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In our newest Deep Dive interview, Sameer Awsare, MD, FACP, associate executive director for The Permanente Medical Group, addresses biosimilar uptake in the United States and his predictions for the near future, with Associate Editor Matthew Gavidia.

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If 2020 was dominated by the news of how COVID-19 spread across the globe, then 2021 has so far been focused on ending the pandemic through vaccine distribution.

A Timeline of COVID-19 Vaccine Developments in 2021

This AJMC® Profiles in Care provides an in-depth look into the results of the outcomes-based agreement between Boehringer Ingelheim and Highmark Inc.

AJMC® Profiles in Care Launches

 (CKD) presenting with a lower health-related quality of life at the onset of a recent study, men were found to have their quality of life decline more rapidly over time, investigators concluded.

Clinical Journal of the American Society of Nephrology

, showed declines in in physical and mental aspects of quality of life in both men and women diagnosed with advanced kidney disease, it revealed the stark differences in the speed at which the declines may occur.

“It is increasingly being accepted that the patient's health-related quality of life is as equally important as other clinical outcomes when assessing a patient’s health status….Very few studies have investigated the interdependence of health-related quality of life and sex over time in older patients with advanced CKD. CKD is highly prevalent in this age group, and given the rising life expectancy, efforts to improve health-related quality of life in the elderly should remain in focus,” said Nicholas Chesnaye, PhD, the lead study author from the Amsterdam Public Health Research Institute, in a 

The researchers analyzed responses to questionnaires collected as part of the European Quality Study on treatment in patients with advanced CKD, which included patients aged 65 years and older with advanced CKD who were not receiving hemodialysis therapy. The patients had to be receiving routine medical care in Germany, Italy, the Netherlands, Poland, Sweden, or the United Kingdom.

Responses from 1421 patients were utilized in the analysis. At baseline, women were reported to have considerably lower physical and mental health scores on average compared with their male counterparts. However, during the follow-up period, the investigators found that the physical (2.5 per year; 95% CI, 1.8-3.1) and mental (2.7 per year; 95% CI, 2.0-3.4) scores for men declined about twice as fast compared with women (physical: 1.1 per year; 95% CI, 0.1 to 2.0; mental: 1.6 per year; 95% CI, 0.7 to 2.6).

After adjusting for confounding factors, including kidney function decline, the differences were lessened somewhat, suggesting that the faster declines in men could be explained by gender differences. The association between men and women remained when adjusting for potential informative censoring due to mortality (23% vs 22%, respectively) or dialysis initiation (38% vs 31%, respectively).

Higher phosphate levels and lower hemoglobin levels were found to have an association with lower physical and mental scores in men. Additionally, pre-existing 

 was associated with lower scores in men. These associations were also detected in women but to a lesser extent.

“An understanding of sex-specific health-related quality of life over the course of pre-dialysis CKD, as well as the potential mechanisms underlying any differences, may provide insights into a patient’s health and needs, and aid sex-specific clinical monitoring, decisions related to kidney replacement therapy, and patient-centered care,” said Chesnaye.

Chesnaye NC, Meuleman Y, de Rooji ENM, et al. Health-related quality-of-life trajectories over time in older men and women with advanced chronic kidney disease. 

. January 24, 2022;17(1): doi: 10.2215/CJN.08730621

Articles

Although men and women with advanced kidney disease experienced physical and mental declines in health-related quality of life (QOL), men’s declines occurred at a significantly faster rate, researchers concluded.

Gender Differences for Health-Related QOL Detected Among Patients With Advanced Kidney Disease

 since 2019 and has a BA in philosophy and journalism & professional writing from The College of New Jersey. 

highlighted the negative impacts of mask and disinfectant use on migraineurs during the COVID-19 pandemic.

Previous research on COVID-19 and migraine has revealed initial lockdowns resulted in a decrease in headache frequency and severity for some patients, potentially due to the reduction of stressors experienced in everyday life. However, other authors have found the opposite in their work, noting the increased stress of the global health crisis worsened migraines for some patients.

Taking a different angle, the researchers in the current study sought to investigate how widespread use of personal protective equipment (PPE) and disinfectants within the scope of long-lasting pandemic restrictions impacted migraineurs.

A total of 310 migraineurs recruited from Ankara City Hospital in Turkey between May and July of 2021 were included in the survey-based study. “The complete lockdown was applied in the first 15 days of the patient admission period,” while “pandemic restrictions, including social distance and masks, were applied throughout Turkey in the study's remaining 2 and a half months,” authors wrote.

The majority of patients included (90.3%) were female and any patients with a migraine diagnosis of less than 2 years were excluded. Participants were categorized into migraine worsening (increase in any of migraine frequency, migraine days per month, migraine attack duration, or headache severity [n = 177; 57.1%]), stable (no or minimal change in any of these parameters [n = 96; 31%]) or improving (a decrease in at least one of these parameters [n = 37; 11.6%]) groups.

