Higher levels of the omega-3 fatty acid eicosapentaenoic acid (EPA) found in the blood appear to explain why icosapent ethyl drives down the risk of a cardiovascular (CV) event.

REDUCE-IT: Serum EPA Levels Key to Vascepa's CV Benefits

We interview experts on investigational treatments such as liso-cel, and ask how to bring them to community practice.

Spotlight on CAR T-Cell Therapy

The American Journal of Accountable Care® features research and commentary on new payment models.

New Members for AJAC Board

's parent company, MJH Life Sciences, since 2011. She has an MA in business and economic reporting from New York University.

Patients with pulmonary arterial hypertension (PAH) who are treated with selexipag within 6 months of their diagnosis had a reduced risk of morbidity/mortality compared with patients who were treated longer than 6 months after diagnosis, according to a study 

Selexipag is an oral selective prostacyclin receptor agonist that targets the prostacyclin pathway. Because selexipag is an oral therapy, it does not need to be titrated to an individual dose nor does it have a complex administration, both of which are challenges with other agents targeting the prostacyclin therapy.

“The benefits of prostacyclin pathway agents are well-documented, yet administration is often delayed and a significant proportion of patients never receive a drug targeting this pathway,” the authors explained.

In a post hoc analysis of GRIPHON, a large, randomized controlled trial in PAH, 1156 patients with PAH were assigned randomly to receive selexipag or placebo. They were split into 2 groups at time of randomization: 6 months or less from time of diagnosis and more than 6 months from time of diagnosis.

In the overall study, GRIPHON demonstrated a 40% reduction in the risk of a primary composite outcome of morbidity/mortality with selexipag compared with placebo. After the study, all patients were categorized based on time from diagnosis. The time from diagnosis was used to define newly diagnosed patients who were treated earlier (≤ 6 months) and patients who were treated later (> 6 months).

The majority of patients (n = 752; 65.1%) were treated later. In general, patients treated when they were newly diagnosed were younger. The post hoc analysis found that among patients taking placebo, those newly diagnosed were more likely to experience morbidity/mortality even than patients diagnosed longer (50.3% vs 37.1%). However, among patients taking selexipag, the percentage of those who experienced a morbidity/mortality event was similar among the 2 groups (27.5% for newly diagnosed patients vs 26.7% for patients diagnosed longer).

Compared with placebo, selexipag reduced the risk of morbidity/mortality by 55% for newly diagnosed patients (HR, 0.45; 95% CI, 0.33-0.63) and by 26% for patients diagnosed longer (HR, 0.74; 95% CI, 0.57-0.96). The mean exposure time to selexipag was similar in both groups (76.7 weeks in newly diagnosed patients vs 76.3 weeks in patients diagnosed longer), while patients with a longer time from diagnosis had a longer exposure time in the placebo group (74.7 weeks vs 64.4 weeks).

A slightly higher percentage of patients with a longer time from diagnosis discontinued treatment with selexipag compared with newly diagnosed patients (26.9% vs 23.7%). Until the end of the study, 38 newly diagnosed patients on selexipag and 62 patients diagnosed longer on selexipag had died compared with 44 and 61, respectively, on placebo.

The authors noted that the results of the post hoc analyses confirm that newly diagnosed patients with PAH have a worse prognosis than those who had a longer time from diagnosis, but that the reduced risk of a morbidity/mortality event on selexipag was more pronounced in newly diagnosed patients.

“From a clinical perspective, these data indicate that, despite their poorer prognosis, newly diagnosed PAH patients can respond to and benefit from early targeting of the prostacyclin pathway with selexipag, adding to the body of evidence showing that newly diagnosed patients benefit from early initiation of therapy,” the authors concluded.

Gaine S, Sitbon O, Channick RN, et al. Relationship between time from diagnosis and morbidity/mortality in pulmonary arterial hypertension: results from the phase III GRIPHON study. 

. Published online February 2, 2021. doi:10.1016/j.chest.2021.01.066

Articles

Patients with pulmonary arterial hypertension (PAH) who are treated with selexipag within 6 months of their diagnosis had a reduced risk of morbidity/mortality compared with patients who were treated longer than 6 months after diagnosis.

Newly Diagnosed Patients With PAH Benefit From Earlier Initiation of Therapy

Every week, The American Journal of Managed Care® recaps the top managed care news of the week, and you can now listen to it on our podcast, Managed Care Cast.

This week, the top managed care news included President Biden updating production timeline for nationwide vaccine availability; efforts by the National Quality Forum to measure telehealth quality and value; FDA approves first treatment for rare genetic metabolic pediatric disorder.

