Dr. Castro and Dr. Rizzo discuss the evolving world of monoclonal antibodies for severe asthma. Plus, the ALA team discusses September's annual Asthma Peak Week, and what it means for reopening schools.

ALA Discusses Severe Asthma Biologics with Mario Castro, MD, MPH

Listen to an expert discuss the heterogenous, and potentially fatal, lysosomal storage disorder.

The Rare Disease Report Podcast: Niemann-Pick Disease

On this episode of Coping After COVID, Dr. Craig Chepke discusses the challenges for schizophrenia patients.

 Coping After COVID: A Troubling Time for Schizophrenia Patients

The vitiligo expert discusses new tactics and therapeutic options in treating inflammatory skin disorders like vitiligo, alopecia areata, and atopic dermatitis.

John E. Harris, MD, PhD: The Current State of Vitiligo and Alopecia Areata Research

Manesh Patel, MD, kicks off his first podcast by discussing HFpEF findings in EMPEROR-Preserved, the GUIDE-HF trial and more with his Duke colleague.

New Heart Failure Data from ESC 2021 with Marat Fudim, MD

Episode 2 of HCPLive Crisis Point tackles the clinical aspects and potential burdens clinicians face in the pursuit of obesity care.

Burdens of Clinical Care in the Obesity Crisis

Armand Butera is the assistant editor for 

. He attended Fairleigh Dickinson University and graduated with a degree in communications with a concentration in journalism. Prior to graduating, Armand worked as the editor-in-chief of his college newspaper and a radio host for WFDU. He went on to work as a copywriter, freelancer, and human resources assistant before joining 

. In his spare time, he enjoys reading, writing, traveling with his companion and spinning vinyl records. Email him at 

A scoping review from the Stanford School of Medicine found 3 issues in data sets that were used to develop and test clinical artificial intelligence (AI) algorithms for 

The issues pertained to the sparsity of data set characterization and a lack of transparency, nonstandard and unverified disease labels, and inability to fully assess patient diversity used for algorithm development and testing.

The study was led by Roxana Daneshjou, MD, PhD, Stanford Department of Dermatology.

Daneshjou and investigators noted the potential of clinical AI to improve clinical care, but added that generalizable algorithms depended on clinical care that they are tested and trained on.

Over a 5-year period of data, the team performed the scoping review that assessed data set availability and data set descriptions such as labeling and patient diversity in order to better understand the characteristics of data sets used for developing AI algorithms and assess potential problems in dermatology AI sets.

Daneshjou and investigators initially searched PubMed for peer-reviewed articles published between January 1, 2015, and November 1, 2020.

Articles that defined a clinically relevant task and developed a deep learning algorithm or that tested an existing deep learning algorithm using clinical or dermoscopic images of skin disease were included in the study.

Of these studies, 57 developed a new deep learning algorithm and 13 tested an existing algorithm on an additional data set.

A majority of the studies were published in the past 2 years.

Data set audit criteria were determined by consensus of all au- thors after reviewing existing literature to highlight data set transparency and sources of bias, and data set descriptions were based on how data were presented in the study.

The team identified 70 studies that met their criteria.

Among those studies, 57 trained and tested a new algorithm, and only 14 had test data that were from a different source than the training set or an additional external validation.

Additionally, 56 studies included at least 1 cutaneous malignant neoplasm in their task, and 36 (64.3%) met gold standard criteria for histopathological diagnosis. This suggested that a substantial number of studies were trained and/or tested on noisy annotations, which could affect diagnostic accuracy.

Among all studies, only 14 of 70 (20.0%) described any information on the ethnicity or race of patients in at least 1 data set and only 7 of 70 (10.0%) included any information on the Fitzpatrick skin types of images used in at least 1 data set.

Investigators noted that data on the prevalence of Fitzpatrick skin types in the US population were inadequate.

They also recorded a lack of clear labeling in many studies. They estimated that of a total 1,065,291 images, only 257,372 (24.2%) were publicly available or available on request, whereas 807,919 (75.8%) were private.

Most of the AI literature addressing skin conditions was developed from private data sets used once to generate a single study, with no ability for replication, which greatly limited their effect and generalizability.

