Type 1 Diabetes Diagnoses Spiked During the Pandemic

 Significantly more children were diagnosed with type 1 diabetes (T1D) during the COVID-19 pandemic compared with previous years, a single-institution study suggested.

From March 2020 to March 2021, a total of 187 children were admitted for new onset T1D at a San Diego children's hospital, a 57% increase over the 119 children in the prior year, according to Jane Kim, MD, of the University of California San Diego, and colleagues.

And for part of this pandemic period (July 2020 to February 2021), they found significantly more new diagnoses than would be predicted based on averages from the previous 5 years. For example, it was expected there would be 10 new diagnoses in February 2021, but in reality there were 21, the group wrote in a JAMA Pediatrics research letter.

Not only were there more new cases of T1D than expected, but more children initially presented with diabetic ketoacidosis (DKA) during the 1-year pandemic period as well (50% compared to an average of 41% over the prior 5 years).

"By measuring a 12-month interval after the onset of the COVID-19 pandemic, our cross-sectional study accounted for seasonal variation in the onset of new T1D cases," Kim's group pointed out. They also noted that they included data on the 5 years prior in order to account for the expected annual increases in cases, which have been increasing globally each year.

Despite the noted increase in DKA frequency, the researchers observed no significant difference in the percentage of kids that needed to be admitted to pediatric intensive care (8.6% during the pandemic vs 6.4% in the years prior), nor were there differences in average age at presentation (9.6 vs 9.7 years, respectively), BMI z-score (-0.39 vs -0.43), or HbA1c levels (11.6% vs 11.7%).

The study was limited to individuals 18 and younger admitted to Rady Children's Hospital San Diego for a new case of T1D from March 2015 to March 2021. Patients had to have at least one positive T1D antibody titer. During the 5 years prior to the pandemic, 641 children were admitted to the hospital.

For kids diagnosed during the pandemic, 2.1% (4 of 187) were positive for COVID-19 at the time of diagnosis.

"As the only children's hospital in the greater San Diego area, we routinely admit children with new-onset diabetes who require initiation of insulin treatment, and we monitor almost all patients newly diagnosed with T1D," the group explained.

Kim's group did note that despite the increase in the number of new cases, the number of children seen in their pediatric endocrine clinic didn't "substantially" change.

Although all children diagnosed during the pandemic were tested for COVID-19 upon admission, the group didn't perform antibody testing to check for past infection, an important limitation as recent CDC data have suggested that kids who test positive for COVID-19 may have an increased risk for T1D as well as other types of diabetes.

Disclosures

Kim's group reported no disclosures.

Primary Source

JAMA Pediatrics

Source Reference: Gottesman BL, et al "Incidence of new-onset type 1 diabetes among US children during the COVID-19 global pandemic" JAMA Pediatr 2022; DOI: 10.1001/jamapediatrics.2021.5801.

https://www.medpagetoday.com/endocrinology/type1diabetes/96835

USPSTF Not Backing Afib Screening, Even With Wearables

 While experts agreed with the U.S. Preventive Services Task Force's (USPSTF) finalized recommendations that affirmed no recommendation for atrial fibrillation (Afib, AF) screening in middle-age and older adults without symptoms, they noted that there might be no stopping it anyway.

The "I" statement of insufficient evidence for such screening among adults 50 and older without a history of transient ischemic attack or stroke, published in JAMA, matched the draft recommendations released last May and a similar statement from 2018 that said there isn't enough evidence that benefits outweigh potential harms.

The update extended that determination to cover not only in-office ECG but also wearables with ECG capabilities, like the Apple Watch, as well as smart devices using photoplethysmography, and even pulse oximeters or blood pressure cuffs that use algorithms to detect irregular heartbeats indicative of Afib.

There's plenty of evidence now that more screening catches more Afib, especially when using continuous-monitoring devices, said the USPSTF members in their statement.

"We find this conclusion reasonable because most asymptomatic AF is intermittent, and it stands to reason that continuous monitoring will detect more AF than intermittent monitoring over short time periods," commented John Mandrola, MD, of Baptist Health Louisville in Kentucky, and Andrew Foy, MD, of Pennsylvania State University College of Medicine in Hershey, in an editorial in JAMA Internal Medicine.