While the frequency of odor as a migraine trigger was higher in the worsening group compared with the stable and improving groups (

= .038), there was no difference between the stable and improving groups

The frequency of disinfectant usage was significantly higher in the worsening group than the stable group (

= .011) but did not differ between the improving group and either worsening or stable groups

The use of scalp contact masks and double masks was more common in the worsening group than in the stable (

= .018), but there were no differences between the stable and improving groups

While the duration of mask use per day was higher in the worsening group compared to the stable and improving groups (

= .027), there was no difference between the stable and improving groups

Furthermore, binary logistic regression analyses showed “mask type [scalp contact masks, double masks], duration of mask use, presence of allodynia, being a health worker, BDI [Beck Depression Inventory] score, and odor were determined as independent risk factors for migraine worsening in the pandemic period.”

Researchers noted the impacts of pandemic restrictions are different in different societies based largely on economic and socio-cultural factors and existing health systems.

Changes overtime can also take place, they added, citing an example of a study in Italy. In that analysis, “the authors stated that restrictions during the first wave of the pandemic led to a reduction in migraine attacks because of a reduction in stress. However, in the second study conducted by the same authors during the second wave, they found that the prolonged pandemic period increased stress and worsened migraines,” researchers said. 

Future studies should further investigate the relationship between disinfectants and migraine, they noted, while a lack of regular migraine diaries kept by participants marks a limitation to the current analysis.

Based on the findings, migraineurs “should be directed to use optimal protection methods in terms of mask type, the number of masks, and disinfectant usage frequency, taking into account their working and social life conditions, rather than exaggerated protection methods,” authors wrote.

“Considering that the COVID-19 pandemic will continue to have an impact in the coming years, a personalized optimal protection approach may increase the quality of life and economic efficiency of migraine sufferers, who constitute a substantial patient population,” they concluded.

Yuksel H, Kenar SG, Gursoy GT, and Bektaş H. The impact of masks and disinfectants on migraine patients in the COVID-19 pandemic. 

Published online January 12, 2022. doi:10.1016/j.jocn.2022.01.006

Researchers in Turkey analyzed the impacts of mask and disinfectant use among patients with confirmed migraine diagnoses. 

Study Details Impacts of Mask, Disinfectant Use on Migraine Severity During COVID-19

Findings of a cohort study carried out in Hawaii revealed racial and ethnic disparities in 

 screening (LCS) completion rates following disaggregation of Native Hawaiian, Pacific Islander, and Asian individuals and their subgroups. Results were published in 

Lung cancer is the leading cause of cancer deaths in the United States, authors explained, adding previous research on cancer incidence and mortality among Asian American, Native Hawaiian, and Pacific Islander (AANHPI) individuals showed disproportional lung cancer incidence and mortality rates among these groups.

In addition, cancer data on AANHPI individuals are typically presented in aggregate, potentially masking differences among racial subgroups, authors noted.

To better understand LCS completion and follow-up rates among men, women, Asian (Chinese, Filipino, Japanese, and Korean) subgroups, Native Hawaiian individuals and Pacific Island individuals, investigators assessed data of those enrolled in the Kaiser Permanente Hawaii (KPHI) LCS program.

The population-based cohort study included electronic medical record (EMR) data of members who met criteria between 2015 and 2019.

All individuals were aged between 65 and 79 years, had a 30 pack-year smoking history, and were cancer free. Participants were also current smokers or had quit within the past 15 years, and were at least 5 years past any lung cancer diagnosis or treatment.

Smoking is estimated to account for between 80% and 90% of all lung cancer cases.

Of the 1030 individuals included in the analysis, 838 (81%) completed LCS, defined as completion of a low-dose computed tomography (LDCT) test based on EMR data. Mean (SD) patient age was 65.6 (5.8) years and 61% were male. “The largest racial and ethnic groups were non-Hispanic White (381 participants [37.0%]), Native Hawaiian or part Native Hawaiian (186 participants [18.1%]), and Japanese (146 participants [14.2%]),” authors wrote.

Men and Filipino, Chinese, Japanese, and non-Hispanic White individuals had a higher proportion of screen orders for LDCT compared with women and individuals of the other racial and ethnic groups

Screening completion rates were not significantly different; but there was a 14% to 15% screening completion rate gap among groups

Asian individuals had the highest screening completion rate (266 participants [86%]) followed by Native Hawaiian (149 participants [80%]) and non-Hispanic White individuals (305 participants [80%]), Pacific Islander (50 participants [79%]) individuals, and individuals of other racial and ethnic groups (68 participants [77%])

Within Asian subgroups, Korean (31 participants [94%]) and Japanese (129 participants [88%]) individuals had the highest completion rates followed by Chinese individuals (28 participants [82%]) and Filipino individuals (78 participants [79%])

Of the 54 participants with Lung-Imaging Reporting and Data System (RADS) stage 3 disease, 93% (50 participants) completed a 6-month surveillance LDCT test

Of 37 individuals with Lung-RADS stage 4 disease, 35 (97%) were followed-up for additional procedures

Lower screening rates could be due to a multitude of factors including no insurance, longer distances to screening sites, or lower income levels. “Social and behavioral factors associated with LCS participation among racial and ethnic groups and by sex should be further examined among disaggregated racial and ethnic groups to identify target groups and areas for intervention,” authors wrote.

To help promote equity in screening eligibility for women, researchers suggested future studies examine LCS completion and follow-up rates in the same racial and ethnic groups and by sex using the US Preventive Services Task Force’s 

Small sample sizes mark a limitation to the current study, as researchers were unable to fully examine racial and ethnic differences and diagnostic outcomes.

