switching to toxin-free products, and reducing plastic (especially when it comes to your food) may significantly improve PMS symptoms.”

Professional help

Sometimes ranting to your friends won’t help, but seeing an expert might.

Dr Datta said: “If you constantly find yourself down in the dumps before your period, it may be helpful to seek counselling or Cognitive Behavioural Therapy

“Your overall mental and physical health have significant impacts on premenstrual symptoms.

“A high-stress lifestyle can throw hormones out of whack. The menstrual cycle is a direct reflection of your overall health.

“Poor mental and physical health can affect menstruation, especially when it comes to any emotional side effects you may experience.

“While it’s a lot easier said than done to be healthy and stress-free, doing what you can to help improve these areas of your life, will give you a smoother luteal phase, and overall menstrual cycle.

“While some PMS symptoms are normal - and there is a wide range of normal - if they are seriously affecting your life and wellbeing, there are steps you can take to help make your cycle smoother.”

Dr Datta recommended seeing a holistic practitioner to treat your hormonal imbalances, or a local acupuncturist, naturopathic doctor, or midwife.

Some chiropractors also have knowledge in hormonal balancing and nutrition, she said.

Source: Express

신종 코로나바이러스 감염증(COVID-19•코로나19)을 일으키는 바이러스가 코에 가장 잘 달라붙는 것으로 나타났다. 코에 먼저 감염을 일으킨 이후 호흡을 타고 기관지와 폐로 점차 퍼져나간다는 것이다. 이를 막기 위해서는 코의 노출을 막는 마스크가 유용하고 코 세척도 초기 바이러스양을 줄일 수 있어 효과적이라는 분석이다.

리처드 바우처 미국 노스캐롤라이나대 미생물학 및 면역학부 교수와 랠프 배릭 교수 공동연구팀은 코로나19가 감염되는 주 경로인 호흡기를 부위별로 분석한 결과 호흡기를 따라 감염력이 점차 줄어들었다는 연구결과를 지난달 29일 국제학술지 ‘셀’에 발표했다.

연구팀은 코로나19를 일으키는 사스코로나바이러스-2(SARS-CoV-2)가 감염되는 호흡기 부위가 얼마나 잘 감염되는지를 분석했다. 연구팀은 바이러스가 세포에 침투할 때 이용하는 돌기단백질을 가진 형광 바이러스를 설계해 코와 기관지, 기관지에서 폐로 뻗어나가는 세기관지, 폐포 바깥 세포인 1형과 속 세포인 2형 폐포세포 등을 감염시키는 능력을 살폈다. 사스코로나바이러스-2는 돌기단백질을 인간 세포의 ‘안지오텐신전환효소2(ACE2)’에 결합시키며 세포 속으로 침투하는 능력을 만든다.

그 결과 사스코로나바이러스-2는 호흡기 중 코 세포에서 가장 감염이 잘 일어난 반면 폐포 세포에서는 감염이 잘 일어나지 않았다. 감염력은 코, 기관지, 세기관지, 1형 폐포, 2형 폐포 순으로 나타나 호흡기 속으로 들어갈수록 점차 떨어졌다. 연구팀은 이러한 원인이 ACE2 양에 있다고 보고 세포들의 ACE2 양을 분석했다. 여기서도 마찬가지로 코에서는 ACE2 양이 가장 많았고 호흡기를 지나갈수록 점차 줄어들어 폐포에서는 ACE2가 가장 적었다.

연구팀은 코가 처음 감염된 이후 호흡을 통해 코에서 자란 바이러스가 점차 몸속으로 퍼져나가는 감염 모델을 제시했다. 코의 감염을 막기 위해서는 마스크 착용과 코 세척 등이 유용하리라 분석했다. 연구팀은 “콧속이 에어로졸과 침방울, 손으로부터 노출되는 걸 막기 위해선 마스크를 사용해야 한다”며 “감염 초기 코의 바이러스양을 줄이는 코 세척이나 코에만 항바이러스제를 투여하는 것도 유익할 수 있다”고 결론지었다.

출처: 동아사이언스

There is an unprecedented need to manufacture and distribute enough safe and effective vaccine to immunize an extraordinarily large number of individuals in order to protect the entire global community from the continued threat of morbidity and mortality from severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2). The global need for vaccine and the wide geographic diversity of the pandemic require more than one effective vaccine approach. Collaboration will be essential among biotechnology and pharmaceutical companies, many of which are bringing forward a variety of vaccine approaches (1). The full development pathway for an effective vaccine for SARS-CoV-2 will require that industry, government, and academia collaborate in unprecedented ways, each adding their individual strengths. We discuss one such collaborative program that has recently emerged: the ACTIV (Accelerating COVID-19 Therapeutic Interventions and Vaccines) public-private partnership. Spearheaded by the U.S. National Institutes of Health (NIH), this effort brings together the strengths of all sectors at this time of global urgency. We further discuss a collaborative platform for conducting harmonized, randomized controlled vaccine efficacy trials. This mechanism aims to generate essential safety and efficacy data for several candidate vaccines in parallel, so as to accelerate the licensure and distribution of multiple vaccine platforms and vaccines to protect against COVID-19 (coronavirus disease 2019).

We currently know little about what constitutes a protective immune response against COVID-19. Data from SARS-CoV-1 patients as well as recently infected SARS-CoV-2 patients document relatively high levels of immune responses after infection, especially antibody responses to the surface (spike) protein that mediates entry into host cells. However, in vivo data on the type or level of immunity required to protect from subsequent re-infection, and the likely duration of that protection, are currently unknown. In animal models of SARS-CoV-1, immunization with recombinant subunit proteins and viral- and nucleic acid–vectored vaccines, as well as passive transfer of neutralizing antibodies to the spike protein, have been shown to be protective against experimental infection (2, 3). Endpoints vary from protection of infection to modification of viral replication and disease. These data bring optimism that a highly immunogenic vaccine will elicit the magnitude and quality of antibody responses required for protection. The role that T cell immunity plays in preventing acquisition or amelioration of early disease, either in animal challenge models or in human coronavirus disease, is unclear (4); this constitutes another reason why a diversity of vaccine approaches must be pursued.

A high degree of safety is a primary goal for any widely used vaccine, and there is theoretical risk that vaccination could make subsequent SARS-CoV-2 infection more severe. This has been reported for feline coronaviruses and has been observed in some vaccine-challenge animal models of SARS-CoV-1 (5). These preclinical data suggest that the syndrome of vaccine-associated enhanced respiratory disease results from a combination of poorly protective antibodies that produce immune complex deposition together with a T helper cell 2 (TH2)–biased immune response. The potential mechanism behind vaccine-induced immune enhancement and the means to minimize this risk have recently been reviewed (6). It will be important to construct conformationally correct antigens to elicit functionally effective antibodies—a lesson learned from vaccine-induced enhanced lower respiratory illness among infants receiving a formalin-inactivated respiratory syncytial virus (RSV) vaccine. Animal models of SARS-CoV-2 infection are currently being developed, and these models can be used to better understand the immune responses associated with protection (7).

