New Insight with Dr. Veeral Sheth

Diabetes Dialogue

Don’t Miss a Beat

Crisis Point

Tim Smith joined the MJH Life Sciences team as an assistant editor for HCPLive in August 2022. He graduated from UC Berkeley with a degree in political science, working in multimedia journalism as a staff writer prior to joining MJH. In his spare time, he enjoys reading, watching TV, listening to podcasts, and rock climbing. You can contact him at 

 editorial team, Carolyn J. Crandall, MD, MS, MACP, spoke on takeaways from her presentation ‘More News You Can Use: Current Clinical Guidelines in COVID-19 and Type 2 Diabetes.’ Over the course of the interview, Crandall highlighted several important elements of this talk

Crandall serves as professor of medicine at the David Geffen School of Medicine at UCLA and as chair of the 

 clinical guidelines committee. In this interview, she highlighted updates to guidelines related to type 2 diabetes treatment.

 What were the key updates or changes in clinical guidelines that you described for managing type 2 diabetes highlighted in your presentation to clinicians at the ACP Meeting?

 This guideline addressed the newer pharmacological agents that are available to treat Type 2 Diabetes. The ACP recommends adding a sodium-glucose cotransporter-2 (SGLT-2) inhibitor or glucagon-like peptide-1 (GLP-1) agonist to metformin and lifestyle modifications in adults with type 2 diabetes and inadequate glycemic control.

We recommend using an SGLT-2 inhibitor to reduce risk for all-cause mortality, major adverse cardiovascular events, progression of chronic kidney disease, and hospitalization due to congestive heart failure. We recommend using a GLP-1 agonist to reduce the risk of all-cause mortality, major adverse cardiovascular events, and stroke.

ACP recommends against adding a dipeptidyl peptidase-4 (DPP-4) inhibitor to metformin and lifestyle modifications in adults with type 2 diabetes and inadequate glycemic control to reduce morbidity and all-cause mortality.

In your view, how have the ACP guidelines evolved over time with regard to this particular topic?

This new guideline is the first ACP guideline to evaluate these newer drugs: SGLT-2 inhibitors, GLP-2 agonists, long-acting insulin, tirzepatide, and DPP-4 inhibitors.

What do you hope healthcare professionals viewing your talk remember most from your presentation regarding type 2 diabetes management?

It is important to go beyond glycemic control (that is, values of hemoglobin A1C) to evaluate the net clinical benefits of these newer treatments. Our guidelines carefully evaluated the effects of these medications on high-priority, important clinical outcomes, such as risk of death, major adverse cardiovascular events, progression of chronic kidney disease, hospitalization due to congestive heart failure, and stroke.

I believe this is a great strength of this guideline, as these are the important outcomes that persons with diabetes, and their physicians, deserve to know about. These important clinical outcomes, going beyond achieving the optimal level of hemoglobin A1C, are the outcomes that can really inform optimal decisions about diabetes drug therapy in persons whose diabetes is inadequately controlled despite metformin and lifestyle measures.

For further details on interviews with experts featured as presenters at the ACP conference, view the 

Articles

During this Q&A interview, Crandall discussed the takeaways from her portion of an ACP conference presentation on current clinical guidelines in type 2 diabetes.


Type 2 Diabetes

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Carolyn J. Crandall, MD: Key Guideline Updates for Type 2 Diabetes

Inouye discussed some of the major reasons for her presentation titled ‘Delirium During Hospitalization.’

Discussing Delirium During Hospitalization with Sharon K. Inouye, MD, MPH

 as well as individuals dealing with intense illness while hospitalized may end up suffering from delirium due to their state at the time. This has been known to frequently occur for patients who are in the intensive care unit (ICU) of a hospital.

In a new interview, conducted on site at the 2024 

American College of Physicians (ACP) Internal Medicine Meeting

 in Boston, Sharon K. Inouye, MD, MPH, MACP, spoke with the 

 editorial team on this topic, detailing the major takeaways from her presentation titled ‘Delirium During Hospitalization.’