“Disaggregation of these racial and ethnic groups is needed in future research involving larger samples to validate our findings and allow for a deeper dive into the social and behavioral factors that may be associated with LCS completion rates,” authors concluded. 

“This would inform the work toward mitigating racial and ethnic disparities that may exist in LCS and provide specific guidance to the care delivery system in developing targeted, culturally sensitive intervention," they said. 

Oshiro CES, Frankland TB, Mor J, et al. Lung cancer screening by race and ethnicity in an integrated health system in Hawaii. 

. Published online January 20, 2022. doi:10.1001/jamanetworkopen.2021.44381

Researchers examined differences in lung cancer screening and follow-up rates among individuals residing in Hawaii. 

Assessing Potential Racial, Ethnic Differences in Lung Cancer Screening in Hawaii

Sara A. Hurvitz, MD, is a medical oncologist and breast cancer specialist with UCLA Health. She practices in the Santa Monica Parkside location, which is home to the integrative breast cancer practice and high-risk breast cancer clinic. Hurvitz leads the Translation Oncology Research Laboratory at UCLA in preclinical evaluation of novel breast cancer targets and has won numerous awards for her research. She is associate professor at the David Geffen School of Medicine at UCLA and medical director of the Jonsson Comprehensive Cancer Center Clinical Research Unit, co-director of the Santa Monica-UCLA Outpatient Oncology Practice, and director of Breast Cancer Clinical Trials at UCLA. Hurvitz is also a member of the National Comprehensive Cancer Network committee for clinical practice guidelines in breast cancer.

®) about advanced hormone receptor–positive (HR+), HER2-negative breast cancer and the emergence of cyclin dependent kinase 4/6 (CDK4/6) inhibitors with endocrine therapy as the “gold standard” for first-line treatment.

This interview has been edited lightly for clarity.

For those who are unfamiliar, could you tell us what is advanced breast cancer?

 Advanced breast cancer is breast cancer that has spread outside the breast and lymph nodes, the regional lymph nodes in the axilla, or armpit region, and has been detected elsewhere in the body—for example the bone, the liver, or the lungs.

:How are patients screened and diagnosed with advanced breast cancer? Does this occur with a patient who starts with a more localized form of breast cancer and progresses, or do we find patients who come into the clinic and present with metastatic or advanced breast cancer?

: In general, patients are diagnosed first with early stage breast cancer. And then at some point after treatment for early stage breast cancer, they may develop advanced disease. In the United States, only about 10% of patients diagnosed with advanced breast cancer or incurable metastatic breast cancer are diagnosed [at that stage] when first diagnosed with breast cancer. That's called de novo metastatic breast cancer. It's relatively uncommon, in part because we implement very strict screening guidelines in the United States, where patients generally are undergoing screening mammography to detect breast cancer at an earlier stage.

:We'll be talking today about HR+, HER2-negative breast cancer. Could you explain how these terms that tell us the status of a patient are defined in breast cancer? How do we learn that a patient is HR+, HER2-negative during diagnosis?

 When a patient is initially diagnosed with breast cancer, and then when a recurrence happens, the patient's tumor is tested by a staining mechanism, in essence called immunohistochemistry, to look for the presence or absence of certain proteins. These proteins include the estrogen receptor and the progesterone receptor. Collectively, they are called hormone receptors, and the immunohistochemical assay tests for that. And they're also tested for something called HER2, which is human epidermal growth factor receptor number 2—it’s easier to say HER2—which in about 15% to 20% of patients is amplified at the gene level, leading to overexpression that can be detected by the protein stain or immunohistochemical stain.

It is critical that we know a patient's tumor’s hormone receptor status and HER2 status because these weigh heavily in treatment decision-making. We have therapies available that target HER2, and they are very effective at managing HER2-amplified or -positive [HER2+] breast cancer. And we have therapies that are very effective for HR+ breast cancer.

There is a class of breast cancer about 15% of patients have that's called triple-negative breast cancer. That’s a class that is based more on what the cancer is 

expressing rather than what the cancer is distinguished by on a molecular level. Triple-negative breast cancer currently doesn't have targeted therapies available—although we are seeing the use of immunotherapy and antibody drug conjugates now making their way into the clinical setting—but it tends to be a more challenging type of breast cancer. So, it's important for clinicians to know what [type] of breast cancer a patient has when developing a treatment strategy to manage the disease.

:One last question to frame our conversation here, and I think you touched on it: Metastatic or advanced breast cancer is generally considered incurable. Could you elaborate on that? Why is this so? Do you think this is something that might change—is this something we're just living with at the moment?

 In general, advanced breast cancer is considered incurable. There are select patients that may have a prolonged survival in HER2+ breast cancer; for example, I do have patients in my own practice who've had no evidence of disease progression and no evidence of disease on their scans for many years. Now, we don't know if they're truly cured, and we don't know whether we can stop treatment to control the disease. But this is an area that is of interest and a lot of investigators are studying right now to better understand how frequently that occurs for each of the subtypes of breast cancer.

In general, we treat patients for a lifetime with medicine or systemic therapy to control disease, because it's impossible to know who's going to have a durable remission that lasts forever—otherwise known as a cure—from a patient who would have a prolonged control of their disease and then have progression later.