Clinical and Immunological Endpoints

The primary endpoint for defining the effectiveness of a COVID vaccine also requires discussion. The two most commonly mentioned are (i) protection from infection as defined by seroconversion, and (ii) prevention of clinically symptomatic disease, especially amelioration of disease severity, including the frequency of disease requiring high-intensity medical care with some assessment of a decrease in hospitalization. This requires the close evaluation of the effect of vaccination on the severity of COVID-19 disease in a wide variety of epidemiological and medical settings among both younger and elderly populations as well as underserved minorities. All of these issues need to be evaluated in the context of these initial efficacy trials. Achieving these endpoints could also be associated with reduced transmissibility on a population basis.

Primary endpoints that involve reduction of disease require greater numbers of enrollees into trials, given that asymptomatic infection is estimated to be 20 to 40% of total cases of COVID-19 (8). Initial efficacy trials may then require a large initial enrollment, with ongoing monitoring of both serologic and clinical endpoints. A major challenge leading to a degree of complexity in developing clinical trial protocols for serological endpoints is the lack of precise knowledge of incidence rates (9). A critical requirement for such a multi-trial strategy is the establishment of independent laboratories with similar or identical validated serologic assays to provide a harmonizing bridge between multiple vaccine products and multiple vaccine efficacy trials. The use of these laboratories for each clinical trial, or the sharing of critical specimens from a trial, should be required. Parameters that would distinguish the immune response resulting from vaccination versus from infection are under intense investigation, and there is an immediate need to develop assays to address this issue.

Efficacy trials need to be evaluated for both benefit and harm. The likelihood of SARS-CoV-2 reexposure is much higher than that of SARS-CoV-1, which has disappeared from community circulation, and hence longer-term evaluation of potential enhancement with reexposure is needed. This requirement does not preclude licensure based on the endpoints outlined above; however, it does indicate that more prolonged follow-up of the initial vaccine cohorts should be undertaken. The durability of clinical and serologic endpoints will also need to be explored, as waning of immunity is common with human coronavirus infections (10). Coronaviruses have a single-stranded RNA genome with a relatively high mutation rate. Although there has been some genetic drift during the evolution of the SARS-CoV-2 epidemic, major alterations in the spike protein are not extensive to date, especially in the regions thought to be important for neutralization; this enables cautious optimism that vaccines designed now will be effective against circulating strains 6 to 12 months in the future (11).

The possibility of performing controlled human challenge trials, in which a small number of volunteers are vaccinated and subsequently challenged with SARS-CoV-2, has been suggested. Such experiments, if designed to define potential immune correlates or winnow out less effective vaccine approaches, may have utility. However, this approach has shortcomings with respect to pathophysiology and safety (12). Although the risk of severe disease or death in young healthy individuals from COVID-19 is quite low, it is not zero, and we do not yet have proven effective therapies for COVID-19 to rescue volunteers with complications from such a challenge. It is likely that a SARS-CoV-2 challenge strain will, by design, cause mild illness in most volunteers and thus may not recapitulate the pulmonary pathophysiology seen in some patients. Moreover, partial efficacy in young healthy adults does not predict similar effectiveness among older adults with major cofactors associated with COVID-19 disease, nor would it prove reduction of transmissibility to major susceptibility groups. Whether such experiments may be worthy of pursuit or would have a beneficial impact on timelines for vaccine development needs careful evaluation by an independent panel of ethicists, clinical trialists, and experts on vaccine development.

Vaccine Platforms

It is encouraging that vaccine development efforts have moved swiftly, and several major vaccine platforms are moving toward clinical evaluation. These include traditional recombinant protein, replicating and nonreplicating viral vectors, and nucleic acid DNA and mRNA approaches. Each of these vaccine platforms has advantages and limitations. Important characteristics include speed and flexibility of manufacture, safety and reactogenicity, the profile of humoral and cellular immunogenicity, durability of immunity, scale and cost of manufacturing, vaccine stability, and cold chain requirements. No single vaccine or vaccine platform alone is likely to meet the global need, and so a strategic approach to the multi-pronged endeavor is absolutely critical.

Several companies are developing nucleic acid–based vaccines, including Moderna, BioNTech/Pfizer, CureVac (mRNA-based), and Inovio (DNA-based). DNA- and mRNA-based vaccines can be generated quickly on the basis of viral sequence, which allows a rapid pathway to the clinic (13, 14). Currently, optimal immunogenicity of DNA requires an electroporation or an injector delivery device to facilitate DNA entry into cells. mRNA vaccines use lipid nanoparticles to protect and deliver the mRNA and effectively adjuvant the immunogen. The scalability of these lipid nanoparticles and their temperature stability are issues that need to be addressed. Although there is a wide body of early-phase clinical experience with nucleic acid vaccines, none are licensed for widespread usage. As such, the path forward is filled with optimism, but some uncertainty remains, requiring rapid assessment of these products' immunogenicity and safety while addressing the lack of commercial experience with them.

Traditional recombinant protein technology can be used to express the spike protein (e.g., Sanofi, Novavax), and although the time to establish cell lines needed for manufacturing is longer than for nucleic acid vaccines, there is a robust commercial experience with protein and protein particle vaccines, including licensed vaccines for hepatitis B, human papillomavirus, varicella zoster, and influenza. Protein vaccines will require a potent adjuvant, which can be critical for inducing a predominantly TH1-type immune response; however, the availability of certain adjuvants may be limited. Viral vector vaccines encode the viral gene of interest into one of several well-characterized vectors, including adenovirus (Ad) and vesicular stomatitis virus (VSV). The replication-defective adenovirus 26 (rAd26), recently shown to be safe and immunogenic in preventing Ebola virus infection (15), is being developed by Janssen Pharmaceuticals for COVID-19. This platform has the potential to be manufactured at large scale. Preexisting immunity to the specific viral vector can attenuate immunogenicity, and this needs to be addressed in early-stage trials. A recombinant chimpanzee Ad vector (ChAdOx1), developed by the University of Oxford and AstraZeneca, has also entered clinical trials. Similar versions of ChAd vaccine products have been tested in prior clinical trials and shown to be safe and immunogenic. The VSV vector vaccine platform is replication-competent and thus induces a robust, likely durable immune response with a single dose. A licensed VSV Ebola vaccine made by Merck is highly effective after a single dose, although its reactogenicity may be limiting in some populations. These diverse approaches provide the potential for scalable production required for widespread population use.

