“Glucagon-like peptide-1 agonist (GLP-1) drugs have transformed type 2 diabetes care, but weekly injections can be burdensome for patients. A single shot a month could make it much easier for people living with diabetes or obesity to stick to their drug regimens, improving quality of life and reducing side effects and diabetes complications,” said lead author Dr Claire Mégret from ADOCIA, Lyon, France, the biotechnology company who developed the hydrogel.

Semaglutide works by mimicking the hormone glucagon-like peptide 1 (GLP-1), and is currently authorised for the treatment of type 2 diabetes patients with insufficient glycaemic control and long-term weight management.

Clinical studies suggest that adherence to injected semaglutide is 39-67% for type 2 diabetes patients at one year [1a], and 40% for patients who take the drug for weight loss [1b]. Similarly, adherence to daily oral pill formulations is around 40% at one year [2].

Long-acting delivery formulations could increase drug efficacy and safety by maintaining steady drug levels in the body at optimal concentrations.

The new hydrogel delivery platform uses two innovative degradable polymers that are chemically bound to one another to form a gel, but allow slow, sustained release of soluble peptides over 1 to 3 months.

“A small dollop of gel, known as a ‘depot,’ of the semaglutide-laden hydrogel is injected under the skin,” explained Dr Mégret. “The challenge is to formulate the hydrogel to entrap the peptides to limit initial burst (early release) of semaglutide molecules and, at the same time, to allow smooth release and controlled dissolving of the gel over one month, without generating toxic molecules.”

Several formulations of the hydrogel were tested in vitro to investigate the drug release rate, duration of action, and semaglutide load to define the best candidate.

The researchers found that the hydrogel could be easily injected using an off-the-shelf needle. Additionally, the gel started forming within minutes of mixing, ensuring sufficient time for the injection while minimising spread at the injection site, so that the depot is small enough to be comfortable and inconspicuous.

In vitro drug release assessments for all formulations showed extended and constant release rates over 1 to 3 months. The researchers also found that the release duration could be tailored through optimisation of the hydrogel properties and loading.

The hydrogel-semaglutide formulation was also tested in six laboratory rats. In the rats, a single injection of the hydrogel-based therapy, showed limited burst (early release) and a regular release over a one-month period.

Importantly, the hydrogel was well tolerated with no inflammatory reaction over the treatment period.

“Our pre-clinical results demonstrate that the regular, slow release of semaglutide over one month after administering a single dose, with limited early release, is achievable. Next we will be testing the hydrogel platform in pigs, whose skin and endocrine systems are most similar to those in humans. If that goes well, we will move forward the platform development by expecting clinical trials within the next few years,” said Dr Mégret.

This pilot is part of EMA’s regulatory support for medical devices, following the introduction of new legislation in the EU in 2022. The plan could bring new products to people with rare diseases and conditions with unmet need.

Orphan devices are medical devices which are intended to be used for diseases or conditions affecting only a small number of individuals each year (fewer than 12,000 individuals in the EU per year). Often they are used to treat or diagnose rare diseases or conditions for which no or insufficient alternative diagnostic or therapeutic options exist, thereby fulfilling an unmet medical need.

The programme will initially benefit selected manufacturers and notified bodies – the national authorities responsible for assessing devices and awarding the CE mark. While the first phase of the programme is currently scheduled to run until the end of 2025, the Agency said it aims to establish a long-term process for orphan device support.

Manufacturers can consult the expert panels at different stages of the development of the clinical strategy for their device, while notified bodies can request advice at specific moments of the ongoing conformity assessment of the device.

As part of the pilot programme, EMA will prioritise certain types of orphan medical devices, such as devices for treating a medical condition that is life-threatening or that could cause permanent impairment of a body function, devices intended for children, and novel devices with potential major clinical benefit.

In June 2024, the European Commission announced new guidance on the clinical evaluation of orphan medical devices issued by the Medical Device Coordination Group, which is composed of representatives of all EU Member States. This guidance sets out criteria to determine when a medical device should be regarded as an orphan device under the EU Medical Devices Regulation and aims to guide manufacturers and national authorities.

In response to the rapidly evolving use and approval of AI medical devices in healthcare, a multi-institutional team of researchers at the UNC School of Medicine, Duke University, Ally Bank, Oxford University, Colombia University, and University of Miami have been on a mission to build public trust and evaluate how exactly AI and algorithmic technologies are being approved for use in patient care.