So, in general, we treat patients palliatively and to control the disease, not expecting them to be free of the disease ever. But I do think that there are exceptions to that rule. And my hope is with better and better systemic therapy approaches, that perhaps we'll see a greater fraction of patients who truly can overcome the disease and be so-called cured.

:Today we are discussing HR+, HER2-negative breast cancer. Can you walk us through what the treatment landscape looks like now for standard of care, for patients who have HR+, HER2-negative advanced breast cancer?

 Currently, the gold standard therapy in the frontline setting for patients with HR+, HER2-negative advanced breast cancer is the use of endocrine therapy, which is essentially either fulvestrant or an aromatase inhibitor, in combination with a CDK4/6 inhibitor. This is the gold standard doublet regimen. That is based on a number of phase 3 clinical trials that have now established that CDK4/6 inhibitors, when added to endocrine therapy in the firstline setting, significantly prolong progression-free survival—they roughly double it. This is consistent across the different clinical trials with different endocrine partners and different CDK4/6 inhibitors. And now, we have data emerging, at least related to ribociclib (Kisqali) of the CDK4/6 inhibitors, that overall survival is also significantly prolonged in patients who take this in the frontline setting. So, except for very unusual situations where a patient, for example, couldn't tolerate oral therapy or had a contraindication to receiving one of these agents, this would be considered the gold standard of care.

:It sounds like a CDK4/6 inhibitor is incredibly important up front in a patient's care. With that in mind, have you ever encountered any barriers to up-front use? You mentioned some clinical characteristics that might harm a patient, perhaps if they're taking it? Are there any other barriers you've run into, or in your practice, with trying to start a CDK4/6 inhibitor up front?

 Well, there are some barriers to taking CDK4/6 inhibitor–based therapy that I've run into [during] the COVID pandemic. [The pandemic] has certainly created its own set of barriers, and each of the CDK4/6 inhibitors does require that patients come into clinic at least twice monthly for the first 2 months to have blood checks and in some cases, EKGs checked, and then monthly thereafter. I think we've become a little bit better at managing these lab draws. Sometimes, we’re able to use home health visits or a local laboratory rather than making patient come into clinic, and we're utilizing video visits to check in with patients to make they're tolerating [the therapy] well. But that certainly can be a barrier, especially with the current pandemic.

In addition, there are some patients who have very bad comorbidities; breast cancer isn't their only issue. [They may have] out of control diabetes or other immune issues that put them at high risk of infection if they were to develop neutropenia. All the CDK4/6 inhibitors are associated with neutropenia, which is typically asymptomatic and not a problem. But if you have a patient who has a lot of comorbidities and other risk factors for infection, it would certainly be prudent to think carefully about whether adding this in will benefit them.

And then taking oral therapy can be challenging. There are some patients who struggle with remembering to take pills, remembering when to call; ribociclib and palbociclib (Ibrance) are given 3 weeks on, 1 week off. So sometimes that gets a bit confusing to patients. So, I think it's important to help patients with compliance by utilizing frequent visits the first 2 months to make sure they're keeping up with how the medicine should be taken, and so that we can be notified if any problems come up with tolerating it.

:There are a few options in the CDK4/6 inhibitor space right now. What factors do you consider when selecting one of these inhibitors? How do you select among those that are currently available?

 There are 3 CDK4/6 inhibitors that are commercially available to our patients: palbociclib, ribociclib, and abemaciclib (Verzenio). They all have very similar hazard ratios in terms of benefits within progression-free survival, be it in the first- or second-line setting. Ribociclib and abemaciclib are also associated with an improved overall survival; we still don't have data yet with palbociclib to indicate an overall survival benefit, but we are awaiting some phase 3 results to come out.

So, when deciding among the 3 inhibitors, you can keep in mind the overall survival benefits for a given indication, and that certainly sometimes influences me in what I'm recommending for a patient. We also can consider the side effect profile and monitoring profile; ribociclib and palbociclib are associated with grade 3/4 neutropenia on the order of 65% to 75%, so that's something to keep in mind, whereas abemaciclib is only about 25%. On the other hand, abemaciclib has more gastrointestinal toxicity that patients need to contend with. And patients need to take abemaciclib twice daily continuously. So, these are factors that can play into shared decision making—talking to a patient about the different side effect profiles and deciding with her which one to start.

Ribociclib comes with a requirement to follow the EKGs the first 2 months, especially every 2 weeks, given the risk of QT prolongation. So, looking at a patient's concomitant medications to make sure there's not going to be any drug-drug interaction is an important component of decision-making. All other things being equal—side effect profile, etc—I will choose ribociclib for my premenopausal women given Level 1 evidence in that setting with ribociclib. And I think ribociclib and abemaciclib tend to be my choice for postmenopausal women based on the overall survival benefits we're seeing, although palbociclib is well tolerated and we don't know yet if there will be overall survival benefit associated with it.

:You touched on the overall survival benefit of ribociclib. You were recently a co-author on the updated MONALEESA-7 trial results, in the premenopausal/perimenopausal subset of patients with this type of breast cancer. Can you tell us about this trial, and these results that came out recently?

