Dilemma for Biden in naming permanent FDA chief

 Dr Janet Woodcock would at first seem like a safe pair of hands as the new chief of the FDA, an insider who has been part of the organisation since the eighties.

She is already in charge temporarily after Trump appointee Stephen Hahn stepped down, as is the custom following a change of leadership at the White House.

But Woodcock has barely been in post for three weeks and there is already strong opposition against her taking the role on a permanent basis.

There is a fierce lobbying campaign against her appointment because of the stances she took during the ongoing debate about availability of opioid painkillers in the US.

In a letter to the Biden administration 28 groups accused Woodcock of presiding over “one of the worst regulatory agency failures in US history”, because of the number of opioid drugs allowed on the market while Woodcock was involved with the Center for Drug Evaluation and Research (CDER).

Dr Janet Woodcock

Woodcock began working for CDER in 1994, the year before the controversial opioid Oxycontin (oxycodone) from Purdue Pharma was approved.

The FDA did go on to add warning labels in the following years and eventually decided to require a class-wide monitoring programme, with training for doctors.

But that was in 2012 and although the FDA has taken several steps to tighten regulation on opioids, they remain on the market with addiction still a major problem in the US.

The most embarrassing episode for the FDA came in 2017 when it requested that Endo Pharmaceuticals remove the opioid painkiller Opana ER – an extended release formulation of oxymorphone hydroxychloride – from the market.

It turned out that the drug could be too easily abused and turned into an illegal injection and had been linked to serious outbreaks of HIV and hepatitis C in groups of users.

During that period the FDA also approved Zogenix’s opioid Zohydro ER (hydrocodone) even though its own expert advisers voted against it.

Dr Raeford Brown, an anaesthesiologist who chaired the FDA’s Anesthetic and Analgesic Drug Products Advisory Committee began to publicly oppose Woodcock and called for her to resign from her position as CDER chief in 2018 because of her handling of the issue.

The FDA has developed in line with the life sciences industry during Woodcock’s time and has kept pace with development of innovations such as cancer cell therapies, biosimilars and digital therapeutics.

But with the interim post seen as an audition for the permanent role, things have not got off to a good start for Woodcock.

So who else could be in the frame for the permanent position?

Abernethy the newcomer

According to insiders cited by Politico, one option being considered is principal deputy commissioner of Food and Drugs Amy Abernethy.

The FDA’s website says that Abernethy helps oversee the agency’s day-to-day functioning and directs high-priority initiatives overseeing the agency’s regulation of drugs, medical devices, tobacco and food.

Abernethy only joined the agency in 2019 and although she clearly has some fresh ideas about how the FDA could be run, she lacks Woodcock’s experience in the organisation.

Abernethy has avoided being dragged into the opioid controversy as she is a fairly recent appointment and has instead been focused on technical projects.

One high-profile project has been the use of real-world data during the approval of COVID-19 vaccines, something that she discussed in an emailed interview with pharmaphorum earlier in the pandemic.

In the email, Abernethy said that the FDA has been looking to use a system called Sentinel to develop new ways to assess the safety of approved medical products such as drugs, vaccines and medical devices.

Real-world data could also be used to develop strategies to prepare for the next public health emergency, said Abernethy, who has overseen the agency’s switch to a cloud-based data storage system.

Abernethy only joined the agency in 2019 and although she clearly has some fresh ideas about how the FDA could be run, she lacks Woodcock’s experience in the organisation.

A medical scholar and expert, Abernethy is a former president of President of the American Academy of Hospice and Palliative Medicine after training as a haematologist/oncologist at Duke University.

Immediately before she took her job at the FDA, Abernethy worked for the electronic health records firm Flatiron Health, which was bought by Roche in 2018.

Sharfstein in the running?

Another contender tipped for the permanent job is Joshua Sharfstein, vice dean for public health practice and community engagement at Johns Hopkins School of Public Health.

He’s been closely linked to the full time job since Biden was sworn in and formerly worked as principal deputy commissioner of the FDA from 2009 until 2011.

Sharfstein also has close links with Biden after serving as leader of the Obama transition team on the FDA and was touted as potential FDA commissioner at that time.