Strategic Collaborations

Under the ACTIV public-private partnership, NIH has partnered with its sister agencies in the Department of Health and Human Services, including the Food and Drug Administration, Centers for Disease Control and Prevention, and Biomedical Advanced Research and Development Authority; other U.S. government departments including the Departments of Defense and Veterans Affairs; the European Medicines Agency; and representatives from academia, philanthropic organizations, more than 15 biopharmaceutical companies, and the Foundation for NIH. This forum allows for discussions and consensus on vaccine trial designs, rapid data sharing, and close collaborations between the public and private sectors to rapidly and efficiently conduct vaccine efficacy studies. There is an emerging consensus that vaccine trials need to either use common independent laboratories or contribute samples and data for the purpose of generating surrogate markers that ultimately speed licensure and an overall comparison of efficacy. A common Institutional Review Board as well as a common cross-trial Data and Safety Monitoring Board (DSMB) should be used so that the regulatory framework for the entire enterprise is coordinated and the regulatory agencies and the public can make objective assessment of the effect sizes between approaches. As vaccine candidates are poised to enter phase 1, the collective planning for phase 3 must be undertaken. Although much of this focus is on trials in the United States, the COVID-19 Prevention Networks established under the ACTIV program have a global focus, and coordination with the World Health Organization, Coalition for Epidemic Preparedness Innovations, and other global philanthropic partners must also occur.

Harmonized master protocols will be needed to enable transparent evaluation of the relative effectiveness of each vaccine approach. This harmonization can best be achieved through public-private partnerships such as ACTIV, in which government-supported central laboratories and independent biostatisticians serve as key resources for efficacy trials, thereby providing a standardized way to assess the relative immune responses of different types of vaccines (see the figure). Such laboratories enhance the ability to define correlates of protection, which would speed licensure for all vaccines as well as define populations that will achieve protective immunity. Data should be shared among companies and be provided to independent statistical evaluation, allowing the early evaluation of a potential surrogate marker of protection, which would markedly speed licensure and distribution. Such data can only be obtained from harmonization and collaboration early on, during the planning of efficacy trials and the implementation of the collaboration described in the figure: the use of collaborating clinical trial sites, the monitoring of these efficacy trials through a common DSMB, independent statisticians having access to cross-trial data in real time, and centralized immune monitoring laboratories. These innovations in the process of vaccine development are required to achieve the rapid development of the platform technologies entering clinical trials. Global effort, global cooperation, and transparency are needed to maximize the speed, veracity, and decision-making required to deliver scientific advances to the global population in a timely fashion. Models for all of these programs exist, and rapid implementation of these ideas is essential if we are to succeed in the timelines required to return us to pre–COVID-19 social interactions.

Scale Up

The ability to manufacture hundreds of millions to billions of doses of vaccine requires the vaccine-manufacturing capacity of the entire world. Although new technologies and factories can be developed to sustain production, there is an immediate need to fund the necessary biomanufacturing infrastructure, including the fill/finish steps that provide vialed vaccine products for distribution. Cost, distribution system, cold chain requirements, and delivery of widespread coverage are all potential constriction points in the eventual delivery of vaccines to individuals and communities. All of these issues require global cooperation among organizations involved in health care delivery and economics.

To return to a semblance of previous normality, the development of SARS-CoV-2 vaccines is an absolute necessity. To achieve this goal, all the resources in the public, private, and philanthropic sectors need to participate in a strategic manner. The ACTIV public-private partnership and collaborative harmonized efficacy trials are enabling models to achieve our common goal.

출처: Science

중증 급성 호흡기 증후군인 코로나바이러스 2 (SARS-CoV-2)의 지속되는 사망 및 질병의 위협에서 국제 사회 전체를 보호하기 위해서 많은 수의 사람들이 면역력을 갖도록 안전하고 효과적인 백신을 충분히 만들어서 공급해야 한다는 전례 없는 요구가 시급한 상황이다. 백신에 대한 전 세계적인 요구와 광범위한 지역으로 퍼진 세계적인 팬데믹을 다루기 위해서는 한 가지 이상의 효과적인 백신 연구 개발 접근 방법이 필요하다. 생물 공학 및 제약 회사의 협력은 필수이며 다수의 협력 체계가 다양한 백신 접근 방법을 제안하고 있다 (1). SARS-CoV-2 의 효과적인 백신을 개발하기 위해서는 산업계와 정부, 학계가 각계의 힘을 더하는 전례 없는 방법으로 협력해야 할 것이다. 이에 따라, 코로나19 치료제 및 백신 개발 가속화 협력 프로그램인 ACTIV (Accelerating COVID-19 Therapeutic Interventions and Vaccines)이 최근에 떠오르고 있다. 미국 국립 보건원 (NIH)을 선두로 한 이 협력 프로그램은 세계적인 팬데믹 위기에 초점을 맞춰 여러 유관부서 및 이해관계자들의 협력을 이끌고 있다. 이 프로그램의 목적은 여러 개의 백신 후보를 동시에 비교해서 필수 안전 정보 및 효능의 데이터를 구축해 코로나바이러스 19로부터 보호할 수 있는 다양한 백신 플랫폼 과 백신 허가 및 배분을 가속화하기 위한 것이다.

vvvv현재로서는 코로나바이러스로부터 보호할 수 있는 면역 반응에 대해 알려진 바가 거의 없다. SARS-CoV-1 환자들의 자료뿐 아니라 최근 SARS-CoV-2에 감염되었던 환자들의 자료를 보면, 감염 후 상당히 높은 수준의 면역 반응을 볼 수 있으며 특히 인체 세포에 침투하기 위해 이용하는 표면의 (스파이크) 단백질에 대한 항체 반응을 볼 수 있다. 하지만 재감염을 막아주는 면역 유형 또는 면역 수준의 생체 자료 그리고 면역력의 지속 기간에 대한 생체 자료는 현재 없다. 재조합 아단위 단백질 (recombinant subunit protein) 및 바이러스 억제 백신, 핵산 벡터 백신을 이용한 면역법 뿐만 아니라 스파이크 단백질로 중화 항체를 수동적으로 전달하는 방법이 SARS-CoV-1의 동물 모델의 실험 감염 상황에서 효과가 있는 것으로 밝혀졌다 (2, 3). 감염으로부터의 보호에서 시작해서 바이러스 복제와 질병에 이르는 최종 단계는 다양하다. 이런 자료를 통해 면역 효과가 높은 백신이 신체 보호에 필요한 항체 반응을 양과 질적으로 유도할 것이라고 기대해 볼 수 있다. 감염 초기에 T 세포의 면역성으로 감염이 되느냐 극복하느냐가 결정되지만, 이 영향이 동물 모델에서만 보이는 현상인지 인간의 코로나바이러스 질병 상황에서도 보이는 현상인지는 불분명하다 (4); 다양한 백신 접근 방법이 필요한 또 하나의 이유이다.