Initially, Inouye was asked about the motivation behind her decision to pursue the topic as a conference presentation. She cited her background in geriatric medicine and several early experiences.

“I am a geriatrician, which is a physician in internal medicine who specializes in geriatric medicine, or the care of older adults,” she explained. “I got very interested in delirium, actually, when I began my career in internal medicine. So when I just finished my training, and on my very first clinical rotation as an attending…I began to see all these cases of older adults who got very confused during their hospital stay.”

Inouye explained that when she had inquired about this to the more experienced clinicians and her chief of staff, they essentially brushed it aside.

“Still, when I ask trainees in internal medicine ‘what did you learn about delirium during your training’ they'll say, ‘Oh, we got one lecture, in certain rooms, it was on psychiatry or neurology’ and it wasn't even in internal medicine,” Inouye said. “So it's not something that's heavily dwelt upon. I know it occurs in somewhere between 30 - 50% of older adults during the course of hospitalization. If you just think about that number, it's just massive.”

Inouye highlighted 6 specific cases during her presentation on delirium to illustrate her points over the course of the talk.

“When I talked about those 6 cases that I had, my first six cases, those outcomes are kind of representative of what happens to older adults who become delirious,” Inouye said. “They wind up going to the ICU, they have a high mortality rate. If they do survive the hospitalization, they wind up needing long term care, a lot of rehabilitation, a lot of homecare services. The long road to recovery. I think you can tell from the fact that it's very expensive for our healthcare system and many, millions to even billions are spent in excess health care costs worldwide, on the problem of delirium.”

For any additional information from this 

 discussion, view the full interview segment above.

The quotes contained in this interview were edited for the purposes of clarity.

Videos

In this interview at the ACP conference, Inouye discussed some of the major reasons for her presentation titled ‘Delirium During Hospitalization.’

Lana Pine is the editor of HCPLive Rheumatology. She is an experienced editor and technical writer with a demonstrated history of working in the banking and publishing industries. In her free time, she enjoys cooking, yoga, listening to podcasts, and drawing. She can be reached via email at LPine@mjhlifesciences.com.

A Canadian study examined how serologic responses to COVID-19 vaccination and infection are affected by time since last vaccination, among other factors, in a cohort of patients with immune-mediated inflammatory disease (IMID).

Results indicated positive associations for log-transformed Receptor Binding Domain (anti-RBD) titers were linked to the number of doses, self-reported COVID-19 infection, and female sex, while negative associations were seen with prednisone and rituximab use, according to research published in 

Between 2022 and 2023, 4 times as many people in the US were hospitalized for COVID-19 compared with influenza. Currently, the COVID-19 mortality risk is double that of influenza.

 Further, patients with IMID may be unsure about the potential benefits of additional booster vaccinations, and this hesitancy could potentially put these patients at a higher risk for infection.

“Vaccine hesitancy in general is a huge problem, particularly for people with IMID,” wrote a team of investigators led by Dawn Bowdish, PhD, associate professor at McMaster University and a Canada Research Chair in Aging & Immunity. “As the necessity for multiple COVID vaccine doses became clear, social ‘vaccine fatigue’ has caused many individuals to decline additional COVID boosters after the primary series. Since COVID-19 infection is a potentially fatal and vaccine-preventable co-morbidity, it is vital that individuals with IMID have access to relevant information that will help them decide when to get their next COVID vaccination.”

Dried blood spots/sera and other data were obtained from adults with 

 post-vaccination. The first sample was collected at enrollment and again at 2—4 weeks, 3 months, 6 months, and 12 months post-vaccine. The serologic response was determined using multivariate generalized estimating equation regressions, such as medication use, vaccination history, and demographics.

Among the cohort, 64.7% patients were female, the mean age was 53.2 years, and 88.4% were white. The most common inflammatory condition was inflammatory bowel disease followed by RA.