Together, Sammy Chouffani El Fassi, a MD candidate at the UNC School of Medicine and research scholar at Duke Heart Center, and Gail E. Henderson, PhD, professor at the UNC Department of Social Medicine, led a thorough analysis of clinical validation data for 500+ medical AI devices, revealing that approximately half of the tools authorized by the U.S. Food and Drug Administration (FDA) lacked reported clinical validation data. Their findings were published in Nature Medicine.

“Although AI device manufacturers boast of the credibility of their technology with FDA authorization, clearance does not mean that the devices have been properly evaluated for clinical effectiveness using real patient data,” said Chouffani El Fassi, who was first author on the paper. “With these findings, we hope to encourage the FDA and industry to boost the credibility of device authorization by conducting clinical validation studies on these technologies and making the results of such studies publicly available.”

Since 2016, the average number of medical AI device authorizations by the FDA per year has increased from 2 to 69, indicating tremendous growth in commercialization of AI medical technologies. The majority of approved AI medical technologies are being used to assist physicians with diagnosing abnormalities in radiological imaging, pathologic slide analysis, dosing medicine, and predicting disease progression.

Artificial intelligence is able to learn and perform such human-like functions by using combinations of algorithms. The technology is then given a plethora of data and sets of rules to follow, so that it can “learn” how to detect patterns and relationships with ease. From there, the device manufacturers need to ensure that the technology does not simply memorize the data previously used to train the AI, and that it can accurately produce results using never-before-seen solutions.

Regulation During a Rapid Proliferation of AI Medical Devices

Following the rapid proliferation of these devices and applications to the FDA, Chouffani El Fassi and Henderson et al. were curious about how clinically effective and safe the authorized devices are. Their team analyzed all submissions available on the FDA’s official database, titled “Artificial Intelligence and Machine Learning (AI/ML)-Enabled Medical Devices.”

“A lot of the devices that came out after 2016 were created new, or maybe they were similar to a product that already was on the market,” said Henderson. “Using these hundreds of devices in this database, we wanted to determine what it really means for an AI medical device to be FDA-authorized.”

Of the 521 device authorizations, 144 were labelled as “retrospectively validated,” 148 were “prospectively validated,” and 22 were validated using randomized controlled trials. Most notably, 226 of 521 FDA-approved medical devices, or approximately 43%, lacked published clinical validation data. A few of the devices used “phantom images” or computer-generated images that were not from a real patient, which did not technically meet the requirements for clinical validation.

Furthermore, the researchers found that the latest draft guidance, published by the FDA in September 2023, does not clearly distinguish between different types of clinical validation studies in its recommendations to manufacturers.

Types of Clinical Validation and A New Standard

In the realm of clinical validation, there are three different methods by which researchers and device manufacturers validate the accuracy of their technologies: retrospective validation, prospective validation, and subset of prospective validation called randomized controlled trials.

Retrospective validation involves feeding the AI model image data from the past, such as patient chest x-rays prior to the COVID-19 pandemic. Prospective validation, however, typically produces stronger scientific evidence because the AI device is being validated based on real-time data from patients. This is more realistic, according to the researchers, because it allows the AI to account for data variables that were not in existence when it was being trained, such as patient chest x-rays that were impacted by viruses during the COVID pandemic.

Randomized controlled trials are considered the gold standard for clinical validation. This type of prospective study utilizes random assignment controls for confounding variables that would differentiate the experimental and control groups, thus isolating the therapeutic effect of the device. For example, researchers could evaluate device performance by randomly assigning patients to have their CT scans read by a radiologist (control group) versus AI (experimental group).

Because retrospective studies, prospective studies, and randomized controlled trials produce various levels of scientific evidence, the researchers involved in the study recommend that the FDA and device manufactures should clearly distinguish between different types of clinical validation studies in its recommendations to manufacturers.

In their Nature Medicine publication, Chouffani El Fassi and Henderson et al. lay out definitions for the clinical validation methods which can be used as a standard in the field of medical AI.

“We shared our findings with directors at the FDA who oversee medical device regulation, and we expect our work will inform their regulatory decision making,” said Chouffani El Fassi. “We also hope that our publication will inspire researchers and universities globally to conduct clinical validation studies on medical AI to improve the safety and effectiveness of these technologies. We’re looking forward to the positive impact this project will have on patient care at a large scale.”