Across all the studies, models were generally not accessible, with only 21 of the 70 studies (30.0%) stating that the model was available via request or through a commercial product.

Based off their findings, investigators had 3 recommendations improving transparency and reducing the potential for bias in developed clinical algorithms, the first of which dealt with the sharing of data sets and/or models at the time of publication.

The second recommendation suggested a clear description of important data set characteristics, which include patient populations, skin tones represented, and the image labeling process, if data could not be shared. Lastly, a clear description of how data sets were used for training, validation, testing, or additional external validation was also suggested.

“Developing clinically applicable deep learning models in medicine is predicated on the creation of robust models developed from data sets that are either publicly available for scrutiny or well described,” the team wrote. “Clinical AI must be held to a high standard owing to the potential for significant medical harm from errors and bias.”

“Lack of Transparency and Potential Bias

in Artificial Intelligence Data Sets and Algorithms A Scoping Review,”

 was published online in JAMA Dermatology.

Articles

Acknowledging the potential medical harm from errors and bias, investigators believe clinical AI needs to be held to a higher standard.

News

news page, resources on the topics of disease- and specialty-specific medical news and expert insight can be found. Content includes articles, interviews, videos, podcasts, and breaking news on health care research, treatment, and drug development.

Atopic Dermatitis

Atopic Dermatitis condition center page, resources on the topics of medical news and expert insight into eczema can be found. Content includes articles, interviews, videos, podcasts, and breaking news on dermatitis research, treatment, and drug development.

Internal Medicine

Internal Medicine condition center page, resources on the topics of medical news and expert insight into internal medicine can be found. Content includes articles, interviews, videos, podcasts, and breaking news on internal medicine research, treatment, and drug development.

Lack of Data, Potential Bias Reported in AI Algorithms for Skin Disease

The US Food and Drug Administration (FDA) has approved evolocumab (Repatha) injection as an add-on therapy with diet or other treatment for patients aged ≥10 years with 

heterozygous familial hypercholesterolemia (HeFH) and homozygous FH (HoFH).

The new approval expands the indicated use of evolocumab, which was previously approved as an add-on therapy for reducing LDL-C in adults with HeFH and patients with HoFH.

The approval granted to Amgen was based on findings from a pair of pediatric clinical trials. The first, involving patients aged 10-17 years with HeFH, assessed 420 mg monthly subcutaneous injection for 24 weeks; patients reported a mean 38% reduction in LDL-C versus placebo.

In the second trial, patients aged 11-17 years old with HoFH received the same evolocumab dose regimen for 80 weeks, and reported a mean 14% reduction in LDL-C compared to baseline.

Evolocumab previously received orphan drug designation from the FDA in 2013 to treat HoFH. It is not indicated for use in patients with serious hypersensitivity, either by clinical diagnosis or emerging signs or symptoms.

Approximately 1 in 250,000 individuals are diagnosed with HoFH, while HeFH is prevalent in 1 in every 250 individuals. The conditions are rare and life-threatening, characterized by gene mutations that influence the body’s clearance of cholesterol including LDL-C.

The approval is based on 24- and 80-week findings showing significant benefit in LDL-C reduction with the subcutaneous injection drug.

Cardiology

Cardiology condition center page is a comprehensive resource for clinical news and insights on cardiovascular and cardiometabolic diseases. This page consists of interviews, articles, podcasts, and videos on the research, treatment and development of therapies for heart disease and cardiovascular events, as well as associated diabetes, renal failure, and more...

Rare Disease Report®

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Arterial Disease

Arterial Disease condition center page, resources on the topics of medical news and expert insight into PAD / CAD can be found. Content includes articles, interviews, videos, podcasts, and breaking news on peripheral artery and coronary artery disease research, treatment, and drug development.

Pediatrics

Pediatrics page, resources on the topics of medical news and expert insight into childhood health care can be found. Content includes articles, interviews, videos, podcasts, and breaking news on pediatric disease research, treatment, and drug development.

FDA Approves Evolocumab for Pediatric Familial Hypercholesterolemia Indications

Connor Iapoce is an assistant 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 

Although recent Phase 3 study data have assessed the efficacy of sotagliflozin in patients with 

, the entirety of outcome data has not been systematically reviewed, leading to a new review and meta-analysis on efficacy and safety of sotagliflozin in this patient population.