Listen above or through one of these podcast services:

Read more about the stories in this podcast:

What We’re Reading: States Ease COVID-19 Guidelines; Vaccines Widely Available by May; Rise in Younger, Middle Age Mortality Rates

What We're Reading: Merck to Produce J&J Vaccine; Fauci on Shifting Vaccine Strategies; HVAD Pump Implant Kits Recalled

How the National Quality Forum Plans to Measure Telehealth Quality, Value

FDA Approves First Treatment for Rare Genetic Metabolic Pediatric Disorder

Caring for the Whole Patient With Diabetes Drives ChristianaCare Pilot Success

Podcasts

Podcast: This Week in Managed Care—Updates on Nationwide Vaccine Availability and Other Health News

In early March 2020, the Association of Community Cancer Centers (ACCC) was among the last medical groups to hold its in-person meeting before the nation went into lockdown for COVID-19. And on March 1, 2021, a panel of experts shared a year’s worth of lessons from the pandemic:

After scaling up telehealth in a matter of weeks, the next step was figuring out how to use the technology in an efficient schedule

Remote patient monitoring presents new costs, but also new opportunities

It’s not just about keeping nurses motivated, it’s about 

Missed cancer screenings for breast, prostate, and colon cancer will mean a rise of later stage cancers not just for months, but for years, one expert predicted.

Some care must be delivered in person, and lessons about care delivery—starting with the waiting room—will last beyond the pandemic.

For “Cancer Care in the COVID-19 Era,” Leigh Boehmer, PharmD, BCOP, medical director of ACCC, moderated the discussion among Sibel Blau, MD, medical director, Northwest Medical Specialties, and president and chief executive officer, Quality Cancer Care Alliance

David W. Dougherty, MD, MBA, medical director, Dana Farber Cancer Institute Network; Luis M. Isola, MD, director, Cancer Clinical Programs, Mount Sinai Health System & Tisch Cancer Institute; Jody Pelusi, PhD, FNP, AOCNP, oncology nurse practitioner, Honor Health Research Institute; Mary Miller, MSN, RN-BC, OCN, Nurse Manager, Franciscan Health Cancer Center Indianapolis;

and Adam Riker, MD, FACS, chair of oncology, Anne Arundel Medical Center, DeCesaris Cancer Institute.

Panelists described challenges unlike any they had seen in their careers. There were sudden drops in screenings and patient visits, presenting both care delivery and financial crises. Clinic and hospital finances were turned upside down—beds were filled with COVID-19 patients, but with many elective surgeries canceled, revenue sources evaporated overnight. Patients with sudden job losses experienced new levels of financial toxicity—and so did staff, if a spouse lost a job or a clinic had to make cuts. Blau said in her practice, employees donated PTO to fellow staff who needed time off to deal with child care or other issues.

There was great uncertainty over how to administer care itself. Should patients with aggressive cancer have surgery? Could therapy be used instead? If so, for how long?

When the first COVID crisis started, we didn't really know what we were doing,” Riker said. In radiation oncology, “We didn't even have mask mandates the first month. … We were kind of flying by the seat of our pants, just doing what we thought was best. When it came to medical oncology and continuing to treat our patients who needed chemotherapy, we didn't test anybody, we brought them in, and we would treat them.”

Very quickly, however, facilities incorporated masks, social distancing, and extra sanitizing steps to prevent spread of disease. But patient volumes in both medical oncology and radiation oncology dropped by 90% at some points.

When it came to surgery, Riker said, care teams used a tiering system to determine “what was a cancer that needed to be operated on versus a cancer that could wait a bit.” He credited the American Society of Breast Surgeons and the American College of Surgeons for quickly releasing “excellent” recommendations for physicians and hospitals to follow.

Almost overnight, practices adopted telehealth as a way to keep in touch with patients and replace lost revenue. Telehealth was a blessing, panelists agreed, but the technology presented its own challenges. Whole new workflows had to be created overnight. Pelusi said being “on time” for a telehealth visit became an issue if these sessions were mixed in with office visits, so the schedule was adapted to cluster telehealth visits into blocks of time to avoid having patients waiting online.

Cancer centers and community practices alike had to help patients who lacked computers, WiFI or basic technical skills, and this meant new costs, including staff. Mount Sinai has procured a grant of nearly $1 million that Isola said will buy tablets for patients as well as remote monitoring licenses.

But remote monitoring also offers opportunities, he said. “Remote monitoring has provided us with a wealth of new data that we did not have access to, ranging from vitals to oxygen saturation. It really does increase the ability of the Cancer Center to deliver more and more of our care remotely at home, and we hope its going to make a big difference in the lives of our patients.”

Patient engagement is up as well, said Dougherty. By necessity, patients and caregivers had to download software to take part in a remote visit, and Dougherty said the use of MyChart is up from 15% to 20% before the pandemic to 60%, as patients become more involved in their own care.

The importance of families in making this transition cannot be overstated, panelists said. “I've heard from members over and over, they have an even greater appreciation for caregivers and family members and patients who did support folks through a technological kind of eruption around digital health during the COVID pandemic,” Boehmer said.

“I think family members saved us,” Blau said. The partnership between the family caregivers and the investments made by practices allowed care to continue, she said.

