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Latest Alzheimer's News By Marianne (Consumer)Madeiros and Robin Foster HealthDay ReportersTUESDAY, June buy ventolin over the counter nz 15, 2021 An experimental Alzheimer's treatment appears to safely clear abnormal tau protein from the brain, but it's not yet clear whether the shot will be able to save her response brain function. In a Phase 2 clinical trial, the treatment produced high levels of antibodies to target and attack free-floating tau proteins before they can form "tau tangles" that clog neurons and damage brain function. Tau tangles, along with plaques formed by the protein amyloid-beta, buy ventolin over the counter nz serve as one of the main hallmarks of Alzheimer's. "While amyloid influences speed of Alzheimer's progression, there is strong evidence that tau pathology relates to the underlying cause of the disease," said lead researcher Dr. Petr Novak, a senior clinical research scientist at AXON Neuroscience, the Slovakian pharmaceutical company developing the treatment.

"Brain atrophy and cognitive loss buy ventolin over the counter nz closely echo the deposition of pathological tau protein, as evidenced by recent tau PET studies." The treatment also proved safe during the two-year trial, in which eleven doses were administered to randomly chosen patients with mild dementia. People who received the treatment, known as AADvac1, experienced about the same numbers of side effects and adverse events as those who were given a placebo. However, the study did not produce any significant benefits when it came to thinking, reasoning and memory tests performed across the entire patient group -- possibly because there were too few people with clinically diagnosed Alzheimer's participating in the trial. During analysis of the clinical trial data, the researchers realized that about a third of the participants had low levels of abnormal tau protein, "which makes them not very suitable for evaluating the effects of a treatment halting the progression of tau pathology." Novak noted that the research team did see some improvement in standard brain function tests given to a smaller group of trial participants who had actually buy ventolin over the counter nz been diagnosed with Alzheimer's. In that group, the treatment slowed brain decline by around 30% in two different clinical and functional tests, Novak said.

"The results of analysis perfectly align with the tau hypothesis -- simply put, if the patient is tau biomarker positive, then tau pathology is responsible for his/her cognitive decline, and halting tau pathology should slow or halt progression," Novak said. "If the patient is negative for markers of tau pathology, then this patient's impairment is mainly due to other pathologies, buy ventolin over the counter nz and treating tau pathology in this patient won't be meaningful." AXON is planning a follow-up trial that will include a better-defined group of Alzheimer's patients suffering from both amyloid plaques and tau tangles, Novak said. If the results from that trial are positive, the company might apply to the U.S. Food and Drug Administration for the buy ventolin over the counter nz same accelerated approval pathway recently used to bring the controversial Alzheimer's drug aducanumab to market, Novak said. In the current trial, a total of 196 patients were randomly chosen to receive either the treatment or a placebo.

Nearly all patients who got the treatment developed antibodies designed to head off the spread of abnormal tau while leaving healthy tau proteins intact, Novak said. The treatment significantly reduced buy ventolin over the counter nz -- by 58% -- the accumulation of neurofilament light chain in the blood. This is an important biomarker of neurodegenerative diseases, Novak said -- damaged nerve cells release the substance, which leaks into the blood. Patients given the treatment also experienced a reduction in cerebrospinal fluid biomarkers of abnormal tau, results show. The findings buy ventolin over the counter nz were published June 14 in the journal Nature Aging.

There's still hope for this approach to treating Alzheimer's disease despite the somewhat mixed results from this trial, said Rebecca Edelmayer, senior director of scientific engagement at the Alzheimer's Association. "When they do design their phase 3, they're going to need to be better about that part of the study design, and really focus on enrolling individuals that have the right biomarkers to be able to look at not only the safety and tolerability but also the efficacy on cognition and function," Edelmayer said. The treatment approach is promising because using the body's immune system to fight Alzheimer's would sidestep one of the problems in developing a drug to treat the disease -- namely that it's difficult to design medications that can easily enter the brain and buy ventolin over the counter nz attack a specific target, Edelmayer explained. Through booster doses given every three months, the treatment is "training your body over time how to react to the pathological tau," Edelmayer said. "You will likely need additional shots of this particular therapeutic to keep it as productive as possible in targeting that tau." More information The Alzheimer's Association has more about tau protein.

QUESTION One buy ventolin over the counter nz of the first symptoms of Alzheimer's disease is __________________. See Answer SOURCES. Petr Novak, MD, buy ventolin over the counter nz PhD, senior clinical research scientist, AXON Neuroscience. Rebecca Edelmayer, PhD, senior director, scientific engagement, Alzheimer's Association. Nature Aging, June 14, 2021 Full text_ 43587_2021_70_OnlinePDF.pdf Copyright © 2021 HealthDay.

All rights reserved buy ventolin over the counter nz. From Healthy Resources Featured Centers Health Solutions From Our SponsorsLatest High Blood Pressure News MONDAY, June 14, 2021 (American Heart Association News) After years of improvement, high blood pressure control in the U.S. Dropped regardless of age, race or ethnicity, according to new research. Previous studies buy ventolin over the counter nz found Americans with high blood pressure were better managing the condition in the early years of the 21st century before rates leveled off from 2009 to 2014. The new study, published Monday in the American Heart Association journal Hypertension, zoomed in on nationwide health survey data of more than 4,000 adults from 2015 to 2018.

Researchers then compared high blood pressure control, awareness, treatment and treatment effectiveness to nearly 6,000 adults surveyed during the prior six years. They discovered the rate of control – getting blood pressure down buy ventolin over the counter nz to a specific number – had fallen by 7.5%. "That's a very strong decline," said the study's lead author, Dr. Brent Egan. "We lost about 10 years of progress in four years." Expecting to find disparities in the fall of buy ventolin over the counter nz blood pressure control by age, race or ethnicity, the researchers found none.

"We were surprised by how broad-based the decline (in blood pressure control) was," said Egan, vice president for cardiovascular health at the American Medical Association. But control buy ventolin over the counter nz rates weren't all that fell. Awareness of having high blood pressure slipped by 3.4%, and being treated for it dropped by 4.6%. Among those being treated, 6% fewer had the condition under control. The study also found buy ventolin over the counter nz an increase in people being prescribed just one medicine despite a rise in obesity and diabetes, two conditions that require "more intensive (drug therapy) for hypertension control," according to the study.

If health care professionals are reluctant to prescribe multiple medications – and if patients are hesitant to take them – one potential answer is "a combination where you have two or three blood pressure meds in a single pill," Egan said. Falling rates of awareness, treatment and treatment effectiveness occurred even though people had the same access to health care, the findings showed. That suggests a worsening in the quality of care for diagnosing and managing high blood pressure, Egan said, which could be a result of primary care doctors being overwhelmed by patients who have multiple chronic buy ventolin over the counter nz conditions such as diabetes and obesity. "It's extremely difficult to manage all these conditions in a 15-minute visit," he said. "We need new approaches.

We need lean, efficient improvement programs, more self-monitoring, and better public health campaigns to engage patients and get them to understand their hypertension." Current guidelines from the AHA and American College of Cardiology for treating high blood pressure, updated buy ventolin over the counter nz in 2017, define stage 1 high blood pressure as 130 and higher for systolic blood pressure (the top number) or 80 and higher for diastolic (the bottom number). Since the study relied on older data, it defined high blood pressure as 140/90 and higher. The study also was limited by its relatively small size and its design, Egan said. "We're not following a group of buy ventolin over the counter nz individuals. We're just taking snapshots in time." Dr.

Gbenga Ogedegbe, who was not involved in the research, called buy ventolin over the counter nz it an important study that shows there are still many questions to be answered about high blood pressure control. In particular, he said there's a need for more research about the role obesity plays in hypertension control, especially among Black people in the U.S. Because AHA statistics show more than half have high blood pressure. "Given the role of obesity as a major risk factor for uncontrolled hypertension, we have to focus our efforts on how to do a better job with it," said Ogedegbe, professor of population health and director of buy ventolin over the counter nz the Institute for Excellence in Health Equity at NYU Langone Health in New York City. He stressed the importance of addressing the upstream factors that contribute to the rise of obesity in communities of color, such as the need for more parks and better access to areas that allow people to be physically active.

"If we know lifestyle behaviors are important," Ogedegbe said, "then what are we doing to encourage healthy behaviors like exercise?. " QUESTION buy ventolin over the counter nz Salt and sodium are the same. See Answer American Heart Association News covers heart and brain health. Not all views expressed in this story reflect the official position of the American Heart Association. Copyright is buy ventolin over the counter nz owned or held by the American Heart Association, Inc., and all rights are reserved.

If you have questions or comments about this story, please email [email protected]. By Thor Christensen American Heart Association News buy ventolin over the counter nz Copyright © 2021 HealthDay. All rights reserved. From Heart Health Resources Featured Centers Health Solutions From Our SponsorsLatest Diet &. Weight Management News By Alan Mozes HealthDay ReporterMONDAY, June 14, 2021 (HealthDay News) The American South and Midwest are home to the buy ventolin over the counter nz highest obesity rates in the nation, but a new study reveals that severely obese residents of those regions are the least likely to choose lifesaving weight-loss surgery.

"Bariatric surgery has been shown to provide long-term weight loss, sustained improvements in cardiovascular and metabolic health, and even prolonged longevity," noted study author Dr. Scott Schimpke, but the analysis "shows we continue to underutilize the best treatment for morbid obesity and associated metabolic syndrome." Schimpke, an assistant professor in the Division of Minimally Invasive and Bariatric Surgery at Rush Medical College in Chicago, and his colleagues point out that obesity is linked to a considerably higher risk for developing upwards of 40 different serious illnesses, including heart disease and diabetes. The American Heart Association explains that metabolic syndrome -- a grouping buy ventolin over the counter nz of five different conditions -- elevates the risk for such illnesses. Abdominal obesity is one such condition. The other four include high blood sugar, high triglycerides, high blood pressure and low levels of "good" HDL cholesterol.

