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.

Videos

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

Pulmonary rehabilitation may be most effective when including exercise training, breathing techniques, and education and psychosocial components for patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD), according to a recent review.

Past studies have shown pulmonary rehabilitation to improve exercise capacity, muscle strength, functional capacity, and health related quality of life (HLQOL) in patients with AECOPD. It can reduce symptoms, hospitalizations, and unscheduled healthcare visits for patients while also enhancing patients’ ability to self-manage their AECOPD and achieve self-efficacy.

However, such programs vary widely, not only in terms of which components are included, but also by where they are delivered (home, outpatient, inpatient, etc), for how long, at what intensity, and whether the patient is alone or in a group. The authors of this review wanted to determine which program designs appeared to be the most effective.

looked at 6029 studies and narrowed their analysis to 42 studies published before March 2020 from 19 countries. 

The studies included at least 1 component of pulmonary rehabilitation, included patients within 3 weeks of AECOPD onset or until 2 weeks after hospital discharge, were written in English, French, Portuguese, or Spanish, and were randomized, controlled trials.

Results from a total of 3569 patients with a mean age of 69.1 years and a mean forced expiratory volume in 1 second of 39.4% predicted.

The list of components used in the studies included education and psychosocial support, aerobic training, strength training, breathing techniques, exercise training, electrostimulation, positive expiry pressure therapy performed with noninvasive ventilation or devices, home diaries, respiratory muscle training, nutrition, and whole body vibration.

Of the 42 included studies, only 38.1% (16) used pulmonary rehabilitation officially as an intervention. Of the studies that only used 1 or some of the intervention components, the most common ones used were exercise training (30/42), education and psychosocial support (24/42), aerobic training (23/42), strength training (23/42), and breathing techniques (23/42).

The combination of exercise and breathing techniques presented the largest weighted mean difference (WMD) (−41.06; 95% CI, −131.70-49.58). This combination intervention also presented a greater WMD than control groups.

Breathing techniques was the best performing intervention at decreasing dyspnea in patients (WMD 1.90; 95% CI, 0.53–3.27). Breathing techniques (effect sizes [ES] 0.15; 95% CI, −0.28-0.57) and breathing techniques in combination with exercise (ES 0.11; 95% CI, −0.28–0.50) were the interventions that reduced the length of hospitalization the most, but again, significant differences between the interventions were not found.

In addition, “patient’s knowledge was one of the outcome measures presenting larger ES, showing how empowering pulmonary rehabilitation can be during AECOPD,” wrote investigators.

Investigators also found that short-term programs presented better results and increased exercise capacity compared to longer-term programs.

Most of the evidence published described hospitalized patients, who often present more severe exacerbations and/or have a more severe underlying conditions than those managed in an outpatient setting. Investigators said that because more than 80% of patients with COPD are managed on an outpatient basis, future research should focus on those patients.

Investigators concluded that additional research should compare the included interventions in programs of different lengths, durations and frequencies of sessions, and intensities of exercise training to further establish what program design would be most effective.

Machado A, Silva PM, Afreixo V, Caneiras C, Burtin C, Marques A. Design of pulmonary rehabilitation programmes during acute exacerbations of COPD: a systematic review and network meta-analysis.

. November 20 2020;33(6):978-985. doi: 10.1183/16000617.0039-2020

A review found that including exercise, breathing techniques, and education components in pulmonary rehabilitation for patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) optimizes such programs.

Study Finds 3 Key Components That Could Make Pulmonary Rehabilitation More Effective for AECOPD

Delayed care due to the coronavirus disease 2019 pandemic has created a lot of uncertainty around alternative payment models (APMs) like the Oncology Care Model (OCM), said Basit Chaudhry, MD, PhD, founder of Tuple Health.

There has been a lot of delayed care and cancer diagnoses because of the pandemic. How do you expect this will impact practices participating in the Oncology Care Model and planning to transition to Oncology Care First?

That's a great question. I think it creates quite a bit of uncertainty in the field. I think Medicare has done a really nice job in terms of creating flexibility, particularly on the downside risk components of advance alternative payment models, including OCM. So, it was a very welcome kind of flexibility and relief there, and I think that's given practices space to think about how do they want to transition to the future?

I do think just because of the pandemic, and unfortunately, the current rise in cases, I think it's unclear on what's going to happen with the public health emergency. And in turn, I think that just creates uncertainty, broadly speaking with respect to advanced alternative payment models, in general. So, I think it's a little bit unclear right now, how long this interim period will last. And I think, in turn, it makes evaluation of the models really difficult because, well, having a downside risk component to them, it makes it very difficult for Medicare to figure out what's working what's not.