Staffing presented challenges on many fronts, from communication to motivation to just keeping them from fleeing. Oncology nurses were often rotated or “floated” to other parts of a hospital to care for COVID-19 patients, which put the nurses at higher risk and then raised questions whether they should care for cancer patients. Hospitals began to lose their nurses to better-paying travel nursing opportunities, Miller said. Riker said the travel nurse phenomenon is making surgeries hard to schedule at his center, too.

Communication is key. Working through the pandemic is hard enough, but lack of information about what the job would look like day to day or week to week added to stress, said Miller. She facilitated “chats” every few days to keep nurses informed and engaged.

“We had a very rough summer from about March until August or September, our census was way down. And then we rebounded, and now we're constantly full. And we don't have enough staff, because I couldn't hire anyone when I was floating everybody. We've been on a roller coaster for a year now, just trying to keep staff happy, trying to keep them from quitting, trying to keep them from jumping on the travel nurse bandwagon and going everywhere,” said Miller. “We’re very short staffed in the hospital setting. And it's had a very dramatic impact on all the nursing staff support staff, because we've been so busy. [There are] patients in the hallway, patients and on ventilators in the hallway. It’s been pretty traumatic on nursing staff and they're exhausted.”

Hospital finances are shaky due to the loss of elective procedures, and the pandemic is far from over. Many health care workers are suffering from burnout and will have mental health needs for months or years to come. At the practice level, unanticipated investments in technology and added staff come in the midst of ongoing challenges in healthcare transformation, Blau said. And the fallout in outcomes from deferred care is just beginning, Isola said.

“The full effects of the lack of screening for cancer is going to be felt for years to come. It's not going to be completed in the next few months. It will become evident in the next few years,” he said.

Large cancer centers have already seen “anecdotal cases” of patients with rapidly progressing multiple myeloma or other cancers that progressed quickly because patients did not see a doctor. But Isola said what’s to come are the later stage diagnoses of slower progressing cancers, such as breast, prostate, or colorectal cancer.

But some lessons of the pandemic will be positive. Some care will continue to be delivered through telehealth, and the waiting room as we know it could be a relic, Riker said.

Even before the pandemic, sitting in the waiting room was source of poor patience experience ratings, so this is an area ripe for change. “It’s a wasted experience for patients and providers alike,” he said. By doing a better job with scheduling providers, and making sure they don’t fall off schedule during the day, “We really shouldn’t have to use waiting areas for patients.”

A panel at the Association of Community Cancer Centers discusses lessons from the year of COVID-19.

Cancer Care From the COVID-19 Frontlines: “Flying by the Seat of Our Pants”

Vamshi Rao, MD, is an attending physician of Neurology at Ann and Robert H. Lurie Children’s Hospital of Chicago and assistant professor of Pediatrics (Neurology and Epilepsy) at Northwestern University Feinberg School of Medicine.

Now that there are 3 treatments options for patients with spinal muscular atrophy [SMA], do you foresee any clinical guidelines being developed and if so, what do you think would be their focus?

 I think we'd have been, over time, modifying our standard of care guidelines. The most recent modification was 2 to 3 years ago and that happened after a long time after the previous modification. This modification to the standard of care guidelines was pushed because nusinersen [Spinraza] was approved. Now, we have 2 drugs [approved] after that. So, I'm confident that we need more modification or change in our standard of care, especially because our natural history, in terms of what an individual with SMA looks like, is absolutely modified. It's different. And thank goodness, it's different. What do we do with these modified natural histories is going to be the subject of the new standard of care guidelines. The child that was not destined to sit up or walk is now sitting up and walking. What does that mean for bone health? What does that mean for their orthopedic manipulations in the future? How do we deal with scoliosis in children who were not supposed to get scoliosis? And vice versa? It's a very vast question and I don't think we'll be able to deal with every aspect of it today, but I think we will need to change and modify our standard of care guidelines. And those standard of care guidelines will also need to talk about or touch upon what we think about combination therapies.
My analogy to that I use comes from the world of oncology. When we started looking at cancers in children, we started using drugs and we found that those drugs were riddled with side effects, but they had some benefit of prolonging life. So, we kept using them. Then, we found out that we could make better drugs but we realized that we actually had to combine those drugs. Over time, we realized we not only had to combine them, but we also had to look at the genetics of the particular cancer to personalize those drugs. I think we're moving in that same direction with SMA. We started with a drug, and there were nowhere close to the side effects that we experienced with the cancer drugs, so that's definitely better. The cost of the drugs is sometimes limiting in terms of how the insurance companies allow us to combine drugs. We have to look at each child and say what stage they are, what developmental milestones they haven't hit. What is the gap that we still have in terms of these children attaining the next level? What standard of care guidelines should be put into place, as well as combination therapies and potentially new therapies in the future? So, it's a very it's a very hopeful world, but it's a world and a future filled with a ton of questions that we need to answer before we get there.

Videos

Vamshi Rao, MD, attending physician of Neurology at Ann and Robert H. Lurie Children’s Hospital of Chicago discusses how new treatments will influence future care guidelines for spinal muscular atrophy (SMA).