The problem was in finding evidence to support improved clinical outcomes in the face of known small to moderate risks of harm from increased risk of major bleeding when starting anticoagulation for screen-detected Afib.

The accompanying evidence review turned up no trials that have assessed benefits and harms of anticoagulation in asymptomatic screen-detected Afib. Two recent trials didn't provide much help in that regard.

The STROKESTOP trial randomized all 75- to 76-year-old adults in two regions of Sweden to be invited to screening with twice-daily single-lead ECG for 14 days or standard care. It showed no greater rate of detected Afib or use of oral anticoagulation in the screening group after 7 years, "suggesting that, given time, standard care will discover most cases of AF," Mandrola and Foy pointed out.

And while the primary endpoint was met, the absolute risk reduction in the composite of ischemic or hemorrhagic stroke, systemic embolism, bleeding requiring hospitalization, and all-cause death was just 0.23%. One additional event in the screening group would have rendered that finding nonsignificant, the editorialists pointed out. There was also no difference in ischemic stroke alone.

The LOOP trial, published in August after the USPSTF had already finished its review, randomized individuals 70 and older without known Afib to either an implantable loop recorder or standard care, with oral anticoagulation encouraged for any detected episodes longer than 6 minutes. In this case, Afib diagnoses and oral anticoagulation roughly tripled with the loop recorder over the median 64 months of follow-up. Yet, the 1.1% absolute risk reduction in the primary outcome of time to first stroke or systemic embolism was not statistically significant.

The European Society of Cardiology, using the same admittedly "scarce" evidence base, concluded in favor of Afib screening (class I for opportunistic screening in patients 65 and older, class IIa for systematic ECG screening in patients with high stroke risk or those 75 and older) in 2020 guidelines, citing the likely benefits of early detection and treatment in selected older adults as justification.

The American Heart Association also supports Afib screening as potentially useful for adults 65 and older in the primary care setting, using pulse assessment followed by ECG as indicated, the task force members noted.

However, Mandrola and Foy argued that "nonbeneficial interventions that add cost are not helpful for patients and create a net harm to society."

Other concerns include "anxiety generated by abnormal findings, misinterpretation of the ECG results that could result in overdiagnosis and overtreatment, and the possibility of unnecessary downstream testing," added Philip Greenland, MD, of Northwestern University Feinberg School of Medicine in Chicago, in an editorial in JAMA.

"Despite the caution appropriately emphasized by the USPSTF, screening will likely increasingly occur outside of physician encounters," acknowledged Matthew Kalscheur, MD, and Zachary Goldberger, MD, both of the University of Wisconsin-Madison, in an editorial in JAMA Network Open.

When consumer-available devices land these patients in the office, there just isn't enough evidence to guide management decisions in a way to ultimately improve outcomes, Mandrola and Foy wrote.

The way forward might be very large trials enrolling only higher-risk patients with longer-duration monitoring and longer-duration thresholds for identifying Afib, Greenland suggested.

Another possibility are clinical trials of structured, patient-specific behavior interventions for screen-detected Afib targeting modifiable risk factors, including obesity, hypertension, alcohol use, sleep apnea, smoking, and diabetes, Kalscheur and Goldberger added.

"The hope is that a future USPSTF report will eventually be able to either endorse -- or advise clearly against -- AF screening by ECG based on clear, objective evidence from well-conducted randomized trials," Greenland concluded.

Disclosures

Mandrola, Foy, Kalscheur, and Goldberger disclosed no relevant relationships with industry.

Greenland disclosed research grants from the NIH and the American Heart Association.

Primary Source

JAMA

Source Reference: U.S. Preventive Services Task Force "Screening for atrial fibrillation: US Preventive Services Task Force recommendation statement" JAMA 2022; DOI: 10.1001/jama.2021.23732.

Secondary Source

JAMA

Source Reference: Kahwati LC, et al "Screening for atrial fibrillation: updated evidence report and systematic review for the US Preventive Services Task Force" JAMA 2022; DOI: 10.1001/jama.2021.21811.