The team of investigators, led by Ioannis Avgerinos, MD, Clinical Research and Evidence-Based Medicine Unit, Aristotle University of Thessaloniki, observed a reduction in blood glucose, body weight, and systolic blood pressure with sotagliflozin use, showing overall benefit on heart failure and myocardial infarction.

Within the study parameters, investigators searched Medline, Embase, and the Cochrane Library until August 2021.

Inclusion criteria included randomized controlled trials (RCTs) with an ≥8 week treatment duration that compared sotagliflozin to placebo or other antidiabetes agent in the patient population with T2D.

In all outcomes, investigators extracted data for once-daily sotagliflozin 200 mg and 400mg. The primary efficacy outcome consisted of the change in HbA1c from baseline, while secondary efficacy outcomes included change in body weight, systolic blood pressure, and diastolic blood pressure.

They observed 15 safety outcomes, including serious adverse events, all-cause mortality, heart failure, and stroke.

In the meta-analysis, the team synthesized efficacy outcomes through weighted mean differences (WMD) and 95% confidence intervals (CI), as well as odds ratios in safety outcomes.

Avgerinos and colleagues noted that efficacy outcomes utilized data from RCTs with treatment duration of ≥12 weeks, while safety outcome data came from trials with duration of ≥8 weeks.

The systematic review included 11 trials with 16,411 patients. Data show patients had a mean HbA1c at baseline of 8.2%, mean systolic blood pressure of 135.6 mmHg, and mean age of 62.9 years.

In the analysis, sotagliflozin reduced HbA1c by 0.42% (95% CI, -0.56 to -0.29) in comparison to placebo. They found no difference in comparison to other antidiabetic agents, including empagliflozin and glimepiride.

Further, in a dose-dependent subgroup analysis, investigators observed both 200mg and 400mg of sotagliflozin reduced HbA1c level in comparison to placebo.

This was noted regardless of trial duration (WMD -0.48%; 95% CI, -0.72 to -0.25, 5 studies <52 weeks; WMD -0.35%, -0.53% to -0.17, 4 studies <52 weeks).

In terms of secondary efficacy, data show treatment with sotagliflozin reduced body weight by 1.33 kg (95% CI, 1.57 - 1.09). Compared to placebo, sotagliflozin reduced systolic blood pressure by 2.44 mmHg (95% CI, 2.18 - 2.07) and diastolic blood pressure by 0.81 mmHg (95% CI, 0.56 - 1.06).

Further, investigators observed sotagliflozin reduced incidence of heart failure by 32% (OR 0.68, 95% CI, 0.58 - 0.79) and myocardial infarction by 28% (OR 0.72, 95% CI 0.54 - 0.97), but neutral effect on all-cause mortality, cardiovascular mortality, and stroke.

They noted sotagliflozin treatment was safe regarding adverse events (OR versus placebo, 0.90, 95% CI, 0.83 - 0.97).

As a takeaway, sotagliflozin treatment showed improvement in glycemic control, body weight and blood pressure in patients with T2D, without serious adverse events. Moreover, sotagliflozin reduced CV events, including heart failure and myocardial infarction.

“Future trials should further explore its comparative effectiveness against other antidiabetic drugs, and verify its long-term beneficial effect on cardiovascular outcomes, given the early stop of the dedicated cardiovascular outcomes trials,” investigators wrote.

Sotagliflozin for patients with type 2 diabetes: a systematic review and meta- analysis

Sotagliflozin reduced HbA1c by 0.42% and heart failure by 32% in comparison to placebo. 

Diabetes

Diabetes condition center page is a comprehensive resource for clinical news and insights on diabetic and cardiometabolic diseases. This page consists of interviews, articles, podcasts, and videos on the research, treatment and development of therapies for type 1 and type 2 diabetes, as well as related endocrinological conditions and illnesses. 

Endocrinology

The HCPLive endocrinology page is a comprehensive resource for clinical news and insights on endocrine system conditions. This page consists of interviews, articles, podcasts, and videos on the research, treatment and development of therapies for diabetes, hormonal disease, and more.