Dr Vamshi Rao Discusses Possible Future Guidelines for SMA Care

 (CLL) or CLL-like disease may accelerate the development of myeloid neoplasms, with the risk estimated to be 13 times higher in those with treatment than those without, according to a new study.

, may have implications for the treatment of CLL/CLL-like disease. CLL is the most common leukemia among adults in the Western world. Small lymphocytic lymphoma (SLL) is its nonleukemic variant, which can show up in the nodes, the spleen, or in tumors outside the bone marrow in the other tissues or organs. It usually has a slow course, with a median survival of more than 10 years. The introduction of more aggressive first-line drugs, including antimetabolites that mimic the structure of metabolic purines in combination with alkylating agents, has led to improved survival, particularly for myelodysplastic syndrome and acute myeloid leukemia.

The authors noted that it is well documented that the risk of secondary neoplasms in patients with other primary malignances is higher than in the general population. Some have theorized that the higher risk might be from the effects of chemotherapy or radiation, while those without prior treatment might simply be predisposed to developing the malignancies.

However, since myeloid neoplasms occur with some frequency in patients with CLL/CLL-like diseases who have not been treated, the authors said, that would have seemed to rule out the therapy causing the myeloid leukemia’s progression. The motivation for this study, therefore, was to better understand the development of myeloid neoplasms in this setting.

The authors compared the clinical and pathologic features of myeloid malignancies in 33 patients who had received treatment with 33 who had not. The cases with primary bone marrow involvement were selected from a 20-year period between 1999 and 2019. All patients with CLL/CLL-like disease diagnosed within 3 months preceding of identification of myeloid neoplasm were considered as cases “without treatment” regardless of whether treatment began in that timeframe or not.

The study showed that those who had been treated were younger (median age 65 vs 71); had a higher fraction of myelodysplastic syndrome (64% vs 36%; odds ratio [OR], 3.1; 

 <.05); a higher rate of adverse unbalanced changes to the structure and function of chromosomes, including complex changes,−5/5q- and/or −7/7q- (83% vs 28%; OR, 13.1; 

 <.001) and a shorter overall survival (median, 12 vs 44 months; 

The increase in risk may be based on the latency of myeloid progression of the leukemia and the cytogenetic profile, the authors said.

Twenty-three (70%) patients died of disease progression or complications among the 33 who were treated; 18 of 30 patients who had information available for analysis (60%) died in the group that was not treated (

The authors said they believe their study of myeloid malignancies in the setting of CLL/CLL-like disease is the first to compare patients with prior treatment for neoplasms to those without. The study shows that the 2 categories of patients with myeloid neoplasms have distinct features in clinical presentation, spectrum of myeloid neoplasm, morphology, cytogenetic profile, and clinical outcome.

More sophisticated epidemiological studies are needed to understand why these differences exist, the authors said. Previous work has suggested that the combination of several agents including fludarabine and other agents, including cyclophosphamide, rituximab and/or other therapeutic agents could have a synergistic effect. In the current study, 80% of the patients had been treated with fludarabine and alkylating agents.

They suggested that fludarabine may enhance chromosomal aberrations and mutational events by promoting the activity of the alkylating agents. Another explanation would be that it facilitates myeloid leukemogenesis by preferential selection of a myeloid clone with a mutator phenotype.

The introduction of new drugs, such as Bruton’s tyrosine kinase inhibitors, PI3 kinase inhibitors, BCL2 inhibitors (venetoclax), immunomodulators, and chimeric antigen receptor T-cell therapy may affect the epidemiology of myeloid malignancies, the authors said.

et al. Myeloid neoplasms in the setting of chronic lymphocytic leukaemia/chronic lymphocytic leukaemia-like disease: A clinicopathological study of 66 cases comparing cases with prior history of treatment to those without. 

 Published online: February 4, 2021. doi:10.1136/jclinpath-2020-207334

A recent study tries to discern if treatment for chronic lymphocytic leukemia (CLL) or CLL-like disease accelerates the risk of myeloid neoplasms.




Does Treatment for CLL Accelerate Myeloid Neoplasms? 

A recent report describes how researchers used a more precise bone marrow test in an effort to improve the outcome of a 72-year-old man with 

 (MM) by pinpointing the sensitivity of his myeloma cells to the most effective options. 

Such tests could help oncologists determine more precise therapies for older, frail patients.

The authors note that while advances in drug development have improved outcomes for younger patients, older, frail patients have not seen similar benefit. Clinical trials in hematology and oncology tend to focus on younger subjects, leaving the applicability to older patients somewhat unknown.

 researchers from the University of Colorado Anschutz Medical Campus described a test they developed called Myeloma Drug Sensitivity (My-DST) that correlates well with clinical outcomes. My-DST is a rapid drug sensitivity test of plasma cells that can deliver results within a week.

The authors surmised that frail patients have not benefited from MM advances because younger patients can tolerate 3-drug combinations, while frail patients can often tolerate only 2 at a time.