광범위하게 사용되는 백신은 높은 수준의 안전성이 필수인데 백신으로 인해 SARS-CoV-2 감염이 더 심각해질 수도 있다는 이론적인 위험 요소를 고려해야 한다. 이런 경우가 고양잇과의 코로나바이러스 사례에서 보고되었으며 SARS-CoV-1의 동물을 대상으로 한 백신 실험에서도 발견되었다 (5). 이러한 임상 전 단계의 자료를 보면, 면역 복합체를 생성하는 항체가 약하고 그와 동시에 헬퍼 T 세포(helper T cell)에 치우친 면역 반응이 일어날 때 백신으로 인해 호흡기 질환이 더 심해지는 증상이 나타난다. 최근에는 백신으로 강화되는 면역력을 뒷받침하는 잠재적인 방법 및 호흡기 질환이 더 심해지는 위험을 감소하는 방법을 검토하는 중이다 (6). 효과적인 기능의 항체를 유발하는 정확한 형태의 항원을 구성하는 것이 중요한데, 포르말린 비활성 호흡기 세포 융합 바이러스 (RSV) 백신을 맞은 영아가 하부 호흡기 질환을 더 심하게 앓는 경우에서 얻은 교훈이다. 현재 개발 중인 SARS-CoV-2 감염의 모형 동물 실험을 이용해서 감염으로부터의 보호에 관련된 면역 반응 이해를 도울 수 있을 것이다 (7).

임상 및 면역학적 최종 단계

코로나바이러스 백신의 효과를 결정하는 기본적인 최종 단계 역시 논의가 필요하다. 가장 많이 논의되고 있는 두 가지 단계는 (i) 혈청 전환으로 생기는 감염으로부터의 보호와 (ii) 질병의 임상적인 증상 예방 특히, 집중적인 의료 관리를 필요로 하는 질병의 빈도수와 입원 환자의 감소 수치 평가를 포함하는 질병의 심각성 개선이다. 젊은 인구층과 노년 인구층뿐 아니라 혜택을 받지 못하는 소수 취약층에 걸쳐 매우 다양한 전염병학, 의학적인 환경에서 심각한 질병인 코로나바이러스 19 백신의 효과를 면밀하게 평가할 필요가 있다. 초기의 백신 효과 실험에서 이런 이슈를 모두 평가해야 한다. 이런 최종 단계를 성취하면 인구 단위의 전염성을 감소시킬 수도 있을 것이다.

코로나바이러스 19 전체 사례의 20-40%가 무증상 감염인 것을 고려하면, 질병 감소를 위한 기본적인 최종 단계에서는 상당한 수의 실험 참여자가 필요하다 (8). 그러려면 초기의 백신 효과 실험에 참여하는 참여자 수가 아주 많아야 하고 혈청학적, 임상적인 최종 단계 모두를 지속해서 모니터링하는 것도 필요하다. 혈청학적인 최종 단계를 위한 임상시험 계획안을 개발하는 데 더 걸림돌이 되는 것은 정확한 발병률을 알 수 없다는 것이다 (9). 다수의 실험 전략에 꼭 필요한 것은 다수의 백신 제품과 다수의 백신 효과 실험 사이의 차이점을 메꾸어 줄 검증된 혈청학적 분석 평가를 동일하게 혹은 유사하게 진행할 수 있는 독립적인 검사실들을 설립하는 것이다. 이 검사실에서 각 임상시험을 진행하거나 실험의 중요한 표본을 공유하도록 한다. 백신에 대한 면역 반응을 감염에 대한 면역 반응과 구별할 수 있는 기준치에 대한 연구가 현재 활발히 진행되고 있으며 이 쟁점을 다루기 위한 분석 평가 개발이 시급하다.

백신 효과 실험을 평가할 때는 장단점을 모두 다루어야 한다. SARS-CoV-2에 재노출될 가능성은 지역 사회에서 사라진 SARS-CoV-1에 비해 상당히 높기 때문에 재노출을 고려한 백신의 잠재적인 효과의 장기적인 평가가 필요하다. 하지만 이런 요구 조건 때문에 위에 강조한 내용에만 기반해서 백신 허가 대상을 제한해서는 안 된다. 다만, 초기 백신 코호트 (cohort)의 더 장기적인 후속 연구가 필요하다는 뜻이다. 임상적, 혈청학적인 최종 단계 기간 역시 결정해야 하는데, 인간의 코로나바이러스 감염에서 면역력 저하가 빈번하기 때문이다 (10). 코로나바이러스는 변형률이 높은 한 가닥의 RNA 게놈 (genome, 유전체)로 구성되어 있다. SARS-CoV-2 전염병의 진화 과정에서 어느 정도의 유전적인 변이가 생기긴 했지만, 특히 바이러스 중화에 중요하다고 생각되는 부분에서 스파이크 단백질 변형은 지금까지 크게 없었다. 이를 근거로 지금 개발하는 백신의 효과가 앞으로 6-12개월 후에 순환할 바이러스 유형에도 효과가 있을 것이라고 조심스럽게 낙관해 볼 수 있다 (11).

적은 수의 지원자에게 백신을 투여하고 SARS-CoV-2에 접촉하게 하는 인간을 대상으로 한 통제 실험 가능성이 제시되었다. 잠재적인 면역 상관관계를 정의하는 실험을 설계하거나 덜 효과적인 백신을 골라내는 실험을 설계할 수 있다면 인간을 대상으로 한 실험이 실용적일 수도 있다. 하지만 이 접근법은 병리 생리학과 안전성의 관점에서 볼 때 아직 부족한 점이 많다 (12). 건강한 젊은 세대가 코로나바이러스 19로 인해 심각한 질병을 앓거나 사망에 이를 위험성은 낮다고 하지만 전무한 것은 아니며, 코로나바이러스 19의 위험에 노출된 지원자를 효과적으로 치료할 검증된 치료법이 없어서 위험하기 때문이다. 대부분의 지원자가 SARS-CoV-2 바이러스에 감염되면 가벼운 질병 증상을 앓도록 설계해서 소수 환자의 경우에서 볼 수 있는 폐 관련 병태생리학적인 증상을 반복해서 겪지 않도록 실험이 진행될 가능성이 높다. 게다가, 젊고 건강한 성인에게만 효과적인 백신이라면 노인층이 코로나바이러스 19 관련 심각한 공통 인자를 가졌다고 해서 백신의 비슷한 효과를 기대할 수 없으며 백신의 효과로 주요 감염 집단에 대한 전염성이 감소할 거라고 증명할 수도 없다. 이런 실험을 진행할 가치가 있을지, 그리고 이런 실험이 백신 개발 일정에 이득이 될지에 관해 윤리학자들, 임상시험자들, 백신 개발 전문가들로 구성된 독립적인 패널의 평가가 필요하다.