In patients with IMID, positive associations for log-transformed anti-RBD titers were shown in self-reported COVID-19 infections between 2021 and 2023, female sex, and number of vaccinations. Negative associations were demonstrated in patients who received prednisone, rituximab, and tumor necrosis factor (TNF) inhibitors.

Most (94%) anti-nucleocapsid positivity was linked to a self-reported COVID-19 infection within the prior 3 months. Between March 2021 and February 2022, 5—15% of samples exhibited anti-nucleocapsid positivity. This positivity increased to 30—35% or higher in the post-Omicron era (March 2023). The anti-nucleocapsid positivity among patients with IMID was lower when compared with Canada’s general population seroprevalence (> 50% in 2022 and > 75% in 2023.

Negative associations with log-transformed anti-RBD titers were seen in the time since last vaccination, especially after 210 days.

Investigators noted the comprehensive inclusion of factors related to serologic COVID-19 vaccine response among a large cohort of patients with IMID strengthened the study. However, the lack of detailed drug exposure information hindered their ability to determine certain issues, including if a patient received a particular drug in the week prior- or post-vaccination. Additionally, they were unable to evaluate interactions between drugs, IMID type, or vaccination type and its impact on COVID-19 infection.

“Ensuring adequate vaccination against SARS-CoV-2 in IMID can be difficult,” investigators concluded. “If individuals have access to relevant information that will help them decide when to get their next COVID vaccine, they may be more open to receiving additional doses. We believe that our findings will help patients, clinicians, and other stakeholders make personalized vaccination decisions, including consideration of additional doses when more than 6 months has elapsed since last COVID vaccination/infection.”

Bowdish DME, Chandran V, Hitchon CA, et al. When Should I Get My Next COVID Vaccine? Data from the SUrveillance of responses to COVID-19 vaCcines in systEmic immunE mediated inflammatory Diseases (SUCCEED)study. 

. Published online April 15, 2024. doi:10.3899/jrheum.2023-1214

Xie Y, Choi T, Al-Aly Z. Risk of Death in Patients Hospitalized for COVID-19 vs Seasonal Influenza in Fall-Winter 2022-2023. JAMA. 2023 May 16;329:1697-99.

Most (94%) anti-nucleocapsid positivity was linked to a self-reported COVID-19 infection within the prior 3 months. 

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Study Investigates Optimal COVID-19 Vaccination Timing in Inflammatory Disease

Connor Iapoce is an associate editor for 

 and joined the MJH Life Sciences team in April 2021. He graduated from The College of New Jersey with a degree in Journalism and Professional Writing. He enjoys listening to records, going to concerts, and playing with his cat Squish. You can reach him at 

Elna Saah, MD joins HCPLive to discuss the current care landscape in sickle cell disease and new advancements benefiting clinical care. 

Elna Saah, MD: Unraveling the Current Care Landscape in Sickle Cell Disease

 impacts approximately 70,000 to 1000,000 people in the United States, making it the most common form of an inherited blood disorder. The condition is marked by the production of abnormal hemoglobin from birth, with complications of the disease leading to severe pain and other health complications, including infection, acute chest syndrome, and stroke.

, Elna Saah, MD, a hematologist at the Emory University School of Medicine, described the public health concerns stemming from the condition and the importance of screening newborns to make a diagnosis immediately after birth.

“It’s a real big problem, a public health issue because it is progressive and complications continue to evolve as patients get older and older,” Saah told HCPLive. “In adults, there’s a lot of multiple organ involvement, which reduces the lifespan, causes earlier mortality and morbidity, and burdens both the patient and the healthcare system.”

Saah pointed to the variety, and potential disparity, in care resources between pediatric and adult populations with SCD. Children with SCD are typically treated by a general pediatric hematologist-oncologist, not necessarily an SCD specialist.

The care team also includes psychosocial support, including a social worker, psychologist, and teachers, to help manage trauma from the pain, as well as extensive support from advanced practice providers and nurse practitioners. As children reach adulthood, a transition is prepared for them to move from the pediatric side of care to adult providers.