Heart Failure

The HCPLive heart failure page is a resource for medical news and expert insights on HF. This page features expert-led coverage, articles, videos and research on the therapies and development of treatments for heart disease, reduced and preserved ejection fraction, and more.

Sotagliflozin Improved Glycemic Control, Reduced CV Events in Patients with T2D

In the September 2021 episode of Lungcast, Al Rizzo, MD, Chief Medical Officer of the American Lung Association (ALA), touched on the future of 

Castro is the Chief of Pulmonary, Critical Care and Sleep Medicine; Vice-Chair for Clinical and Translational Research; and Director of Rainbow Clinical and Translational Science Unit, Frontiers at the University of Kansas School of Medicine.

He noted that it was an “exciting time” for the future of asthma therapy, as clinicians continue to find agents that will modify the disease process for affected patients.

We have some good drugs now, so I think that what we're really studying now (is) whether or not they're truly disease modifying,” Castro said. “None of these therapies have that indication approved by the FDA, but we might have some candidates; these biologic therapies, as I mentioned, they're achieving control, they're improving lung function, and we think that they might have a chance of disease modification.”

For Castro, disease modification would entail improving a patient’s lung function and normalizing their disease to the extent that they do not have progressive disability.

“My goal is not to take away (or) cure the disease, I think that's an unrealistic expectation at this point with the current therapies that we have available,” Castro said. “But, if I can modify that disease to the point that their lung function is preserved, long-term...so they don't ever reach the point of disability from reduced lung function then that, to me, is a disease modifier.”

He added that he is often asked of early introductions of disease modification in children, with an example being the change of progression of chronic obstructive lung disease from childhood to adulthood.

Though he is optimistic about those possibilities, Castro mentioned that the best way to aim for those results is through increased, safe studies on biologics and the 

Rizzo and Castro briefly discussed the implications of the

Though recent CDC data suggested the virus posed no increased risk to patients with asthma, Castro mentioned that patients who received the vaccine experienced very mild disease in comparison to unvaccinated people.

“I truly believe that the vaccine is effective and my patients with asthma, and certainly encourage them (to get vaccinated),” Castro said.

Lungcast is a monthly respiratory health podcast series from the ALA, produced by 

Subscribe or listen to Lungcast on your favorite platforms:

https://open.spotify.com/show/1F3u1hKrwxi9snSQ0q3nti

https://podcasts.apple.com/us/podcast/lungcast/id1524712350

Videos

Dr. Castro considers it to be a fruitful and exciting time in the study of asthma-modifying therapy, with some biologic therapies achieving control in patients with severe asthma.

Asthma

The HCPLive asthma page is a comprehensive resource for clinical news and insights on asthmatic disease. This page consists of interviews, articles, podcasts, and videos on the research, treatment and development of therapies for allergic and severe asthma, and more.

Podcasts

podcasts page features a feed of medical news and interview podcast series, including DocTalk, Lungcast, Derm Discussions, Rare Disease Report, and Heart Trials.

Mario Castro, MD, MPH: The Future of Asthma-Modifying Therapy

. Prior to joining MJH Life Sciences in 2019, he worked as a digital reporter covering nanotechnology, life sciences, material science and more with 

. He graduated with a degree in journalism from Temple University in 2008 and began his career as a local reporter for a chain of weekly newspapers based on the Jersey shore. When not working, he enjoys going to the beach and enjoying the shore in the summer and watching North Carolina Tar Heel basketball in the winter.

 (CDI) genotypes are more prevalent in hospital-acquired infections than others, information that could help identify hypervirulent strains earlier.

A team, led by Elena Novakova, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, analyzed the phenotypic and genotypic patterns of C difficile isolates of patients with CDI.

While representing the most common nosocomial pathogen and antibiotic-related cause of diarrhea in health care facilities, the rates of C difficile infections have still increased in recent years in Slovakia.

The study included data from patients with CDI from July to August 2016 from hospitals in the Horne Povazie region of northern Slovakia. The investigators also identified hypervirulent strains such as the presence of RT027 or RT176.

