Renuka Tipirneni, MD, of the University of Michigan, was named the recipient of the 2020 Seema S. Sonnad Emerging Leader in Managed Care Research Award.

Congratulations to the 2020 Recipient of the Emerging Leader in Managed Care Research Award!

The Mediterranean diet, which is known to have health benefits, may help prevent rheumatoid arthritis in current or previous smoker.

Mediterranean Diet May Prevent RA in Current or Previous Smokers

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 Hold Key to Vascepa's Dramatic CV Benefits

The inappropriate use of direct-acting oral anticoagulants (DOACs) increases the risk of adverse events (AEs), but use of a population health management tool (PMT) may reduce AEs by identifying questionable prescribing practices early.

 sought to determine if the use of a PMT improved the quality of DOAC dosing compared with traditional delivery approaches by analyzing the Veterans Health Administration (VHA) PMT for monitoring patients on DOACs.

Though DOACs do not require therapeutic monitoring, they are considered high-risk medications with specified dosing related to both indication and patient-specific factors. Off-label dosing of DOACs has been connected with both bleeding and thrombotic events, so given these potential risks there is great value in assessing the impact of a DOAC PMT on dosing.

This retrospective, cross-sectional study was conducted with existing data pulled from the VHA Corporate Data Warehouse across 40 VHA medical centers. The 20 medical centers in the “lowest quintile,” defined as the frequency of PMT report executions over the prior 365 days, were classified as the standard of care (SOC) group while the remaining 20 medical centers were classified as the “PMT User Group.” The latter accessed the tool between 5231 and 19,585 times per year.

In the PMT user medical centers, there were 47,491 DOAC patients analyzed while the SOC centers analyzed data from 27,288 DOAC patients. The authors found that within the 20 PMT user medical centers, 25% (n = 5) were classified as “high” questionable dosage rates and 75% (n = 15) were classified as “low” questionable dosage rates. Within the SOC group, the opposite was found: 75% (n = 15) were classified as “high” questionable dosage rates while 25% (n = 5) were “low” questionable dosage rates.

Though the findings were statistically significant (

 = .002), they were not found to be clinically significant due to the relatively few absolute differences between groups with respect to age, weight, creatinine clearance, disease indication, and medication prescribing rates. Importantly, the PMT user group was determined to have a significantly lower questionable dosage rate (13.2%) compared with the SOC group (17.5%).

The most pronounced impact was seen among the subgroup of patients with atrial fibrillation (AF). The tool was associated with a 5.1% absolute reduction in questionable dosing rates in AF. These questionable dosing rates were also reduced through the use of the tool in the subgroups of patients taking apixaban and dabigatran, as well patients with AF plus venous thrombolism.

This finding provides reason to believe that more widespread adoption of the tool would meaningfully improve patient outcomes given the risks of DOAC dosages, according to the authors.

“Fully evaluating the impact of PMTs on clinical outcomes is still necessary,” they concluded. “For the DOAC PMT specifically, future research studies could include a prospective study evaluating changes in dosing, serious bleeding, thromboembolic events, hospitalizations, and mortality before and after transition to using a DOAC PMT.”

Rossier C, Spoutz P, Schaefer M, Allen A, Patterson M. Working smarter, not harder: evaluating a population health approach to anticoagulation therapy management. 

Published online November 22, 2020. doi:10.1007/s11239-020-02341-y

Articles

The use of a population health management tool may reduce adverse events that may arise from the inappropriate prescribing of direct-acting oral anticoagulants (DOACs).

Population Management Tool Reduces Adverse Events of DOACs

 (AYA) are known to be a distinct population when it comes to cancer incidence and care, but long-term data on the trends and characteristics of those cancers is still lacking. A new 

 from the Penn State College of Medicine published in 

 aiming to identify those trends found that the rate of 

 increased by nearly 30% from 1973 to 2015.

"Adolescents and young adults are a distinct cancer population," study author Nicholas Zaorsky, assistant professor of radiation oncology and public health sciences at Penn State, said in a 

 "But they are often grouped together with pediatric or adult patients in research studies. It is important to study how this group is distinct so that 

 can be developed to address the increase in cases."

Study authors wrote that although there has been a significant increase in 

-focused research recently, the fact that research has historically focused on childhood and adult cancers still leaves a knowledge gap regarding guidelines for diagnosis, treatment, and monitoring of AYA patients.

The main objectives of the study were to identify the patient demographic characteristics, frequencies of cancer types, and cancer incidence trends over time in AYAs aged 15 to 39. The retrospective, cross-sectional, population-based study included 497,452 AYAs diagnosed between 1973 and 2015, using data from the Surveillance, Epidemiology, and End Results (SEER) database. The population of the U.S.-based study was geographically diverse, 59.1% female, and 79.9% White, meant to represent the demographics of the country’s population.