Thus, they said, it is critical to do more to ensure that the 2 selected drugs have the best chance of success. Using personalized treatment could help move the needle in treating frail patients by avoiding undertreatment, limiting attrition of subsequent lines of therapy, reducing exposure to ineffective drugs, and streamlining the management of relapses. Older patients on average attempt subsequent lines of therapy less frequently, contributing to worsened survival outcomes.

Other cancers have seen progress with personalized medicine, the authors said. For example, inhibitors of epidermal growth factor receptor mutations have been shown to be tolerated even in patients 80 or older with non

However, no precision instruments have been available for MM, which comprises 10% of all malignant cancers, with a median age of onset of 70 years. MM is a more difficult disease for which to provide a rational targeted therapy design due to the genetic heterogeneity of the disease, the study said, with multiple causes and a lack of targetable abnormal gene products.

My-DST is a phenotype-targeted approach profiling primary tumor samples. Unlike other published platforms, the functional assay avoids CD138+ cell selection of bone marrow, optimizing the viability of plasma cells and maintaining their microenvironment, the study said. As a result, indirect drug effects that occur via other immune cell populations can be measured, such as monoclonal antibody responses via antibody-dependent cellular cytotoxins.

My-DST involves bone marrow aspirants that undergo mononuclear cell selection, followed by incubation for 48 hours with a panel of antimyeloma drugs and untreated controls. Each treatment condition is then assayed for plasma cell survival after treatment using multiparameter flow cytometry.

The panel of therapies includes proteasome inhibitors, immunomodulatory drugs, steroids, alkylator chemotherapies, and monoclonal antibodies. The percentage of cell death is measured with high-throughput multiparameter flow cytometry. Drugs that kill more than 20% of cells are predicted to be active agents, the authors said.

The man in the case was diagnosed with IgA‐lambda multiple myeloma after presenting with pain in his sacrum and had a Karnofsky Performance Score (KPS) of 60; an MRI showed multilevel metastatic disease and a bone marrow biopsy showed 10%–15% monoclonal plasma cells. Cytogenetic abnormalities included an atypical IGH rearrangement, monosomy 13, and loss of 1copy of 14q32. He was staged as low-risk as per the Revised International Staging System criteria.

The My‐DST showed sensitivity to proteasome inhibitors and dexamethasone, but relative resistance to the immunomodulatory drugs.

However, the treating physician was unaware of the testing results, and the patient began induction treatment with immunomodulatory drug‐based therapy lenalidomide and dexamethasone weekly. After finishing 2 cycles of therapy, he achieved only a minor response (< 25%) in reduction in monoclonal protein.

He was then switched to bortezomib and dexamethasone as the next line of therapy. As predicted by his My‐DST result, he rapidly achieved a very good partial response as determined by an M‐spike detectable only by immunofixation and a significant decline in the lambda free light chains to normal levels and his KPS improved to 100. He did well for the next 2 years, and died a year later of natural causes, prompting the authors to call the treatment a success.

Hematologic malignancies are more promising targets for personalized medicine because patients’ bone marrow samples are readily available and are amenable to culture for measuring drug effects, the researchers said.

The authors said even though advancing age is the greatest risk factor of cancer, clinicians can’t rely on chronological age as a way to predict drug tolerance or treatment outcomes in older patients.

“Thus, going forward, it is of utmost importance to include a universally accepted frailty scoring system in cancer clinical trial enrollment to quantify the bias toward younger patients and allow better subanalyses of broader findings in frail persons,” the authors wrote.

Reiman, LT, Walker, ZJ, Babcock, LR, et al. A case for improving frail patient outcomes in multiple myeloma with phenotype‐driven personalized medicine. 

. Published online February 16, 2021. doi:10.1002/aac2.12022

Researchers describe the case of an older patient who underwent myeloma drug sensitivity testing as part of an effort to identify the therapies most likely to produce a response in this difficult-to-treat population.



Report Describes Case of Improved Outcome in MM With Personalized Medicine 

 to clinical trials based on their next-generation sequencing (NGS) testing results carries poor predictive value, claim researchers, who say efforts are needed to alleviate this burden put on the provider.

According to the researchers, 88% of trials initially matched to patients were eventually classified as false positives when manually screened by a provider 

Typically, when a patient gets their NGS report with clinical trial recommendations based on their diagnosis and identified biomarkers, physicians review the report to eliminate any false-positive trials to best determine appropriate trials for their patients. Data has indicated that research nurses can spend between 4 to 9 hours determining a patient’s eligibility for a clinical trial.

“As the cost of sequencing decreases and the clinical focus moves from limited gene-panel testing to whole-exon sequencing, RNA sequencing, and ultimately to whole-genome sequencing, the pool of potentially matching trials—that requires manual review—will expand,” reflected the researchers. “Informatics tools that assist in refining the trials that need to be manually reviewed or suggest potential matches based on the patient’s clinical and biomarker profile may reduce the manual burden of this process and reduce the barrier to trial enrollment.”

Across the 82 patients included in the study, the algorithms curated 808 trials, which were then filtered to 755. Of these, just 87 were considered matched trials following the manual prescreening.