“The accurate and fast diagnosis of CDI is essential for optimal patient care and preventing the spread of infection,” the authors wrote. “Diagnostic methods for the identification of different targets determine the presence of free toxins or toxigenic strains in the diarrheal feces.”

The team collected biological samples of suspected CDI using glutamate dehydrogenase enzyme

(GDH), anaerobic culture, enzyme immunoassay on toxins A/B, multiplex “real-time” polymerase chain reaction (PCR), and PCR capillary-based electrophoresis ribotyping, and by MALDI TOF MS.

The median age of the patient population was 77 years. Samples were taken from patients in internal medicine (n = 29), long-term care (n = 26), and surgery (n = 1), as well as from 4 non-hospitalized patients.

Patients in the study were also hospitalized for a number of comorbid conditions, including cardiovascular (29%), gastro-intestinal (24%), pulmonary (11%), renal (5%) and oncological diseases (1%), as well as other chronic diseases.

Current recommendations for diagnosing CDI include multi-step diagnostic algorithms combining GDH and toxin EIA with PCR, which can be very sensitive to the disease, but do not distinguish between symptomatic CDI and asymptomatic colonization.

 isolates included in the studied samples were tested for the presence of toxin genes by multiplex real-time PCR assay.

A total of 44 C difficile isolates were identified using PCR ribotyping, with 5 prominent ribotypes—RT001, RT011, RT017, RT081, and RT176.

However, the presence of hypervirulent RT027 was not identified.

RT001, RT011, RT081, and RT176 were deemed susceptible to metronidazole and vancomycin, while RT017 had reduced susceptibility to vancomycin.

There was also not a statistically significant difference between RT001 and RT176, the most prevalent PCR ribotype from both inpatient and outpatient individuals, regarding various variables, including albumin, CRP, creatinine, the length of hospitalizations (

“The results of PCR capillary-based electrophoresis ribotyping in the studied samples showed a high prevalence of RT176 and 001,” the authors wrote. “Accurate and fast diagnostics of CDI are essential for optimal patient care and preventing the spread of infection. Laboratory diagnosis involving a high-sensitivity screening assay, followed by a high specificity assay, is important for the treatment and diagnosis of the disease.”

Diagnostic Methods of Clostridioides difficile Infection and Clostridioides difficile Ribotypes in Studied Sample

RT001 and RT176 were the most prevalent C difficile ribotypes found from C difficile isolates using PCR testing. 

Infectious Disease

Infectious Disease condition center page is a comprehensive resource for clinical news and insights on viruses, infections, and bacteria. This page consists of interviews, articles, podcasts, and videos on the research, treatment and development of therapies for COVID-19, influenza, vaccine-preventable diseases, and more.

C Difficile Infection

C. difficile condition center page, resources on the topics of medical news and expert insight into Clostridium difficile can be found. Content includes articles, interviews, videos, podcasts, and breaking news on C. diff research, treatment, and drug development.

Gastroenterology

Gastroenterology condition center page is a comprehensive resource for clinical news and insights on digestive and GI conditions. This page consists of interviews, articles, podcasts, and videos on the research, treatment and development of therapies for 

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

Hospital Medicine

The HCPLive hospital medicine page is a comprehensive resource for clinical news and insights on the emergency medicine specialty. This page consists of interviews, articles, podcasts, and videos on the research, treatment and development of therapies for emergent care, and more.

Geriatrics

Geriatric medicine condition center page is a comprehensive resource for clinical news and insights on frequent geriatric-related diseases and conditions. This page consists of interviews, articles, podcasts, and videos on the research, treatment and development of therapies for sleep disorder, dementia, Alzheimer's disease, and more.

Investigators Identify Prevalent C Difficile Genotypes in Slovakia

Hazard ratios for CHD included 1.57 for cumulative LDL-C level, 1.69 for TWA LDL-C level, and 0.88 for LDL-C slope. 

Lipid Management

Lipid Management condition center page, resources on the topics of medical news and expert insight into lipidology can be found. Content includes articles, interviews, videos, podcasts, and breaking news on dyslipidemia research, treatment, and drug development.