Additional Source

JAMA Internal Medicine

Source Reference: Mandrola J, Foy A "Screening for atrial fibrillation -- new devices, same challenges" JAMA Intern Med 2022; DOI: 10.1001/jamainternmed.2021.7283.

https://www.medpagetoday.com/cardiology/arrhythmias/96842

AI Could Analyze Speech to Help Diagnose Alzheimer’s

 Alzheimer’s disease is notoriously difficult to diagnose. Typically, doctors use a combination of cognitive tests, brain imaging, and observation of behavior that can be expensive and time-consuming. But what if a quick voice sample, easily taken at a person’s home, could help identify a patient with Alzheimer’s?

A company called Canary Speech is creating technology to do just that. Using deep learning, its algorithms analyze short voice samples for signs of Alzheimer’s and other conditions. Deep learning provider Syntiant recently announced a collaboration with Canary Speech, which will allow Canary to take a technology that is mostly used in doctor’s offices and hospitals into a person’s home via a medical device. While some research has found deep learning techniques using voice and other types of data to be highly accurate in classifying those with Alzheimer’s and other conditions in a lab setting, it’s possible the results would be different in the real world. Nevertheless, AI and deep learning techniques could become helpful tools in making a difficult diagnosis.

Most people think of Alzheimer’s disease, the most common form of dementia, as affecting memory. But research suggests that Alzheimer’s can impact speech and language even in the disease’s earliest stages, before most symptoms are noticeable. While people can’t usually pick up on these subtle effects, a deep learning model, trained on the voices of tens of thousands of people with and without these conditions, may be able to distinguish these differences.

“What you’re interested in is, what is the central nervous system telling you that is being conveyed through the creation of speech?” says Henry O’Connell, CEO and cofounder of Canary Speech. “That's what Canary Speech does—we analyze that data set.”

Until now, O’Connell says that the algorithm has been cloud-based, but Canary’s collaboration with Syntiant allows for a chip-based application, which is faster and has more memory and storage capacity. The new technology is meant to be incorporated into a wearable device and take less than a second to analyze a 20- or 30-second sample of speech for conditions like Alzheimer’s, as well as anxiety, depression, and even general energy level. O’Connell says that Canary’s system is about 92.5 percent accurate when it comes to correctly distinguishing between the voices of people with and without Alzheimer’s. There is some research to suggest that conditions like depression and anxiety impact speech, and O’Connell says that Canary is working to test and improve the accuracy of algorithms to detect these conditions.

Other voice-based technologies have had similar success, says Frank Rudzicz, an associate professor of computer science at the University of Toronto and cofounder of Winterlight Labs, which makes a similar product to Canary Speech. In a 2016 study, Rudzicz and other researchers used simple machine learning methods to analyze the speech of people with and without Alzheimer’s with an accuracy of about 81 percent.

“With deep learning, you would just give the raw data to these deep neural networks, and then the deep neural networks automatically produce their own internal representations,” Rudzicz says. Like all deep learning algorithms, this creates a “black box”—meaning it’s impossible to know exactly what aspects of speech the algorithm is homing in on. With deep learning, he says, the accuracy of these algorithms has risen above 90 percent.

Previously, programmers have used deep learning alongside medical imaging of the brain, such as MRI scans. In studies, many of these methods are similarly accurate—usually above 90 percent accuracy. In a December 2021 study, programmers successfully trained an algorithm to not only distinguish between the brains of cognitively normal people and those with Alzheimer’s, but also between those with mild cognitive impairment, in many cases an early precursor to Alzheimer’s, whose brains were either more similar to those of healthy people or more similar to those with Alzheimer’s. Distinguishing these subtypes is especially important because not everyone with mild cognitive impairment goes on to develop Alzheimer’s.

“We want to have methods to stratify individuals along the Alzheimer’s disease continuum,” says Eran Dayan, an assistant professor of radiology at the University of North Carolina, Chapel Hill and an author of the 2021 study. “These are subjects who are likely to progress to Alzheimer's disease.”

Identifying these patients as early as possible, Dayan says, will likely be crucial in effectively treating their diseases. He also says that, generally, scan-based deep learning has a similarly high efficacy rate, at least in classification studies done in the lab. Whether these technologies will be just as effective in the real world is less clear, he says, though they are still likely to work well. He says more research is needed to know for sure.

Another reason for concern, Dayan says, is potential biases, which recent research has shown that AI can harbor if there is not enough variety in the data the algorithm is trained on. For instance, Rudzicz says it’s possible that an algorithm trained using speech samples from people in Toronto would not work as well in a rural area. O’Connell says that the algorithm that Canary Speech analyzes nonlanguage elements of speech, and that they have versions of the technologies used in other countries, like Japan and China, that are trained using data from native language speakers.