The high rate of false positives identified by the researchers in the study stem from several factors, most often due to administrative details of the trials. For example, patients were often matched to a clinical trial that was either closed to enrollment, did not have openings, was never opened at the study site, or was halted while other arms of the trial continued.

On a global level, data is sometimes not readily be available to the local institution in real time, particularly for phase 1 trials.

“it is important to uncover the factors that result in a high rate of false positives while generating clinical trial recommendations,” explain the researchers. “Such studies can help to drive efficiency and improve the design for future trial matching efforts. Furthermore, such studies should be designed such that trial recommendations are sent to physicians in real time to maximize patient impact and generate enough learnings to inform design of a larger pragmatic study.”

Other factors influencing the false-positive rate included the presence of multiple malignancies.

Jain N, Culley A, Micheel C, Osterman T, Levy M. Learnings from precision clinical trial matching for oncology patients who received NGS testing. 

 Published online February 24, 2021. doi:10.1200/CCI.20.00142

According to new research, 88% of trials initially matched to patients were eventually classified as false positives when manually screened by a provider.



Automated Clinical Trial Matching Based on NGS Yields High Rates of False Positives

Patients with a lower socioeconomic status or more severe or treatment-refractory 

 were more likely to stop biologic use than other patients with severe asthma, according to a poster presented at the American Academy of Allergy, Asthma & Immunology 2021 Annual Meeting.

These patients were also more frequently living in urban areas and receiving care from pulmonologists instead of allergists or immunologists.

Severe asthma is estimated to impact between 5% and 10% of individuals with asthma. Patients with severe asthma often need care from a subspecialist and intensive therapy.

Although biologic therapies have been shown to reduce exacerbation risks associated with severe uncontrolled asthma and are increasingly being used, real-world data characterizing their use in subspecialist-treated patients with severe asthma is not well known.

The CHRONICLE clinical trial is an ongoing observational study incorporating real-world data on the patterns of patients aged 18 years or older stopping, switching, and continuing use of biologics in the severe asthma population. Patients had to be receiving a monoclonal antibody therapy, a systemic corticosteroid, or other systemic immunosuppressants for 50% or more during the previous year.

Investigators compared clinical characteristics and outcomes associated with asthma for patients enrolled from February 2018 through February 2020 who switched from 1 biologic to another, stopped biologic therapy, or continued biologic use. Data was collected at the time of study enrollment and was updated every 6 months.

Of the 1884 patients enrolled, 1294 (69%) used at least 1 biologic during the study period. In total, there were 1494 biologics uses recorded for 5 biologics:

There were 134 switches, 101 stops, and 1222 continuations, with several of the 1294 patients qualifying for more than 1 category of biologic use. More than 90% of patients with severe asthma taking a biologic continued taking a biologic through the last data collection compared to 10% of patients who switched biologics and 8% of patients who stopped.

Patients who stopped biologics were more often diagnosed with severe asthma at a younger age, less likely to have full-time employment, more likely to have Medicaid insurance, and more likely to be living in urban areas than patients who continued using a biologic or switched to another biologic.

These patients were also more often treated by a pulmonologist, more likely to have disability related to their asthma, had more maintenance systemic corticosteroid use, and had a lower quality of life as characterized by lower scores for the St. George Respiratory Questionnaire.

Patients who switched from 1 biologic to another were found to have a higher prevalence of nasal or sinus polyps and sensitivity to nonsteroid medications with anti-inflammatory effects.

Investigators noted that the most common reasons reported for switching from or stopping biologic therapy were worsening asthma, reduced medication effectiveness, and medication ineffectiveness.

The investigators noted that patients who continued biologic use likely had better disease control at study enrollment, suggesting that patients with less asthma control at baseline may not see a benefit with biologic therapy. For these patients, more therapeutic options might need to be explored in the future.

Soong W, Ambrose CS, Carstens D, Trudo F, Moore WC, Panettieri RA. Which severe asthma patietns are switching, stopping, or continuing biologic treatments? Presented at the American Academy of Allergy, Asthma & Immunology 2021 Annual Meeting, February 26-March 1, 2021; Poster 178.

Although 90% of patients with severe asthma choose to continue using a biologic, patients with worse disease control at baseline or with lower socioeconomic status (SES) may be more likely to cease biologic use, according to a poster presented at the American Academy of Allergy, Asthma & Immunology 2021 Annual Meeting.

Patients With Lower SES or Uncontrolled Disease May Be More Likely to Stop Biologic Therapy

 is well known, little information has been available about the renal effect on pediatric patients hospitalized with the virus and multisystem inflammatory syndrome in children (MIS-C).

But a retrospective study out this week examining the effects of COVID-19 and the associated inflammatory syndrome on 

 (AKI) in these young patients found that the complication was not uncommon.

, was carried out in the New York City area in 4 hospitals owned by Northwell Health, looking at hospitalizations from March 9, 2020, through August 13, 2020.