Algorithms Can Save Lives

Chouffani El Fassi is currently working with UNC cardiothoracic surgeons Aurelie Merlo and Benjamin Haithcock as well as the executive leadership team at UNC Health to implement an algorithm in their electronic health record system that automates the organ donor evaluation and referral process.

In contrast to the field’s rapid production of AI devices, medicine is lacking basic algorithms, such as computer software that diagnose patients using simple lab values in electronic health records. Chouffani El Fassi says this is because implementation is often expensive and requires interdisciplinary teams that have expertise in both medicine and computer science.

Despite the challenge, UNC Health is on a mission to improve the organ transplant space.

“Finding a potential organ donor, evaluating their organs, and then having the organ procurement organization come in and coordinate an organ transplant is a lengthy and complicated process,” said Chouffani El Fassi. “If this very basic computer algorithm works, we could optimize the organ donation process. A single additional donor means several lives saved. With such a low threshold for success, we look forward giving more people a second chance at life.”

Other contributors to the study include Adonis Abdullah, Ying Fang, Sarabesh Natarajan, Awab Bin Masroor, Naya Kayali, Simran Prakash, Manesh R. Patel, William Ratliff, Zeshan Hussain, Justin Castillo, Ihsan Yüksel, Haonan Chen, Pengyu Guo, Hamilton McInnis, James E Hancock, Barbara J Evans, and Aurelie Merlo.

– Written by Kendall Daniels

COPD comprises several conditions, including chronic bronchitis and emphysema, and can be caused by irritants like smoke or pollution and genetics. The disease affects more than 30 million Americans, yet awareness of the disease’s symptoms, methods to reduce risk, and disease management remains poor. Symptoms, which include breathlessness, fatigue, and chronic cough, are primarily treated using inhaled medications.

In a new study, “Prevalence of Critical Errors and Insufficient Peak Inspiratory Flow in Patients Hospitalized With COPD in a Department of General Internal Medicine: A Cross-Sectional Study,” the authors examined how often inhalers were misused by patients hospitalized with COPD over the course of nine months at Fribourg Hospital in Switzerland.

Inhaler misuse was categorized as either a critical error in inhalation technique or insufficient peak inspiratory flow. These errors result in a lesser dose of medication reaching the person’s lungs, which impacts the person’s ability to manage their symptoms and can lead to increased exacerbations.

“Misuse of inhalers is common, and in our study, we found that approximately two-thirds of inhalers were misused,” said Gaël Grandmaison, M.D., an assistant physician in internal medicine at University and Hospital of Fribourg in Fribourg, Switzerland. “If an inhaler was misused, a physiotherapist conducted up to three teaching sessions with the patient. These sessions helped reduce the number of critical errors in inhaler use. However, despite this education, more than one in 10 inhalers continued to be used suboptimally, either due to an inability to generate sufficient inspiratory effort or because the inhaler was unsuitable for the patient’s characteristics. These results highlight the importance of regular therapeutic education, assessing the patient’s ability to generate a sufficient inspiratory effort, and selecting an inhaler suited to the patient’s characteristics.”

In a perspective article, “Real-World Use of Inhaled COPD Medications: the Good, the Bad, the Ugly,” the author discusses the decreased effectiveness of inhaled medications as the result of inhaler misuse (often due to intricacies and multiple steps required to use the inhaler) and the high cost of inhaler-based therapies. The author also highlights several advances in inhaler use, including the ability to combine therapies and to choose the right inhaler based on patient-centered decisions.

“Education is key to increasing the effectiveness of inhaled medications, and many clinicians – and often even the patients themselves – are unaware that patients are having difficulty getting enough medication into their lungs,” said Valerie G. Press, M.D., MPH, an associate professor of medicine at the University of Chicago. “Additional inhaler technique education is needed to ensure patients are using the device correctly, especially when multiple inhaled medications are prescribed. Additional education, supported by the necessary resources, would help ensure patients are receiving optimal treatment and avoiding adverse health outcomes.”

To access current and past issues of Chronic Obstructive Pulmonary Diseases: Journal of the COPD Foundation, visit journal.copdfoundation.org.

Now, a new study offers hope that while they wait to get care, patients could still get some relief by using evidence-based smartphone apps and wearable devices to track sleep and activity.