 The MONALEESA-7 clinical trial was a very uniquely designed study. It's the only study of a CDK4/6 inhibitor that’s phase 3 and was conducted solely in pre- or perimenopausal women—so really focusing on the younger patient population to interrogate whether a CDK4/6 inhibitor, in this case ribociclib, improves outcomes for young women with HR+ metastatic disease. And indeed, ribociclib when added to endocrine therapy did significantly improve not only progression-free survival, but it was the first clinical trial of a CDK4/6 inhibitor to demonstrate an improvement in overall survival as well. Which is why I feel that for pre- and perimenopausal women, the use of ribociclib is supported by the best level of evidence in phase 3 clinical trials. Patients can receive ribociclib in combination with an aromatase inhibitor and, of course, ovarian function suppression is required. We would not want to give ribociclib with tamoxifen, given that tamoxifen itself can add to QT prolongation. So, although it was studied with tamoxifen by investigators’ choice in MONALEESA-7, that would not be my clinical choice to use ribociclib with tamoxifen in in the clinical setting.

:To focus on this a little more, this patient population is unique. Do you suspect we'll see more trials in a pre- or perimenopausal population following the results of this trial? Will this become the FDA standard for new agents coming to market—making sure that these agents are tested in this population?

: I'm not sure that we're going to see phase 3 trials that specifically home in on pre- or perimenopausal women. However, my hope is that we will see studies [that do] not exclude these patients. The first clinical trial to lead to the FDA approval of a CDK4/6 inhibitor in PALOMA-2 was conducted only in postmenopausal women, and to exclude premenopausal women who are placed on ovarian suppression I think is not the right answer. These patients do have serious illness, and their outcomes may be worse than a patient diagnosed with metastatic disease at an older age. And so, I think it's important to include them in our clinical trials, which does appear to be the trend moving forward. More and more clinical trials in HR+ disease, at least, are allowing women regardless of menopausal status.

:Let’s talk about patients who continue to have their disease progress despite CDK4/6 inhibitor use. What's your approach to this, for a patient with HR+, HER2-negative advanced breast cancer?

: Unfortunately, the majority of patients treated with the CDK4/6 inhibitor in the first- or second-line setting will develop disease progression, indicating resistance has developed [to] this agent. A number of groups have modeled CDK4/6 inhibitor resistance, and there are no real good data from a preclinical perspective that continuing a CDK4/6 inhibitor or swapping for a different CDK4/6 inhibitor will benefit patients, at least not based on the in vitro and in vivo assays that have been done. However, there are a number of clinical trials ongoing that are interrogating this question where patients whose disease is progressing on a CDK4/6 inhibitor are randomly assigned to a different independent therapy or a different CDK4/6 inhibitor or having a PI3K pathway inhibitor added in. And so, I think in the next few years, we will have some clinical data to guide our treatment decisions.

At this point, I am not giving a patient a CDK4/6 inhibitor after progression outside of a clinical trial. The one exception may be with the use of single-agent abemaciclib in a patient who's run out of all endocrine therapy options, and previously did well on a CDK4/6 inhibitor, because abemaciclib is a less specific inhibitor, meaning it targets other cyclin dependent kinases besides 4 and 6. It may have a broader efficacy across tumors that have developed resistance to CDK4/6, but I would prefer to do that in a clinical trial setting. In the clinic setting, what I am typically doing is giving patients endocrine therapy with a PI3 kinase pathway inhibitor, which would be everolimus (Afinitor) if the patient does not have a tumor with PIK3CA mutations or alpelisib (Piqray) if they have PIK3CA mutations.

:Would you like to provide any closing thoughts on this type of breast cancer?

This is an exciting time for us as clinicians and investigators treating HR+ metastatic disease. Keeping in mind this disease subtype reflects about 70% of all breast cancer, it is critical for us to continue to support clinical trials and clinical Investigation of novel therapies to target this disease subtype. Although patients can do very well for many years, they will ultimately develop disease resistance, so novel therapies are going to be very important for us to continue improving outcomes for patients. I'm really excited about oral SERDS [selective estrogen receptor degraders], elacestrant, oral PROTAC [proteolysis-targeting chimera] molecules, other agents that target ERs [estrogen receptors], and really excited to see combination strategies with these oral ER degraders. I think it's going to be potentially practice changing in the long term.

Sara A. Hurvitz, MD, of UCLA Health spoke with The American Journal of Managed Care® (AJMC®) about advanced hormone receptor–positive (HR+), HER2-negative breast cancer and the emergence of CDK4/6 inhibitors with endocrine therapy as the “gold standard” for first-line treatment.

Hurvitz: CDK4/6 Inhibitors With Endocrine Therapy Is the “Gold Standard” in the First Line for HR+, HER2-Negative Advanced Breast Cancer

Guidelines for eosinophilic esophagitis (EoE), which may follow a waxing and waning pattern, were released in 2020, said David R. Stukus, MD, FACAAI, of Nationwide Children's Hospital and The Ohio State University College of Medicine.

Can you discuss the guidelines for EoE, which were presented at the American College of Allergy, Asthma & Immunology Annual Scientific Meeting, and would you describe EoE as a chronic disease?

These guidelines were first published in the spring of 2020, so they've been available for about 18 months now. And these are new guidelines. They actually use something called a grade analysis to ask very specific clinical questions and then they evaluate the body of evidence related to that question, offering both clinical recommendations as well as information about the strength of the evidence. So they're very practical and hopefully useful for people to use. We also know that it can take years before clinical guidelines actually change practice, because people have, you know, limited ability to stay up with the latest and greatest. So that's why this session ['Implementing New Guidelines Into Practice"] is really important, to really help all of our colleagues in allergy and immunology best understand what the guidelines do and don't say, as well as how they can apply that to direct patient care.