Researchers found that overall, the rate of cancer in AYAs increased by 29.6% between 1973 and 2015. The mean annual percentage change (APC) in the rate of cancer in AYAs was 0.537 per 100,000 persons (95% CI, 0.426-0.648; 

 < .001), and kidney cancer incidence increased at the greatest rate in both males and females ([APC, 3.572; 95% CI, 3.049-4.097; 

 < .001] and [APC, 3.632; 95% CI, 3.105-4.162; 

Despite kidney cancer having the greatest incidence increase, the authors note that its relatively low absolute incidence rate means it may have minimal impact on the increased rate of cancer overall. Cancers with larger absolute incidence numbers—including gastrointestinal tract carcinoma, thyroid carcinoma, melanoma, non-Hodgkin lymphoma, and germ cell and trophoblastic neoplasms of the gonads—contributed more significantly to the overall increase in the AYA cancer rate.

In females, 24.7% were diagnosed with breast carcinoma, 16.6% with thyroid carcinoma, and 11.5% with cervix and uterus carcinoma. In males, 18.5% were diagnosed with testicular cancer, 10.2% with melanoma, and 9.6% with non-Hodgkin lymphoma. In general, the relative incidence of carcinomas increased while the relative incidence of leukemias, lymphomas, germ cell and trophoblastic neoplasms, and neoplasms of the central nervous system decreased as AYAs aged.

The data show that cancer in AYAs is a growing problem and that it has a distinct distribution, the study authors concluded. While more research is needed, the findings regarding the unique patterns in AYA cancers can also help inform diagnosis and treatment options in this age group.

"These cancers all have unique risk factors," Zaorsky said. "Now that there is a better understanding of the types of cancer that are prevalent and rising in this age group, prevention, screening, diagnosis and treatment protocols specifically targeted to this population should be developed.”

1. Scott AR, Stoltzfus KC, Tchelebi LT, et al. Trends in Cancer Incidence in US Adolescents and Young Adults, 1973-2015. 

. 2020;3(12):e2027738. doi:10.1001/jamanetworkopen.2020.27738

2. Cancer cases are rising in adolescents and young adults. News release. Penn State College of Medicine; December 1, 2020. Accessed December 3, 2020. 

https://news.psu.edu/story/640279/2020/12/01/research/cancer-cases-are-rising-adolescents-and-young-adults

A new study published in JAMA Network Open found that the rate of cancer in adolescents and young adults increased by nearly 30% from 1973 to 2015.

AYA Cancer Rates Are Rising, New Study Finds 

Bill Kramer, MBA, is the executive director for National Health Policy at Pacific Business Group on Health.

The appointment of a new conservative justice to the Supreme Court raised serious concerns that the legal challenge to the Affordable Care Act (ACA) would be successful. Following oral arguments over the law’s individual mandate in front of the Supreme Court on November 10, however, it appears most of the law is likely to survive. Still, we’re not out of the woods and it will be sometime before we know the outcome.

Overturning the law would entirely be cataclysmic. The primary impact, of course, would be on the estimated 12 million people covered under Medicaid who became eligible because of the ACA who would lose their coverage, the 9 million who receive subsidized health insurance through the federal and state exchanges, and those with preexisting conditions who would likely be screened out of individual coverage.

Although people who get their health insurance on the job were largely untouched by the ACA, large employers—and by extension, their employees—have an interest in the outcome of the SCOTUS decision. Here, we explore 3 ways a ruling against the ACA could impact employer-sponsored health insurance.

The ACA ushered in coverage for adult children up to age 26 and did away with lifetime dollar limits on insurance coverage, a critical protection for people with serious illnesses, such as cancer, who easily wrack up eye-popping medical bills. Paying in full for preventive services with no cost-sharing, such as colonoscopies and mammograms, was also a requirement of the ACA with which large, self-insured employers were required to comply. If the law were overturned, employers would have to decide whether to eliminate these enhanced benefits. Based on surveys of our members, who are jumbo private employers and public organizations, it’s unlikely that many would do so. The story for midsize employers, however, may be very different.

2) Add Costs to Employee Health Insurance

 the Pacific Business Group on Health found that a big increase in the number of uninsured people due to a full repeal of the ACA would dramatically reduce hospital revenues. That’s likely to put upward pressure on prices paid by those with employer-sponsored coverage. It would also likely lead to poorer health for millions of people no longer able to access health care services such as preventive screenings, treatment for chronic conditions, mental health, and opioid abuse. This means that the pool of potential employees would be less healthy, leading to higher health benefits costs for newly hired employees. In other words, employers have a stake in ensuring that everyone has coverage and access to needed health services.

3) Tools to Encourage Competition and Lower Prices

The ACA also created tools intended to increase market competition and lower costs. Under the law, for example, a new mechanism for approving biosimilars offered the potential of new drugs that could introduce price competition for expensive biologic medicines. The Center for Medicare & Medicaid Innovation was established with the goal of changing the way doctors and hospitals are paid to reward improved quality and/or lower costs. And the development of accountable care organizations created the potential for improved care coordination and quality, as well as lower costs. While less direct in their impact, over time the loss of these tools could lead to higher overall costs for employers and the millions of Americans who get their health insurance on the job.