The study shows that depression and anxiety symptoms, and suicidality, all decreased measurably when patients were assigned to mobile applications that incorporated mindfulness practices, cognitive-behavioral therapy skills, or prompts that encouraged mood-enhancing activities.

The study, conducted at Michigan Medicine, the University of Michigan’s academic medical center, is published in JAMA Network Open. It involved just over 2,000 patients scheduled to get care in coming weeks from a mental health provider at outpatient U-M Health or U-M student clinics.

Adam Horwitz, Ph.D., the U-M Medical School psychologist who is the paper’s lead author, called the results encouraging, with implications for individuals and clinics alike.

“Having this type of option, especially for people who are motivated enough to seek an appointment and wait for it, could be very valuable when providers have long wait lists,” said Horwitz, who is an assistant professor in the Department of Psychiatry. “These individuals want to be doing something about their mental health but don’t yet have access, so this suggests that providing them with some sort of digital option when their motivation is already high, and they are ready to do something, could begin to make a difference.”

Combining app prompts and wearable device data

Nearly all the patients completed standardized mental health assessments both at the start of the study and after six weeks of using the app they had been randomly assigned to install on their smartphone. All participants also wore a study-provided Fitbit or their own Fitbit or smartwatch, to track sleep and physical activity.

The study randomly assigned most participants to one of two commercial apps – Silvercloud, which is based on cognitive behavioral therapy principles, and Headspace, which coaches users in mindfulness techniques. Both apps have been shown separately to help alleviate mental health symptoms, but have never been tested against one another.

Some study participants were randomly assigned to receive a customized version of the study app called MyDataHelps, either alone or together with one of the commercial apps. Those randomized to receive this app received positive encouraging prompts twice per day based on their activity tracker data — for example, applauding them for walking or getting a good amount of sleep, or suggesting a simple act to improve their mood.

Improvement in all groups

Surprisingly, no matter what group they were in, the participants’ scores on standard mental health scales changed for the better by the end of the study period.

At the start of the study, depression scores on average were just under 13 on the 27-point PHQ-9 scale; all groups dropped by two to three points by six weeks. Scores on the 21-point GAD-7 anxiety scale dropped by 1.5 to 2 points across the board.

Meanwhile, scores on measures of protection against suicide risk increased slightly, with the most improvement among participants using Headspace. Scores on the suicide risk measurement dropped slightly across the board, indicating lower risk for suicidal behavior.

Most of the study participants had their initial appointment with a U-M mental health provider before the end of that six-week period, but the drop in mental health scores was similar for those who hadn’t yet started professional treatment.

More research ahead

Horwitz notes that the newly published study, called PROMPT, helped inform the development of a much larger study called COMPASS based at U-M that just got $17.9 million in funding from the National Institute of Mental Health.

The COMPASS study will involve not only smartphone apps, wearable activity trackers and standardized mental health assessments, but also genetic tests and other types of data collection. It will involve thousands of U-M Health and U-M student clinic patients who are waiting for their first mental health-related appointment.

Both PROMPT and COMPASS seek to help researchers develop a more personalized approach to mental health care.

They hope to identify which characteristics make someone more likely to respond positively to different forms of treatment or support, so they can use this knowledge to reduce the time it takes to find the approach that helps each individual.

Future directions

Horwitz notes that people seeking mobile-based mental health support have many apps to choose from – and that most of those apps haven’t gotten scrutiny through objective research. Headspace and Silvercloud have more objective evidence behind them than most of these apps, he notes.

He and his colleagues were surprised but encouraged to see improvement in the group using the customized version of MyDataHelps, too.

Part of the reason may have to do with the study population: people who were motivated to seek help for mental health concerns, had already been on a waiting list to get scheduled, and now had been scheduled and were waiting to be seen.

Because mental health conditions can wax and wane in their symptom severity, apps that support someone during an especially low-mood or high-anxiety time could be important for helping them endure the time until their first appointment.

Horwitz notes that the study participants’ clinical providers didn’t have access to their app data. But, he said, this might be a potential option for clinics moving forward if patients want to grant that access by allowing their app to share a summary with their clinic.

Data from mental health apps could even potentially help providers or systems understand which patients need the most-intensive approaches to psychiatric care, and which might be able to do all right with less-intensive care. That could also improve the waiting list situation for all patients, he notes.

He likens this to a relay race.