EoE often is chronic for both children and adults, but it tends to follow a waxing-waning pattern. So part of what the guidelines address are really long-term management and monitoring. Some people do suffer more of an acute course, and then they improve, whereas others have a long-standing disease.

Videos

David R. Stukus, MD, FACAAI, of Nationwide Children's Hospital and The Ohio State University College of Medicine, and a board member of the American College of Allergy, Asthma & Immunology, discusses guidelines for eosinophilic esophagitis, as well as some disease patterns that may occur.

 Dr David R. Stukus on Eosinophilic Esophagitis Guidelines and the Pattern of Disease

® since 2019 after receiving his Bachelor's degree at Rutgers University–New Brunswick in journalism and economics.

Patients with early-onset and late-onset colorectal cancer showed no significant differences in regards to tissue and plasma genomic profiles, but a greater enrichment of the 

 mutations were noted in the tissue of those with early-onset disease. 

 were presented at the 2022 ASCO Gastrointestinal Cancers Symposium.

Although colorectal cancer remains rare among younger adults, diagnosis trends exhibit a growing phenomenon with a 51% increase in cases among patients under the age of 50 since 1994. Notably, early-onset colorectal cancer serves as the deadliest cancer for men aged 20 to 49 years, as well as the third most deadliest cancer for women of the same age group.


Seeking to examine and compare the genetic profiles of patients with early-onset and late-onset colorectal cancer, the study authors used Sarah Cannon’s web-based analytics platform that included commercial next-generation sequencing information from oncology practices nationwide.

"Testing performed in oncology practices are routinely extracted and harmonized into the Genospace database," they noted. "Data from colorectal cancer adenocarcinomas were selected; patients with unknown microsatellite instability (MSI) status were excluded."


For the study, only MSI-stable (MSS) tumors were analyzed to reduce the confounding effect of MSI-high hypermutated tumors. Reports generated from archival tissue samples were assessed separately from those generated from plasma, since liquid biopsies were indicated to be more likely conducted during post-treatment.

Overall, next-generation sequencing data of 1477 patients with MSS colorectal cancer were analyzed, of which 1029 were tissue (18.7% early-onset) and 448 plasma (17.8% early-onset) tests. Same sex distribution was shown between both groups, with early-onset patients showing a significantly lower prevalence of Caucasian ethnicity vs late-onset counterparts (43% vs 53%; 

Of 68 colorectal cancer-related genes examined in tissue, 2 were significantly more enriched in those with early-onset disease vs late-onset—the 

Across panel-wide gene association, 19 genes from tissue were enriched in those with early-onset disease, but none were significant after multiple testing correction. Plasma samples showed significantly higher 

 alterations in patients with late-onset vs early-onset colorectal cancer (17.3% vs. 3.8%; 

 < .001; false discovery rate = 0.16), which researchers said was likely due to clonal hematopoiesis.

Moreover, no difference in tissue or plasma tumor mutational burden (TMB) was observed:

TMB in tissue of late-onset patients (median [interquartile (IQ)], 5.04; CI, 3.5-7; TMB > 10, 7%)

TMB in tissue of early-onset patients (median [IQ], 4.39; CI, 2.5-6.1; TMB > 10, 6%)

TMB in plasma of late-onset patients (median [IQ], 8.73; 5.7 – 13.4); TMB > 10, 12%)

TMB in plasma of early-onset patients (median [IQ], 7.19; CI, 2.9-12.6); TMB > 10, 14%)

Tissue and plasma genomic profiles were concordant overall, except for 

 alterations (4.5% tissue; 21.6% plasma), which researchers said was possibly due to acquired amplification post-

“Epigenetic and transcriptional events should be investigated,” concluded the study authors. “Enrichment for 

 mutations in early-onset patients may have important screening and therapeutic implications; germline status will be further investigated.”

Fontona E, Jones C, Misch A, et al. Early-onset colorectal cancer: Real-world genomic data from the community-based Sarah Cannon Cancer Centers Network. Presented at: 2022 ASCO Gastrointestinal Cancers Symposium. Abstract: 198. doi:10.1200/JCO.2022.40.4_suppl.198

Findings presented at the 2022 ASCO Gastrointestinal Cancers Symposium showed no significant differences in tissue and plasma genomic profiles of patients with early-onset and late-onset colorectal cancer, but a greater enrichment of the BRCA1 and PTEN mutations were noted in the tissue of those with early-onset disease.

Genomic Profiling Uncovers Mutations More Enriched in Early-Onset Colorectal Cancer

 is 2 times higher among Iranian patients with a recent history of depressive disorder compared with those without such a history, according to new research published in 

 Among these patients, those who were female, had a higher socioeconomic status, lower physical activity, and were tobacco users were more likely to be polymedicatied, authors wrote.

Despite the growing public health challenge of polypharmacy, the majority of studies carried out on this topic have been conducted in developed regions and focused on elderly populations, researchers explained.

Past research has also revealed depressive disorders (DD) are highly correlated with polypharmacy prevalence, while the relationship may be bidirectional. Identifying patients with DD and at a higher risk of polypharmacy could help improve their quality of health care as well.