Whoever is appointed will need strong leadership and decision making in the difficult few months ahead as the US healthcare system continues to struggle against the pandemic.

https://pharmaphorum.com/views-and-analysis/dilemma-for-biden-as-woodcocks-audition-for-fda-chief-stumbles/

The outlook for complex robotic surgery

 Zimmer’s decision to restructure will create a new competitor in robotic surgery. While Zimmer's move concerns orthopaedic procedures, it is also worth looking at the market for the larger, more complex general surgery robots. This too will see big changes in the coming year, with Medtronic’s modular Hugo system expected to make its market debut. Two companies, CMR Surgical and Avatera Medical, sell their machines in Europe but not yet in the US, though CMR’s Versius could make the leap this year. Johnson & Johnson’s Ottava, announced with much fanfare in November, remains some way behind the competition. So far, however, only two companies contest the US market: Intuitive Surgical, whose 2020 revenues topped $2.4bn, and Transenterix, which is to report its 2020 sales in the coming weeks that might reach $2.4m.

Selected major surgical robots
Company	Robot	Status	Source
Intuitive Surgical	Da Vinci Xi	FDA-approved Apr 2014	In-house R&D
	Da Vinci X	FDA-cleared May 2017
	Da Vinci SP	FDA-cleared April 2014
Transenterix	Senhance	FDA-cleared Oct 2017	$100m acq of surgical robotics division of Sofar in 2015
Avatera Medical	Avatera	CE marked Nov 2019	In-house R&D
CMR Surgical	Versius	US approval poss 2021	In-house R&D
Medtronic	Hugo	Filing expected in 2021	In-house R&D
Johnson & Johnson	Ottava	US approval poss 2024	Verb Surgical acq in 2019
Source: EvaluateMedtech, company websites. https://www.evaluate.com/vantage/articles/news/snippets/outlook-complex-robotic-surgery

Zimmer ditches slow-growing business to refocus

 Zimmer Biomet has had a pretty tragic year. Deferrals and cancellations of the elective orthopaedic procedures in which its products tend to be used meant that its 2020 sales came in at just $7bn – nearly $1bn below 2019's number. 

With Covid-19 vaccines beginning to roll out, 2021 and the years beyond ought to be rosier for the company. But Zimmer is helping the recovery process along by spinning out its slow-growing spinal and dental businesses, allowing it to sharpen its focus on hip and knee implants, which are seeing greater demand. Zimmer’s Rosa range of surgical robots is also expected to provide a boost in the months to come – though it appears that one of these will also be spun out.

In common with all the ortho specialists, Zimmer had a poor first quarter and a dreadful second (Orthopaedics companies’ nightmare quarter, August 25, 2020). A brief return to the sun in the form of 2% third-quarter sales growth was followed by another dip in 2020’s last period as another wave of Covid-19 infections swept the globe. Zimmer recorded a 12% sales slide and a net loss of $137m across all of last year.

Zimmer Biomet's dismal year
Period	Sales ($bn)	Change YoY	Profit/(loss) ($m)
Q1 2020	1.8	(10%)	(509)
Q2 2020	1.2	(38%)	(208)
Q3 2020	1.9	2%	246
Q4 2020	2.1	(2%)	334
Full year 2020	7.0	(12%)	(137)
Source: EvaluateMedTech & company releases.

Thanks to the advent of vaccines the fight back against the pandemic is under way, and Zimmer expects to see a recovery in the summer; if elective procedures are given the go-ahead by hospitals, the backlog of untreated patients could give sales a bump. 

Bone structure

But any potential recovery will not be enough long term, the company seems to have decided. By 2022 it is to divest its dental and spine businesses into an independent, publicly traded company, the idea being that the sharper focus of both companies will allow faster growth and more targeted business development activities, including tuck-in acquisitions. 

Zimmer’s dental, spine, craniomaxillofacial and thoracic business unit had sales of just over $1bn in 2020, though this represented a 10% fall. Craniomaxillofacial and thoracic will be staying with Zimmer. 

The decision has “clear positive implications for both growth and margins”, Stifel analysts wrote, and could accelerate Zimmer’s plan to achieve 4-5% topline growth and 30% operating margins by 2030. 

There are also implications for Zimmer’s involvement in the robotics arena. Its Rosa Knee machine was one of the stars of the fourth quarter, with 115 placements; over the entire year sales of the system topped $100m. The system is used for total knee replacement, and competes with similar offerings from Smith & Nephew and Stryker, as well as Johnson & Johnson, whose Velys system was launched last month. 