백신 플랫폼

다행히 백신 개발을 위한 노력이 빠르게 진행되고 있으며 몇 가지 백신 플랫폼이 임상 평가를 앞두고 있다. 기존의 재조합 단백질과 복제 및 비 복제 바이러스 벡터, 핵산 DNA 및 mRNA 접근법 등을 예로 들 수 있다. 각 기본 백신 플랫폼에는 장점과 한계점이 있다. 백신 개발에서 중요한 특성에는 백신 생산 속도와 융통성, 안전성과 백신의 반응원성, 체액 및 세포 면역원성의 윤곽, 면역력의 내구성, 백신 생산의 규모와 비용, 백신의 안정성, 냉장 유통이 필요한지의 여부가 포함된다. 한 개의 백신 또는 한 개의 백신 플랫폼으로 전 세계의 백신 요구량을 다 채우는 것은 불가능하기 때문에 다각적인 노력이 절대적으로 중요하다.

핵산에 기반한 백신을 개발하는 업체가 여러 개 있으며, 모더나 (Moderna), 바이온텍/화이자 (BioNTech/Pfizer), 큐어백 (CureVac) (mRNA 기반), 이노비오 (Inovio) (DNA 기반)에서 개발 중이다. DNA- 및 mRNA 기반 백신은 바이러스 서열을 바탕으로 빠르게 생산이 가능해서 의료 시설 공급에 속도를 낼 수 있다 (13, 14). 현재는, DNA의 면역원성을 최적화하기 위해서 DNA가 세포 안에 침투할 수 있도록 전기 천공법 또는 주사 방법을 사용한다. mRNA 백신은 mRNA를 보호해서 전달하며, 면역원을 효과적으로 보조하기 위해서 지질 나노입자를 이용한다. 지질 나노입자의 크기 확장성 및 온도 안정성이 문제가 될지 논의가 필요하다. 핵산 백신을 대상으로 한 초기 임상시험은 많지만 광범위하게 사용하도록 허가를 받은 백신은 없다. 그래서 전망은 낙관적이지만 불확실한 부분이 남아있어서 이런 백신 제품의 면역원성 및 안전성을 신속하게 평가하는 동시에 상업적으로 사용된 적이 별로 없다는 사실도 다루어야 할 것이다.

핵산 백신의 경우, 기존의 재조합 단백질 기술을 이용해서 스파이크 단백질을 표시할 수 있고 (예, 사노피 (Sanofi)사와 노바백스 (Novavax)사), 핵산 백신 생산에 필요한 세포계를 확립하는 데 걸리는 시간이 더 길긴 하지만 단백질 백신과 단백질 입자 백신은 상업적으로 많이 사용되어 B형 간염, 인체 유두종 바이러스, 수두 대상 포진, 독감에 허가를 받아 사용 중이다. 단백질 백신을 사용할 때는 두드러지는 TH1 유형의 면역 반응을 유도하기 위해서 효과적인 보조제가 필요한데 특정한 보조제 사용에 제한이 있을 수 있다. 바이러스 벡터 (매개체) 백신은 타켓으로 하는 바이러스 유전자를 잘 짜인 벡터 중 하나로 부호화하며 (encode) 아데노바이러스 (Ad)와 수포성 구내염 바이러스 (VSV)를 포함한다. 복제 결손 아데노바이러스 25 (rAd26)은 최근에 에볼라 바이러스 감염 예방에 효과가 있는 안전한 면역원으로 입증되었으며 (15), 코로나바이러스 19에 사용하기 위해서 얀센 (Janssen) 제약 회사에서 개발 중이다. 이 백신 플랫폼은 잠재적으로 대량 생산이 가능하다. 특정한 바이러스 벡터에 이미 면역성을 가지고 있는 경우 면역원성을 떨어뜨릴 수 있기 때문에 실험 초기 단계에서 이 문제를 다루어야 할 것이다. 옥스퍼드 대학과 아스트라제네카 (AstraZeneca)사에서 공동으로 개발한 재조합 침팬지 아데노바이러스 벡터 (ChAdOx1) 역시 임상시험에 들어갔다. 비슷한 유형의 침팬지 아데노바이러스 (ChAd) 백신 제품은 이전에 진행한 임상시험에서 안전하고 면역 효과가 있는 것으로 입증되었다. VSV 벡터 백신 플랫폼은 복제가 가능하며 한 번의 접종으로 효과적이고 오래 지속되는 면역 반응을 유도한다. 머크 (Merck) 사에서 허가받은 VSV 에볼라 백신은 한 번의 접종으로 충분한 효과를 볼 수 있지만, 백신에 대한 반응원성은 인구 집단에 따라 제한적일 수 있다. 백신에 대한 이런 다양한 접근 방법을 사용하면 광범위한 인구가 사용할 수 있는 대규모의 백신 생산이 가능할 수도 있다.

전략적인 협력

ACTIV 공공-민간 협력 프로그램에 따라, 미국 국립 위생 연구소 (NIH)는 식품 의약품국, 질병 관리 센터, 생명 의학 연구 개발 당국을 포함하는 보건 사회 복지부의 자매기관들과 협력 중이며 국방부 및 재향 군인국을 포함하는 미국의 기타 정부 부처, 유럽 의약청, 학계의 대표자들, 자선 단체들, 15개가 넘는 바이오 제약 회사, NIH 재단과 협력 중이다. 이렇게 구성된 포럼에서 백신 실험 설계에 대해 논의해서 합의하고 공공 부문과 민간 부분이 긴밀히 협력한다면 백신 효과 실험을 신속하고 효율적으로 진행할 수 있을 것이다. 백신 실험을 일반적인 독립 연구소에서 진행하든지 아니면 샘플과 자료를 제공해서 대리 표지자 (surrogate markers)로 사용하도록 해서 백신 허가 및 백신 효과의 전반적인 비교에 속도를 내자는 의견이 점점 많아지고 있다. 일반적인 기관 감사 위원회뿐 아니라 교차 실험 자료를 감시하는 일반적인 자료 및 안전성 모니터링 위원회 (Data and Safety Monitoring Board (DSMB))를 이용해서 백신 개발 업체의 규제 틀을 조정하고 규제 기관 및 공공 기관이 다양한 백신 개발 접근 방법의 효과를 객관적으로 평가할 수 있어야 한다. 백신 지원자들이 실험 1단계 준비에 들어가면 3단계를 공동으로 준비하는 속도가 필요하다. 주로 미국에서 진행하는 백신 개발 실험에 집중하고 있기는 하지만, AVTIV 프로그램의 하나로 설립된 코로나바이러스 19 예방 네트워크 (COVID-19 Prevention Networks)는 전 세계적인 관점에서 세계 보건 기구 (World Health Organization), 전염병 대비 혁신 연합 (Coalition for Epidemic Preparedness Innovations)과 협력하고 있으며 기타 자선 단체와의 전 세계적인 협력도 필요하다.