Although the repeal of the ACA would have serious consequences, it is not the only important health policy issue for employers and their employees. In addition to dealing with the coronavirus disease 2019 pandemic, policymakers must address the ongoing crisis of high health care costs. 

 is not getting the attention it deserves. We need to find ways to strengthen primary care, accelerate the movement to population-based payment models for hospitals and clinicians, prohibit anticompetitive practices by certain health care industry players, and address the problem of industry consolidation.

Our nation faces serious health care challenges, including the possibility of ACA repeal. We will need to find ways to overcome partisan differences to address the ongoing problems of inadequate coverage and access, high costs, inconsistent quality, and health inequities. Employers can and should make their voices heard in these debates.

Contributor: 3 Reasons Employers Should Be Concerned About ACA Repeal

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

Using machine learning methods researchers were able to extract records of patients with 

 (RA) from electronic health record (EHR) data with high precision, enabling research on very large populations with this condition for limited costs. Study 

Although financial codes are often used to extract diagnoses from EHRs, this methodology can lead to false positives. To circumvent this issue, query-like algorithms can be constructed but require knowledge on the diagnosis of interest and are highly language- and center-specific, the researchers explained.

“Advancements in natural language processing and machine learning have created great potential for processing format-free text data such as those in EHRs,” the authors wrote. “A major advantage of machine learning is that it can learn extraction patterns from a set of training examples, relieving the need for extensive domain knowledge.”

To develop an easily implementable workflow that builds a machine learning algorithm in order to accurately identify patients with RA from format-free test fields in EHRs, the researchers employed 2 EHR health data sets: Leiden from the Netherlands and Erlangen from Germany.

The Leiden data set consisted of information from 23,300 patients who visited the rheumatology outpatient clinic of a university medical center since 2011. A total of 11,786 patients were eligible for inclusion. Researchers randomly selected 3000 patients and extracted the entries for up to 1 year of follow-up. Data were then divided into 2 independent sets: Leiden-A (n = 2000) for model selection, training, and validation and Leiden-B (n = 1000) for independent testing.

After these analyses were performed, investigators evaluated the universal application of the pipeline by applying it to the Erlangen data set divided into model (Erlangen-A; n = 4293) and testing (Erlangen-B; n = 478) sets. A health care professional manually reviewed all entries in the Leiden and Erlangen sets.

The pipeline consisted of word segmentation, lowercase conversion, stop word removal, word normalization and vectorization while default scikit-learn implementations were used to create the machine learning models. Seven different machine learning methods were tested and for each sample set, different models were trained and evaluated in equally sized training and validation sets.

Researchers also “employed a naïve word-matching algorithm that assigns RA status to a sample when the text contained RA (in German or Dutch) or its abbreviation appeared in the chart. Each classifier gives a score between 0 and 1 that [researchers] interpreted as a probability for each sample to be a case.”

The word-matching algorithm demonstrated mixed performance (area under the receiver operating characteristic curve [AUROC] 0.90; area under the precision recall curve [AUPRC] 0.33; F1 score 0.55)

4 methods significantly outperformed word-matching, with support vector machines performing best (AUROC 0.98; AUPRC 0.88; F1 score 0.83)

Applying this support vector machine classifier to the test data resulted in a similarly high performance (F1 score 0.81; positive predictive value [PPV] 0.94)

Using the support vector machines, researchers could identify 2873 patients with RA in less than 7 seconds out of the complete collection of 23,300 patients

gradient boosting performed best (AUROC 0.94; AUPRC 0.85; F1 score 0.82) in the training set

gradient boosting resulted in good results in the test data (F1 score 0.67; PPV 0.97)

When cut-offs for case selection from the first data sets (in both Leiden and Erlangen) were defined aiming for a high sensitivity or high PPV, researchers observed robust performances in the second data sets (Leiden-B: PPV 0.94 and sensitivity 0.93; Erlangen-B: PPV 0.97 and sensitivity 0.84). In other words, depending on the chosen cut-off, case selection can be tailored to being highly precise or sensitive.

Because this approach is more precise, doesn’t require standardization, and ensures high performance within the center, the investigators argue their approach of making a center-specific algorithm is more viable and efficient than an application of an algorithm developed outside the center.

Deploying the pipeline does require user familiarity with implementation software, marking a limitation. To determine ease of use, a future usability study ought to be conducted, the researchers wrote. Additional limitations include the evaluation of the workflow in only 2 centers and the potential for fine-tuning hyperparameters to optimize the model’s performance.

“The workflow facilitates the production of highly reliable center-specific machine learning methods for the identification of patients with rheumatoid arthritis from format-free text fields,” the authors concluded. “Our results suggest that our workflow can easily be applied to other EHRs or other diseases and is not restrained by specific language, EHR software, or treatments. This methodology of machine learning for EHR data extraction facilitates cohort studies (with regard to cost and size).”