Future Rosa applications for hip and partial knee replacements are expected to come in 2021. According to Zimmer’s chief executive, Bryan Hanson, the launch of Rosa Hip will allow the group to grow faster than the rest of the hip market.

Selected surgical robots for orthopaedic and other procedures
Company	Robot	Purpose	FDA clearance	Source
Hip and knee
Stryker	Mako	Hip and knee replacement	Feb 2010	$1.7m Mako acq in 2013
Smith & Nephew	Navio	Knee replacement	Jul 2014	$275m Blue Belt acq in 2015
Zimmer Biomet	Rosa Knee	Total knee replacement	Jan 2019	$78m Medtech acq in 2018
Johnson & Johnson	Velys	Knee replacement	Jan 2021	Orthotaxy acq in 2018
Zimmer Biomet	Rosa Knee	Partial knee replacement	Poss 2021	$78m Medtech acq in 2019
Zimmer Biomet	Rosa Hip	Hip replacement	Poss 2021	$78m Medtech acq in 2020
Spine
Globus Medical	Excelsius GPS	Spine surgery	Aug 2017	Excelsius Surgical acq in 2014
Medtronic	Mazor X Stealth	Spine surgery	Nov 2018	$1.6bn Mazor acq in 2018
Zimmer Biomet	Rosa One Spine*	Spine surgery	Mar 2019	$78m Medtech acq in 2016
Johnson & Johnson	Velys	Spine surgery	Poss 2023	Orthotaxy acq in 2018
Other
Siemens Healthineers	CorPath GRX	Vascular interventions	Oct 2016	$1.1bn Corindus acq in 2019
Johnson & Johnson	Monarch	Bronchoscopy	Mar 2018	$3.4m Auris acq in 2019
Zimmer Biomet	Rosa One Brain	Neurosurgery	Feb 2019	$78m Medtech acq in 2017
*Will be spun out from Zimmer as part of new company. Source: EvaluateMedtech & company websites.

Two other versions of Rosa are on the market. The one used for spinal surgeries will become part of the spin-off company, whereas the neurology one will stay with Zimmer. 

J&J is also planning additional indications for its Velys robot. Currently this may be used by surgeons to plan and perform knee replacements, but J&J hopes to expand into hip, shoulder, trauma, spine and cranial maxillofacial procedures in future, putting it on a similar footing to Zimmer’s Rosa franchise. 

Leerink analysts believe that Velys’s approval for spinal use could be two years away. By that time the Zimmer spinout will be concluded, that new group, along with Medtronic and Globus Medical, will be J&J’s competition. 

https://www.evaluate.com/vantage/articles/news/corporate-strategy/zimmer-ditches-slow-growing-business-refocus

EU finalizes second deal with Pfizer for 300 million vaccine doses

 The European Union has finalised a deal with Pfizer and BioNTech for the supply of an additional 300 million doses of their COVID-19 vaccine, a European Commission spokesman told Reuters on Monday.

The EU secured 300 million Pfizer doses in November last year and announced a preliminary deal for 300 million more shots on Jan. 8, subject to talks about the terms of the new contract.

“The Commission has adopted the new contract today,” the spokesman said.

An official involved in talks with Pfizer said that under the new deal, EU states have already placed orders for 200 million doses to be delivered this year while talks about the timeline for the other 100 million shots were still underway.

“Discussions with the European Commission are ongoing,” a spokesman for Pfizer told Reuters on Monday. A spokesman for BioNTech declined to comment.

The EU’s executive has been heavily criticised over the last few weeks after vaccines suppliers, including Pfizer, announced delays in deliveries for the first three months of the year.

https://www.reuters.com/article/us-health-coronavirus-eu-pfizer/eu-finalises-second-deal-with-pfizer-for-300-million-vaccine-doses-idUSKBN2A8231

AstraZeneca vax has major role to play: South Africa trial lead

 The lead investigator on the South African trial of AstraZeneca’s vaccine said he believed it had a major role to play in Africa and globally, despite data showing the vaccine offered minimal protection against mild-to-moderate COVID-19 disease caused by the country’s dominant virus variant.

Shabir Madhi from the University of the Witwatersrand in Johannesburg told Reuters he would begin rolling out the 1 million AstraZeneca doses already in the country immediately, since they expire in April and it would be reckless to waste them.

“It doesn’t make any sense to have 1 million doses of vaccine available to us which are known to be safe and to not start distributing it at least for high-risk groups,” Madhi said in an interview.