Bariatric surgery -- including sleeve gastrectomy and gastric bypass -- offers an opportunity to reduce such risk by helping patients achieve considerable weight loss, the investigators said buy ventolin over the counter nz. In fact, the study team noted that bariatric surgery is the standard of care for severely obese patients. Severe obesity is defined as having a body mass index (BMI) of 40, or a BMI of 35 and up alongside obesity-related complications such as diabetes. Using insurance claims data, Schimpke and his team focused on a pool of nearly 1.8 million patients across the United States who were severely obese -- buy ventolin over the counter nz and therefore eligible for bariatric surgery -- in the decade beginning 2010. Of those, roughly 100,000 actually underwent bariatric surgery during that time frame.

But procedure patterns varied widely by state buy ventolin over the counter nz. For example, while between roughly 9% and 10.4% of eligible patients in New Jersey, Rhode Island and Delaware opted for surgery, less than 3% did so in West Virginia, Alabama and Arkansas. Overall, the researchers determined that the lowest in opt-in rates by region was the Midwest, where just over 4% of eligible patients underwent surgery, despite the fact that nearly 34% of Midwesterners are obese (making the region home to the highest overall obesity rates in the country). By contrast, the highest opt-in surgery rate (nearly 8%) was seen buy ventolin over the counter nz in the Northeast region, where the overall obesity rate is lower (29%). The findings were presented last week at a virtual meeting of the American Society for Metabolic and Bariatric Surgery.

Such research is considered preliminary until published in a peer-reviewed journal. "There are likely several contributing factors to the wide variation in utilization," said buy ventolin over the counter nz Schimpke. He highlighted differences in. Levels of access to medical care. Beliefs and buy ventolin over the counter nz attitudes among patients and referring physicians.

Number of available hospitals and surgeons. And insurance coverage requirements. Schimpke also pointed to the "negative psycho-social connotation associated with bariatric surgery among both physicians/practitioners and patients, which needs to be addressed with strategic campaigns detailing the safety and efficacy of bariatric surgery." Ultimately there's likely a broad mix of social, cultural and economic drivers at play, suggested Lona Sandon, program director of the Department of Clinical Nutrition in the School of Health Professions buy ventolin over the counter nz at the UT Southwestern Medical Center in Dallas. She was not part of the research. For one, "people who are surrounded by others of similar body size may not perceive their weight to be outside of the norm and therefore not seek out bariatric surgery," said Sandon buy ventolin over the counter nz.

"[And] there are differences in ethnicities and culture between states with the highest rates of obesity compared to states with lower rates." QUESTION What is weight loss surgery?. See Answer Also, "states with higher obesity rates also tend to have higher rates of food insecurity, which means lower incomes in general," she noted. "Bariatric surgery is an expensive proposition, especially if one does not have good insurance coverage for it." But even though weight-loss success depends on adopting a "challenging" change in post-operation diet and lifestyle, the process can certainly "help people to lose weight and get comorbid [other negative health] conditions buy ventolin over the counter nz under better control," Sandon said. So it's important, she said, to help eligible patients better "understand the treatment options and potential for success," by sharing surgery success stories and highlighting the benefits of reducing high-risk health issues such as blood pressure and diabetes. More information There's more about weight-loss surgery at the U.S.

National Institute buy ventolin over the counter nz of Diabetes and Digestive and Kidney Diseases. SOURCES. Scott Schimpke, MD, assistant professor, Division of Minimally Invasive and Bariatric Surgery, Rush Medical College, Chicago. Lona Sandon, PhD, RDN, LD, program buy ventolin over the counter nz director and associate professor, Department of Clinical Nutrition, School of Health Professions, UT Southwestern Medical Center, Dallas. American Society for Metabolic and Bariatric Surgery, presentation, virtual annual meeting, June 10-12, 2021 Copyright © 2021 HealthDay.

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€œI would like to commend the finalists and winners for their tremendous work in partnering ventolin weight gain with multicultural communities to deliver culturally http://www.col-foch-strasbourg.ac-strasbourg.fr/francais-6e3/ and linguistically tailored health information that enhances their access to, and experience of care”, Ms Elizabeth Koff said. Ms Lisa Woodland, Director, NSW Multicultural Health Communication Service said this year's winners demonstrate excellence in multilingual health communication. €œTheir commitment to delivering effective health messages to multicultural communities via NSW Health and NSW Health-funded non-government organisations is to be highly commended.” The winners were announced during an online awards presentation, coordinated by the NSW Multicultural Health Communication Service. The 2021 winners are:Keeping People Healthy CategorySydney Local Health District. HIV Multilingual Booklets Patients Safety First CategoryCancer Institute ventolin weight gain NSW.

Patient Information Multilingual Cancer Information Web Portal Transforming the Patient Experience CategoryFairfield Hospital, South Western Sydney Local Health District. Way Finding Signage ventolin Response – asthma treatment CategoryPopulation Health, Western Sydney Local Health District. Going to a asthma treatment Testing Clinic - Children's booklet Staff Member of the Year CategoryDipti Zachariah, Western Sydney Local Health District Dr Jan Fizzell, NSW Health Volunteer of the Year CategoryNasrin Delshad, Fairfield Hospital, South Western Sydney Local Health District Resources produced by winners and finalists are available on the NSW Multicultural Health Communication Service websiteFor more information on the Awards visit Multicultural Health Communication Awards 2021A list of the 2021 Multicultural Health Communication Awards winners and finalists is available on our website..

€œI would like to commend the finalists and winners for their tremendous work in partnering with multicultural communities to deliver culturally buy ventolin over the counter nz and linguistically tailored health information that enhances their access to, and experience of care”, Ms Elizabeth Koff said. Ms Lisa Woodland, Director, NSW Multicultural Health Communication Service said this year's winners demonstrate excellence in multilingual health communication. €œTheir commitment to delivering effective health messages to multicultural communities via NSW Health and NSW Health-funded non-government organisations is to be highly commended.” The winners were announced during an online awards presentation, coordinated by the NSW Multicultural Health Communication Service. The 2021 winners are:Keeping People Healthy CategorySydney Local Health District. HIV Multilingual Booklets Patients Safety First CategoryCancer Institute NSW buy ventolin over the counter nz.

Patient Information Multilingual Cancer Information Web Portal Transforming the Patient Experience CategoryFairfield Hospital, South Western Sydney Local Health District. Way Finding Signage ventolin Response – asthma treatment CategoryPopulation Health, Western Sydney Local Health District. Going to a asthma treatment Testing Clinic - Children's booklet Staff Member of the Year CategoryDipti Zachariah, Western Sydney Local Health District Dr Jan Fizzell, NSW Health Volunteer of the Year CategoryNasrin Delshad, Fairfield Hospital, South Western Sydney Local Health District Resources produced by winners and finalists are available on the NSW Multicultural Health Communication Service websiteFor more information on the Awards visit Multicultural Health Communication Awards 2021A list of the 2021 Multicultural Health Communication Awards winners and finalists is available on our website..

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Tell your doctor or health care professional if your symptoms do not improve. Do not take extra doses. If your asthma or bronchitis gets worse while you are using Ventolin, call your doctor right away. If your mouth gets dry try chewing sugarless gum or sucking hard candy. Drink water as directed.

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A new school does ventolin need a prescription in Northern Westchester is transitioning to remote learning after asthma treatment cases.Three people, two at Westlake Middle School and one at Hawthorne Elementary School, are being treated as positive for asthma treatment in the Mount Pleasant Central School District, Superintendent Kurtis M. Kotes announced in does ventolin need a prescription an email to the community early Sunday night, Nov. 15."The individual related to Hawthorne Elementary School has not been in or around the building since Oct.

29," Kotes does ventolin need a prescription said. "Therefore no additional quarantine orders will be necessary for Hawthorne Elementary School and the building will remain open for hybrid, in-person instruction."The two individuals related does ventolin need a prescription to Westlake Middle School were both in the building on Friday, Nov. 13.

There will be 100 students, 12 teachers, and potentially more support staff who will be does ventolin need a prescription subject to quarantine orders. "We will does ventolin need a prescription not be able to safely staff the building with this many people not in attendance."Beginning Monday, Nov. 16, Westlake Middle School will transition to full remote learning for a period of two weeks.

Pending no does ventolin need a prescription further issues, the middle school will reopen for hybrid, in-person instruction on Monday, Nov. 30, Kotes does ventolin need a prescription said. The middle school administration will follow up with additional communication to families to ensure that students have the needed resources for this time period.

Click here to sign up for Daily Voice's free daily emails and news alerts.There are now numbers behind the mass exodus of New York City residents to the suburbs and beyond amid the asthma treatment ventolin.From March does ventolin need a prescription 1 through Oct. 31 this year, a total of 295,103 NYC residents have made change-of-address requests.That's according to data The New York Post obtained from the US Postal Service.Most went to Long Island -- a total of more than 40,000 (21,362 to Suffolk County, with 6,500 of that number in six zip codes on the East End, and 18,731 to Nassau County), followed by Westchester County (15,850) and 9,356 to Hudson County, New Jersey (which includes Jersey City and Hoboken), the Post reported.Between July and September, nearly a billion dollars worth of property along the East End of Long Island was sold, according to a Brown does ventolin need a prescription Harris Stevens.According to Miller Samuel Real Estate Appraisers &. Consultants:Westchester County saw a 112 percent increase in home sales in July.In Connecticut, Fairfield County saw a 73-percent increase in July home sales.Farther north of the city, Putnam and Dutchess counties both saw double-digit percent increases.The Brown Harris Stevens report found that sales prices in the Hamptons averaged $2.17 million during the third quarter, which is up 33.2 percent from the same time last year.

The median price jumped 26.2 does ventolin need a prescription percent to $1.26 million. Click here to sign up for Daily Voice's free daily emails and news alerts..