“We validate our model and train it in that system, in that environment, for performance,” he says.

Though Canary’s collaboration with Syntiant may make remote, real-time monitoring possible, O’Connell personally believes a formal diagnosis should come from a doctor, with this technology serving as another tool in making the diagnosis. Dayan agrees.

“AI, in the coming years, I hope will help assist doctors, but absolutely not replace them,” he says.

https://spectrum.ieee.org/ai-to-detect-alzheimers

Accuracy of Federal Stats on Most-Unvaxxed Hospitals in Question

 A federal database that tracks hospital COVID vaccinations for personnel in each healthcare system is extremely erroneous, according to five hospital systems that appear to have the highest numbers of unvaccinated workers in the country.

"When we've looked at these numbers in the past, they've been inaccurate," Jeff Grainger, director of external communications for AdventHealth in Central Florida, wrote in an email to MedPage Today.

The federal database showed that for the data collection week that began Jan. 7, Adventist Health Orlando had 18,576 unvaccinated workers and 637 workers who had received one vaccine in a multi-dose series. Another 25,253 workers were fully vaccinated.

"We don't have 44,000 employees in one hospital," Grainger said. As of last count, Grainger said, 96% of his hospital's team members had complied with the CMS vaccine mandate. He said AdventHealth strongly encourages vaccination as a safe and effective way to reduce the risk of becoming infected and the level of harm in the case of a breakthrough infection.

MedPage Today reached out to these hospital systems and also called and emailed multiple times to reach several HHS officials with requests for an explanation. Federal officials did not reply by publication time. It is not clear whether this dataset will be used to enforce healthcare worker vaccination mandates.

The information is critical in light of the U.S. Supreme Court decision two weeks ago that upheld a Nov. 5 federal mandate that nearly all people who work in certain healthcare organizations such as hospitals that receive federal Medicaid or Medicare reimbursement must be fully vaccinated.

A spokeswoman for the University of Illinois Hospital in Chicago -- the health system that the federal database showed had the second highest number of unvaccinated personnel -- also said the numbers in the database are incorrect. It showed 12,049 workers had not received any vaccination, and 272 had received just one dose.

The data "includes not only our hospital personnel, but also our health science colleges in the denominator," wrote Jacqueline Carey, of the hospital system's public affairs department. She added that the federal spreadsheet only provides data on vaccinations provided by the UI health system and employee health services. Vaccinations administered to personnel elsewhere, such as through an employee's personal provider or pharmacy, are not included in the data so those workers appear to be unvaccinated when they have received all their shots.

Carey added that her healthcare system has required vaccination for hospital and clinic employees and all active university employees who "are engaged in work with our healthcare system," including students, residents, College of Medicine faculty, security, building service workers, and others. The deadline to comply was Oct. 1, 2021.

While the federal website indicates UI has some 23,174 workers, in fact there were only 6,530 as of Jan. 19, Carey said. Of those, 6,270 or 96% were fully vaccinated, 329 were unvaccinated including those with approved exemptions, and 21 were partially vaccinated. She said all of this information was reported to CMS.

Those individuals who aren't fully vaccinated must undergo testing twice a week, at least 48 hours apart, Carey wrote.

A spokesman for one of the five organizations that appears to have one of the highest numbers of unvaccinated personnel speculated on background during a phone interview one possible reason for the discrepancy. The representative said hospitals contract with a variety of agencies for short-term nursing staff or travelers. While the agencies assure the hospital as part of its contract that the nurses sent to the organization are vaccinated, the hospital does not independently verify that information.

It is likely that those personnel will show up as unvaccinated in the federal database, the spokesman said.

Mount Sinai Hospital in New York was listed last week as having the third highest number of unvaccinated workers. But spokeswoman Lucia Lee also told MedPage Today that their data are inaccurate. Mount Sinai Health System -- including Mount Sinai Hospital, Mount Sinai Morningside, Mount Sinai West, Mount Sinai Queens, Mount Sinai Beth Israel, Mount Sinai Brooklyn, Mount Sinai South Nassau and New York Eye and Ear at Mount Sinai -- has vaccinated 99% of its 43,000-plus employees, Lee wrote.