The researchers used the CDC definition for MIS-C, which includes children who presented with fevers, significant evidence of inflammation, and evidence of dysfunction in 2 or more organs, and tested positive for current or recent SARS-CoV-2 infection.

Of the 166 children admitted for acute COVID-19 or MIS-C, 152 patients were included in the study, with 97 patients (63%) admitted for acute COVID-19 and 55 patients (36.2%) diagnosed with MIS-C.

Overall, AKI developed in 18 (11.8%) of all patients.

Of children diagnosed with COVID-19 alone, the median age was 8.2 years and more than half were male. Eight patients (8.2%) developed AKI; 4 presented with AKI on admission; 6 had stage 1 AKI, and 2 had stage 3 AKI. There were no significant differences in age, sex, race, and body mass index (BMI) among children with and without AKI. Other findings showed that 50% of patients with AKI had gastrointestinal symptoms, and AKI was linked with significantly lower serum calcium and albumin and significantly higher baseline white blood cell count.

Children hospitalized with MIS-C were a little younger (median age, 7.5 years) and again largely male. AKI was higher in these patients (10, or 18.2%) than in those with COVID-19; 80% had AKI on admission. Those with AKI had greater BMI and all had gastrointestinal symptoms. In addition, patients with AKI had lower median left ventricular ejection fraction as well as systolic dysfunction.

In addition, children identified as Black were 2.86 times more likely to have AKI (95% CI, 1.04-7.93; 

Patients with AKI had higher rates of vasopressor treatment and ionotropic support. Continuous kidney replacement therapy was needed in 2 children with COVID-19; 2 others needed extracorporeal membrane oxygenation. Two patients in the COVID-19 group died; no patients died in the MIS-C cohort.

The cases of AKI resolved by the time of discharge, the authors said, although these children had longer hospital stays.

Previous estimates of AKI in children have varied from 1.4% to 44%, and the authors said that likely reflects the heterogeneity of study populations or definitions of AKI. 

"Further research in larger cohorts is needed to characterize AKI risk factors in children with acute-COVID-19 and MIS-C," the authors concluded.

Basalely A, Gurusinghe S, Schneider J, et al. Acute kidney injury in pediatric patients hospitalized with acute COVID-19 and Multisystem Inflammatory Syndrome in Children associated with COVID-19. 

Published online March 3, 2021. doi:10.1016/j.kint.2021.02.026

A retrospective study looking at pediatric patients hospitalized in 4 New York hospitals in 2020 with COVID-19 or multisystem inflammatory syndrome in children (MIS-C) found that acute kidney injury (AKI) occurred in 11.8% of patients. 

Study Describes AKI Incidence in Children With COVID-19, MIS-C 

Although federal guidelines recommend patients with 

 have regular physical activity, actual exercise rates lag. Survey results presented recently at the American Academy of Allergy, Asthma & Immunology (AAAAI) 2021 Annual Meeting found that most specialists were not aware of these physical recommendations, however, suggesting a possible role for them to play.

The researchers sent a 15-item survey to 979 randomly selected AAAAI members to ask about their self-reported awareness of physical activity recommendations and their current clinical practices. Respondents were asked to rate their knowledge about a variety of topics related to asthma and physical activity on a scale of 1 to 5 (1 = no knowledge, 5 = very knowledgeable).

The overall survey response rate was small (9.3%); of those who did answer, the majority were allergists or immunologists with an average of 18.1 years in independent practice.

Of those who responded, 80% of participants were not aware of specific physical activity guidelines for patients with asthma, while 66% said they were aware that moderate exercise has shown improved outcomes for these patients.

The survey also revealed the 3 main barriers to more direct involvement for providers to counsel their patients with asthma about exercise: limited time to discuss, lack of knowledge about how and when to refer patients, and the need to prioritize other health behaviors.

The survey asked about existing knowledge gaps that needed to be filled in order to provide assistance to their patients. Most were unsure about how much they knew about how to refer patients to a supervised exercise program, which patients to refer, or how to counsel patients. Some respondents reported having no knowledge about any of those considerations.

97% agreed that patients with asthma should exercise, while 84% agreed when asked if patients with severe asthma should exercise

90% support the idea of incorporating exercise counseling into practice, while only 69% actually did so

62% indicated they were knowledgeable about when to counsel patients on exercise

53% said they knew how to encourage patients to participate in exercise

Most agreed that there are 5 ways to facilitate this kind of knowledge to their patients, including patient handouts, posters in the waiting room, exercise referral forms, practitioner education, or emailed information to providers.

Nyenhuis SM, Gregory KL, Kahwash BM, Sharp LK. Asthma care provider perspectives on exercise promotion in people with asthma: An examination of knowledge, practices, barriers, and facilitators. Presented at the American Academy of Allergy, Asthma & Immunology 2021 Annual Meeting, February 26-March 1, 2021; Poster 127.

Asthma and immunology specialists responding to a survey about physical activity for patients with asthma were mostly unaware of any guidelines but seemed willing to learn more about how to incorporate them into practice.