So, all of this, there's a ton of some pieces. Unfortunately, I think this makes it quite difficult for Medicare to kind of locate and situate what they want to do. But I do think there's potential that we could see an extension of OCM for an additional period of time whether that’s that 6 months, a year—I think it really is going to depend on what the public health emergency looks like. And then that, in turn, obviously will roll into what the next Medicare model in cancer care looks like.

The big change from OCM to OCF is the movement to a bundled payment framework in oncology. Is it possible to even move to that kind of framework if we are still in a pandemic?

So, if we still are in a pandemic, I think it's very difficult to ascertain what's going to happen with respect to risk. So, I think, as long as we have rising cases, as long as there's a public health emergency, I think it's very difficult to ask people in the provider system to absorb risk, because simply the variance is enormously high. Right? We don't really know what's going to happen, I think, when variance is high in any field. Really, what you need is a very large sample size.

And one of the trade-offs you're making in moving to value-based payments or risk-based arrangements, you're moving from payers covering large bodies of patients with large samples to practices that will have much smaller samples. So, they're much more prone to variance, and outlier effects. So, I think it's very difficult for providers to absorb risk outright, during the pandemic.

Dr Basit Chaudhry Discusses the Impact of Delayed Care on APMs Like OCM

 has instructed Avazo-Healthcare to take immediate action and cease the sale of 2 coronavirus disease 2019 (

) antigen test kits and several serology test kits, citing they do not have market approval or authorization for direct-to-consumer sales. The FDA is also accusing the limited liability corporation of failing to notify the federal agency that it would be introducing the tests for distribution. The letter also included a warning to rectify potential false claims that the company’s cannabidiol products can prevent, mitigate, and treat COVID-19.

UK Gives First Approval to Pfizer, BioNTech COVID-19 Vaccine

An emergency authorization was handed down from the United Kingdom’s Medicines and Healthcare Products Regulatory Agency for Pfizer and BioNTech’s 

. A total of 800,000 doses could be ready for distribution next week, and 40 million doses have been pre-ordered. The fast-tracked approval came about due to Britain being allowed to circumnavigate the European Union’s typical regulatory process in public health emergencies. The FDA is set to meet on December 10 and 17 to discuss approving the 

Flu Vaccine Benefits Outweigh Risk for Guillain-Barré Syndrome

 nerves, is statistically insignificant in light of the benefits the flu vaccine bestows on older Americans. Just 1 case of Guillain-Barré was seen in the risk (days 8-21 and 1-42 post vaccination) and control (days 43-84 post vaccination) windows of the study, which saw close to 22 million patients receive the high-dose influenza vaccine during the 2018-2019 flu season.

Avazo-Healthcare warned by the FDA about its coronavirus disease 2019 (COVID-19) testing kits; Pfizer, BioNTech get first COVID-19 vaccine approval; risk for Guillan-Barré syndrome from flu vaccine deemed insignificant. 

What We’re Reading: FDA Issues Warning Letter; UK Approves COVID-19 Vaccine; Flu Vaccine Safe

Progression of HER2+ mBC

HER2+ mBC: Diagnosing Patients With Brain Mets

Monitoring Brain Mets in HER2+ mBC

Healthcare Utilization for HER2+ mBC With Brain Mets

Treatment Beyond Second-line Therapy in HER2+ mBC

Managing At-Risk Patients for Brain Mets in HER2+ mBC

HER2CLIMB Study

Phase 2 LANDSCAPE Trial

Examining current treatment options for brain metastases in metastatic HER2+ breast cancer and assessing the clinical and economic burden.

Defining Value for the Treatment of Brain Metastases in Metastatic HER2-Positive Breast Cancer

Studies show giving preventive medication while taking away offending drugs is superior to continuing offending medication and adding preventive drugs in patients with medication overuse headache, said Rigmor Jensen, MD, professor of neurology at The University of Copenhagen and director of the Danish Headache Center.

The American Journal of Managed Care® (AJMC®): 

What are some common misconceptions about medication overuse headache?