“If we can use apps to give the patient a bit of momentum on understanding and managing their symptoms, even before they get to clinic, then perhaps that will help them get more out of therapy once they get to clinic and pass the baton from the app to a professional provider,” he said. “The apps don’t have the same effect as therapy, but doing something while waiting is still important.”

In addition to Horwitz, the study’s authors are Elizabeth D. Mills, Ph.D., of the U-M Department of Anesthesiology, Srijan Sen, M.D., Ph.D., and Amy S.B. Bohnert, Ph.D. Sen, a professor of psychiatry, directs the U-M Eisenberg Family Depression Center and is a member of the Michigan Neuroscience Institute; Bohnert is co-director of the U-M Opioid Research Institute and a professor of anesthesiology. Bohnert and Sen are two of the three leaders of the COMPASS study.

The PROMPT study was funded by Precision Health at U-M and the Eisenberg Family Depression Center as well as the National Institute of Mental Health (MH131761).

Comparative Effectiveness of Three Digital Interventions for Adults Seeking Psychiatric Services, JAMA Network Open, DOI:10.1001/jamanetworkopen.2024.22115

The research team from The Hong Kong Polytechnic University, led by Dr. Arkers Kwan Ching Wong, reviewed data from 3 randomized controlled trials involving over 150 older adults. The evaluation showed that the interventions that focused on increasing awareness of being monitored and used collaborative goal-setting and feedback tools, such as the SystemCHANGE approach, improved adherence to WMDs.

WMDs can offer valuable health insights, but their long-term use can be challenging for older adults who may not be comfortable with technology or not see the value in using it. As this research highlights, providing targeted support to help older adults overcome these barriers and integrate WMDs into their daily routines can help maximize the potential health benefits of these devices.

“Healthcare professionals play a pivotal role in facilitating the adoption of wearable monitoring devices among older adults,”  remarked Dr. Wong.

By working with health care professionals to set specific goals related to the use of wearables, older adults are more likely to benefit from these devices in the long term. Future research should focus on developing and testing interventions that prioritize awareness and collaborative goal-setting to further enhance adherence among older adults.

Chan CSW, Kan MMP, Wong AKC

Effects of Peer- or Professional-Led Support in Enhancing Adherence to Wearable Monitoring Devices Among Community-Dwelling Older Adults: Systematic Review of Randomized Controlled Trials

J Med Internet Res 2024;26:e53607

URL: https://www.jmir.org/2024/1/e53607

doi: 10.2196/53607

Marina Walther-Antonio, Ph.D., and colleagues at Mayo Clinic’s Center for Individualized Medicine are on a mission to catch these cancers early.

Their research dives deep into the microbiome, a community of trillions of microorganisms — including bacteria, fungi and viruses — that influence health and disease. Through their investigations, they have uncovered specific microbial signatures linked to endometrial and ovarian cancers and are working toward developing innovative home swab tests for women to assess their susceptibility.

“Screening the microbiome for early detection may improve patient outcomes,” says Dr. Walther-Antonio, also a researcher at the Departments of Surgery and Obstetrics and Gynecology, and the Mayo Clinic Comprehensive Cancer Center.

The team discovered a cluster of 17 bacterial microbes associated with the presence of endometrial cancer, with a “lightning rod” in the group: Porphyromonas somerae.

To validate this connection, they drew parallels between Porphyromonas somerae and its closest relative, which is known to be linked to oral cancer. The team hypothesized that Porphyromonas somerae might play a similarly invasive role in endometrial cancer. After extensive testing, they confirmed the ability of this microbe to invade endometrial cells and alter their function, especially under estrogen exposure — a common risk factor for endometrial cancer.

In their research on ovarian cancer, the team found a distribution of microbes in the reproductive tract of women with the disease. They also revealed changes in the microbiome compositions that are correlated with patient treatment outcomes. These findings may open investigation avenues into applicability of these markers to detecting and predicting treatment response.

According to World Cancer Research Fund International, endometrial cancer ranks as the sixth most common cancer among women globally, with 417,367 new cases and 97,370 deaths reported in 2020. Ovarian cancer follows as the eighth most common, recording 313,959 new cases and 207,252 deaths in the same year.

The Mayo scientists are also collaborating with the Waitematā District Health Board officials on Pacific Islander and Māori populations in New Zealand, which has one of the highest incidences of endometrial cancer globally. Factors such as high obesity rates, a known risk factor, are a likely contributor, but the high incidence rates among younger women remain unresolved.