Maarseveen TD, Meinderink T, Reinders MJT, et al. Machine learning electronic health record identification of patients with rheumatoid arthritis: algorithm pipeline development and validation study. 

Using machine learning methods researchers were able to extract records of patients with rheumatoid arthritis (RA) from electronic health record data with high precision, enabling research on very large populations with this condition for limited costs.

Algorithm Pipeline Aids in Identification of Patients With RA

Making sure patients have a strong medical home and close follow-up is one way to reduce glomerular disease 

 among children, said Jill Krissberg, MD, a pediatric nephrology fellow at Stanford University School of Medicine.

What strategies can help prevent socioeconomic consequences of glomerular disease in Black children or more effectively treat the disease in this population?

We acknowledge that this is really just the beginning for this work, but you can start to try to see what are specific areas we could target. So, one could be making sure that they have a strong medical home and close follow-up. Patients who you know are at increased risk of complications, making sure that they are comfortable in managing their disease, strategies to improve medication adherence and accessibility. Sometimes that's where policy can come in to make sure they have good access to medications that patients can afford. There is also the need of, maybe we need to be looking at different, more effective strategies and seeing how our treatments differ across racial/ethnic groups because maybe the effectiveness differs across these groups. We should be treating diseases differently based on other risk factors.


While this cohort was only in pediatrics, you can start to think sometimes about how a child with focal segmental glomerulosclerosis, where this disease is going to be chronic, how this could affect them long term. If somebody is already at risk of lower academic achievement and they have a chronic disease that decreases their school success. Then they have difficulty getting higher education, having a steady job, having reliable access to insurance. Then you can kind of see how these things interplay and interplay longitudinally as the disease is on a chronic trajectory.

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Making sure patients have a strong medical home and close follow-up is one way to reduce glomerular disease disparities among children, said Jill Krissberg, MD, a pediatric nephrology fellow at Stanford University School of Medicine.

Dr Jill Krissberg on Addressing Racial Disparities in Glomerular Disease

Among 11 developed countries, the United States has the highest maternal mortality rate, a relative undersupply of maternity care providers, and is the only country not to guarantee access to provider home visits or paid parental leave in the postpartum period, a recent 

 from The Commonwealth Fund concluded. Compared with any other wealthy nation, the United States also spends the 

 of its gross domestic product on health care.

Maternal deaths have been increasing in the United States since 2000, and although 700 pregnancy-related deaths 

, two-thirds of these deaths are considered to be preventable.

In an issue brief, researchers assessed maternal mortality, maternal care workforce composition, and access to postpartum care in 10 high-income nations and compared findings with the United States. Data from Australia, Canada, France, Germany, the Netherlands, New Zealand, Norway, Sweden, Switzerland, and the United Kingdom were gleaned from 2020 health statistics compiled by the Organization for Economic Co-operation and Development. US data were taken from the CDC’s Pregnancy Mortality Surveillance System.

According to the World Health Organization (WHO), maternal mortality is defined as “the death of a woman while pregnant or within 42 days of termination of pregnancy, irrespective of the duration and site of the pregnancy, from any cause related to or aggravated by the pregnancy or its management but not from accidental or incidental causes.”

Overall pregnancy-related mortality in the United States occurs at an average rate of 17.2 deaths per 100,000 live births. Leading causes of death include cardiovascular conditions, hemorrhage, and infection. However, in the Netherlands, Norway, and New Zealand, that rate drops to 3 or fewer women per 100,000.

More than 50% of pregnancy-related deaths in the United States occur after the birth of the child, or post partum. Any death within 1 year of the end of pregnancy due to a pregnancy complication or a death during pregnancy is classified as a pregnancy-related death. Deaths that occur within 1 week post partum (19% of all maternal deaths) are largely attributed to severe bleeding, high blood pressure, and infection.

When it comes to care providers, the United States and Canada “have the lowest overall supply of midwives and obstetrician-gynecologists (OB-GYNs) — 12 and 15 providers per 1000 live births, respectively,” whereas all other countries have a supply that is between 2 and 6 times greater.

Midwives differ from OB-GYNs in that they help manage a normal pregnancy, assist with childbirth, and provide care during the postpartum period. In contrast, OB-GYNs are physicians trained to identify issues and intervene should abnormal conditions arise. OB-GYNs typically only provide care in hospital-based settings.

The role of midwives has been found to be comparable or preferable to physician-led care in terms of mother and baby outcomes and more efficient use of health care resources. WHO recommends midwives as an evidence-based approach to reducing maternal mortality.

According to the American College of Nurse Midwives, the “US maternity workforce is upside down relative to patient needs.” Although OB-GYNs outnumber midwives in the United States and Canada, in most other countries the inverse is true.

“Midwives provide most prenatal care and deliveries in the U.K. and the Netherlands— countries considered to have among the strongest primary care systems in Europe. Dutch midwives also deliver home births, which represent 13% of all births, the highest rate of any developed countries,” the report reads.