Representatives of Ochsner Medical Center in New Orleans and Orlando Health Regional Medical Center, which the federal database showed had the fourth and fifth highest numbers of unvaccinated workers, echoed concerns that their statistics were wrong as well.

A spokeswoman for Ochsner responded that 99.57% of its more than 34,000 employees are compliant with our COVID-19 vaccine policy, with 95% of Ochsner Health and Ochsner LSU Health Shreveport employees fully vaccinated, and the remainder having approved medical or religious exemptions or deferrals.

Kena Lewis, a spokeswoman for Orlando Regional Medical Center, did not give that health system's vaccination rates, but took issue with the federal data claiming the hospital has 44,154 workers.

The hospital is one of 10 hospitals in the Orlando network, and the network has a total of 23,709 personnel. She said the system "continues to review the guidelines regarding COVID-19 vaccination requirements for healthcare organizations and will take appropriate steps."

https://www.medpagetoday.com/special-reports/exclusives/96851

CDC: Omicron Stresses the Healthcare System in a Different Way

 Once Omicron took hold, the U.S. saw a higher percentage of inpatient beds in use than prior high transmission periods, but lower rates of serious outcomes and deaths, researchers found.

From Dec. 19, 2021 to Jan. 15, 2022, COVID patients used a maximum of 21% of "staffed inpatient beds," which was seven percentage points higher than the Delta period and three percentage points higher than the 2020-2021 winter surge, reported A. Danielle Iuliano, PhD, of the CDC, and colleagues.

However, staffed intensive care unit (ICU) bed use for COVID patients during Omicron (30.4%) was slightly lower than either Delta or the previous winter, and the Omicron period had lower peak emergency department (ED) visits, hospital admission, and death-to-case ratios than the prior two high transmission periods, the authors wrote in an early edition of the Morbidity and Mortality Report.

Moreover, among hospitalized patients, the mean length of stay and the percentages admitted to ICU, requiring mechanical ventilation, or dying while in the hospital were all lower during Omicron than previously, the team noted.

"This apparent decrease in disease severity is likely related to multiple factors, most notably increases in vaccination coverage among eligible persons, and the use of vaccine boosters among recommended subgroups," Iuliano's group wrote.

They examined data from three surveillance systems and a healthcare facility database to examine COVID-related data from three time periods of high COVID transmission: the Omicron period (Dec. 19, 2021 to Jan. 15, 2022), the Delta period (July 15-Oct. 31, 2021), and the 2020-2021 winter surge (Dec. 1, 2020-Feb. 28, 2021).

As of Jan. 15, 2022, the authors noted, the maximum daily 7-day moving average of cases, ED visits, and admissions outpaced both the Delta and prior winter periods:

• 798,976 cases (+386% over Delta period, +219% over prior winter)

• 48,238 ED visits (+86%, +137%)

• 21,586 admissions (+76%, +31%)

However, the 1,854 average of deaths during Omicron was 4% lower than Delta, and 46% lower than winter 2020-2021, the authors said.

Event-to-case ratios were also lower during Omicron than during Delta or the prior winter, respectively:

• ED visits: 87 per 1,000 cases (vs 167 and 92 per 1,000)

• Hospitalizations: 27 per 1,000 (vs 78 and 68 per 1,000)

• Deaths: 9 per 1,000 (vs 13 and 16 per 1,000)

Iuliano's group also found that the percentage of hospitalized patients admitted to an ICU during Omicron was a relative 26% lower than during Delta and 29% lower than during the prior winter (P<0.05).

Mean length of hospital stay during Omicron (5.5 days) also fell compared with Delta (7.6 days) and the prior winter (8.0 days, P<0.001).

They added that hospitals are not necessarily being strained by disease severity, but there was a "high volume of hospitalizations resulting from high transmission rates during a short period," and noted that unvaccinated individuals have higher risk for more severe outcomes.

Iuliano's team stressed the importance of "national emergency preparedness, specifically, hospital surge capacity and the ability to adequately staff local health care systems when critical care needs arise and before the system is overwhelmed."

Disclosures

Iuliano disclosed no conflicts of interest; one co-author disclosed support from Becton, Dickinson and Company.