In an effort to elucidate the correlations between polypharmacy and a recent history of DD, investigators assessed data from a population-based sample of patients residing in a less developed region of southwestern Iran.

The Pars Cohort Study (PCS) is a 10-year cohort study that was launched in 2016. Participants underwent face-to-face interviews, physical examinations, and biological sampling. All those who answered "yes" to the prompt, "Has your physician told you that you have a depressive disorder and you need treatment for that during the last 12 months?" were classified as having a recent history of depression.

Researchers noted currently used drugs, including over-the-counter medications and complementary products; polypharmacy was defined as using 5 or more different medications concurrently.

Of the 9264 participants, mean (SD) age was 52.6 (9.7) years, and a slight majority of patients (54%) were female. The prevalence of polypharmacy was 22.6% (95% CI, 20.7–24.6) while genitourinary system (55.4%) and nervous system (29.1%) medications were the most commonly reported drug classes used.

A total of 1795 (19.4%) of individuals were found to have a DD in the past year. Mean patient age of this cohort was 53.3 (9.5) years and 70% were female. Data recorded between 2016 and 2019 were included in the current study.

Researchers found, “factors associated with polypharmacy included female gender (odds ratio [OR]: 1.51), Fars ethnicity (OR: 1.52), lower physical activity (OR: 1.74), and higher socioeconomic status (OR: 1.40). The prevalence of antidepressant use among males was higher than females (

More than 40% (n = 3027) of participants without a recent history of DD were not on any medication, compared with 17.2% (n = 309) among patients with a recent history of DD

More than 51.7% of individuals with a recent history of DD and 76.6% of participants without a recent history of DD were on less than 2 different drugs at the time of the study

Non-selective monoamine reuptake inhibitors and selective serotonin reuptake inhibitors were used comparably in females (around 14%), males (around 41%), and elderly people (around 20%)

Polypharmacy constitutes a leading cause of medication nonadherence and nonadherence among those taking antidepressants can result in complications in DD management, potentially leading to a higher chance of relapse.

Authors hypothesized their findings could “be a result of the health-seeking and medication utilization behaviors of patients [whose] DD has been diagnosed in a society without any active specialized psychiatric clinic.”

They also stressed the importance of recognizing the higher risk of polypharmacy among younger females with a recent history of DD.

In the current analyses, researchers were unable to investigate the effects of untreated or relapsed depression on polypharmacy, marking a limitation. The study also excluded any patients under the age of 40 and was cross-sectional in nature.

Ghaed-Sharaf M, Hariri S, Poustchi H, et al. The pattern of medication use, and determinants of the prevalence of polypharmacy among patients with a recent history of depressive disorder: results from the pars cohort study. 

. Published online January 18, 2022. doi:10.1186/s40359-022-00716-9

Results of a study carried out in Iran found those with a recent history of depressive disorders were more likely to suffer from polypharmacy, or taking 5 or more medications concurrently. 

Study Finds High Polypharmacy Rates Among Those With History of Depression

) is a costly global health problem, but a new study has shown that simple assessments can successfully identify patients at high risk of the disease.

Journal of the American Medical Association

, was conducted in 3 low- and middle-income countries (LMICs): Nepal, Peru, and Uganda. Although COPD is a worldwide concern, previous research has indicated 90% of deaths from the disease occur in LMICs.

Investigators wanted to better understand the feasibility of screening patients in LMICs for COPD using low-cost methods. Specifically, they decided to look at the COPD Assessment in Primary Care to Identify Undiagnosed Respiratory Disease and Exacerbation Risk (CAPTURE) tool, the COPD in LMICs Assessment questionnaire (COLA-6), and the Lung Function Questionnaire (LFQ). The first 2 (CAPTURE and COLA-6) were designed to be paired with a measurement of peak expiratory flow (PEF); the LFQ was designed to stand alone.

“Screening tools for COPD have been shown to have reasonable diagnostic accuracy in high-income countries, but due to better population health and treatment in these settings, this has tended to identify milder disease, not requiring much intervention,” explained the study’s principal investigator, John Hurst, MBBS, PhD, of University College London, in a 

Hurst said the screening tools had not yet been sufficiently studied as a diagnostic tool in LMICs.

To change that, Hurst and colleagues enrolled 10,709 patients from the 3 countries into a study. The patients had a mean age of 56.3 years, and half were female. About one-third (35%) had a history of smoking, and 30% reported currently being exposed to biomass smoke.

The investigators found that rates of COPD varied significantly between the sites, with 18.2% of participants in Nepal found to have COPD, compared with 7.4% of patients in Uganda and 2.7% in Peru. Of 1000 COPD cases identified in the study, the vast majority (95.3%) were previously undiagnosed, and half (49.3%) were considered clinically important (with Global Initiative for Chronic Obstructive Lung Disease classifications between B and D). Many patients (16.4%) had severe or very severe airway obstruction, Hurst and colleagues found.

The analysis showed that all 3 screening tools were quick and feasible to administer, taking just 7 to 8 minutes on average. The results suggest the tools could be used to identify more patients with COPD, even in low-income settings.

“Our findings support the accuracy and feasibility of using simple screening tools to identify people affected by COPD living in diverse low- and middle-income settings,” Hurst said.