각 백신 개발 방법의 효과를 투명하게 평가하려면 조화를 이룬 마스터 프로토콜을 만들어야 한다. ACTIV와 같은 공공-민간 협력 프로그램을 통해 정부가 지원하는 중앙 연구소와 독립된 생물 통계학자들이 백신 효과 실험의 핵심 자원으로 참여해서 상이한 백신 유형의 면역 반응을 평가하는 표준화된 방법을 제공한다면 조화로운 프로토콜을 만들 수 있다 (도표 참조). 정부가 지원하는 중앙 연구소에서는 백신 보호 효과의 상관관계를 알아내어 모든 백신의 허가 속도를 빠르게 할 뿐 아니라 면역성을 보유하게 될 인구 분포를 파악할 수 있을 것이다. 업체 간에 자료를 공유하고 독립적으로 자료 통계를 분석하면 백신 효과의 대리 표지자를 초기에 평가해서 백신의 허가 및 배분의 속도를 빠르게 할 수 있다. 이런 자료 수집은 백신 효과 실험의 계획 초기 단계에서 조화로운 협력으로 가능하며, 도표에서 볼 수 있듯이 임상시험 장소 공유, 일반적인 자료 및 안전성 모니터링 위원회 (DSMB)를 통한 백신 효과 실험 모니터링, 독립적인 통계학자들에게 교차 실험 자료 실시간 제공, 면역성을 모니터하는 중앙 연구소를 이용하는 협력 방법 실행으로 가능하다. 백신 개발 과정에서 이런 혁신적인 방법을 사용해야 임상시험을 시작하는 플랫폼 기술의 빠른 개발이 가능하다. 전 세계적인 노력, 전 세계적인 협력, 투명성이 있어야 시기적절하게 전 세계 인구에게 필요한 과학적인 진보의 길을 속도와 정확성, 의사 결정에 있어 최고의 수준으로 제시할 수 있다. 이런 모든 프로그램 모델이 이미 현존하며 이런 아이디어를 신속하게 적용하는 것만이 코로나바이러스 19 이전 수준의 사회 상호 작용으로 시기적절하게 성공적으로 되돌아갈 수 있는 유일한 길이다.

규모 확대

백신의 접종량을 수억 개에서 수십억 개 단위로 생산하려면 전 세계의 백신 생산 시설을 모두 사용해야 한다. 새로운 기술과 공장을 개발해서 생산량을 유지할 수는 있겠지만 지금 당장은 바이얼 병에 담긴 백신을 공급하기 위해서 필요한 필/피니쉬 제조 방법 (fill/finish step)을 포함한 필수적인 바이오 생산 기반 시설에 재정적으로 지원해야 한다. 비용, 공급 시스템, 냉장 유통이 필요한지의 여부, 광범위한 지역을 커버하는 배송 모두 개인과 지역 사회에 백신을 공급하는 데 제한요소가 될 수 있다. 전 세계적인 수준에서 공중 보건을 제공하는 기관 및 경제 기관 간에 협력이 이루어져야 이런 이슈를 모두 다룰 수 있겠다.

이전의 일상 모습으로 돌아가기 위해서는 SARS-CoV-2 백신 개발이 절대적으로 필요하다. 백신을 개발하기 위해서 공공, 민간, 자선 부문의 모든 자원을 전략적인 방법으로 사용해야 한다. ACTIV 공공-민간 협력 프로그램 및 조화롭게 협력하는 백신 효과 실험을 모델로 삼아 전 세계가 추구하는 목적을 이룰 수 있을 것이다.

출처: Science

Genetically-tailored nutrition advice can be used in research and clinical practice to motivate greater long-term dietary change and adherence to dietary guidelines, according to a new randomized controlled trial.

It is challenging to achieve long-term dietary change and adherence to dietary guidelines; typically, nutrition interventions result in short-term dietary change, but these changes are not sustained long-term.

Nutrigenomics, which explores interactions between individual genetic variation, dietary intake and changes in gene expression, structure and function, has garnered significant attention in recent years with a number of companies now offering nutrigenetic testing for weight management. Yet there is little research in human intervention studies deciphering the effectiveness of this method. And any genetic testing behavior change research previously done had not incorporated the Theory of Planned Behaviour (TPB), and incorporation of behavior change theory in general is fundamentally lacking.

A team of Canadian researchers therefore decided to carry out a Nutrigenomics, Overweight/Obesity, and Weight Management (NOW) parallel-group, clinical trial involving 140 participants a t East Elgin Family Health Team (EEFHT) in Ontario, to address the limitations of previous work. They considered the TPB in the dietary interventions and statistical analyses, and providing a high-quality, personalized, genetic-based lifestyle intervention.

Their results indicated that the addition of an actionable nutrigenomics intervention enhanced dietary change and adherence to dietary guidelines over 12 months.

Their report states: “The results of this study provide convincing evidence that the addition of nutrigenomics to one of the most effective public health weight management and diabetes prevention programs can help motivate and optimize long term, clinically meaningful differences in nutritional intake and adherence to dietary guidelines.”

The study

Participants were pre-randomized 1:1 to receive either the standard Group Lifestyle Balance (BLB) program or a modified GLB+nutrigenomics (GLB+NGx) program

Three 24-hour recalls were collected at baseline, 3, 6 and 12 months using the validated multiple pass method. Research assistants collecting the three 24-hour recalls were blinded to the participants’ group assignments.

Statistical analyses included split plot analyses of variance (ANOVAs), two-way ANOVAs, binary logistic regression, X2 and Fisher’s exact tests. Using the Theory of Planned Behaviour as guidance, key confounding factors of behavior change were considered in the analyses. This study was registered with clinicaltrials.gov.

Results revealed that only the GLB+NGx group significantly reduced their total fat intake from baseline to 12-month follow-up (from 36.0%±4.8%kcal to 30.2%±8.7%kcal, p=0.02). Long-term dietary adherence to total fat and saturated fat guidelines was also significantly (p<0.05) greater in the GLB+NGx group compared to the standard GLB group.

The researchers conclude that weight management interventions guided by nutrigenomics can motivate long-term improvements in dietary fat intake above and beyond gold-standard population-based interventions.

Background

This research is one of only four completed RCTs assessing change in dietary intake resulting from a nutrigenetic intervention over a 12-month period. Previously, Hietarnata-Luoma et al similarly found that a nutrigenetic cardiovascular disease intervention motivated greater long-term changes in dietary intake, and further motivated greater short-term and moderate-term changes compared to a control group.

Nielsen and El-Sohemy’s and Chao et al’s 12-month RCTs also found that nutrigenomics interventions motivated greater long-term (12months) changes in nutritional intake.

There have been no RCTs demonstrating that nutrigenomics is ineffective at motivating changes in dietary intake after 12-month follow-up

출처: NUTRA ingredients.com

새로운 무작위 대조 연구 (RCT) 결과를 보면, 연구와 임상 실험에서 유전자에 맞춘 영양학적인 개선 방법을 제공했을 때 더 효과적으로 장기적인 식생활 변화를 유도하고 식생활 지침을 따른다는 것을 알 수 있다.