Primary Source

Morbidity and Mortality Weekly Report

Source Reference: Iuliano AD, et al "Trends in disease severity and health care utilization during the early omicron variant period compared with previous SARS-CoV-2 high transmission periods -- United States, December 2020–January 2022" MMWR 2022; DOI: 10.15585/mmwr.mm7104e4.

https://www.medpagetoday.com/infectiousdisease/covid19/96854

Incyte withdraws application for lymphoma med

 Incyte (Nasdaq:INCY) today announced updates regarding the clinical development of parsaclisib, the Company’s next-generation oral inhibitor of phosphatidylinositol 3-kinase delta (PI3Kδ), and MCLA-145, its CD137/PD-L1 bispecific antibody co-developed under a global collaboration and license agreement with Merus.

Incyte is withdrawing the New Drug Application (NDA) for parsaclisib for the treatment of patients with relapsed or refractory follicular lymphoma (FL), marginal zone lymphoma (MZL) and mantle cell lymphoma (MCL). The decision to withdraw the NDA follows discussions with U.S. Food and Drug Administration (FDA) regarding confirmatory studies to support an accelerated approval, which Incyte determined cannot be completed within a time period that would support the investment. The withdrawal of the NDA is a business decision and is not related to any changes in either the efficacy or safety of parsaclisib. The decision impacts only the FL, MZL and MCL indications in the U.S., and does not affect other ongoing clinical trials in the U.S. or other countries.

Additionally, as part of its ongoing portfolio prioritization and capital allocation review, Incyte has decided to opt-out of the continued development of MCLA-145. Incyte will continue to collaborate with Merus and leverage their platform to develop a pipeline of novel agents.

https://finance.yahoo.com/news/incyte-provides-parsaclisib-mcla-145-213000797.html

Team behind RECOVERY trial of COVID drugs casts its net wider

 The UK scientists that ran one of the largest trials of experimental COVID-19 drugs have formed a non-profit company that will apply the methodology to other disease areas – with $6.8 million in funding from French drugmaker Sanofi.

The non-profit – called Protas – is led by Sir Martin Landray,  professor of medicine and epidemiology at Oxford University and one of the chief investigators of the RECOVERY trial, which showed that dexamethasone was an effective treatment for COVD-19 and that hydroxychloroquine was not.

RECOVERY was unusual in that it tested several different therapies and had an adaptive design, so new drug candidates could be added to the protocol as needed. It also used a digital approach to patient recruitment, informed consent and randomisation, and enrolled tens of thousands of patients.

Now, that ‘smart trial’ approach will be used to find therapies for a host of other diseases, including common chronic conditions like heart and lung disease, arthritis, depression and dementia, according to Landray.

Sir Martin Landray

He told the BBC today that without a trial like RECOVERY it would not have been possible to establish the value of dexamethasone – an immune-suppressing steroid that some argued might actually be harmful to administer to COVID-19 patients.

“The pandemic isn’t special,” he said. “We have many common conditions that cause ill health for individual patients and real tress on health systems – heart disease, cancer, depression, dementia and so on – and we need better treatment for those conditions too.”

Those trials also need to be large, involve a diverse range of individuals, and able to be run at reduced cost, said Landray.

Protas will design and run smart clinical trials through collaborations with charities, foundations, academic research teams and industry partners, and will take on both repurposed and experimental drugs.

“The cost of developing a new drug is extortionately high,” said Landray, adding that a very large proportion of those costs is in phase 3, and that means many promising therapies may never be taken forward by pharma companies.

In fact, the economics for developing new treatments for chronic diseases is so challenging that fewer therapies are being developed for the conditions that place the greatest burden on patients and the health systems which care for them.

“It’s not about making money from the trials, it’s about driving public health benefit,” he told the BBC.

Sanofi’s chief medical officer Dietmar Berger said that the collaboration will give the company a way to significantly reduce the cost of some of its trials, and to focus on what matters the most for patients, doctors, regulators and payers.

“Protas offers a unique opportunity to anchor clinical research at the heart of patient care across the NHS, making participation as easy as possible and ensuring all health and care staff feel empowered to support research,” he added.

Protas will be building its organisation, technology and collaborations throughout 2022 and said it expects to begin designing its first clinical trials in 2023.

https://pharmaphorum.com/news/team-behind-recovery-trial-of-covid-drugs-casts-its-net-wider/