However, according to Saah, the resources for SCD treatment are much more sparse and not as generous in adult care.

“We have fewer and fewer adult hematologists or hematologist oncologists who are willing and able and have the bandwidth to take on SCD patients,” Saah told 

. “We also do not have a lot of supportive resources, including social workers and psychologists or neuropsychologists, to support this progressive disease and the patients end up with chronic pain.”

Saah also touched on the care landscape from the 1970s to the modern day, from early trial data indicating the proficiency of hydroxyurea to recent US Food and Drug Administration (FDA) approvals, including L-glutamine, Crizanlizumab, and Voxelotor. Other recent FDA approvals touched on included two gene therapies for SCD, including exagamglogene autotemcel (exa-cel) and lovotibeglogene autotemcel (lovo-cel) for children aged ≥12 years.

Saah also elaborated on recent data pointing to the unintentional negative effect of the 2016 Centers for Disease Control and Prevention on opioid prescriptions in patients with SCD. The release of the guidelines inadvertently curbed opioid prescribing for patients with SCD and those patients tended to seek hospitalization more frequently for their pain.

“I think we should take these results a bit more guarded, it is difficult to broadly analyze and extrapolate these Medicaid data on any individual patient,” Saah told HCPLive. “While we have seen that to be true in other patients, it behooves us to look for alternative support for long-term opioid and non-opioid prescribing in patients with chronic pain. It is unfortunate some patients did have opioids when they needed to have been withheld from them or delayed.”

Watch the full interview with Saah in the above video.

What is sickle cell disease? Centers for Disease Control and Prevention. July 6, 2023. Accessed April 18, 2024. https://www.cdc.gov/ncbddd/sicklecell/facts.html.

Sickle cell disease. Hematology.org. Accessed April 18, 2024. https://www.hematology.org/education/patients/anemia/sickle-cell-disease.

Treatment. National Heart Lung and Blood Institute. Accessed April 18, 2024. https://www.nhlbi.nih.gov/health/sickle-cell-disease/treatment

Iapoce C. CDC opioid guidelines linked to negative consequences in sickle cell disease. HCP Live. March 12, 2024. Accessed April 18, 2024. https://www.hcplive.com/view/cdc-opioid-guidelines-linked-negative-consequences-sickle-cell-disease.

Elna Saah, MD joins HCPLive to discuss the current landscape in sickle cell disease and recent advancements benefiting clinical care.

Hematology

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Elna Saah, MD: Unraveling the Current Landscape in Sickle Cell Disease

A recent head-to-head cross-sectional study found state-of-the-art large language models (LLMs), including ChatGPT-4, are nearing expert-level clinical knowledge and reasoning in the field of 

In the analysis, GPT-4 fared well with expert ophthalmologists and specialty trainees, achieving a pass-worthy performance on a mock ophthalmological examination. However, as top-performing doctors remained superior in the knowledge examination, LLMs might be most beneficial for eye-related advice or management suggestions.

“We could realistically deploy AI in triaging patients with eye issues to decide which cases are emergencies that need to be seen by a specialist immediately, which can be seen by a general practitioner, and which don’t need treatment,” lead study author Arun J Thirunavukarasu, MB BChir, University of Cambridge school of clinical medicine, explained in a statement.

 “The models could follow clear algorithms already in use, and we’ve found GPT-4 is as good as expert clinicians at processing eye symptoms and signs to answer more complicated questions.”

LLMs have proven revolutionary in natural language processing and their introduction into medicine is the center of a significant discussion around its utility and ethical concerns. In eye care, ChatGPT showed superiority on eye-related questions in an examination for general practitioners and achieved significant improvement over time on ophthalmic knowledge assessments after GPT-3.5 was succeeded by GPT-4.

However, Thirunavukarasu and colleagues suggested these analyses are impacted by the potential for “contamination,” or an inflated performance related to previously recalled text, rather than clinical reasoning.