Midwife services are not uniformly covered by private insurance plans in the United States, whereas both midwifery and obstetrician care services are covered by universal health insurance in some other countries.

), Medicaid programs are required to cover midwifery care, but “the supply of providers is often so low that beneficiaries are often unable to access these services.” State licensure laws, restrictive scope-of-practice laws, and rules requiring physician supervision of midwives may all contribute to the low supply of midwives in the United States. Medicaid also currently covers 

 in the United States but only extends coverage for a maximum of 60 days post partum.

Furthermore, in some states, appeals courts have ruled to 

 to Planned Parenthood clinics, which provide a number of health services to low-income women, including 

Postpartum care, including home visits by midwives, also improves mental health and breastfeeding outcomes among new mothers and is associated with reduced health care costs. Some Medicaid beneficiaries can receive these services in the United States, but all other countries included in the report guarantee at least 1 visit within 1 week of birth.

 of nearly 600,000 commercially insured childbearing individuals found that the prevalence of suicidal ideation and intentional self-harm (suicidality) occurring in the year preceding or following birth increased substantially from 2006 to 2017.

In 2006, suicidality prevalence was estimated at 0.2% per 100 individuals and rose to 0.6% per 100 individuals in 2017, whereas diagnoses of suicidality with comorbid depression or anxiety increased from 1.2% in 2006 to 2.6% in 2017 (per 100 individuals for both). Over the course of the study period, younger, non-Hispanic Black, and lower-income individuals experienced larger increases in suicidality.

“Policy makers, health plans, and clinicians should ensure access to universal suicidality screening and appropriate treatment for pregnant and postpartum individuals and seek health system and policy avenues to mitigate this growing public health crisis, particularly for high-risk groups,” the authors of that analysis wrote.

In the United States, non-Hispanic Black women are more than 3 times more likely to have a maternal death than White women. Non-Hispanic Black women are also significantly more likely to have a severe maternal morbidity event at the time of delivery.

Importantly, these numbers reflect official tallies of maternal morbidity in the United States and do not account for 

, many of whom postpone prenatal care and give birth at home in response to recent immigration enforcement policies.

When it comes to paid maternity leave, the Commonwealth Fund report found the United States was the only high-income country that does not guarantee paid leave to mothers after childbirth. All other 10 countries guarantee at least a 14-week paid leave time from work while several provide more than a year of maternity leave.

Despite these bleak trends, some gains have been made to improve maternal morbidity and mortality in the United States. The passing of the ACA helped women gain access to maternity care in that it mandated coverage for free preventive services, expanded Medicaid eligibility, offered premium subsidies for low-income women, and provided coverage for young women.

But the authors noted that more changes need to be enacted to reverse these trends which disproportionately affect 

. Solutions include strengthening postpartum care, guaranteeing paid maternity leave, and working to close the racial disparity gap in this population.

“Addressing systemic racism so that Black and Indigenous people are not at risk when they are pregnant is critical to reducing U.S. maternal mortality, while offering paid maternity leave to all birthing people would contribute to their health and the health of their babies, as well as strengthen the financial security of families,” wrote Laurie Zephyrin, MD, and Roosa Tikkanen of The Commonwealth Fund in 

“The U.S. is clearly willing to invest in health care, yet it does not invest enough in its birthing people…When it comes to maternal health care, it is time we started investing wisely to ensure that no one dies a preventable death while bringing life into the world.”

1. Admon LK, Dalton VK, Kolenic GE, et al. Trends in suicidality 1 year before and after birth among commercially insured childbearing individuals in the United States, 2006-2017. 

. Published online November 18, 2020. doi:10.1001/jamapsychiatry.2020.3550

Among 11 developed countries, the United States has the highest maternal mortality rate, a relative undersupply of maternity care providers, and no guaranteed access to provider home visits or paid parental leave in the postpartum period, a recent report from The Commonwealth Fund concluded. 

US Ranks Worst in Maternal Care, Mortality Compared With 10 Other Developed Nations 

Results of a retrospective case series published in 

 revealed an association between blood-brain barrier disruption (BBBD)–related 

 and the number of BBBD treatment sessions patients underwent, suggesting a dose-dependent effect of the treatment.

BBBD, first introduced in the early 1980s, is a systemic therapy for malignant central nervous system (CNS) tumors. Specifically, the treatment aims to increase the penetration of chemotherapeutics into the CNS and “involves intra-arterial injection of a warmed, hypertonic mannitol solution to disrupt the tight junctions of vascular endothelial cells that form the blood-brain barrier followed by intra-arterial or intravenous chemotherapy,” researchers wrote.