A new school in Northern Westchester is transitioning to remote learning after buy ventolin over the counter nz asthma treatment cases.Three people, two at Westlake Middle School and one at Hawthorne Elementary School, are being treated as positive for asthma treatment in the Mount Pleasant Central School District, Superintendent Kurtis M. Kotes announced in buy ventolin over the counter nz an email to the community early Sunday night, Nov. 15."The individual related to Hawthorne Elementary School has not been in or around the building since Oct. 29," Kotes buy ventolin over the counter nz said. "Therefore no additional quarantine orders will be necessary for Hawthorne Elementary School and the building will remain open for hybrid, in-person instruction."The two individuals related to Westlake Middle School were both in buy ventolin over the counter nz the building on Friday, Nov.

13. There will be 100 students, 12 teachers, and buy ventolin over the counter nz potentially more support staff who will be subject to quarantine orders. "We will not be able to safely staff the building with this many people not in attendance."Beginning Monday, Nov buy ventolin over the counter nz. 16, Westlake Middle School will transition to full remote learning for a period of two weeks. Pending no buy ventolin over the counter nz further issues, the middle school will reopen for hybrid, in-person instruction on Monday, Nov.

30, Kotes buy ventolin over the counter nz said. The middle school administration will follow up with additional communication to families to ensure that students have the needed resources for this time period. Click here to sign up for buy ventolin over the counter nz Daily Voice's free daily emails and news alerts.There are now numbers behind the mass exodus of New York City residents to the suburbs and beyond amid the asthma treatment ventolin.From March 1 through Oct. 31 this year, a total of 295,103 NYC residents have made change-of-address requests.That's according to data The New York Post obtained from the US Postal Service.Most went to Long Island -- a total of more than 40,000 (21,362 to Suffolk County, with 6,500 of that number in six zip codes on the East End, and 18,731 to Nassau County), followed by Westchester County (15,850) and 9,356 to Hudson County, New Jersey (which includes Jersey City and Hoboken), the Post reported.Between July buy ventolin over the counter nz and September, nearly a billion dollars worth of property along the East End of Long Island was sold, according to a Brown Harris Stevens.According to Miller Samuel Real Estate Appraisers &. Consultants:Westchester County saw a 112 percent increase in home sales in July.In Connecticut, Fairfield County saw a 73-percent increase in July home sales.Farther north of the city, Putnam and Dutchess counties both saw double-digit percent increases.The Brown Harris Stevens report found that sales prices in the Hamptons averaged $2.17 million during the third quarter, which is up 33.2 percent from the same time last year.

The median price jumped 26.2 percent to $1.26 million buy ventolin over the counter nz. Click here to sign up for Daily Voice's free daily emails and news alerts..

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Over the last decade, Medicare Advantage, the private plan alternative to traditional Medicare, ventolin without prescription has taken on a larger role in the Medicare program. In 2020, more than 24 million Medicare beneficiaries are enrolled in a Medicare Advantage plan. This brief provides an overview of the Medicare Advantage plans that are available for 2021 and key trends over time.Plan Offerings ventolin without prescription in 2021Number of PlansNumber of Plans Available to Beneficiaries. For 2021, the average Medicare beneficiary has access to 33 Medicare Advantage plans, the largest number of options available in the last decade (Figure 1).Figure 1. The average Medicare beneficiary has access to 33 Medicare Advantage plans in 2021, an increase from prior yearsAmong the 33 Medicare Advantage plans generally available for individual enrollment to the average Medicare beneficiary, 27 of the plans include prescription drug ventolin without prescription coverage (MA-PDs).

These numbers exclude employer or union-sponsored group plans, Special Needs Plans (SNPs) and PACE plans, which are only available to select populations.Total Number of Plans. In total, 3,550 ventolin without prescription Medicare Advantage plans are available nationwide for individual enrollment in 2021 – a 13 percent increase (402 more plans) from 2020 and the largest number of plans ever available (Figure 2. Appendix Table 1). The vast ventolin without prescription majority (89 percent) of all Medicare Advantage plans offered include prescription drug coverage in 2021. .As in prior years, HMOs continue to account for about two-thirds (62%) of all plans offered in 2021.

The availability of local PPOs has increased ventolin without prescription rapidly over recent years. In 2021, one-third of plans offered are local PPOs, compared to a quarter in 2018. Between 2020 and 2021, the number of ventolin without prescription regional PPOs has remained constant, while the number of private fee-for-service plans has continued to decline.The growth in number of plans varies across states and counties, with the preponderance of the growth occurring in Florida and California (41 more and 30 more plans, respectively. Data not shown). Virginia has 6 fewer plans available for 2021 than in 2020, while South Carolina has 3 fewer plans, and Maryland and Nebraska each have one fewer plan available in 2021 than in 2020.While many employers and unions also offer Medicare Advantage plans to their retirees, no information about these 2021 plan offerings is made available by CMS to the public during the Medicare open enrollment period because these plans are not available to the general Medicare population.One notable change for 2021 is that people with end-stage renal ventolin without prescription disease (ESRD) are eligible to enroll in Medicare Advantage plans.

Prior to this change, people with ESRD were not able to enroll in most Medicare Advantage plans, subject to limited exceptions, such as C-SNPS for people with ESRD.Special Needs Plans (SNPs). More SNPs are available for 2021 than in any year since they were authorized, increasing from 855 plans in 2020 to 975 plans in 2021, a 14 percent increase (Figure 3). .The rise in SNPs for people who require an institutional-level of care (I-SNPs) has been particularly notable, more than doubling from 83 plans in 2017 to 174 plans in ventolin without prescription 2021. I-SNPs may be attractive to insurers because they tend to have much lower marketing costs than other plan types since they are often the only available option for people to receive their Medicare benefits in certain retirement communities and nursing homes. The number of SNPs for people dually eligible for Medicare and Medicaid (D-SNPs) has also increased sharply over the past five years, rising from 373 dual SNPs in 2017 to 598 dual SNPs in 2021, a 60% increase, suggesting insurers’ continue to be interested in managing the care of this high-need population.The number of SNPs offered for people with chronic conditions (C-SNPs) is also increasing in 2021, most of which focus on people with diabetes, heart disease, or lung ventolin without prescription conditions, as has been the case since the inception of C-SNPs.

For 2021, three firms are offering C-SNPs for people with dementia (the same as 2020), two firms are offering a C-SNP for people with mental health conditions (up one from 2020), three firms are offering C-SNPs for people with end-stage renal disease (one fewer than 2020) and two firms are offering C-SNPs for people with HIV/AIDS (similar to 2020).Variation in the Number of Plans, by Geographic Area. On average, beneficiaries in metropolitan areas can choose from about twice as many Medicare Advantage plans as beneficiaries in non-metropolitan areas (36 plans versus 20 plans, respectively).In 11 percent of counties (accounting for 41% of beneficiaries), beneficiaries can choose from more than 35 plans in 2021, including eleven counties in Ohio and five counties in Pennsylvania ventolin without prescription where more than 60 Medicare Advantage plans are available (Figure 4). In contrast, in 4 percent of counties (accounting for 1% of beneficiaries), beneficiaries can choose from two or fewer Medicare Advantage plans. The number of counties with no Medicare Advantage plans for 2021 is 82, similar ventolin without prescription to 2020. As in prior years, there are no Medicare Advantage plans offered in Alaska.

Additionally, no Medicare Advantage plans are available in territories other than Puerto ventolin without prescription Rico. .Access to Medicare Advantage Plans, by Plan TypeAs in recent years, virtually all Medicare beneficiaries (99%) have access to a Medicare Advantage plan as an alternative to traditional Medicare, including almost all beneficiaries in metropolitan areas (99.9%) and the vast majority of beneficiaries in non-metropolitan areas (97.7%). In non-metropolitan counties, a smaller share of beneficiaries have access to HMOs (87% in non-metropolitan versus 99% in metropolitan counties) ventolin without prescription or local PPOs (89% in non-metropolitan versus 96% in metropolitan counties), and a slightly larger share of beneficiaries have access to regional PPOs (77% in non-metropolitan counties versus 72% in metropolitan counties). Number of FirmsThe average Medicare beneficiary is able to choose from plans offered by 8 firms in 2021, one more than in 2020 (Figure 5). Despite most beneficiaries having access to plans operated by several different firms, enrollment is concentrated in plans operated by UnitedHealthcare, Humana, and Blue Cross Blue ventolin without prescription Shield affiliates.Figure 5.

More than one-quarter of beneficiaries can choose among Medicare Advantage plans offered by 10 or more firmsMore than one-quarter of beneficiaries (27%) are able to choose from plans offered by 10 or more firms. Fifteen or more firms are offering Medicare Advantage plans in three counties. Orange County, California and Summit and Medina Counties in ventolin without prescription Ohio. In contrast, in 109 counties, most of which are rural counties with relatively few Medicare beneficiaries (1% of total), only one firm will offer Medicare Advantage plans in 2021. Over the past several years, the number of counties with a single firm offering Medicare Advantage plans has ventolin without prescription fallen substantially.

As recently as 2019, there was a single firm offering plans in nearly 200 counties.UnitedHealthcare and Humana, the two firms with the most Medicare Advantage enrollees in 2020, have large footprints across the country, offering plans in most counties. Humana is ventolin without prescription offering plans in 84 percent of counties and UnitedHealthcare is offering plans in 66 percent of counties in 2021 (Figure 6). More than 8 in 10 (87%) Medicare beneficiaries have access to at least one Humana plan and 86 percent have access to at least one UnitedHealthcare plans. .Most major Medicare Advantage firms have also expanded the number of ventolin without prescription counties where they are offering plans. UnitedHealthcare is offering plans in 2,117 counties in 2021, an increase of 245 from 2021, while Humana is offering plans in 2,703 counties in 2021, an increase of 33 from 2020.

Centene is offering plans in 1,129 counties in 2021, an increase of ventolin without prescription 261 plans from 2020. Blue Cross Blue Shield Affiliates are offering plans in 1,181 counties, an increase of 152 plans. CVS Health is offering plans in 1,759 ventolin without prescription counties, an increase of 119 plans. And Cigna is offering plans in 369 counties, an increase of 67 plans. Kaiser Permanente had the smallest growth and is offering plans in 109 counties, an increase of 4 plans.New Market Entrants and ExitsMedicare Advantage continues to be an attractive market for insurers, with 14 firms entering ventolin without prescription the market for the first time in 2021, collectively accounting for about 6 percent of the growth in the number of plans available for general enrollment and about 10 percent of the growth in SNPs (Appendix Table 2).