 In addition, the examination performance does little to indicate the potential of LLMs to improve clinical practice as a medical assistance tool.

For this analysis, investigators used the United Kingdom’s FRCOphth Part 2 examination to evaluate the capability of state-of-the-art LLMs, with fully qualified and current training ophthalmologists serving as a robust clinical benchmark, rather than raw examination scores. As these questions were not fully available online, the risk of contamination was minimized.

Each eligible question was inputted into ChatGPT (GPT-3.5 and GPT-4 versions) between April and May 2023. If the LLM did not provide a definitive answer, the question was re-trialed up to three times and regarded as “null” if no answer was provided. After their release, the PaLM 2 and LLaMA models were trialed on the 90-question examination between June and July 2023.

To evaluate the performance and accuracy of the LLM outputs, five expert ophthalmologists who had passed the examination, three trainees currently in residency, and two unspecialized junior doctors answered the 90-question mock examination, independently, without reference to textbooks, the internet, or the LLMs’ recorded answers.

Ultimately, 347 of 360 questions from the textbook were used for analysis, including 87 of the 90 questions from the mock examination chapter. Overall performance across the 347 questions was significantly higher for GPT-4 than for GPT-3.5 (61.7% vs. 48.41%; 

Performance in the mock examination revealed GPT-4 compared well with other LLMs, junior and trainee doctors, and ophthalmology experts. GPT-4 was the top-scoring model (69%), compared with GPT, performing higher than GPT-23.5 (48%) and LLaMA (32%), but statistically similar to PaLM 2 (56%), despite a superior score.

Moreover, the performance of GPT-4 was statistically similar to the mean score achieved by expert ophthalmologists (

 = .28). Overall, GPT-4 performed favorably to expert ophthalmologists (median, 76%; range, 64–90%), ophthalmology trainees (median, 59%; range, 57–63%), and unspecialized junior doctors (median, 43%; range, 41–44%).

Low agreement between LLMs and doctors indicated idiosyncratic differences in knowledge and reasoning with consistency across subjects and type (

 >.05). LLM knowledge and reasoning ability may be general across ophthalmology, rather than strong for a particular subspecialty or question type.

The LLM examination performance translated to subjective preference, as all ophthalmologists preferred responses from GPT-4. In particular, they rated the accuracy and relevance of GPT-4 higher than GPT-3.5 (

Thirunavukarasu and colleagues noted the remarkable performance of GPT-4 in ophthalmology may provide its usefulness in clinical contexts, particularly in areas without access to ophthalmologists. Its ophthalmic knowledge and reasoning ability are likely superior to non-specialist doctors and could assist clinicians in their day-to-day work.

“Even taking the future use of AI into account, I think doctors will continue to be in charge of patient care,” Thirunavukarasu said.

 “The most important thing is to empower patients to decide whether they want computer systems to be involved or not. That will be an individual decision for each patient to make.”

Thirunavukarasu AJ, Mahmood S, Malem A, et al. Large language models approach expert-level clinical knowledge and reasoning in ophthalmology: A head-to-head cross-sectional study. PLOS Digital Health. April 17, 2024. Accessed April 17, 2024. https://journals.plos.org/digitalhealth/article?id=10.1371%2Fjournal.pdig.0000341

Cambridge_Uni. Artificial intelligence beats doctors in accurately assessing eye problems. EurekAlert! April 17, 2024. Accessed April 17, 2024. https://www.eurekalert.org/news-releases/1040936.

Thirunavukarasu AJ, Hassan R, Mahmood S, et al. Trialling a Large Language Model (ChatGPT) in General Practice With the Applied Knowledge Test: Observational Study Demonstrating Opportunities and Limitations in Primary Care. 

. 2023;9:e46599. Published 2023 Apr 21. doi:10.2196/46599

Mihalache A, Popovic MM, Muni RH. Performance of an Artificial Intelligence Chatbot in Ophthalmic Knowledge Assessment. 