However, BBBD has been linked to poorly understood pigmentary maculopathy unique to patients who undergo the therapy. This condition was first reported in 1986 in patients with primary CNS 

To evaluate the rate of and potential risk factors for maculopathy development in patients with a variety of malignant CNS tumors treated with BBBD therapy, researchers conducted a case series study of patients presenting to the Oregon Health & Science University between February 2006 and December 2019. Functional and structural changes in eyes with BBBD-associated maculopathy were also evaluated after the completion of systemic therapy. 

Using electronic health records, researchers collected and reviewed data of 238 patients treated with osmotic BBBD and chemotherapy for a CNS tumor. Of these patients, 68 individuals underwent an ophthalmoscopic examination and/or retinal imaging after their therapy start date. The mean (SD) patient age was 46 (17.9) years, and the majority (n = 43) of patients were male. However, 3 patients were excluded from final analyses “because the presence of maculopathy was unable to be determined because of dense bilateral vitritis or retinal disease attributable to intraocular lymphoma.”

Of the 65 individuals included, patients underwent a mean (SD) of 19.8 (10.9) BBBD treatment sessions. Thirty-three patients were diagnosed with primary CNS lymphoma, 21 had glioma, 6 had pineal tumor, and the remaining 5 had other types of tumors.

Pigmentary maculopathy was present in 32 of 65 patients (49.2%) treated with BBBD.

The number of BBBD treatment sessions was associated with maculopathy development (odds ratio [OR], 1.30; 95% CI, 1.12-1.50; 

Age, CNS malignant cancer type, and systemic chemotherapy agent were not associated with development of maculopathy.

After completion of BBBD therapy, progressive enlargement of geographic atrophy occurred in 5 eyes of 3 patients, and choroidal neovascularization developed in 1 eye.

Notably, the study documented the first observation of BBBD-associated maculopathy in patients treated for malignant tumors other than primary CNS lymphoma, researchers wrote. They also concluded that their results suggest the treatment can be associated with late-onset and progressive retinal pigment epithelium (RPE) and outer retinal atrophy.

The absence of uniform follow-up among patients marks a limitation to the study, as researchers were unable to draw definite conclusion about the timeline of structural changes. Patients may also have alternative causes of the maculopathy, such as atypical age-related macular degeneration.

Future studies ought to include standardized imaging and follow-up intervals, in addition to OCT angiography and histopathologic correlation to help address the underlying mechanism of maculopathy. 

“These findings may have implications for patient education and ophthalmic monitoring,” the authors concluded. “We propose that patients undergo a baseline ophthalmic examination before the start of BBBD therapy, as well as yearly ophthalmic examinations during and after systemic treatment with retinal imaging if a pigmentary maculopathy or RPE atrophy is detected.”

Simonett JM, Skalet AH, Lujan BJ, Neuwelt EA, Ambady P, Lin P. Risk factors and disease course for blood-brain barrier disruption-associated maculopathy. 

 Published online December 3, 2020. doi:10.1001/jamaophthalmol.2020.5329

Results of a retrospective case series revealed an association between blood-brain barrier disruption (BBBD)–related maculopathy and the number of BBBD treatment sessions patients underwent, suggesting a dose-dependent effect of the treatment. 

Understanding the Relationship Between BBBD Therapy and Maculopathy

Ophthalmologic safety monitoring is not necessary for patients with 

 (SMA) receiving treatment with risdiplam (Evrysdi), say researchers, who studied the impact of the treatment in patients across 3 trials. Their results were published in 

Annals of Clinical and Translational Neurology

Reviewing data from the FIREFISH, SUNFISH, and JEWELFISH studies, 

 outcomes of 245 risdiplam-treated patients, who ranged from age 2 months to 60 years at enrollment, including infants with retinas that were not fully matured. From the data, they determined that the treatment does not elicit 

The results follow a previous study in which retinal toxicity was observed in cynomolgus monkeys receiving risdiplam daily for 39 weeks. In that study, photoreceptor degeneration was only observed with mid and high doses of the treatment.

In the current study, monitoring determined that there were no retinal structural or functional changes for the risdiplam-treated patients, and adverse events involving eye disorders were unrelated to risdiplam treatment, not suggestive of risdiplam-induced effects, and resolved with ongoing treatment.

“The comprehensive set of ophthalmologic assessments, which included imaging and visual function testing, was tailored to evaluate all aspects of ophthalmologic safety, with a special focus on retinal structure using [spectral domain optical coherence tomography (SDOCT)],” explained the researchers. “The central reader developed an innovative SD-OCT protocol scan that was capture following nasal, temporal, superior, and inferior fixation when possible to enhance even further the exploration of the peripheral retina.”

No risdiplam-treated patients who received the recommended dose of treatment had a change that indicated risdiplam-induced toxicity at their last visit.

Throughout the studies, 206 patients accounted for 477 ophthalmologic findings at the last visit, most of which were attributable to: changes in retinal layer thickness due to angulation variability during SD-OCT assessment, measurement variability in intraocular pressure, Best Corrected Visual Acuity, Sloan Low Contrast Visual Acuity, or threshold perimetry, which were not clinically significant.