Hurst added that he was “alarmed” by the high rate of clinically important cases, particularly since most patients did not realize they had COPD.

“In addition, only a minority of people had a history of smoking, further highlighting the poor conditions, exacerbated by biomass smoke, that people in low- and middle-income countries are living,” he said.

Although the study affirmed the value of these screening tools, the investigators said more research will be needed to find out if the screening tools can be incorporated into routine medical exams in LMICs, whether such incorporations are cost-effective, and whether better screening will eventually lead to improved outcomes.

Siddharthan T, Pollard SL, Quaderi SA, et al. Discriminative accuracy of chronic obstructive pulmonary disease screening instruments in 3 low- and middle-income country settings. 

. published online January 11, 2021. doi:10.1001/jama.2021.23065

The screening tools were found to be feasible measurements and took just 7.6 minutes to complete on average. 

Questionnaires, PEF Identify COPD in Patients in Low- and Middle-Income Countries

 (RA) are at a significantly higher risk of developing hypothyroidism.

The retrospective cohort study also found the risk to be even greater in women and patients aged 60 and older.

RA is known to be more prevalent in women than men, and past studies have continued to demonstrate the increased risk of developing hypothyroidism among people with RA. However, the role of comorbidities in hypothyroidism development has not been evaluated.

Using the Taiwan National Health Insurance Research Database, researchers collected data on 16,714 patients who received a RA diagnosis between 2000 and 2008, matching by sex, age, and index year to a control group of 66,856 individuals without RA. All patients were over age 20, with the mean age being 51.7 in the RA group and 51.4 in the control group.

Women included in the study were affected by RA 3 times more often compared with men, and made up approximately 75% of the total study population. The authors also noted that the RA group had more blue-collar workers and rural residents compared with the control group.

The authors found that hypothyroidism incidence was 1.74 times higher in patients with RA than patients without RA (adjusted hazard ratio [aHR], 1.67; 95% CI, 1.39-2.00). Based on sex, women with RA were 3.6 times more likely to develop hyperthyroidism compared with men, and women in the control group still had a higher incidence than men without RA.

“Therefore, the mechanism associating with hormonal abnormality for both RA and the development of hypothyroidism may be valid,” the authors said.

RA development has been linked to inflammation and proinflammatory cytokines, the latter of which are involved in the pathogenesis of RA and atherosclerosis—a thickening or hardening of the arteries caused by plaque buildup—and growing evidence has shown a higher prevalence of related comorbid disease.

“In our study, most baseline comorbidities were more prevalent in the RA cohort than in the controls, with the exception of DM [diabetes] and hyperlipidemia,” the authors wrote. “Factors associated with RA and associated comorbid diseases may underlie the association between RA and hypothyroidism.”

Hypothyroidism incidence also increased with age. In individuals with RA aged 20 to 39, incidence was 12.1 per 1000 person years, while incidence was 20 per 1000 person years in those aged 60 and older. Both age groups saw a higher incidence among those with RA compared with those without RA.

The researchers also measured how comorbidities were related to incidence. All comorbidities—hypertension, ischemic heart disease, stroke, diabetes, hyperlipidemia, and chronic kidney disease—were associated with an increased hyperthyroidism incidence in both groups, but significantly higher in the RA group. They found that stroke had the strongest association in the RA group (aHR, 3.85; 95% CI, 1.24-12.0).

The findings further support the association between autoimmune disease and the development of hypothyroidism, and the authors said closely monitoring RA patients and timely intervention could improve the prognosis of those who develop hypothyroidism.

“Further study may consider the treatment of using biological antirheumatic agents, comparing with nonsteroidal anti-inflammatory drugs and disease-modifying antirheumatic drug,” the authors said.

Huang CM, Sung FC, Chen HJ, Lin CC, Lin CL, Huang PH. Hypothyroidism risk associated with rheumatoid arthritis: A population-based retrospective cohort study. 

. Published online January 7, 2022. doi:10.1097/MD.0000000000028487

Women in the study were 3 times more likely to be affected by rheumatoid arthritis (RA) and nearly 4 times more likely to develop hypothyroidism, compared with men.

Older Women With RA at Higher Risk of Developing Hypothyroidism

CDC to Revise Fully Vaccinated Designation for COVID-19

During a briefing this past Friday, CDC Director Rochelle Walensky, MD, said the agency is working to change its language on who would fit the criteria of being fully vaccinated against COVID-19. As reported by 

, Walensky said the language would be pivoted based on how up to date individuals are with their primary series, including when the shots were initially distributed, the level of antibody protection remaining, and whether one is eligible for a booster. Currently, 210 million Americans are considered fully vaccinated, with 83 million having received a booster dose.

Study Finds COVID-19 May Cause Short-term Infertility in Men

 indicated that men who tested positive for COVID-19 showed a short-term decline in fertility. Conversely showing no reduction in fertility among people who received COVID-19 vaccines, the study dispels misinformation that vaccines cause infertility, which was believed by 3 in 10 US adults in a 

 by the Kaiser Family Foundation. The study also reinforces CDC recommendations for pregnant women to be vaccinated as to protect themselves and 

The CDC is working to change its definition of being fully vaccinated against COVID-19; a study finds that men who tested positive for COVID-19 showed a short-term decline in fertility; a nonprofit group of scientists seeks to optimize the clinical trial process and reduce cost.