식생활 변화를 장기적으로 유지하고 식생활 지침을 따르기는 쉽지 않은데, 대부분 영양학적인 개선 방법을 제시하는 중재는 단기적인 식습관 변화만 유도할 뿐 장기적인 유지는 어렵기 때문이다.

개인적으로 다양한 유전적 변이, 식이 섭취 습관, 유전자 발현 및 구조, 기능의 변화를 탐구하는 영양 유전체학에 최근 많은 관심이 쏟아져 여러 기업이 체중 관리를 위해 영양 유전체 테스트를 제공하고 있다. 하지만 이 방법의 효과를 설명할 만한 사람 대상 연구 (human intervention studies)는 여전히 부족하다. 그리고 지금껏 진행된 유전자 검사 행동 변화 연구들은 계획 행동 이론 (TPB)을 반영하지 않았으며 일반적으로 행동 변화 이론을 고려해서 연구를 진행하지 않는다.

이에 따라, 캐나다의 연구팀이 온테리오에 위치한 East Elgin Family Health Team (EEFHT)에서 140명의 참여자를 대상으로 영양 유전체학, 과체중/비만, 체중 관리 (Nutrigenomics, Overweight/Obesity, and Weight Management (NOW)) 평행 설계 임상 연구를 진행하였다. 연구팀은 계획 행동 이론 (TPB) 및 통계적인 분석을 고려하여 식생활 개선 방법 및 유전자 기반 개인 맞춤 라이프 스타일 개선 방법을 제공했다.

연구 결과에 따르면, 실행 가능한 영양 유전체학적인 개선 방법을 제공했을 때 식생활을 개선하고 식생활 지침을 따르는 데 12개월 이상 효과가 있었음을 알 수 있다.

보고서에 따르면, “이 연구의 결과를 보면, 가장 효과적인 체중 관리 및 당뇨병 예방 프로그램에 영양 유전체학을 추가하면 영양 섭취 및 식생활 안내 지침에 임상적으로 의미 있는 장기적인 효과를 유도하고 최적화할 수 있다.”라고 한다.

연구

연구 참여자들은 미리 무작위로 순서를 정해 기준 그룹 라이프 스타일 밸런스 (Group Lifestyle Balance (GLB)) 또는 변조된 GLB + 영양 유전체학 ((GLB+NGx)) 프로그램을 1:1 로 받았다.

24시간 회상 검사 결과를 기준치로, 3, 6, 12개월마다 검증된 다중 통과 방법 (multiple pass method)을 사용하였다. 연구 참여자의 24시간 회상 검사 자료를 수집한 연구 조수들은 연구 참여자가 어느 프로그램에 참여했는지 몰랐다.

분산 및 분할 분석 (ANOVAs)과 이원 분산 분석, 이항 로지스틱 회귀 (binary logistic regression), X2 분할표, 피셔 정확 검증 (Fisher’s exact tests) 을 포함한 통계 분석을 진행했다. 계획 행동 이론을 지침으로 삼고, 행동 변화의 핵심 변수를 고려해서 분석을 진행했다. 이 연구는 clinicaltrials.gov. 에 등록되어 있다.

연구 결과를 보면, GLB+NGx 집단에서만 기준치에서 시작해서 12개월 추적 기간에 전체 지방 섭취량이 상당히 줄었다 (36.0%±4.8%kcal 에서 30.2%±8.7%kcal 으로 감소, p=0.02). GLB+NGx 집단이 표준 GLB 집단에 비해 전체 지방 및 포화 지방의 섭취 권장량을 훨씬 더 엄격하게 장기적으로 따랐다 (p<0.05).

영양 유전체학에 따라 체중 관리 개선 방법을 제공했을 때 최적의 인구 집단 기반 중재 방법 이상으로 식생활 지방 섭취량을 장기적으로 개선할 수 있다고 연구자들은 결론을 내렸다.

배경

이 연구는 완료된 4개의 무작위 대조 연구 (RCT) 중 하나로 영양 유전체학적인 중재를 12개월 동안 제공했을 때 식생활 습관에 변화가 있었는지 평가하였다. 이전에, Hietarnata-Luoma & 그 외.의 비슷한 연구 결과를 보면, 심혈관 질환 예방을 위해 영양 유전체학적인 방안을 제공했을 때 통제 집단에 비해 식생활 습관에 장기적으로 상당한 변화가 있었고 단기, 중기적으로도 큰 변화가 있었음을 알 수 있다.

Nielsen & El-Sohemy’s & Chao 그 외.의 12개월 동안 진행했던 연구를 보아도, 유사하게 영양 유전체학적인 개선 방법을 제시하는 중재를 했을 때 식생활 습관에 더 효과적이고 장기적인 (12개월) 변화가 있었다.

12개월 후 후속 연구에서 식생활 습관 변화에 영양 유전체학적인 개선 방법이 비효과적이었다는 무작위 대조 연구 (RCT) 결과는 없었다.

출처: NUTRA ingredients.com

Higher plasma total and LDL cholesterol concentrations in childhood have been reported to be associated with atherosclerosis in adulthood. Researchers at University of Eastern Finland have found in a new study that individualised and family-based physical activity and dietary intervention reduced the plasma low density lipoprotein cholesterol concentration of primary school children. The findings of the Physical Activity and Nutrition in Children (PANIC) Study ongoing at the University of Eastern Finland were published in the European Journal of Nutrition.

The two-year follow-up study explored the effects of an individualised and family-based physical activity and dietary intervention on the plasma lipids of more than 500 Finnish children aged between 6 and 8 years at baseline. The researchers were also interested in which components of the lifestyle intervention had the greatest impact of plasma lipids. "The low density lipoprotein cholesterol concentration of children from families who participated in the lifestyle intervention was slightly reduced during the two-year follow-up, whereas no similar change was observed in children in the control group. The lifestyle intervention did not have an impact on other plasma lipids," Adjunct Professor Aino-Maija Eloranta from the University of Eastern Finland says.

The study showed that increasing the consumption of high-fat vegetable oil-based spreads and decreasing the consumption of butter-based spreads played the most important role in decreasing the low density lipoprotein cholesterol concentration. Replacing high-fat milk with low-fat milk, and doing more physical activity, also explained some of the decrease in the LDL cholesterol concentration. Having an elevated low density lipoprotein cholesterol concentration in childhood is may predict artery wall thickening in adulthood. The results of this newly published study thus suggest that a family-based dietary and physical activity intervention may prevent the development of atherosclerosis in adulthood.