In the U.S., there is a long-term initiative designed to engage Black women, particularly those who are postmenopausal. “Black women don’t have a higher incidence rate of endometrial cancer, but they have a higher mortality rate and morbidity rates. This is influenced by several factors, including limited access to healthcare.  Symptoms frequently go unrecognized or are mistakenly attributed to other conditions, such as fibroids, which are common among Black women,” Dr. Walther-Antonio says.

Through the long-term study, Mayo’s scientists hope to engage participants to contribute samples every six months for three years, including vaginal swabs and environmental samples to identify potential risk factors.

Ultimately, Dr. Walther-Antonio and her team hope to use these microbiome signatures to predict and intervene in the development of cancer before it materializes.

Mayo Clinic has a financial interest in the swabs mentioned in this article.

About three million people in the U.S. have glaucoma, a group of diseases that damage the optic nerve and lead to vision loss, according to the Centers for Disease Control and Prevention. Doctors use flinch-inducing “air puff tests” during eye exams to take one-time measurements of eye pressure. A slight elevation in pressure, an otherwise imperceptible symptom caused by fluid buildup around the cornea, can lead to a glaucoma diagnosis. Researchers have been testing ways to continuously and more comfortably detect these tiny fluctuations in pressure, such as contact lenses that transmit signals to receptor glasses. However, changing temperatures — like stepping outside into cold weather — can throw off the lenses’ measurements. So, Dengbao Xiao and coworkers wanted to develop a contact lens that accurately measures and wirelessly transmits real-time signals about eye pressure across a wide range of temperatures.

First, Xiao and the team designed two miniature spiral circuits, each with a unique natural vibration pattern that would change when stretched by minute amounts, such as with changes to an eye’s pressure and diameter. To create pressure-detecting contact lenses, the researchers sandwiched these tiny circuits between layers of polydimethylsiloxane, a typical contact lens material. Then they wirelessly read the embedded circuits’ vibration patterns by holding a coil near the lens that was connected to a computer. The transmitted signals were unaffected by tests meant to mimic eye movement, extended exposure to moisture (to simulate damp conditions in the eye), and daily wear and tear.

In laboratory tests, the researchers placed the new lenses on three individual pig eye specimens while controlling the ocular pressures and temperatures. The contact lenses monitored and wirelessly transmitted pressure data from 50 to 122 degrees F. When pressures were calculated from the signal of only one circuit in the lens, the results deviated up to 87% from the true values. However, when information from both circuits was used, the pressure readings differed by only 7% from the true value because the combination removed temperature-related errors. The researchers say that their dual-circuit “smart” lens design has potential to be used for accurate early detection and monitoring of glaucoma, even in a wide range of temperatures.

The authors acknowledge funding from the National Natural Science Foundation of China.

IMAGE: THIS “SMART” CONTACT LENS COULD SOMEDAY HELP MEASURE EYE PRESSURE AND SEND WIRELESS SIGNALS TO ENABLE EARLY DETECTION OF GLAUCOMA.

view more CREDIT: ADAPTED FROM ACS APPLIED MATERIALS & INTERFACES 2024, DOI: 10.1021/ACSAMI.4C02289

“We found that adults with hearing loss who regularly used hearing aids had a 24% lower risk of mortality than those who never wore them,” said lead investigator Janet Choi, MD, MPH, an otolaryngologist and assistant professor of medicine at the University of Southern California Keck School of Medicine in Los Angeles. “These results are exciting because they suggest that hearing aids may play a protective role in people’s health and prevent early death.”

As background, the authors noted that hearing loss is a known factor for negative health outcomes and mortality. But to date it has not been established whether hearing aid use is associated with lower mortality.

The researchers evaluated data on 9,885 adults (age 20 years and older) who participated in the (USA) National Health and Nutrition Examination Survey between 1999 and 2012 and completed audiometry and hearing aid use questionnaires, revealing 1,863 adults with hearing loss.

Main measures included hearing loss, hearing aid use (never users, non-regular users, and regular users) and death (up to 2019).

Of the subjects with hearing loss, 237 were regular hearing aid users (i.e. wearing a hearing aid at least once a week, five hours a week or half the time) and 1,483 were never-users. Those wearing a hearing aid once a month or less were categorized as non-regular users.