Nine new entrants are offering HMOs available for individual enrollment. Five of the new ventolin without prescription entrants are offering SNPs. Three firms are offering D-SNPs for people dually eligible for Medicaid, three firms are offering C-SNPs for people with select chronic conditions, and one firm is offering an I-SNPs Four of the new firm entrants are offering plans in California, two are offering plans in Indiana, and the remainder are offering plans in at least one of ten other states (Colorado, Georgia, Illinois, Mississippi, Missouri, Ohio, Texas, Utah, and Wisconsin).Six firms that previously participated in the Medicare Advantage market are not offering plans in 2021. Two of the firms (ApexHealth, Inc. And Clarion Health) offered plans for the first time in 2020, but ventolin without prescription did not appear to enroll any participants.

The other four firms had very low enrollment in 2020. Three of the six exiting firms offered plans in New York.PremiumsThe vast majority of Medicare Advantage plans for individual enrollment (89%) will include prescription drug coverage (MA-PDs), and 54 percent of these plans will charge no premium, other than the Part B premium, ventolin without prescription similar to 2020. More than nine out of ten beneficiaries (96%) have access to a MA-PD with no monthly premium in 2021. However, in Wyoming, beneficiaries do not have access to a zero-premium MA-PD, and in Idaho, less than half of beneficiaries have access to a zero-premium MA-PD.In 2020, 60 percent ventolin without prescription of enrollees in MA-PD plans pay no premium other than the Medicare Part B premium of $144.60 per month. Based on enrollment in March 2020, nearly one in five enrollees (18%) pay at least $50 a month, and 6 percent pay $100 or more.

CMS announced that the average monthly plan premium among all Medicare Advantage enrollees in 2021, including those who pay no ventolin without prescription premium for their Medicare Advantage plan, is expected to decrease 11 percent from 2020 to $21 a month. CMS does not disclose the methods or assumptions used in deriving their calculations, but since most Medicare Advantage enrollees pay no additional premium, the average they report is heavily influenced by zero-premium plans, and does not reflect the average premium paid by those who are in plans with an additional premium.Extra BenefitsMedicare Advantage plans may provide extra benefits that are not available in traditional Medicare, are considered “primarily health related,” and can use rebate dollars (including bonus payments) to help cover the cost of these extra benefits. Beginning in 2019, CMS expanded the definition of “primarily health related” to ventolin without prescription allow Medicare Advantage plans to offer additional supplemental benefits. Medicare Advantage plans may also restrict the availability of these extra benefits to certain subgroups of beneficiaries, such as those with diabetes or congestive heart failure, making different benefits available to different enrollees.Beginning in 2020, Medicare Advantage plans have also been able to offer extra benefits that are not primarily health related for chronically ill beneficiaries, known as Special Supplemental Benefits for the Chronically Ill (SSBCI). Information on the availability of SSBCI for 2021 has not yet been published by CMS, but may include services such as pest control, ventolin without prescription food and produce (beyond a limited basis), and non-medical transportation.

Since plans are permitted to offer these benefits non-uniformly to enrollees, it will be important to examine how these benefits are distributed across subgroups of enrollees.Availability of Extra Benefits in Plans for General Enrollment. Historically, the ventolin without prescription most offered extra benefits were fitness, dental, vision, and hearing. Nearly two-thirds of plans (68%) provide all four of these benefits for 2021. Though these benefits are widely available, the scope of specific services varies. For example, a dental benefit may include ventolin without prescription cleanings only or more comprehensive coverage.

As of 2020, Medicare Advantage plans have also been allowed to offer more telehealth benefits than traditional Medicare (though Medicare has temporarily expanded these benefits during the ventolin). The vast majority (98%) of Medicare Advantage plans are offering ventolin without prescription telehealth in 2021 (up from 91% in 2020) (Figure 7).Figure 7. Most Medicare Advantage plans provide fitness and dental benefits but much fewer provide in-home or caregiver supportOther extra benefits that are frequently offered for 2021 include over the counter items (75%), meal benefits, such as a cooking class, nutrition education, or meal delivery (55%), and transportation benefits (36%).Less than 10 percent of plans provide bathroom safety devices (6%) or in-home support (6%).Availability of Extra Benefits in Special Needs Plans. SNPs are designed to serve a disproportionately high-need population, and a somewhat larger percentage of SNPs than plans for other Medicare beneficiaries provide their enrollees with over the counter ventolin without prescription items (91%), transportation benefits (85%) and meal benefits (63%). Similar to plans available for general enrollment, a relatively small share of SNPs provide bathroom safety devices (11%) or in-home support (18%).Access to Extra Benefits.

Virtually all Medicare beneficiaries live in a county where at least one Medicare Advantage plan ventolin without prescription available for general enrollment has some extra benefits not covered by traditional Medicare, with 98% having access to some dental, fitness, vision, and hearing benefits for 2021. The vast majority of beneficiaries also have access to telehealth benefits (99%), over the counter items (99%), transportation assistance (95%) and a meal benefit (98%), but far fewer have access to bathroom safety (55%) or in-home support (62%).DiscussionMore Medicare Advantage plans are being offered for 2021 than in any other year. Fourteen insurers are entering the Medicare Advantage market for the first time, and six insurers ventolin without prescription are exiting the market, suggesting thatMedicare Advantage remains an attractive, profitable market for insurers. As in prior years, some (mostly non-metropolitan) counties are less attractive to insurers, with fewer firms and plans available, though the number of areas where this is the case has declined over time. Overall, more than 99 percent of ventolin without prescription beneficiaries will have access to one or more Medicare Advantage plans in 2021, similar to prior years.

With more firms offering SNPs and the number of SNPs rapidly growing, there may be greater focus on how well high-need, vulnerable beneficiaries are being served by Medicare Advantage plans, including SNPs as well as plans for general enrollment. As Medicare Advantage enrollment continues to grow, insurers seem to ventolin without prescription be responding by offering more plans and choices to the people on Medicare. This analysis focuses on the Medicare Advantage marketplace in 2021 and trends over time. The analysis includes more than 24 million enrollees in Medicare Advantage plans in 2020.Data on Medicare Advantage plan availability, enrollment, and premiums were collected from a set of data files released by the Centers for Medicare &. Medicaid Services (CMS):Medicare Advantage plan landscape files, released ventolin without prescription each fall prior to the annual enrollment periodMedicare Advantage plan and premium files, released each fallMedicare Advantage plan crosswalk files, released each fallMedicare Advantage contract/plan/state/county level enrollment files, released on a monthly basisMedicare Advantage plan benefit package files, released each fallMedicare Enrollment Dashboard files, released on a monthly basisIn previous years, KFF has used the Medicare Advantage Penetration Files to calculate the number of Medicare beneficiaries eligible for Medicare.

The Medicare Advantage Penetration Files includes people who were previously, but no longer covered by Medicare (e.g., people who obtained employer-sponsored health insurance coverage after initially enrolling in Medicare). It also includes people within 5 months of their ventolin without prescription 65th birthday, but not yet age 65. In addition, CMS has identified an issue where beneficiaries with multiple addresses were double counted in the Penetration File. KFF has refined its approach this year and is using the Medicare Enrollment Dashboard to calculate the number of Medicare beneficiaries because it only includes Medicare beneficiaries with either Part A or Part B coverage, which is a ventolin without prescription more accurate estimate of the Medicare population. The numbers published here supersede all prior estimates by KFF of the number of Medicare beneficiaries.Jeannie Fuglesten Biniek, Meredith Freed, and Tricia Neuman are with KFF.Anthony Damico is an independent consultant.During the Medicare open enrollment period from October 15 to December 7 each year, beneficiaries can enroll in a plan that provides Part D drug coverage, either a stand-alone prescription drug plan (PDP) as a supplement to traditional Medicare, or a Medicare Advantage prescription drug plan (MA-PD), which covers all Medicare benefits, including drugs.

Among the 46 million Part D enrollees in 2020, 20.2 million (44%) are in PDPs and 19.3 million (41%) are in MA-PDs (excluding the 7.0 million (15%) in ventolin without prescription employer-only group PDPs and MA-PDs). This issue brief provides an overview of Medicare Part D drug plans that will be available in 2021 and key trends over time.Part D Plan AvailabilityThe Average Medicare Beneficiary Has a Choice of Nearly 60 Medicare Plans with Part D Drug Coverage in 2021, Including 30 Medicare Stand-alone Drug Plans and 27 Medicare Advantage Drug PlansFigure 1. The Average ventolin without prescription Medicare Beneficiary Has a Choice of Nearly 60 Medicare Plans Offering Drug Coverage in 2021, Including 30 Stand-alone Drug Plans and 27 Medicare Advantage Drug PlansA larger number of Part D plans will be offered in 2021 than in recent years. The average Medicare beneficiary will have a choice of 30 stand-alone PDPs in 2021, two more PDP options than in 2020, and eight more than in 2017, a 36% increase (Figure 1). Although the number of PDP options in 2021 is half of what it was at the peak in 2007 (when there were 56 ventolin without prescription PDP options, on average), this is the fourth year in a row with an increase in the average number of stand-alone drug plan options.In 2021, beneficiaries will also have access to 27 MA-PDs, on average, a 71% increase in MA-PD options since 2017 (excluding Medicare Advantage plans that do not offer the drug benefit and plans not available to all beneficiaries.