Exposure to LDL-C in Young Adults Linked to Risk of Incident Coronary Heart Disease

Investigators believe these findings can help identify high-risk groups and prevent exacerbations through tailored treatments.

Allergy

Allergy condition center page is a comprehensive resource for clinical news and insights on allergic and inflammatory diseases. This page consists of interviews, articles, podcasts, and videos on the research, treatment and development of therapies for food and seasonal allergies, as well as allergic asthma and related conditions.

Patients with Persistent Cough Prone to Severe Asthma Presentation

Patients with pediatric solid tumors and hematological malignancies were more prone to C difficile infections. 

No Correlation Found in Association Between Malignancies and C Difficile Infections

Episode 2 of HCPLive Crisis Point tackles the clinical aspects and potential burdens clinicians face in the pursuit of obesity care. 

Obesity Management

Obesity Management condition center page, resources on the topics of medical news and expert insight into clinical weight management can be found. Content includes articles, interviews, videos, podcasts, and breaking news on obesity research, treatment, and drug development.

Surgery

The HCPLive surgery page is a resource for medical news and expert insights on invasive medicine. This page features expert-led coverage, articles, videos and research on the therapies and development of treatments for surgery, and more.

Arthritis

The HCPLive arthritis page is a resource for medical news and expert insights on arthritic disease. This page features expert-led coverage, articles, videos and research on the therapies and development of treatments for rheumatoid arthritis, psoriatic arthritis, osteoarthritis, and more.

Burdens of Clinical Care in the Obesity Crisis 

Dr. Castro talks of the available biologic therapies that can be used to treat asthma and other respiratory disorders.

COPD

COPD condition center page, resources on the topics of medical news and expert insight into chronic obstructive pulmonary disease can be found. Content includes articles, interviews, videos, podcasts, and breaking news on COPD research, treatment, and drug development.

Inflammation

On the HCPLive Inflammation condition center page, resources on the topics of medical news and expert insight into inflammatory disease can be found. Content includes articles, interviews, videos, podcasts, and breaking news on psoriatic, rheumatic, and allergic disease research, treatment, and drug development.

Mario Castro, MD, MPH: Optimizing Biologic Therapy for Asthma

Experts in hematology address unmet needs and precautions patients can take to avoid complications of sickle cell disease.

Sickle Cell

Sickle Cell condition center page, resources on the topics of medical news and expert insight into sickle cell disease can be found. Content includes articles, interviews, videos, podcasts, and breaking news on sickle cell research, treatment, and drug development.

Unmet Needs in the Management of SCD

Investigators found that exposure to surgical smoke and disinfectants over a long period of time led to increased risk of COPD in US female nurses.

Pulmonology

Infectious Disease condition center page is a comprehensive resource for clinical news and insights on respiratory health. This page consists of interviews, articles, podcasts, and videos on the research, treatment and development of therapies for asthma, COPD, interstitial lung disease, COVID-19, and more.

Long-Term OR Employment Linked to COPD in Female Nurses

Drs Sophie M. Lanzkron, Jeffrey D. Lebensburger, and John J. Strouse, share insights on the safety profile and cost of gene therapy for the management of sickle cell disease.

Role of Gene Therapy in Sickle Cell Disease

Details of the head-to-head SEAVUE study of ustekinumab vs adalimumab for induction and maintenance therapy in patients with moderate to severe Crohn disease.

Peer Exchange

HCPLive® Peer Exchange panel discussions feature authoritative insights, opinions, and perspectives on important issues facing today's care professionals.

SEAVUE: Ustekinumab vs Adalimumab in Crohn Disease

Edward Loftus Jr, MD, and William Sandborn, MD, review the 5-year remission data from the IM-UNITI trial for ustekinumab and post hoc analysis from the GEMINI 2 trial for vedolizumab in patients with Crohn disease.

Latest News

Lack of Data, Potential Bias Reported in AI Algorithms for Skin Disease

FDA Approves Evolocumab for Pediatric Familial Hypercholesterolemia Indications

Sotagliflozin Improved Glycemic Control, Reduced CV Events in Patients with T2D

Mario Castro, MD, MPH: The Future of Asthma-Modifying Therapy

Investigators Identify Prevalent C Difficile Genotypes in Slovakia