 2023;141(6):589–597. doi:10.1001/jamaophthalmol.2023.1144

Modern large language models perform strongly on ophthalmic knowledge assessments and approach or exceed the scores of fully qualified and trainee ophthalmologists.

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GPT-4 Nears "Expert-Level" Performance in Ophthalmology Examination

Patrick Campbell is the managing editor of HCPLive. Formerly the editorial lead of Endocrinology Network, Practical Cardiology, and Rheumatology Network, Patrick has spent years spearheading coverage surrounding cardiometabolic health and rheumatic disease for MJH Life Sciences. He now helps to lead coverage in each of these respective areas for HCPLive. Before joining MJH Life Sciences in 2019, he spent time as a beat reporter with the Pocono Record in Stroudsburg, PA, and Star News Group in Manasquan, NJ. He also touts experience in multimedia, having spent time as a multimedia specialist with NJ Advance Media and multimedia coordinator at the Pocono Record. Follow him on Twitter @RealPatCampbell or reach him via email at PCampbell@mjhlifesciences.com.

A new analysis of the REDUCE-IT trial reveals the benefits of icosapent ethyl in reducing cardiovascular outcomes regardless of LDL-C levels.

Dyslipidemia

REDUCE-IT Analysis Outlines Benefit of Icosapent Ethyl Across Range of LDL-C Levels

New phase 3 findings show daily oral budesonide reduces eGFR decline while maintaining patient quality of life over 2 years.

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Budesonide Maintains IgA Nephropathy Kidney Failure Reduction, Quality of Life at 2 Years

A propensity score-matched, new-user analysis suggests SGLT2 inhibitors may reduce gout risk in type 2 diabetes patients relative to other second-line therapies.

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SGLT2 Inhibitors Reduce Risk of New Gout Diagnoses in T2D Relative to Sulfonylurea

Results of the SELECT-GCA study demonstrated approximately half of patients with giant cell arteritis treated with upadacitinib plus a steroid tapering regimen were able to achieve sustained remission through week 52.

Phase 3 Upadacitinib Study Achieves Positive Results for the Treatment of Giant Cell Arteritis 

A new study found an intervention targeting proton pump inhibitor overuse was linked to an absolute reduction of 7.3%.

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, IBS and IBD, Crohn's disease, and more.

Pharmacy-Based Intervention Linked to Reduced Proton Pump Inhibitor Overuse

Meta-analysis of 11 phase 3 trials shows SGLT2 inhibitors reduce cardiovascular event risk by 9% across diverse patient populations.

Chronic Kidney Disease

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SMART-C Meta-Analysis: SGLT2 Inhibitors Reduce Cardiovascular Events

Experts discuss the management of dry eye in the presence of concurrent ocular conditions, as well as managing dry eye before undergoing cataract and refractive surgery.

Treating Dry Eye in The Presence of Ocular Comorbidities

Almost 50% of fibromyalgia patients use cannabis for symptom relief, according to new study. Experts suggest results underline need for clinician awareness, further research.

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Survey Finds Many Fibromyalgia Patients Finding Symptom Relief with Medical Cannabis

A recent study found Black individuals had a sharp increase in midlife deaths from suicide, drug overdose, and alcoholic liver disease after 2015.

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2022 Spike in “Deaths of Despair” Among Black Population Surpasses White People

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The modified difference-in-differences analysis found notable increases in DAA use after state Medicaid programs relaxed certain coverage restrictions.

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Latest News

Carolyn J. Crandall, MD: Key Guideline Updates for Type 2 Diabetes

Discussing Delirium During Hospitalization with Sharon K. Inouye, MD, MPH

Study Investigates Optimal COVID-19 Vaccination Timing in Inflammatory Disease

Elna Saah, MD: Unraveling the Current Landscape in Sickle Cell Disease

GPT-4 Nears "Expert-Level" Performance in Ophthalmology Examination