South African health officials said on Sunday they were putting AstraZeneca vaccinations on hold temporarily while they sought scientific advice on how to proceed. Vaccinations had been due to start soon, after the first vaccine doses arrived by plane from India last week.

The country, which has recorded the most coronavirus infections on the African continent and over 46,000 deaths, aims to vaccinate 40 million people, or two-thirds of its population to reach some level of herd immunity.

Madhi said it was likely the AstraZeneca shot would protect against severe COVID-19, since it was developed using a similar technology to the Johnson & Johnson vaccine, which has been shown to be effective in preventing severe COVID-19.

South Africa needed to recalibrate its expectations about vaccines this week after the trial showing reduced efficacy against mild-to-moderate illness caused by the more contagious 501Y.V2 variant, as well as to decide which groups to target and to start rolling out doses next week, he said.

“To start turning your back on a vaccine that could potentially save lives, I couldn’t understand the logic behind it,” Madhi said.

He said he would use the AstraZeneca vaccine to start protecting South Africa’s elderly and those with co-morbidities.

The country’s initial vaccination plan was to meant to start with health workers, but Madhi said the majority of the illness that was likely to occur among that group was mild-to-moderate infection and so the AstraZeneca jab would be better deployed on those at greater risk of severe illness.

https://www.reuters.com/article/us-health-coronavirus-safrica-astrazenec/astrazeneca-vaccine-has-major-role-to-play-south-africa-trial-lead-says-idUSKBN2A821A

What Goes Missing in the Rush to Virtual Care?

 Healthcare providers have aggressively climbed onto the virtual care bandwagon since last March, conducting half or more of their patient visits by phone or computer. From mid-March to mid-October, nearly 40% of Medicare beneficiaries received a covered telemedicine service.

Now, with barely a year's worth of experience and few studies to rate outcomes, researchers are asking if virtual care standards -- whatever they are -- and patient access to telehealth platforms are good enough. The question will be particularly relevant if payers continue reimbursing at in-person visit rates after the pandemic subsides, as the Centers for Medicare & Medicaid Services (CMS) said it was considering in August.

In addition, it is of concern that overuse, waste and, yes, perhaps fraud, as well as poor computer access and low rates of Zoom-savvy patients, may lead to inaccurate or missed diagnoses, and ultimately, much poorer care.

These are topics addressed in four articles published in JAMA, whose authors wonder if and how parity payment policies should continue in the absence of comparative effectiveness studies that confirm virtual care benefits outweigh its harms, and in which settings.

Yes, there are obvious efficiencies, especially in behavioral health or in refilling prescriptions.

But "there is limited high-quality evidence that virtual primary care does not harm patients, such as through misdiagnosis, and achieves the same or better clinical outcomes as traditional care," wrote Kurt R. Herzer, MD, PhD, of Johns Hopkins School of Medicine in Baltimore, and Peter Pronovost, MD, PhD, of Case Western University School of Medicine in Cleveland, in a JAMA Viewpoint.

And what about checking blood pressure or cholesterol? It's much tougher in a virtual encounter, they noted. Could a lot of dangerous hypertension conditions get missed?

There also has been limited discussion dealing with "the principles that should inform its [virtual care] development and assimilation into the U.S. health care system," Herzer and Pronovost wrote.

There could be overuse as well, with unnecessary ordering of tests among providers concerned they might miss something because they can't see or examine the patient's full body. Ordering tests might "mitigate liability concerns around misdiagnosis given the lack of established practice norms and standards of care in the virtual setting," they noted.

Cheap 'Virtual Only' Plans

There is reason to be wary of market evolution, as now some health insurers "are selling plans in 2021 offering lower premiums and minimal or no cost sharing for virtual primary care compared with traditional care." Is it possible that patients who are lured to these plans by lower costs get inappropriate care? There's no opportunity for them to evaluate that before signing up, Herzer and Pronovost said.

In a JAMA research letter, investigators funded by the California Health Care Foundation found a different issue. After the pandemic subsides, payment policies may revert to reimbursement for video visits only, disqualifying audio-only visits, the sole way many low-income and senior patients have been able to access telehealth.

That would be cause for concern, said Lori Uscher-Pines, PhD, of the RAND Corporation in Arlington, Virginia, and colleagues, who studied access to care in 41 federally qualified health centers at 534 locations in California. Her group compared the year before the pandemic to the period from March to August 2020.