Overall, an average of 33 Medicare Advantage plan options will be available in 2021).Based on September 2020 enrollment, 8 out of 10 PDP enrollees (80%) in 2021 are projected to be in PDPs operated by just four firms. UnitedHealth, Centene (which acquired WellCare in 2020), Humana, and ventolin without prescription CVS Health (based on PDP enrollment as of September 2020). All four firms offer PDPs in all 34 PDP regions in 2021.A Total of 996 Medicare Part D Stand-Alone Prescription Drug Plans Will Be Offered in 2021, a 5% Increase From 2020 and a 34% Increase Since 2017 Figure 2. A Total of 996 Medicare Part D Stand-Alone Prescription Drug Plans Will Be Offered in 2021, a 5% Increase From 2020 and a 34% Increase Since 2017​A total of 996 PDPs will be offered in the 34 PDP regions in 2021 (plus another 11 PDPs in the territories), an increase of 48 PDPs (5%) over 2020, and 250 more PDPs (a 34% increase) since 2017 (Figure 2). This increase is primarily due to the Trump Administration’s elimination of the “meaningful difference” ventolin without prescription requirement for enhanced benefit PDPs offered by the same organization in the same region.

Eliminating this requirement means that PDP sponsors no longer have to demonstrate that their enhanced PDPs offered in the same region are meaningfully different in terms of enrollee out-of-pocket costs. In 2021, 62% of PDPs (618 plans) will offer enhanced Part D benefits—a 60% increase in the availability of enhanced-benefit PDPs since 2017, when just over half of PDPs (387 plans) offered enhanced benefits.The number of PDPs per region in 2021 will range from 25 PDPs in Alaska to ventolin without prescription 35 PDPs in Texas and will be the same or higher in 32 of the 34 PDP regions compared to 2020 (see map, Table 1). Part D PremiumsThe Estimated Average Monthly Premium for Medicare PDPs Is Projected to Increase by 9% to $41 in 2021, Based on Current EnrollmentFigure 3. The Estimated Average Monthly Premium for Medicare PDPs Is Projected to Increase by 9% to $41 in 2021, Based on Current Enrollment​The estimated national average monthly PDP premium for 2021 is projected to increase by 9% to $41, from ventolin without prescription $38 in 2020, weighted by September 2020 enrollment (Figure 3). It is likely that the actual average weighted premium for 2021, after taking into account enrollment choices by new enrollees and plan changes by current enrollees, will be somewhat lower than the estimated average.

CMS reported that the average premium for basic Part D coverage offered by PDPs and MA-PDs will be an estimated ventolin without prescription $30 in 2021. Our premium estimate is higher because it is based on PDPs only (excluding MA-PDs) and includes PDPs offering both basic and enhanced coverage (enhanced plans, which account for 62% of all PDPs in 2021, have higher premiums than basic plans, on average).Average Monthly Premiums for the 21 National Part D Stand-alone PDPs Are Projected to Range from $7 to $89 in 2021, with Higher Average Premiums for Enhanced Benefits and Zero-Deductible PDPsFigure 4. Average Monthly Premiums for the 21 National Part D Stand-alone Drug ventolin without prescription Plans Are Projected to Range from $7 to $89 in 2021​PDP premiums will vary widely across plans in 2021, as in previous years (Figure 4, Table 2). Among the 21 PDPs available nationwide, average premiums will range from a low of $7 per month for SilverScript SmartRx to a high of $89 per month for AARP MedicareRx Preferred.Changes to premiums from 2020 to 2021, averaged across regions and weighted by 2020 enrollment, also vary widely across PDPs, as do the absolute amounts of monthly premiums for 2021.The 1.9 million non-LIS enrollees in the largest PDP, CVS Health’s SilverScript Choice (which had a total of 3.9 million enrollees in 2020, including those receiving low-income subsidies) will face a modest $1 (2%) decrease in their average monthly premium, from $29 in 2020 to $28 in 2021.In contrast, the 1.8 million non-LIS enrollees in the second largest PDP, AARP MedicareRx Preferred, will face a $10 (12%) increase in their average monthly premium between 2020 and 2021, from $79 to $89. This is the highest monthly premium among the national PDPs in 2021.The 1.3 million non-LIS enrollees in the fourth largest PDP, Humana Premier Rx, will see a $7 (13%) increase in their monthly premium, from $58 in 2020 to $65 in 2021.Most Part D ventolin without prescription stand-alone drug plans in 2021 (62% of PDPs) will offer enhanced benefits for a higher monthly premium.

Enhanced benefits can include a lower (or no) deductible, reduced cost sharing, or a higher initial coverage limit than under the standard benefit design. The average premium in 2021 for enhanced benefit PDPs is $51, which is 55% higher than the monthly premium for PDPs offering the basic benefit ($33) (weighted by September 2020 enrollment).In 2021, a large majority of PDPs (86%) will charge a deductible, with most PDPs (67%) charging the standard amount of $445 in 2021 ventolin without prescription. Across all PDPs, the average deductible in 2021 will be $345 (weighted by September 2020 enrollment). The average monthly premium in 2021 for PDPs that charge no deductible is $88, nearly three times the monthly premium for PDPs that charge the standard deductible ($34) or a partial deductible ($31) (weighted by September 2020 enrollment).Nearly 8 in 10 Part D Stand-alone Drug ventolin without prescription Plan Enrollees Without Low-income Subsidies Will Pay Higher Premiums in 2021 If They Stay in Their Current PlanFigure 5. Nearly 8 in 10 Part D Stand-alone Drug Plan Enrollees Without Low-income Subsidies Will Pay Higher Premiums in 2021 If They Stay in Their Current Plan​Most (78%, or 10 million) of the 13.4 million Part D PDP enrollees who are responsible for paying the entire premium (which excludes Low-Income Subsidy (LIS) recipients) will see their monthly premium increase in 2021 if they stay in their same plan, while 2.8 million (21%) will see a premium reduction if they stay in their same plan (Figure 5).Nearly 2 million non-LIS enrollees (13%) will see a premium increase of $10 or more per month, while significantly fewer (0.2 million non-LIS enrollees, or 1%) will see a premium reduction of the same magnitude.

One-third (34%) of non-LIS enrollees (4.6 million) are projected to pay monthly premiums of at least $60 if they stay in their current plans, and more than 230,000 (2% of non-LIS enrollees) are projected to pay monthly premiums of at least $100.The Average Monthly Part D Premium in 2021 for the Subset of Enhanced Stand-alone Drug Plans Covering Insulin at a $35 Monthly Copay Is Substantially Higher Than Premiums for Other PDPsFigure 6. The Average Monthly Part D Premium in 2021 for the Subset of Enhanced Stand-alone Drug Plans Covering Insulin at a $35 Monthly Copay is Substantially Higher than ventolin without prescription Premiums for Other Plans​New for 2021, beneficiaries in each state will have the option to enroll in a Part D plan participating in the Trump Administration’s new Innovation Center model in which enhanced drug plans cover insulin products at a monthly copayment of $35 in the deductible, initial coverage, and coverage gap phases of the Part D benefit. Participating plans do not have to cover all insulin products at the $35 monthly copayment amount, just one of each dosage form (vial, pen) and insulin type (rapid-acting, short-acting, intermediate-acting, and long-acting).In 2021, a total of 1,635 enhanced Part D plans will participate in this model, which represents just over 30% of both PDPs (310 plans) and MA-PDs (1,325 plans) available in 2021, including plans in the territories. Between 8 and 10 enhanced PDPs in each region are participating ventolin without prescription in the model, in addition to multiple MA-PDs (see map). The average premium in 2021 for the subset of enhanced PDPs participating in the insulin $35 copay model ($59) is nearly twice as high as the monthly premium for basic PDPs ($33) and 61% higher than the average premium for enhanced PDPs that are not participating in the model ($37) (weighted by September 2020 enrollment).

Part D ventolin without prescription Cost SharingPart D Enrollees Will Pay Much Higher Cost-Sharing Amounts for Brands and Non-preferred Drugs Than For Drugs on a Generic Tier, and a Mix of Copays and Coinsurance for Different Formulary TiersFigure 7. In 2021, Part D Enrollees Will Pay Much Higher Cost-Sharing Amounts for Brands and Non-preferred Drugs than for Drugs on a Generic Tier, and a Mix of Copays and Coinsurance for Different Formulary Tiers​In 2021, as in prior years, Part D enrollees will face much higher cost-sharing amounts for brands and non-preferred drugs (which can include both brands and generics) than for drugs on a generic tier, and a mix of copayments and coinsurance for different formulary tiers (Figure 7). The typical five-tier ventolin without prescription formulary design in Part D includes tiers for preferred generics, generics, preferred brands, non-preferred drugs, and specialty drugs. Among all PDPs, median standard cost sharing in 2021 is $0 for preferred generics and $5 for generics (an increase from $4 in 2020), $40 for preferred brands (a decrease from $42 in 2020), 40% coinsurance for non-preferred drugs (an increase from 38% in 2020. The maximum ventolin without prescription allowed is 50%), and 25% coinsurance for specialty drugs (the same as in 2020.

The maximum allowed is 33%).Among the 21 national PDPs, 13 PDPs, covering 9.3 million enrollees as of September 2020, are increasing cost-sharing amounts for drugs on at least one formulary tier between 2020 and 2021 (Table 3). Five PDPs are increasing copayments for generics, with increases ranging ventolin without prescription from $1 to $4. Six PDPs are increasing copayments for preferred brands, with increases ranging from $3 to $10. And 10 PDPs are increasing coinsurance for non-preferred drugs, with increases ranging from 2 percentage points (e.g., from a 38% coinsurance rate to 40%) to 14 percentage points (e.g., from a 35% coinsurance rate to 49%).Low-Income Subsidy Plan AvailabilityIn 2021, 259 Part D Stand-Alone Drug ventolin without prescription Plans Will Be Premium-Free to Enrollees Receiving the Low-Income Subsidy (Benchmark Plans)Figure 8. In 2021, 259 Part D Stand-Alone Drug Plans Will Be Available Without a Premium to Enrollees Receiving the Low-Income Subsidy (“Benchmark” Plans)​In 2021, a larger number of PDPs will be premium-free benchmark plans—that is, PDPs available for no monthly premium to Medicare Part D enrollees receiving the Low-Income Subsidy (LIS)—than in recent years, with 259 premium-free benchmark plans, or roughly a quarter of all PDPs in 2021 (Figure 8).