There's this misconception that it is just a purely treated migraine, and if the migraine is properly treated the medication overuse headache will disappear. Yes and no, there can be both sides of the coin, but there are studies that we have seen that in patients who don't withdraw the medication and only 

 preventive, the outcome is not as good as if you both do preventive and take the offending drug away. So, the number 1 action in headache treatment is to take the drug away. Medication overuse is a significant trigger for chronification. But we see patients too late. We see them very late and they have had this overuse for years and they can be more dependent on this and have a psychological dependence. It is not a dependence disorder as such. But it could develop into that. From the beginning, it's not a dependence disorder, but it can develop into that. Patients are more depressed, more anxious, and they have to have that drug every day. So it's difficult.


What's really the key message here is that in every headache patient you see, inform them that there is a risk of overuse and overuse can make it worse. Treat them properly with a proper prevention and a proper limit. Limits are the number of days you're allowed to take medication. And if you hit that limit, we have to have a talk again and have a follow-up because something is wrong here. You have to be very careful that you don't take too much. That's really important because all the acute drugs can also have a negative effect on other things in your body, your stomach, you have gastrointestional symptoms. Recent studies show they also have an effect on your hormones, on your sex hormones. It is not an easy task. Information, education is key here.

Dr Rigmor Jensen Dispels Common Misconceptions About Medication Overuse Headache

 is on the rise, thereby emphasizing the importance of these discussions that focus on fertility and reproduction among younger survivors. A recent study from Sweden, 

, investigated the long-term outcomes of fertility preservation among female survivor of breast cancer of reproductive age, finding they were more likely to have a live birth if they underwent FP and utilized assisted reproductive technology.

“Cryopreservation of oocytes and embryos after controlled ovarian stimulation is the standard strategy for fertility preservation (FP) in adult women. Until now, few studies have evaluated the long-term reproductive outcomes of FP in young women with BC,” the authors noted.

Their nationwide cohort study investigated the primary outcome of HRs for live births and assisted reproductive technology among 425 female breast cancers exposed to FP and 850 matched controls who were not, for a ratio of 1:2, respectively. The exposed group underwent FP at 1 of 7 Swedish university hospitals between January 1, 1994, and June 30, 2017.

The investigation found that more women in the exposed group had lower 

 compared with the unexposed group: 71.1% vs 20.1%. These women were also younger, at a mean (SD) age of 32.1 (4.0) vs 33.3 (3.6) years for the unexposed group; had a higher rate of estrogen receptor-positive tumors, for 68.0% vs 60.6%; and had treatment schedules that included more chemotherapy treatments, at 93.9% vs 87.7%.

Additional analyses of the rate of live births among the exposed group resulted in higher numbers across the board compared with the unexposed controls:

At least 1 post-breast cancer live birth: 22.8% vs 8.7%, with a mean 4.6-year follow-up

A 2-fold higher rate of live births after the breast cancer diagnosis (hazard ratio [HR], 2.6; 95% CI, 1.9-3.5; adjusted HR [aHR], 2.3; 95% CI, 1.6-3.3)

5-year cumulative incidence: 19.4% (95% CI, 15.2%-24.6%) vs 8.6% (95% CI, 6.4%-11.4%)

10-year cumulative incidence: 40.7% (95% CI, 33.0%-49.5%) vs 15.8% (95% CI, 12.0%-20.7%)

Significantly higher overall birth rate (aHR, 2.3; 95% CI, 1.6-3.3)

Higher utilization of assisted reproductive technology (aHR, 4.8; 95% CI, 2.2-10.7)

Two measures were lower, however, but with positive implications: FP was linked to lower all-cause mortality (aHR, 0.4; 95% CI, 0.3-0.7) and 5-year cumulative incidence of death (5.3% [95% CI, 3.1%-9.0%] vs 11.1% [95% CI, 8.7%-14.1%]) in the exposed group.

 at diagnosis meant a 19% (95% CI, 14.2%-25.1%) 5-year cumulative incidence of live birth compared with 12.7% (95% CI, 7.6%-214.1%) seen in the exposed group. For those who had at least 1 child at diagnosis, the respective numbers were 20.2% (95% CI, 12.7%-31.3%) and 7.5% (95% CI, 5.3%-10.5%).

“Results of this nationwide cohort study indicate that although successful pregnancy after BC is possible both in women with and without FP, FP is associated with significantly higher rates of post-BC live births and use of [assisted reproductive technology] treatments, without any deleterious association with all-cause survival during a mean follow-up of 5.2 years,” the authors concluded. “These findings add to the current knowledge regarding FP treatments in women with BC.”

They believe their findings could enable oncologists and reproductive counselors to better initiate these conversations with their female patients who receive a breast cancer diagnosis.