While there was minimal telehealth use prior to COVID-19, during the pandemic period studied, a worrisome 48.5% of primary care visits were by phone alone, 48.1% were in person, and only 3.4% were by video. If reimbursement for audio-only care were to be cut off -- as CMS has said it may do when the public health emergency ends -- many patients would be left stranded, Uscher-Pines said.

Low Computer Literacy

"Right now, our data show that many patients aren't ready for video telehealth. So limiting telehealth to only video telehealth would leave certain patients behind," Uscher-Pines told MedPage Today in an interview.

"Our goal should be to get all patients prepared for video telehealth visits and narrow the digital divide as best we can with the intention of moving exclusively to video visits in the future," she added.

How to pay for telemedicine after the pandemic was the topic of a second JAMA Viewpoint by Ateev Mehrotra, MD, of Harvard Medical School in Boston, and colleagues, who looked at international implications.

While there are clear benefits with improved access for patients in rural or underserved areas, by reducing no-show rates, travel time, or need to take off time from work, there could be underlying incentives for overuse. "Clinicians may schedule frequent but shorter phone visits that may not improve outcomes, but do increase government spending," they wrote.

They suggest limiting telehealth coverage to certain populations, certain conditions, and certain telehealth modalities. And many questions remain unanswered. For example, in December 2020, Congress expanded telemedicine coverage for mental health conditions based on "the assumption" that the result would be of higher value. "However, in many cases there is no evidence, which means the decision may be based on estimated clinical use," Mehrotra's group wrote.

The authors also note the concern "that clinicians will choose between a telemedicine and in-person visit based on their relative reimbursement." If telehealth is reimbursed at a lower rate, clinicians may choose an in-person visit over a telehealth one.

"The counterargument is that governments should pay less for telemedicine visits to deter overuse," they added.

The Need for Virtual Empathy

In an accompanying editorial, Donna Zulman, MD, and Abraham Verghese, MD, both of Stanford University School of Medicine in California, noted a third element that policy makers should take into account: how to reinforce the human connection in a virtual visit.

"The shift in care from in-person to virtual encounters risks jeopardizing the human interaction that is pivotal to effective clinical care and is deeply meaningful to both patients and clinicians," they wrote. Little is known about what happens when physical presence is removed from the clinical encounter.

What's needed are non-verbal communication tools clinicians can use, "such as sitting up and leaning forward, using heightened facial expressions and head gestures, and optimizing eye contact by gazing into the web camera."

In the absence of visually noting "emotional cues such as a patient's closed body posture, nervous toe-tapping, or wringing hands," clinicians need to pay attention to a patient's tone and volume, and use gestures, such as putting a hand over the heart to convey emotion and empathy.

Primary Source

JAMA

Source Reference: Herzer KR, Pronovost PJ "Ensuring quality in the era of virtual care" JAMA 2021; DOI: 10.1001/jama.2020.24955.

Secondary Source

JAMA

Source Reference: Uscher-Pines L, et al "Telehealth use among safety-net organizations in California during the COVID-19 pandemic" JAMA 2021; DOI: 10.1001/jama.2021.0282.

Additional Source

JAMA

Source Reference: Mehrotra A, et al "Paying for telemedicine after the pandemic" JAMA 2021; DOI: 10.1001/jama.2020.25706.

Additional Source

JAMA

Source Reference: Zulman DM, Verghese A “Virtual care, telemedicine visits, and real connection in the era of COVID-19: unforeseen opportunity in the face of adversity” JAMA 2021; DOI: 10.1001/jama.2020.27304.

https://www.medpagetoday.com/practicemanagement/telehealth/91085

Should Prediabetes Management Be Low Priority in Older Adults?

 While prevalence of prediabetes was high among elderly patients in a cohort study, the proportion of individuals actually progressing to diabetes was low, a finding with important clinical implications, according to the researchers.

In patients ages 70 to 90 with prediabetes, regression to normoglycemia or death was more common than developing diabetes, reported Mary Rooney, PhD, of Johns Hopkins Bloomberg School of Public Health in Baltimore, and colleagues.

As shown in the team's study online in JAMA Internal Medicine, of the 3,412 older adults included, 44% had prediabetes at baseline as defined by elevated glycated hemoglobin (HbA1c), 59% had prediabetes as defined by impaired fasting glucose, and 29% had both of those conditions at baseline.