Through the Part D LIS program, enrollees with low incomes and modest assets are eligible for assistance with Part D plan premiums and cost sharing. As of 2020, approximately 13 million Part D enrollees are receiving LIS, including 6.7 million (52%) in PDPs and 6.1 million (48%) in MA-PDs.On average (weighted by Medicare enrollment), LIS ventolin without prescription beneficiaries have eight benchmark plans available to them for 2021, or about one-fourth the average number of PDP choices available overall. All LIS enrollees can select any plan offered in their area, but if they enroll in a non-benchmark plan, they must pay some portion of their chosen plan’s monthly premium. In 2021, 10% of all LIS PDP enrollees who are eligible for premium-free Part D coverage (0.6 million LIS enrollees) will pay Part D premiums averaging $33 per month unless they switch or are reassigned by CMS to premium-free plans.The number of benchmark plans available in 2021 will vary ventolin without prescription by region, from five to 10 (see map). In 2020, 89% of the 6.6 million LIS PDP enrollees are projected to be in PDPs operated by five firms.

CVS Health, Centene, ventolin without prescription Humana, UnitedHealth, and Cigna (based on 2020 enrollment). DiscussionOur analysis of the Medicare Part D stand-alone drug plan landscape for 2021 shows that millions of Part D enrollees without low-income subsidies will face premium and other cost increases in 2021 if they stay in their current stand-alone drug plan. There are ventolin without prescription more plans available nationwide in 2021, with Medicare beneficiaries having 30 PDP choices during this year’s open enrollment period, plus 27 Medicare Advantage drug plan options. Most Part D PDP enrollees who remain in the same plan in 2021 will be in a plan with the standard $445 deductible and will face much higher cost sharing for brands than for generic drugs, including as much as 50% coinsurance for non-preferred drugs.Some Part D enrollees who choose to stay in their current plans may see lower premiums and other costs for their drug coverage, but nearly 8 in 10 non-LIS enrollees will face higher premiums if they remain in their current plan, and many will also face higher deductibles and cost sharing for covered drugs. Some beneficiaries might find the best coverage and costs for their specific medications in a plan with a relatively low ventolin without prescription premium, while for other beneficiaries, a higher-premium plan might be more suitable.

Because Part D plans vary in a number of ways that can have a significant effect on an enrollee’s out-of-pocket spending, beyond the monthly premium, all Part D enrollees could benefit from the opportunity to compare plans during open enrollment.Juliette Cubanski is with KFF.Anthony Damico is an independent consultant. This analysis focuses on the Medicare Part D stand-alone prescription drug ventolin without prescription plan marketplace in 2021 and trends over time. The analysis includes 20.2 million enrollees in stand-alone PDPs, as of March 2020. The analysis excludes 17.4 million MA-PD enrollees (non-employer), and another 4.6 million enrollees in employer-group only PDPs and 2.3 million in employer-group only MA-PDs for whom plan premium and benefits data ventolin without prescription are unavailable.Data on Part D plan availability, enrollment, and premiums were collected from a set of data files released by the Centers for Medicare &. Medicaid Services (CMS):– Part D plan landscape files, released each fall prior to the annual enrollment period– Part D plan and premium files, released each fall– Part D plan crosswalk files, released each fall– Part D contract/plan/state/county level enrollment files, released on a monthly basis– Part D Low-Income Subsidy enrollment files, released each spring– Medicare plan benefit package files, released each fallIn this analysis, premium estimates are weighted by September 2020 enrollment unless otherwise noted.

Percentage increases are calculated based on non-rounded estimates and in some cases differ from percentage calculations calculated based on rounded estimates presented in the text..

Over the buy ventolin over the counter nz last decade, Medicare Advantage, the private plan alternative to traditional Medicare, has taken on a larger role in the Medicare program. In 2020, more than 24 million Medicare beneficiaries are enrolled in a Medicare Advantage plan. This brief provides an overview of the Medicare Advantage plans that are available for 2021 and key trends over time.Plan Offerings in buy ventolin over the counter nz 2021Number of PlansNumber of Plans Available to Beneficiaries.

For 2021, the average Medicare beneficiary has access to 33 Medicare Advantage plans, the largest number of options available in the last decade (Figure 1).Figure 1. The average Medicare beneficiary has access to 33 Medicare Advantage plans in 2021, an increase from prior yearsAmong the 33 Medicare Advantage plans generally available for individual enrollment to the average Medicare buy ventolin over the counter nz beneficiary, 27 of the plans include prescription drug coverage (MA-PDs). These numbers exclude employer or union-sponsored group plans, Special Needs Plans (SNPs) and PACE plans, which are only available to select populations.Total Number of Plans.

In total, 3,550 Medicare Advantage plans are available nationwide for individual enrollment in 2021 – a 13 percent increase (402 more plans) from 2020 and the largest number of plans buy ventolin over the counter nz ever available (Figure 2. Appendix Table 1). The vast majority (89 percent) of buy ventolin over the counter nz all Medicare Advantage plans offered include prescription drug coverage in 2021.

.As in prior years, HMOs continue to account for about two-thirds (62%) of all plans offered in 2021. The availability of local PPOs has increased rapidly over recent buy ventolin over the counter nz years. In 2021, one-third of plans offered are local PPOs, compared to a quarter in 2018.

Between 2020 and 2021, the number of regional PPOs has remained constant, while the number buy ventolin over the counter nz of private fee-for-service plans has continued to decline.The growth in number of plans varies across states and counties, with the preponderance of the growth occurring in Florida and California (41 more and 30 more plans, respectively. Data not shown). Virginia has 6 fewer plans available for 2021 than in 2020, while South Carolina has 3 fewer plans, and Maryland and Nebraska each have one fewer plan available in 2021 than in 2020.While many employers and unions also offer Medicare Advantage plans to their retirees, no information about these 2021 plan offerings is made available by CMS to the public during the Medicare open enrollment period because these plans are not available to the general Medicare population.One notable change for 2021 is that people with end-stage renal buy ventolin over the counter nz disease (ESRD) are eligible to enroll in Medicare Advantage plans.

Prior to this change, people with ESRD were not able to enroll in most Medicare Advantage plans, subject to limited exceptions, such as C-SNPS for people with ESRD.Special Needs Plans (SNPs). More SNPs are available for 2021 than in any year since they were authorized, increasing from 855 plans in 2020 to 975 plans in 2021, a 14 percent increase (Figure 3). .The rise in SNPs for people who require an institutional-level of care (I-SNPs) has been particularly notable, more than doubling from 83 plans buy ventolin over the counter nz in 2017 to 174 plans in 2021.

I-SNPs may be attractive to insurers because they tend to have much lower marketing costs than other plan types since they are often the only available option for people to receive their Medicare benefits in certain retirement communities and nursing homes. The number of SNPs for people dually eligible for Medicare and Medicaid (D-SNPs) has also increased sharply over the past five years, rising from 373 dual SNPs in 2017 to 598 dual SNPs in 2021, a 60% increase, suggesting insurers’ continue to be buy ventolin over the counter nz interested in managing the care of this high-need population.The number of SNPs offered for people with chronic conditions (C-SNPs) is also increasing in 2021, most of which focus on people with diabetes, heart disease, or lung conditions, as has been the case since the inception of C-SNPs. For 2021, three firms are offering C-SNPs for people with dementia (the same as 2020), two firms are offering a C-SNP for people with mental health conditions (up one from 2020), three firms are offering C-SNPs for people with end-stage renal disease (one fewer than 2020) and two firms are offering C-SNPs for people with HIV/AIDS (similar to 2020).Variation in the Number of Plans, by Geographic Area.

On average, beneficiaries in metropolitan areas can choose from about twice as many Medicare Advantage plans as beneficiaries in non-metropolitan areas buy ventolin over the counter nz (36 plans versus 20 plans, respectively).In 11 percent of counties (accounting for 41% of beneficiaries), beneficiaries can choose from more than 35 plans in 2021, including eleven counties in Ohio and five counties in Pennsylvania where more than 60 Medicare Advantage plans are available (Figure 4). In contrast, in 4 percent of counties (accounting for 1% of beneficiaries), beneficiaries can choose from two or fewer Medicare Advantage plans. The number of counties with no Medicare Advantage plans for buy ventolin over the counter nz 2021 is 82, similar to 2020.

As in prior years, there are no Medicare Advantage plans offered in Alaska. Additionally, no Medicare Advantage plans are available buy ventolin over the counter nz in territories other than Puerto Rico. .Access to Medicare Advantage Plans, by Plan TypeAs in recent years, virtually all Medicare beneficiaries (99%) have access to a Medicare Advantage plan as an alternative to traditional Medicare, including almost all beneficiaries in metropolitan areas (99.9%) and the vast majority of beneficiaries in non-metropolitan areas (97.7%).

In non-metropolitan counties, a smaller share of beneficiaries have access to HMOs (87% in non-metropolitan versus 99% in buy ventolin over the counter nz metropolitan counties) or local PPOs (89% in non-metropolitan versus 96% in metropolitan counties), and a slightly larger share of beneficiaries have access to regional PPOs (77% in non-metropolitan counties versus 72% in metropolitan counties). Number of FirmsThe average Medicare beneficiary is able to choose from plans offered by 8 firms in 2021, one more than in 2020 (Figure 5). Despite most buy ventolin over the counter nz beneficiaries having access to plans operated by several different firms, enrollment is concentrated in plans operated by UnitedHealthcare, Humana, and Blue Cross Blue Shield affiliates.Figure 5.

More than one-quarter of beneficiaries can choose among Medicare Advantage plans offered by 10 or more firmsMore than one-quarter of beneficiaries (27%) are able to choose from plans offered by 10 or more firms. Fifteen or more firms are offering Medicare Advantage plans in three counties. Orange County, California buy ventolin over the counter nz and Summit and Medina Counties in Ohio.