The investigators reported a 24% difference in mortality risk between regular hearing aid users and never-users. This finding held even after adjustments were made for degree of hearing loss (from mild to severe), age, ethnicity, income, education other demographics and medical history.

They found no difference in mortality risk between non-regular users and never users, suggesting that occasional hearing aid use did not extend life.

The authors concluded, “Regular hearing aid use was associated with lower risks of mortality than in never users in US adults with hearing loss when accounting for age, hearing loss, and other potential confounders. Future research is needed to investigate the potential protective role of hearing aid use against mortality for adults with hearing loss.”

The approach would offer an easier, long-term and less invasive alternative to insulin injections or traditional transplants that require immunosuppression.

The group’s paper published Dec. 5 in Nature Biomedical Engineering.

For the last decade, Minglin Ma, professor of biological and environmental engineering at Cornell, has been trying to develop a better way to control the disease.

In 2017, he unveiled a removeable polymer thread containing thousands of islet cells, protected by a thin hydrogel coating, that could be implanted in a patient’s abdomen. The enclosed islets could secrete insulin in response to the body’s diminished blood-sugar levels while also receiving a steady flow of nutrients and oxygen to stay healthy. Ma’s lab created a more robust version in 2021 that proved effective in controlling blood sugar in diabetic mice for up to six months.

Those projects prompted James Shapiro of University of Alberta, Edmonton to reach out about a possible collaboration. Shapiro had created a method for inserting islets in channels just under a person’s skin, then applying immunosuppression to protect them.

“I was intrigued by the virtue of Ma’s approach as it avoided the need for immunosuppression, and I wondered if we might combine our two innovative strategies to improve cell survival,” Shapiro said. “Indeed it worked.”

The resulting new system is named SHEATH (Subcutaneous Host-Enabled Alginate THread).

The installation is a two-step process. First, a series of nylon catheters are inserted under the skin, where they remain for four to six weeks – long enough for blood vessels to form around the catheters. When the catheters are removed, the islet devices, which are approximately 10 centimeters long, are inserted into the pocket of space the catheters created, and the surrounding vascular system remains intact.

“That channel is a perfect fit for our device,” Ma said. “Putting something under your skin is much easier, much less invasive than in the abdomen. It can be done as an outpatient procedure, so you don’t have to stay in the hospital. It can be done under local anesthesia.”

While additional challenges for the long-term clinical application of the device remain, Ma is hopeful that future versions will be able to last for two to five years before needing to be replaced.

“The challenge is, it’s very difficult to keep these islets functional for a long time inside of the body where you have a device, because the device blocks the blood vessels, but the native islet cells in the body are known to be in direct contact with vessels that provide nutrients and oxygen,” Ma said. “The device is designed in a way that we can maximize the mass exchange of nutrients and oxygen, but we may need to provide additional means to support the cells for a long-term function.”

National authorities notified the EU regulator after the pens, which are labelled in German and appear to have originated from wholesalers in Austria and Germany, were found in several locations in the EU and the UK.

The pens have batch numbers, 2D barcodes and unique serial numbers from genuine Ozempic packs. In the EU, each medicine pack has a unique 2D barcode and serial number so that it can be tracked in an EU-wide electronic system. When the packs of the falsified Ozempic were scanned, the serial numbers were shown to be inactive, thereby alerting operators to a potential falsification.

There are differences in the appearance between the falsified pen and the original pen. There is no evidence that any falsified pens have been dispensed to patients from legal pharmacies and there are no reports of harm to patients in relation to the falsified medicine, the EMA said in a statement.

Ozempic pens (semaglutide, 1 mg, solution for injection) are in high demand across Europe and globally. The drug helps to lower blood sugar in people with diabetes by helping the pancreas to make more insulin. There have been shortages of the medication in several countries, with some social media influencers highlighting its off-label use in weight loss. While it is not authorised for this purpose, it is associated with modest reduction in patients’ weight.

The EMA is assisting national authorities in their investigations. Wholesalers and pharmacies in the impacted countries have been warned about the suspicious offers of Ozempic to wholesalers. In addition, parallel distributors across the EU have been alerted.

In the meantime, the German and Austrian regulatory authorities have issued statements of non-compliance with good distribution practices (GDP) to the concerned wholesalers in their countries for not following required procedures, including compliance with security measures.