After more than 6 years of follow-up, however, only 9% of those with elevated HbA1c progressed to diabetes, while 13% improved to normoglycemia and 19% died. Of those with impaired fasting glucose, 8% progressed to diabetes, 44% reverted to normoglycemia, and 16% died.

"The current study is one of the first to document progression of prediabetes to diabetes in older adults in a community-based setting," the researchers wrote. "The construct of prediabetes is used to identify those individuals at high risk for developing diabetes in the future. In this older population, few individuals who met the definitions of prediabetes progressed to diabetes."

The results suggest prediabetes in older adults need not be treated aggressively, the investigators added. "The findings of the current study support a focus on lifestyle improvement when feasible and safe, especially given the broader benefits of lifestyle modification beyond diabetes prevention. Given the low risk of diabetes progression in this study (especially relative to mortality risk), it is unlikely that pharmacologic intervention or other aggressive approaches to diabetes prevention in older age will provide large benefits and could have unintended harmful effects (e.g., overdiagnosis, anxiety, and implications for insurance coverage)."

In a commentary accompanying the study, Kenneth Lam, MD, and Sei Lee, MD, both of the University of California San Francisco, agreed with that conclusion, writing: "The results of Rooney et al. suggest that the concept of prediabetes may be of limited importance for older adults."

Diabetes was an acute, symptomatic, and invariably fatal disease when originally described, but it has become an asymptomatic chronic condition due to early detection and the widespread availability of effective treatment, the commentary explained. For most patients, it is the end-organ vascular complications that result from years of poorly controlled diabetes that cause symptoms.

"Therefore, the modern definition of diabetes is conceptually closer to being a risk factor itself (e.g., something that portends future disease) than an illness (e.g., something that patients experience)," Lam and Lee said. "Prediabetes, then, is a risk factor twice removed; it is a risk factor for diabetes, which itself may be most accurately described as a risk factor for end-organ vascular disease."

They suggested that current guidelines, which recommend that all patients with prediabetes be monitored annually for the development of type 2 diabetes and referred to prevention programs, may need to be modified in light of this new evidence.

"Guidelines should clarify that prediabetes is a concept that should be reserved for healthier, middle-aged adults rather than older adults with frailty," and in middle-aged adults, pre-diabetes is associated with a 20-fold increase in diabetes risk, Lam and Lee said.

They added that in terms of more specific clinical implications of the study, "first, in older adults with frailty and limited life expectancy, prediabetes is irrelevant and can safely be ignored. Second, in healthy adults older than 75 years (the mean age of the study participants), we should recognize that prediabetes, as a risk factor twice removed, should be lower priority than symptomatic conditions (which are affecting patients immediately) or traditional risk factors."

For the study, Rooney and co-authors evaluated participants from the Atherosclerosis Risk in Communities cohort. These individuals had a mean age of 75, 60% were female, and 17% were Black. Participants were ages 45 to 64 when the study began in 1987-89 and ages 70 to 91 at the baseline of the current prediabetes study, which began in 2011-13.

During 6.5 years of follow up, participants attended periodic clinical visits. Health and mortality information was also gathered through semi-annual follow-up telephone calls, state records, and the National Death Index linkage. Prediabetes was defined as an HbA1c level of 5.7% to 6.4% or a fasting glucose level of 100-125 mg/dL. Incident diabetes was defined by a physician diagnosis, the use of glucose-lowering medication, an HbA1c level of 6.5% or higher, or a fasting glucose level of 126 mg/dL or higher.

A chief limitation of the study was that a substantial proportion of patients (27%) were lost to follow-up, the researchers said. "However, in a sensitivity analysis that accounted for study attrition, the results were not appreciably different."

Last Updated February 08, 2021

Disclosures

The study was supported by the National Heart, Lung, and Blood Institute and the National Institute of Diabetes and Digestive and Kidney Diseases.

Rooney reported no conflicts of interest.

Lam and Lee reported no conflicts of interest.

Primary Source

JAMA Internal Medicine

Source Reference: Rooney MR, et al "Risk of progression to diabetes among older adults with prediabetes" JAMA Intern Med 2021; DOI:10.1001/jamainternmed.2020.8774.

Secondary Source

JAMA Internal Medicine

Source Reference: Lam K, Lee SJ "Prediabetes -- a risk factor twice removed" JAMA Intern Med 2021; DOI:10.1001/jamainternmed.2020.8773.

https://www.medpagetoday.com/endocrinology/diabetes/91099