In contrast, in 109 counties, most of which are rural counties with relatively few Medicare beneficiaries (1% of total), only one firm will offer Medicare Advantage plans in 2021. Over the past several years, the number of counties with a single firm offering Medicare Advantage plans has fallen buy ventolin over the counter nz substantially. As recently as 2019, there was a single firm offering plans in nearly 200 counties.UnitedHealthcare and Humana, the two firms with the most Medicare Advantage enrollees in 2020, have large footprints across the country, offering plans in most counties.

Humana is offering plans in 84 percent of counties and UnitedHealthcare is offering plans in 66 buy ventolin over the counter nz percent of counties in 2021 (Figure 6). More than 8 in 10 (87%) Medicare beneficiaries have access to at least one Humana plan and 86 percent have access to at least one UnitedHealthcare plans. .Most major Medicare Advantage firms have buy ventolin over the counter nz also expanded the number of counties where they are offering plans.

UnitedHealthcare is offering plans in 2,117 counties in 2021, an increase of 245 from 2021, while Humana is offering plans in 2,703 counties in 2021, an increase of 33 from 2020. Centene is offering plans in buy ventolin over the counter nz 1,129 counties in 2021, an increase of 261 plans from 2020. Blue Cross Blue Shield Affiliates are offering plans in 1,181 counties, an increase of 152 plans.

CVS Health buy ventolin over the counter nz is offering plans in 1,759 counties, an increase of 119 plans. And Cigna is offering plans in 369 counties, an increase of 67 plans. Kaiser Permanente had the smallest growth and is offering plans in 109 counties, an increase of 4 plans.New Market Entrants and ExitsMedicare Advantage continues to be an attractive market for insurers, with 14 firms entering the market for the first time in 2021, collectively accounting for about 6 percent of the growth in the number of plans available for general enrollment and about 10 percent of the buy ventolin over the counter nz growth in SNPs (Appendix Table 2).

Nine new entrants are offering HMOs available for individual enrollment. Five of buy ventolin over the counter nz the new entrants are offering SNPs. Three firms are offering D-SNPs for people dually eligible for Medicaid, three firms are offering C-SNPs for people with select chronic conditions, and one firm is offering an I-SNPs Four of the new firm entrants are offering plans in California, two are offering plans in Indiana, and the remainder are offering plans in at least one of ten other states (Colorado, Georgia, Illinois, Mississippi, Missouri, Ohio, Texas, Utah, and Wisconsin).Six firms that previously participated in the Medicare Advantage market are not offering plans in 2021.

Two of the firms (ApexHealth, Inc. And Clarion Health) offered plans for the first buy ventolin over the counter nz time in 2020, but did not appear to enroll any participants. The other four firms had very low enrollment in 2020.

Three of the six exiting firms offered plans in New York.PremiumsThe vast majority of Medicare Advantage plans for individual enrollment (89%) will include prescription drug coverage (MA-PDs), and 54 percent of these plans will charge no buy ventolin over the counter nz premium, other than the Part B premium, similar to 2020. More than nine out of ten beneficiaries (96%) have access to a MA-PD with no monthly premium in 2021. However, in Wyoming, beneficiaries do not buy ventolin over the counter nz have access to a zero-premium MA-PD, and in Idaho, less than half of beneficiaries have access to a zero-premium MA-PD.In 2020, 60 percent of enrollees in MA-PD plans pay no premium other than the Medicare Part B premium of $144.60 per month.

Based on enrollment in March 2020, nearly one in five enrollees (18%) pay at least $50 a month, and 6 percent pay $100 or more. CMS announced that the average monthly plan premium among all Medicare Advantage buy ventolin over the counter nz enrollees in 2021, including those who pay no premium for their Medicare Advantage plan, is expected to decrease 11 percent from 2020 to $21 a month. CMS does not disclose the methods or assumptions used in deriving their calculations, but since most Medicare Advantage enrollees pay no additional premium, the average they report is heavily influenced by zero-premium plans, and does not reflect the average premium paid by those who are in plans with an additional premium.Extra BenefitsMedicare Advantage plans may provide extra benefits that are not available in traditional Medicare, are considered “primarily health related,” and can use rebate dollars (including bonus payments) to help cover the cost of these extra benefits.

Beginning in 2019, CMS expanded buy ventolin over the counter nz the definition of “primarily health related” to allow Medicare Advantage plans to offer additional supplemental benefits. Medicare Advantage plans may also restrict the availability of these extra benefits to certain subgroups of beneficiaries, such as those with diabetes or congestive heart failure, making different benefits available to different enrollees.Beginning in 2020, Medicare Advantage plans have also been able to offer extra benefits that are not primarily health related for chronically ill beneficiaries, known as Special Supplemental Benefits for the Chronically Ill (SSBCI). Information on the availability of SSBCI for 2021 has not yet been published by CMS, but may include services such buy ventolin over the counter nz as pest control, food and produce (beyond a limited basis), and non-medical transportation.

Since plans are permitted to offer these benefits non-uniformly to enrollees, it will be important to examine how these benefits are distributed across subgroups of enrollees.Availability of Extra Benefits in Plans for General Enrollment. Historically, the buy ventolin over the counter nz most offered extra benefits were fitness, dental, vision, and hearing. Nearly two-thirds of plans (68%) provide all four of these benefits for 2021.

Though these benefits are widely available, the scope of specific services varies. For example, a dental benefit may include cleanings only buy ventolin over the counter nz or more comprehensive coverage. As of 2020, Medicare Advantage plans have also been allowed to offer more telehealth benefits than traditional Medicare (though Medicare has temporarily expanded these benefits during the ventolin).

The vast majority (98%) of Medicare Advantage plans are offering telehealth in 2021 (up from 91% buy ventolin over the counter nz in 2020) (Figure 7).Figure 7. Most Medicare Advantage plans provide fitness and dental benefits but much fewer provide in-home or caregiver supportOther extra benefits that are frequently offered for 2021 include over the counter items (75%), meal benefits, such as a cooking class, nutrition education, or meal delivery (55%), and transportation benefits (36%).Less than 10 percent of plans provide bathroom safety devices (6%) or in-home support (6%).Availability of Extra Benefits in Special Needs Plans. SNPs are designed to serve a buy ventolin over the counter nz disproportionately high-need population, and a somewhat larger percentage of SNPs than plans for other Medicare beneficiaries provide their enrollees with over the counter items (91%), transportation benefits (85%) and meal benefits (63%).

Similar to plans available for general enrollment, a relatively small share of SNPs provide bathroom safety devices (11%) or in-home support (18%).Access to Extra Benefits. Virtually all buy ventolin over the counter nz Medicare beneficiaries live in a county where at least one Medicare Advantage plan available for general enrollment has some extra benefits not covered by traditional Medicare, with 98% having access to some dental, fitness, vision, and hearing benefits for 2021. The vast majority of beneficiaries also have access to telehealth benefits (99%), over the counter items (99%), transportation assistance (95%) and a meal benefit (98%), but far fewer have access to bathroom safety (55%) or in-home support (62%).DiscussionMore Medicare Advantage plans are being offered for 2021 than in any other year.

Fourteen insurers are entering the Medicare Advantage market for the buy ventolin over the counter nz first time, and six insurers are exiting the market, suggesting thatMedicare Advantage remains an attractive, profitable market for insurers. As in prior years, some (mostly non-metropolitan) counties are less attractive to insurers, with fewer firms and plans available, though the number of areas where this is the case has declined over time. Overall, more than 99 percent of beneficiaries will have access to one or more Medicare buy ventolin over the counter nz Advantage plans in 2021, similar to prior years.

With more firms offering SNPs and the number of SNPs rapidly growing, there may be greater focus on how well high-need, vulnerable beneficiaries are being served by Medicare Advantage plans, including SNPs as well as plans for general enrollment. As Medicare Advantage enrollment continues to grow, insurers seem to buy ventolin over the counter nz be responding by offering more plans and choices to the people on Medicare. This analysis focuses on the Medicare Advantage marketplace in 2021 and trends over time.

The analysis includes more than 24 million enrollees in Medicare Advantage plans in 2020.Data on Medicare Advantage plan availability, enrollment, and premiums were collected from a set of data files released by the Centers for Medicare &. Medicaid Services (CMS):Medicare Advantage plan landscape files, released each fall prior to the annual enrollment periodMedicare Advantage plan and premium files, released each fallMedicare Advantage plan crosswalk files, released each fallMedicare Advantage contract/plan/state/county level enrollment files, released on a monthly basisMedicare Advantage plan benefit package files, released each fallMedicare Enrollment Dashboard files, released on a monthly basisIn previous years, KFF has used the Medicare Advantage buy ventolin over the counter nz Penetration Files to calculate the number of Medicare beneficiaries eligible for Medicare. The Medicare Advantage Penetration Files includes people who were previously, but no longer covered by Medicare (e.g., people who obtained employer-sponsored health insurance coverage after initially enrolling in Medicare).

It also includes people within 5 months of their 65th birthday, but not yet age 65 buy ventolin over the counter nz. In addition, CMS has identified an issue where beneficiaries with multiple addresses were double counted in the Penetration File. KFF has refined its approach this year and is using the Medicare Enrollment Dashboard to calculate the number of Medicare beneficiaries because it only includes Medicare beneficiaries with buy ventolin over the counter nz either Part A or Part B coverage, which is a more accurate estimate of the Medicare population.

The numbers published here supersede all prior estimates by KFF of the number of Medicare beneficiaries.Jeannie Fuglesten Biniek, Meredith Freed, and Tricia Neuman are with KFF.Anthony Damico is an independent consultant.During the Medicare open enrollment period from October 15 to December 7 each year, beneficiaries can enroll in a plan that provides Part D drug coverage, either a stand-alone prescription drug plan (PDP) as a supplement to traditional Medicare, or a Medicare Advantage prescription drug plan (MA-PD), which covers all Medicare benefits, including drugs. Among the 46 buy ventolin over the counter nz million Part D enrollees in 2020, 20.2 million (44%) are in PDPs and 19.3 million (41%) are in MA-PDs (excluding the 7.0 million (15%) in employer-only group PDPs and MA-PDs). This issue brief provides an overview of Medicare Part D drug plans that will be available in 2021 and key trends over time.Part D Plan AvailabilityThe Average Medicare Beneficiary Has a Choice of Nearly 60 Medicare Plans with Part D Drug Coverage in 2021, Including 30 Medicare Stand-alone Drug Plans and 27 Medicare Advantage Drug PlansFigure 1.