Bipolar disorder (formerly called manic-depressive illness or manic depression) is a mental illness that causes swings in a person’s mood, energy, activity levels, and concentration. These shifts can make it difficult to carry out day-to-day tasks and can make interactions with other people difficult. The degree of mood swing can vary from person to person, from feeling manic (very “up”) to feeling depressed. At present, these mood swings are mostly diagnosed subjectively, through interview with doctors or by questionnaires. This takes time, and requires an immediate medical presence.

Now a group of Barcelona-based psychiatrists, in collaboration with data scientist in Edinburgh, have used a research grade wearable device to continuously collect several physiological biomarkers during the diverse phases and episodes of bipolar disorder. Among the collected physiological biomarkers is electrodermal activity which uses changes in the skin’s electrical conductivity to indicate the level of stress through the reactivity of the nervous system. This is a potential immediate indicator of whether someone is in a manic, depressive or in a normal mood state.

They recruited 38 patients with bipolar disorder, and 19 healthy controls, all from the Barcelona area.

Researcher Diego Hidalgo-Mazzei said “Each participant was fitted with a commercially available Empatica E4 bracelet, which they were asked to wear for around 48 hours. This can measure a variety of physiological changes, but we were most interested in measuring small electrophysiological changes in the skin of the wearer. We found that bipolar disorder patients in their depressed phase had on average a significantly lower skin electrical activity than the rest of the bipolar group or the healthy control group. We also found that as an individual moved from manic to depressive state (or vice versa), this was detectable by a change in skin surface electrical activity.

It is important for the patient and doctor to know how and when these mood fluctuations take place. It is important also to highlight that the treatment is different for manic or depressive states. This can help with a prompt diagnosis and early personalized treatment, but it can also help in preventing adverse outcomes, for example in alerting to an increased risk of suicide, or of mood swings which may lead to dangers with activities such as driving. It is also easier to treat patients if we know if they are in a manic phase or a depressed phase. Until now, these mood swings have mostly been diagnosed subjectively, through interview with doctors or by questionnaires, and this had led to real difficulties. Arriving at the correct drug is difficult, with only around 30 to 40% of treated individuals having the expected response. We hope that the additional information these systems can provide will give us greater certainty in treating patients.

We are still some way from that though. This is an exploratory observational study, so we need to look at a larger sample and use machine learning to analyse all the biomarkers collected by the wearers to confirm the findings to determine patterns which might indicate a specific episode. This may not be ideal for every bipolar disorder sufferer, in every circumstance, but a potential pattern may help in the future the people hardest hit by the mood changes which affect their lives”.

According to a 2019 study between 1% and 2% of Europeans suffer from bipolar disorder (exact numbers are difficult to obtain), meaning that over 700,000 suffer in Europe. That’s equivalent to a city the size of Frankfurt, Washington DC, or Glasgow.  (https://www.thelancet.com/journals/lanepe/article/PIIS2666-7762(22)00034-5/fulltext).

Commenting, Professor Paolo Ossola (of the University of Parma, Italy) said:

“In this seminal study, Dr Hidalgo and collaborators have laid the foundation for a new approach to diagnosing and treating bipolar disorders. Bipolar disorder is defined by the occurrence of episodes (either manic or depressive) interspersed with periods of wellbeing known as euthymia. To date, the course of the illness is entirely unpredictable, and the occurrence of new episodes relies solely on their early recognition at a subjective level through early-warning symptoms.

Having a physiological biomarker that extends beyond the subjective level would enable more timely intervention. More importantly, the fact that it originates from a wearable device could assist individuals who, due to geographical reasons, lack easy access to clinical facilities.

The shift from the subjective to the biological level could also promote understanding of the underlying mechanistic dynamics of mood swings. Previous attempts, based on the study of motor behaviour using wearable devices, failed to differentiate, for example, the restlessness caused by anxiety in a depressive episode from the initial hyperactivation associated with a manic switch. A more finely tuned biomarker, such as skin conductance, could capture these subtle changes and thus determine whether a treatment is effective and the reasons behind it.

As the authors note, this is just a preliminary exploratory study, but their encouraging results could pave the way for future research aimed at unravelling clinical puzzles in the diagnosis and treatment of bipolar disorder.

The exciting collaboration between doctors and data scientists is significantly accelerating the development of this new branch of precision psychiatry. I eagerly anticipate the much-needed transition from “bench to bedside” with these technologies becoming available in community-based mental health settings”.