Marklund A, Lundberg FE, Eloranta S, Hedayati E, Pettersson K, Rodriguez-Wallberg KA. Reproductive outcomes after breast cancer in women with vs without fertility preservation. 

 Published online November 19, 2020. doi:10.1001/jamaoncol.2020.5957

Survival after breast cancer is on the rise, thereby emphasizing the importance of discussions that focus on fertility and reproduction among younger survivors. 

Fertility Preservation Linked to Uptick in Live Births Following Breast Cancer

Managed care pharmacists can influence several aspects of care in 

 (PD), particularly through determining clinical pathways and educating patients and providers on the latest novel agents coming to  market, said Patty Taddei-Allen, PharmD, MBA, BCACP, BCGP, senior director of Clinical Analytics at WellDyne.

:  Hello, I'm Matthew Gavidia. Today on the MJH Life Sciences’ Medical World News, 

, senior director of Clinical Analytics at Welldyne.


: Can you speak on the impact of managed care pharmacists in integrating novel Parkinson disease therapies into patient care?

: Sure, so managed care pharmacists are really able to be involved with 

Parkinson disease in a variety of different ways, both from a patient-facing perspective and a nonpatient-facing perspective. Starting from a patient-facing perspective, if you're in an organization that is involved with medication therapy management or really managing those Medicare patients, then as a pharmacist involved with those managed care organizations, you're able to identify the dosing and make sure that the patient is taking their medication appropriately, and determining how that patient is responding to treatment and whether or not a different agent might be needed in order to help manage their symptoms.

From a nonpatient-facing perspective, managed care pharmacists really have a lot of influence in helping design the different clinical programs that an organization may develop to help treat patients with 

Parkinson disease, as well as help determine clinical pathways or clinical treatment protocols or prior authorization criteria for some of the newer agents, as well as determine formulary status and do a formulary  clinical medication review with all the new agents that are coming onto the market.

: To build on that, how can managed care pharmacists improve current guidelines for treatment of Parkinson disease?

: I think one of the ways that managed care pharmacists can really help improve upon that is really being able to, in essence, kind of translate the difference with some of the new agents and their different delivery systems, and why that is more impactful or what is the clinical value of that. Because some providers may think, "Well, it's the same drug so it's the same thing whether I prescribe one dosage form versus another."


In particular, with Parkinson disease, that may not always be the case. So, managed care pharmacists can really help educate providers [and] patients, as well as determine different clinical treatment pathways to make sure that all of those different nuances of the medications are being addressed.

: Lastly, do you have any other concluding thoughts?

: We're hoping to be able to help manage these patients and really be able to extend the ability to really take advantage of levodopa. It's been around for decades; it is a very well generally tolerated medication, but unfortunately, it does seem to wear off and patients don't get to continue to benefit from it.

So, as we continue to explore new medications or different ways to administer that medication, I'm very hopeful that we'll be able to improve patient quality of life for patients who suffer from PD.

: To learn more, visit our website at AJMC.com. I’m Matthew Gavidia, thanks for joining us!

Managed care pharmacists can influence several aspects of care in Parkinson disease, particularly through determining clinical pathways and educating patients and providers on novel agents coming to market.

How Managed Care Pharmacists Can Improve Current Standards of Treatment for Parkinson Disease

To devise a plan for disseminating optimal pediatric headache education, researchers 

 poverty, and alimentation (including diet and obesity).

Although findings from the narrative literature review led the authors to conclude there is not enough evidence to establish a headache education plan regarding behavioral and lifestyle interventions in this population, they noted that “clinicians should advise patients to avoid certain triggers, such as stress and sleep disorders, and make a few conservative dietary changes.”

The estimated mean prevalence of headache is around 50% in the pediatric population, and the overall mean prevalence of migraine is 9.1%. Roughly half of children suffering from migraine also manifest the condition in adulthood. Early diagnosis and multidisciplinary interventions comprising both pharmacologic and nonpharmacologic approaches can improve long-term migraine outcomes.

Reports showing evidence in favor of cognitive-behavioral therapy (CBT) among adult migraineurs have prompted some researchers to argue that CBT ought to be first-line treatment among pediatric populations. However, CBT can be costly and time consuming and may only benefit older children capable of metacognition.