According to the researchers, the high number of these findings compared with baseline was not surprising because of variability in optical coherence tomography image angles due to patients’ head and neck weakness.

Sergott R, Amorelli G, Baranello G, et al. Risdiplam treatment has not led to retinal toxicity in patients with spinal muscular atrophy. 

. Published online November 24, 2020. doi:10.1002/acn3.51239.

Treatment with risdiplam may not elicit ophthalmologic toxicity in older patients, as well as infants with immature retinas. 

Risdiplam Not Associated With Retinol Toxicity in SMA, Study Says

Record COVID-19 Hospitalizations, Deaths Reported

Hospitalizations due to coronavirus disease 2019 (COVID-19) reached over 100,000 in the United States this week, more than doubling the number recorded at the beginning of November, 

. The country also reported its single-worst daily death toll on December 2, at 2760 deaths, surpassing the previous toll of 2752 recorded on April 15. CDC Director Robert Redfield, MD, 

 the next few months may be even more challenging before a vaccine becomes widely available. Redfield urged stricter adherence to social distancing practices, mask wearing, and hand hygiene and noted the country faces the prospect of a health care system strained to the point of collapse if widespread preventive measures are not taken.

CDC Shortens Recommended Quarantine Period

The CDC has shortened its COVID-19 quarantine recommendations for people exposed to COVID-19 from 14 days to 10 or 7 days, depending on an individual’s test results and symptoms, NPR 

. According to the guidance, if individuals do not develop symptoms, they can quarantine for just 10 days, while if an individual tests negative, they need only quarantine for 1 week. Although the agency noted a 14-day quarantine period is still the safest option, it also acknowledged the demands this period can take on individuals, as some people exposed to the virus may not be able to afford to take 2 weeks off of work. Exposed individuals should still monitor themselves closely for symptoms like a fever, loss of smell, or a cough for 14 days after exposure.

Moderna to Start Pediatric Vaccine Trial 

Moderna announced it would begin testing its experimental COVID-19 vaccine in around 3000 children aged 12 through 17. Reported by 

, half of the children in the trial will receive 2 doses of the vaccine 4 weeks apart while the remaining children will receive placebo shots of salt water. The company applied to the FDA for an emergency use authorization on November 30 based on results from it study that found the vaccine to be 

. Typically, vaccines indicated for adults and children are tested first on adult populations to make sure they are safe for pediatric trials. Moderna’s study is not yet recruiting participants and a spokeswoman said it was not certain when testing sites will start accepting volunteers.

The United States reports record numbers of hospitalizations and deaths due to coronavirus disease 2019 (COVID-19); the CDC updates its quarantine recommendations; Moderna will soon start testing its COVID-19 vaccine in children.

What We’re Reading: Record COVID-19 Deaths, Hospitalizations; CDC Revises Quarantine Guidelines; Moderna to Begin Pediatric Vaccine Trial 

Although the prognosis for connective tissue disease–associated pulmonary arterial hypertension (CTD-PAH) is poorer than for other PAH etiologies, use of selexipag in these patients resulted in outcomes similar to those seen in patients with idiopathic PAH (IPAH), according to an abstract presented at the annual CHEST meeting.

The researchers used real-world data for patients with PAH taking selexipag from the ongoing US-based SPHERE registry. These patients were 18 years or older and were followed up for 18 months. The registry includes data from initiation of selexipag (baseline) and quarterly to the end of the follow up. The researchers analyzed disease characteristics, treatment patterns, and outcomes of the first 500 patients.

The cohort of 500 patients was composed of 132 patients with CTD-PAH, 246 with IPAH, and 122 other patients. The median time from PAH diagnosis to initiation of selexipag was 3.3 years for patients with CTD-PAH. Patients with CTD-PAH, compared with those with IPHA, were also more likely to:

Have a shorter 6-minute walk distance (286.2 meters vs 320 meters)

Have interstitial lung disease (29.5% vs 6.1%)

Have immune system disorders (83.3%) vs 19.1%)

Selexipag treatment duration was similar for patients newly initiating the drug with CTD-PAH (16.4 months) and IPAH (16.9 months). Discontinuation rates were slightly higher among patients with CTD-PAH (46.3% vs 44.9%). The causes of discontinuation were:

PAH worsening–related adverse events (AEs): 19.5% for CTD-PAH and 14.5% for IPAH

Selexipag-related AEs: 17.1% in CTD-PAH and 20.3% in IPAH

Compared with baseline, the majority of patients had improved or stable risk with selexipag. At 18 months, 19.7% of patients with CTD-PAH and 12.2% of patients with IPAH had improved risk; 26.5% of patients with CTD-PAH and 41.5% of patients with IPAH had stable risk; and 17.4% of patients with CTD-PAH and 12.6% of patients with IPAH had worsened risk. The median 18-month survival rate was slightly lower among patients with CTD-PAH (71.0%; 95% CI, 53.7%-82.8%) than IPAH (84.4%; 95% CI, 71.6%-91.8%).