Encouraging Patients With Asthma to Exercise Easier Said Than Done, Survey Finds 

Karen Kobelski is the Vice President and General Manager of Clinical Surveillance, Compliance & Data Solutions at Wolters Kluwer. She brings more than 25 years of experience to her position, which expands her previous leadership role over the Safety & Surveillance group to also include the Health Language portfolio of data normalization solutions.

CMS has made clear its intent to provide patients access to their health information in a user-friendly format, when and where they need it. The 

Interoperability and Patient Access final rule

 applies to CMS-regulated health plans, and the agency fully expects health plans to be ready for enforcement starting on July 1, 2021. That means there are just a few months left to prepare.

CMS further communicated their intent to advance the cause of interoperability when they released the 

Reducing Provider and Patient Burden Proposed Rule

 in December of last year. This rule would require automation of pre-certification activities using fast health care interoperability resources 

The federal push to liberate patient data requires a lot of work on the part of payers and their technology partners. In addition to modernizing legacy IT infrastructures, payers will need to be ready to shoulder the increasing burden of member transparency, and some payers are further along than others.

Plans should make no mistake that enforcement is coming and be prepared to do much more than check a box. Disparate and siloed data across health plan organizations will need to be completely transformed to achieve compliance but also to ensure sensitive patient information is protected and patients can understand the information being shared with them. Balancing compliance with patient comprehension and privacy is no small feat, but best practices are emerging.

CMS has identified FHIR as the key to unlocking valuable data for consumer and developer use and made clear its commitment to FHIR-based APIs in supporting the needs of patients and fueling innovation.

By July 1, payers must have in place a FHIR-based API that “allows patients to easily access their claims and encounter information, including cost, as well as a defined sub-set of their clinical information through third-party applications of their choice.” Further, as part of the 

, the ONC adopted the US Core Data for Interoperability standard for electronic health information to be accessed and shared using certified API technology. This standardized set comprises 16 data classes and 52 data elements.

Health plans will need to have robust data management and governance strategies in place. First, a single source of reverential data is required for the accurate exchange of information through FHIR APIs. Second, the ability to map non-standard data to the common health care terminologies that are identified in the FHIR implementation guides will become an essential component of their interoperability strategy. In short, a FHIR terminology service with advanced data mapping capabilities will prove to be a strategic advantage as health plans strive to capture maximum value from their data.

Certainly, the increased exchange of information will present new challenges to health data security and privacy. As health care organizations deploy the frameworks to support meaningful data sharing and greater care coordination across the continuum, one area that must not be overlooked is the compliant protection of sensitive health information. The mechanism for sharing data may be changing but the need to protect that data as it is exchanged remains the same.

Health plans may consider the use of sensitivity codes to help identify and filter sensitive diagnoses, procedures, labs and drugs across 6 key categories:

Sensitivity codes will require ongoing management and many payers are looking to experienced partners to fill that role.

Consumer-friendly descriptors for comprehension

Perhaps most important is acknowledging that for patients to act on their health data, they need to be able to understand it. The gap that exists between the language that clinicians and payers use and what patients understand is well known, but the Patient Access rule is forcing the issue to the fore.

The right strategy for effectively communicating with members and increasing transparency begins with terminology management that can generate consumer-friendly descriptions alongside industry codes within patient-facing documents. For instance, while a typical claim might designate a foodborne bacillus cereus intoxication, an accompanying consumer-friendly description would simply read food poisoning. These consumer-friendly descriptions may also be used in member portals, 

, and paper-based communications to truly engage patients.

By taking proactive steps to communicate with stakeholders—especially patients—payers can design and execute an implementation plan that not only satisfies the requirements of the Interoperability and Patient Access final rule but also moves the industry closer to the goal of putting patients truly at the center of health care.

In preparing for the upcoming implementation of the Interoperability and Patient Access final rule by CMS, best practices for health plans include prioritizing data mapping, sensitivity codes for privacy, and consumer-friendly language in accessible data for patients.

Contributor: How Balancing Compliance, Comprehension, and Privacy Can Optimize Access to Patient Data

The American system of insurance doesn’t work, because we give the best care at the lowest cost to the people who don't need it and the worst care at the highest cost to the people who do, noted Robert K. Massie, Jr, PhD, MA, of the Society for Progress. He was born with severe factor VIII hemophilia in August 1956 and contracted 

 in 1978, as well as hepatitis C, from contaminated blood products—and received care outside of the United States growing up, which he credits with saving his life.

Is insurance in the United States broken?

I mean, let me be really blunt about this. Most Americans do not realize how ridiculous we look to the rest of the world, which has solved the medical distribution problem going back to 1948.

I've traveled all over the world, and I just want to tell you: the absurdities, the bankruptcies, the failures, the poor medical outcomes that happen in the United States do not take place in most other countries. I've been treated in France, I've been treated in England, which people make fun of, and yet it's wonderful, wonderful care.

The American system of insurance doesn’t work, noted Robert K. Massie, Jr, PhD, MA, of the Society for Progress.