“Although the current treatment guidelines focus on behavioral and lifestyle interventions to correct the factors commonly associated with migraine (negative emotional states, obesity and high body weight, infrequent exercise, and lack of sleep), the focus on dispensing headache and migraine education is inadequate, making this an area that requires extensive research,” the review authors wrote. “Without quality evidence on how proper headache education can improve outcomes, preventing migraines will remain challenging for many children and adolescents.”

Investigators compiled randomized controlled trials, systematic reviews, observational studies and other studies found in the PubMed database that were published through June 2020 with no date limits.

Among the trigger factors documented in the studies, stress was found to be the most problematic and common trigger for pediatric migraineurs. Brain structure can become disrupted by stress as a result of multifactorial and epigenetic processes that alter gene expression. Furthermore, “if registered biologically during the early developmental stages, stress can lead to physiological changes that may increase a child’s susceptibility to other stress-related behavioral disorders, such as depression and anxiety, later in life,” the researchers explained.

Psychiatric disorders, or mood/anxiety disorders, were also commonly reported among pediatric migraineurs. Psychiatric conditions may be comorbid with migraine. However, “behavioral comorbidities have not been observed in the majority of pediatric migraine patients,” the authors wrote, while “currently available screening tools make it difficult to distinguish between the characteristics of migraine and those of psychiatric illness.”

One study found the presence of family-level stressors early in life was associated with a higher likelihood of adolescent migraine and increased symptoms of depression and anxiety in late childhood. Because of this association, the authors argued that psychiatric comorbidities should be addressed in a timely manner to prevent future development of migraines. Additional studies highlighted the strong association between adverse childhood experiences, like child abuse, and recurrent migraines in adulthood.

When it comes to sleep, study findings have shown that migraine might be a result of underlying sleep disorders or could trigger further sleep disturbances. Regardless, improving sleep quality can decrease the occurrence of migraine. “Conventional clinical wisdom, sleep assessment, and adjustment in sleep habits will always be recommended for children suffering from migraines, in addition to which structured sleep hygiene rules can improve both headaches and sleep in the long run,” the authors wrote.

In addition, dietary triggers may affect different stages of the migraine process. Certain foods could influence the release of serotonin and norepinephrine, which could cause vasoconstriction or vasodilation, or could stimulate the trigeminal ganglia, brain stem, and cortical neuronal pathways. But because multiple triggers and variables can modify the pain threshold in an individual, and this factor is usually neglected in favor of a preventive drug therapy, evaluating the role of diet in pediatric migraineurs is complex.

“It is imperative to counsel patients and their parents/caretakers to avoid fasting or skipping meals and encourage a well-balanced diet, along with educating them on good practices to avoid obvious triggers,” the authors wrote. Instead of trying to eliminate uncertain migraine triggers, evidence suggests that maintaining a healthy weight may be more effective in treating migraine.

Following a healthy lifestyle in addition to overall management of sleep, stress, and diet are essential for pediatric migraineurs’ health, the researchers concluded. “Future larger, prospective studies are needed to design a standardized educational and cognitive treatment manual that will contribute to the development of pediatric migraine treatment.”

Yamanaka G, Morichi S, Suzuki S, et al. A review on the triggers of pediatric migraine with the aim of improving headache education. 

. Published online November 19, 2020. doi:10.3390/jcm9113717

Researchers assessed 3 risk factors for migraine in children and adolescents: stress, sleep poverty, and alimentation.  

Review Evaluates Triggers of Pediatric Migraine

A new study suggests a dose of 200 mg of pacritinib taken twice daily is safe and demonstrates clinical activity in patients with advanced 

, helped investigators settle on the appropriate dose for the pivotal phase 3 study.

Pacritinib is a novel therapy that inhibits both Janus kinase 2 (JAK2) and interleukin-1 receptor-associated kinase 1 (IRAK1) and is aimed at patients who are unable to take ruxolitinib (Jakafi). In 2 earlier phase 3 studies (PERSIST-1 and PERSIST-2), the medication showed clinically meaningful spleen volume responses (SVRs), and appeared to have the potential to be effective even in patients with severe thrombocytopenia (platelet counts above 50 x 103/μL). That’s important because the 2 JAK inhibitors currently on the United States market to treat myelofibrosis have not yet been studied in patients who present with severe thrombocytopenia, wrote corresponding author Aaron T. Gerds, MD, of the Cleveland Clinic Taussig Cancer Ins

A new dose-finding study found a twice-daily 200 mg dose of the JAK2/IRAK1 inhibitor pacrinitib led to a spleen volume response in nearly 1 in 10 patients.