The authors concluded that the real-world registry data showed that disease and treatment characteristics were consistent with previous data. “Outcomes for CTD-PAH [patients] receiving selexipag in the real-world setting were broadly similar to those of IPAH,” they wrote.

Chin K, Chakinala M, Hemnes A, et al. Real-world data for selexipag in patients with connective tissue disease-associated pulmonary arterial hypertension: a SPHERE (selexipag: the users drug registry) analysis. Presented at: CHEST Annual Meeting 2020; October 18-21, 2020. https://journal.chestnet.org/article/S0012-3692(20)34061-7/fulltext

Use of selexipag in patients with connective tissue disease–associated pulmonary arterial hypertension (CTD-PAH) resulted in outcomes similar to those seen in patients with idiopathic PAH, despite the traditionally poorer prognosis of CTD-PAH.

Selexipag Improves Outcomes in Patients With CTD-PAH

Distance caregivers of patients with cancer often find it more difficult to enlist a similar level of support compared with local caregivers, who often have access to social workers and health care providers, noted Sara L. Douglas, PhD, RN, the Gertrude Perkins Oliva Professor in Oncology Nursing and associate dean for research at the Frances Payne Bolton School of Nursing at Case Western Reserve University in Cleveland, Ohio.

In your research, you noted that distance caregivers often experience anxiety and distress to a greater degree than the patients whose care they play a large part in. Why is this the case?

This has been reported by others, and we found it as well. So, we found if you look at the distress thermometer, which was the measure that we use for distress—it's a standard measure that's used in the clinical setting—when we looked at patients and then we looked at the distance caregivers and how they scored on this, there was like a 2-point difference, which was enough to move the distance caregivers into the area of concern where the patients were under that threshold of concern.

And part of it is, again, that oftentimes the patient feels a sense of support from the local caregiver if they have one, but also from the extensive team that's there. You know, the social worker, the health care providers... Everyone from the nurses to the medical assistant to the oncologist. That level of support is not available usually to the distance caregiver.

Oftentimes, those people don't even know there is a distance caregiver. And if you are a distance caregiver, oftentimes the people closest to you don't even really know that. So, it's hard for distance caregivers; they're sort of a silent group. It's hard for them to get comparable levels of support that the patient gets and that the local caregiver gets as well. And again, we see that local caregivers, while they are stressed, and I don't mean to minimize it, oftentimes their stress is not quite as high as the distance caregiver.

Distance caregivers of patients with cancer often find it difficult to enlist adequate support, noted Sara L. Douglas, PhD, RN, associate dean for research at the Frances Payne Bolton School of Nursing at Case Western Reserve University.

Dr Sara Douglas: Support Is Often Hard to Come By for Distance Caregivers

FDA approvals for PARP inhibitors in prostate cancer treatment have taken longer than in ovarian cancer treatment. 

, a professor of medicine, physician, and director of the genitourinary oncology program at the University of Utah's Huntsman Cancer Institute, discusses the challenges associated with testing and gaining approval of new drugs in prostate cancer.

Olaparib was approved for ovarian cancer back in 2014, but it took until this year for PARP inhibitors be approved in metastatic prostate cancer. Why did it take so many years for the therapy to be approved in prostate cancer, when in both cases the drug is targeting BRCA1/2 mutations?

This is a great question. And actually, that points out the focus of drug development by pharma or by biotechs. The focus is usually in those disease settings which have inferior survival so that approval can be expedited, and then that can be expanded. That's number 1. Number 2, that speaks about the overall prostate cancer population. This is an older patient population, many of them are ineligible for clinical trials; they have comorbid conditions, and men do not like to talk about their cancer. Many of these [factors], including funding available for prostate cancer research, all these factors have discouraged research in prostate cancer, which was the major reason for a single-agent chemotherapy being approved for advanced prostate cancer patients until 2013—only one drug was approved for the treatment of this patient population.

Fortunately, with the increasing awareness of the research or awareness of the importance of research in patients with advanced prostate cancer, and many foundations such as the Prostate Cancer Foundation, National Cancer Institute, ASCO, the American Society of Clinical Oncology, ACR, all of them coming together, I think research in patients with prostate cancer is also moving forward with a much more rapid pace than before. So we expect many more drugs to be approved in in prostate cancer patients in the next 1, 2, or 3 years.

Neeraj Agarwal, MD, of the University of Utah's Huntsman Cancer Institute, discusses challenges to progress in getting FDA approval for PARP inhibitors in prostate cancer.

Dr Neeraj Agarwal on Why PARP Inhibitor Approval in Prostate Cancer Is Slow-Moving

A final analysis of phase 2 results shows single-agent ibrutinib is safe and effective as a long-term treatment for patients with relapsed/refractory marginal zone 

Patients who previously were treated with rituximab saw durable responses when given single-agent ibrutinib, and the drug’s safety profile in a new study matches earlier findings.