"Individualised and family-based dietary and physical activity counselling could be integrated into the services provided by maternity clinics and school health care. This would prevent the development lifestyle diseases in the long run and, consequently, mitigate health care costs," Professor Timo Lakka from the University of Eastern Finland, the Principal Investigator of the study, says. During the two-year follow-up, families participated in six individualised dietary and physical activity counselling sessions. The sessions were individually tailored to each family and they focused on improving the quality of the family's diet, increasing physical activity and reducing screen time. In addition, children were encouraged to participate in weekly after-school exercise clubs. Children's plasma lipids were analysed at the beginning and at the end of the study.

출처: Medical Dialogues

A research study spearheaded by clinical researchers at Weill Cornell Medicine – Qatar (WCM-Q) has shown for the first time that type-2 diabetes can be reversed in those originating from the Middle East and North Africa (Mena) region.

The internationally competitive work is the first intensive lifestyle intervention trial in the Mena region and the first clinical trial in primary care in Qatar. The clinical trial demonstrated significant weight loss as well as reversal of type 2 diabetes in more than 60% of intervention participants.

Led by Dr Shahrad Taheri, professor of medicine at WCM-Q and a consultant endocrinologist at Hamad Medical Corporation and the Qatar Metabolic Institute, the research team conducted a randomised control trial, comparing the effects of the best medical care for diabetes with intensive lifestyle intervention therapy that included dietary change, physical activity, and behaviour change.

The study participants were younger adults who had all been diagnosed with diabetes within the previous three years. They were all aged between 18 and 50 and had a body mass index (BMI) of 27kg/m² or more. Participants were randomly placed into the control group or the intensive intervention group.

Individuals in the intervention group underwent a total diet replacement phase, in which the participants were given formula low-energy meal replacement products followed by the gradual reintroduction of food combined with physical activity support. This was in conjunction with a weight loss maintenance phase that involved structured lifestyle support.

Participants in the control group received the best currently available diabetes care based on clinical guidelines.

The results were highly significant with participants in the intervention group losing about 12kg on average after 12 months, compared with about 4kg in the control group.

Most importantly, almost two thirds (61%) of participants in the intervention group saw their diabetes go into remission, meaning that their blood sugars were no longer in the diabetes range. Finally, over one third of participants in the intervention group saw their blood sugar levels return completely to normal.

The research is of such importance for its impact on health that it has been published in The Lancet Diabetes and Endocrinology medical journal, one of the world’s leading medical journals. This is the highest impact health publication in which a clinical research study conducted in Qatar has been published. Dr Taheri said: “This study was highly significant, proving for the first time the benefits of an intensive lifestyle intervention for patients with diabetes originating from 13 different countries in the Mena region.

“It is also the first time that a health study originating and conducted in Qatar has featured, because of its high clinical value, in such a prestigious publication as The Lancet.

Our study shows that it is possible to reverse diabetes in young individuals with type 2 diabetes. We can now take this directly into the clinic in Qatar and make a difference to people’s lives.

The study, entitled ‘Effect of intensive lifestyle intervention on bodyweight and glycaemia in early type 2 diabetes (DIADEM-I): an open-label, parallel-group, randomised controlled trial’ was funded by Qatar National Research Fund (QNRF – NPRP 8-912-3-192), a member of Qatar Foundation.

Dr Abdul Sattar al-Taie, executive director of Qatar National Research Fund said: “Funding research which promotes the healthcare of the citizens of Qatar is one of the cornerstones of our mission at Qatar National Research Fund. Type 2 diabetes and its spread in the Middle East is a matter of high concern which requires research that focus on the local populations and conditions.”

“Therefore, I am very glad to learn that QNRF funding has resulted in such a significant research project with positive implications for the Qatari people and all affected by type 2 diabetes.

Such research projects which focus on the local populations will be helpful in developing effective and specialised treatments to help people with type 2 diabetes in Qatar and the region.”

Dr Javaid Sheikh, dean of WCM-Q, said: “Given that diabetes is so prevalent within Middle Eastern populations, this study has the potential to help tens of thousands of people, improving their quality of life and enhancing their life expectancy.

“Not only that, but by revolutionising the way type 2 diabetes is treated in Qatar, we could see more people reverse diabetes, removing the need for lifelong medical care and so improving health budgets.

“It is testament to what can be achieved when different organisations collaborate, in this case WCM-Q has worked in partnership with QNRF, Qatar Foundation, the Primary Health Care Corporation, Hamad Medical Corporation and Qatar Diabetes Association, Weill Cornell Medicine in New York, and Cornell University in the US to achieve remarkable results.

“It also clearly demonstrates that the funding and infrastructure that has been put in place by Qatar’s leadership is bearing fruit and that the country is a Middle Eastern hub for clinical science and research.”

출처: GULF TIMES

Middle age may not be too late for women to substantially reduce their stroke risk by not smoking, exercising, maintaining a healthy weight and making healthy food choices, according to new research published today in Stroke, a journal of the American Stroke Association, a division of the American Heart Association.

In general, women are more likely than men to have a stroke, die from stroke and have poorer health and physical function after a stroke. The average age of first stroke in women is 75 years. Based on this information, researchers theorized that making mid-life lifestyle changes might help reduce stroke's burden among women.

"We found that changing to a healthy lifestyle, even in your 50s, still has the potential to prevent strokes," said Goodarz Danaei, Sc.D., lead study author and Bernard Lown Associate Professor of Cardiovascular Health at Harvard T.H. Chan School of Public Health in Boston. "Women who made lifestyle modifications in middle age reduced their long-term risk of total stroke by nearly a quarter and ischemic stroke, the most common type of stroke, by more than one-third."

Researchers analyzed the Nurses' Health Study, which includes health information on nearly 60,000 women who enrolled at average age of 52 and continued in the study for an average of 26 years. Researchers studied the impact on stroke risk from smoking cessation, exercising 30 minutes or more daily and gradual weight loss if women were overweight. The researchers also studied the impact of making recommended dietary modifications that emphasize eating more fish, nuts, whole grains, fruits and vegetables and less red meat, no processed meat and less alcohol.

During the 26-year follow-up, researchers found:

• 4.7% of women with no lifestyle interventions had a stroke of any type; 2.4% had ischemic stroke; and 0.7% had hemorrhagic stroke.

• Engaging in the three non-dietary interventions -- smoking cessation, daily exercise and weight loss -- was estimated to reduce the risk of total stroke by 25% and ischemic stroke by 36%.

• Sustained dietary modifications were estimated to reduce the risk of total stroke by 23%.

Researchers also found that increasing fish and nut consumption and reducing unprocessed red meat consumption appeared to have positive impacts on reducing stroke risk, although the degree of impact from these dietary changes was not as big as those achieved through increased physical activity, smoking cessation and maintaining a healthy weight.

While this was an observational study that included mostly white, middle-aged women, Danaei said, "there are other studies to support that the proportional changes in stroke risk from lifestyle and dietary modifications may be generalizable to men. We also estimate that exercising 30 minutes or more daily may reduce the risk of stroke by 20%."

출처: Science Daily