The Average buy ventolin over the counter nz Medicare Beneficiary Has a Choice of Nearly 60 Medicare Plans Offering Drug Coverage in 2021, Including 30 Stand-alone Drug Plans and 27 Medicare Advantage Drug PlansA larger number of Part D plans will be offered in 2021 than in recent years. The average Medicare beneficiary will have a choice of 30 stand-alone PDPs in 2021, two more PDP options than in 2020, and eight more than in 2017, a 36% increase (Figure 1). Although the number of PDP options in 2021 is half of what it was at the peak in 2007 (when there were 56 PDP options, on average), this is the fourth year in a row with an increase in the average number of stand-alone drug plan options.In 2021, beneficiaries will also have access to 27 MA-PDs, on average, a 71% increase in MA-PD options since 2017 (excluding Medicare Advantage buy ventolin over the counter nz plans that do not offer the drug benefit and plans not available to all beneficiaries.

Overall, an average of 33 Medicare Advantage plan options will be available in 2021).Based on September 2020 enrollment, 8 out of 10 PDP enrollees (80%) in 2021 are projected to be in PDPs operated by just four firms. UnitedHealth, Centene (which acquired WellCare in 2020), Humana, and CVS Health (based on PDP enrollment buy ventolin over the counter nz as of September 2020). All four firms offer PDPs in all 34 PDP regions in 2021.A Total of 996 Medicare Part D Stand-Alone Prescription Drug Plans Will Be Offered in 2021, a 5% Increase From 2020 and a 34% Increase Since 2017 Figure 2.

A Total of 996 Medicare Part D Stand-Alone Prescription Drug Plans Will Be Offered in 2021, a 5% Increase From 2020 and a 34% Increase Since 2017​A total of 996 PDPs will be offered in the 34 PDP regions in 2021 (plus another 11 PDPs in the territories), an increase of 48 PDPs (5%) over 2020, and 250 more PDPs (a 34% increase) since 2017 (Figure 2). This increase is primarily due to the Trump Administration’s elimination of the “meaningful difference” requirement for enhanced benefit PDPs offered by the buy ventolin over the counter nz same organization in the same region. Eliminating this requirement means that PDP sponsors no longer have to demonstrate that their enhanced PDPs offered in the same region are meaningfully different in terms of enrollee out-of-pocket costs.

In 2021, 62% of PDPs (618 plans) will offer enhanced Part D benefits—a 60% increase in the availability of enhanced-benefit PDPs since 2017, when just over half of PDPs (387 plans) offered enhanced benefits.The number of PDPs per region in 2021 will range from 25 PDPs in Alaska to 35 PDPs in Texas and will be buy ventolin over the counter nz the same or higher in 32 of the 34 PDP regions compared to 2020 (see map, Table 1). Part D PremiumsThe Estimated Average Monthly Premium for Medicare PDPs Is Projected to Increase by 9% to $41 in 2021, Based on Current EnrollmentFigure 3. The Estimated Average Monthly Premium for Medicare PDPs Is Projected to buy ventolin over the counter nz Increase by 9% to $41 in 2021, Based on Current Enrollment​The estimated national average monthly PDP premium for 2021 is projected to increase by 9% to $41, from $38 in 2020, weighted by September 2020 enrollment (Figure 3).

It is likely that the actual average weighted premium for 2021, after taking into account enrollment choices by new enrollees and plan changes by current enrollees, will be somewhat lower than the estimated average. CMS reported that the average premium for basic Part D coverage offered by PDPs and MA-PDs will be buy ventolin over the counter nz an estimated $30 in 2021. Our premium estimate is higher because it is based on PDPs only (excluding MA-PDs) and includes PDPs offering both basic and enhanced coverage (enhanced plans, which account for 62% of all PDPs in 2021, have higher premiums than basic plans, on average).Average Monthly Premiums for the 21 National Part D Stand-alone PDPs Are Projected to Range from $7 to $89 in 2021, with Higher Average Premiums for Enhanced Benefits and Zero-Deductible PDPsFigure 4.

Average Monthly Premiums for the 21 National Part D Stand-alone Drug Plans Are Projected to Range from buy ventolin over the counter nz $7 to $89 in 2021​PDP premiums will vary widely across plans in 2021, as in previous years (Figure 4, Table 2). Among the 21 PDPs available nationwide, average premiums will range from a low of $7 per month for SilverScript SmartRx to a high of $89 per month for AARP MedicareRx Preferred.Changes to premiums from 2020 to 2021, averaged across regions and weighted by 2020 enrollment, also vary widely across PDPs, as do the absolute amounts of monthly premiums for 2021.The 1.9 million non-LIS enrollees in the largest PDP, CVS Health’s SilverScript Choice (which had a total of 3.9 million enrollees in 2020, including those receiving low-income subsidies) will face a modest $1 (2%) decrease in their average monthly premium, from $29 in 2020 to $28 in 2021.In contrast, the 1.8 million non-LIS enrollees in the second largest PDP, AARP MedicareRx Preferred, will face a $10 (12%) increase in their average monthly premium between 2020 and 2021, from $79 to $89. This is the highest monthly premium among the national PDPs in 2021.The 1.3 million non-LIS enrollees in the fourth largest PDP, Humana Premier Rx, will see a $7 (13%) increase in buy ventolin over the counter nz their monthly premium, from $58 in 2020 to $65 in 2021.Most Part D stand-alone drug plans in 2021 (62% of PDPs) will offer enhanced benefits for a higher monthly premium.

Enhanced benefits can include a lower (or no) deductible, reduced cost sharing, or a higher initial coverage limit than under the standard benefit design. The average premium buy ventolin over the counter nz in 2021 for enhanced benefit PDPs is $51, which is 55% higher than the monthly premium for PDPs offering the basic benefit ($33) (weighted by September 2020 enrollment).In 2021, a large majority of PDPs (86%) will charge a deductible, with most PDPs (67%) charging the standard amount of $445 in 2021. Across all PDPs, the average deductible in 2021 will be $345 (weighted by September 2020 enrollment).

The average monthly premium in 2021 for PDPs that charge no deductible is $88, nearly three times the monthly premium for PDPs that charge the standard deductible ($34) or a partial deductible ($31) (weighted by September 2020 buy ventolin over the counter nz enrollment).Nearly 8 in 10 Part D Stand-alone Drug Plan Enrollees Without Low-income Subsidies Will Pay Higher Premiums in 2021 If They Stay in Their Current PlanFigure 5. Nearly 8 in 10 Part D Stand-alone Drug Plan Enrollees Without Low-income Subsidies Will Pay Higher Premiums in 2021 If They Stay in Their Current Plan​Most (78%, or 10 million) of the 13.4 million Part D PDP enrollees who are responsible for paying the entire premium (which excludes Low-Income Subsidy (LIS) recipients) will see their monthly premium increase in 2021 if they stay in their same plan, while 2.8 million (21%) will see a premium reduction if they stay in their same plan (Figure 5).Nearly 2 million non-LIS enrollees (13%) will see a premium increase of $10 or more per month, while significantly fewer (0.2 million non-LIS enrollees, or 1%) will see a premium reduction of the same magnitude. One-third (34%) of non-LIS enrollees (4.6 million) are projected to pay monthly premiums of at least $60 if they stay in their current plans, and more than 230,000 (2% of non-LIS enrollees) are projected to pay monthly premiums of at least $100.The Average Monthly Part D Premium in 2021 for the Subset of Enhanced Stand-alone Drug Plans Covering Insulin at a $35 Monthly Copay Is Substantially Higher Than Premiums for Other PDPsFigure 6.

The Average Monthly Part D Premium in 2021 for the Subset of Enhanced Stand-alone Drug Plans Covering Insulin at a $35 Monthly Copay is Substantially Higher than Premiums for Other Plans​New for 2021, beneficiaries in each buy ventolin over the counter nz state will have the option to enroll in a Part D plan participating in the Trump Administration’s new Innovation Center model in which enhanced drug plans cover insulin products at a monthly copayment of $35 in the deductible, initial coverage, and coverage gap phases of the Part D benefit. Participating plans do not have to cover all insulin products at the $35 monthly copayment amount, just one of each dosage form (vial, pen) and insulin type (rapid-acting, short-acting, intermediate-acting, and long-acting).In 2021, a total of 1,635 enhanced Part D plans will participate in this model, which represents just over 30% of both PDPs (310 plans) and MA-PDs (1,325 plans) available in 2021, including plans in the territories. Between 8 and 10 enhanced buy ventolin over the counter nz PDPs in each region are participating in the model, in addition to multiple MA-PDs (see map).

The average premium in 2021 for the subset of enhanced PDPs participating in the insulin $35 copay model ($59) is nearly twice as high as the monthly premium for basic PDPs ($33) and 61% higher than the average premium for enhanced PDPs that are not participating in the model ($37) (weighted by September 2020 enrollment). Part D Cost SharingPart D Enrollees Will Pay Much Higher Cost-Sharing Amounts for Brands and Non-preferred Drugs Than For Drugs on a Generic Tier, and a Mix of Copays and Coinsurance for Different Formulary TiersFigure 7 buy ventolin over the counter nz. In 2021, Part D Enrollees Will Pay Much Higher Cost-Sharing Amounts for Brands and Non-preferred Drugs than for Drugs on a Generic Tier, and a Mix of Copays and Coinsurance for Different Formulary Tiers​In 2021, as in prior years, Part D enrollees will face much higher cost-sharing amounts for brands and non-preferred drugs (which can include both brands and generics) than for drugs on a generic tier, and a mix of copayments and coinsurance for different formulary tiers (Figure 7).

The typical five-tier formulary design buy ventolin over the counter nz in Part D includes tiers for preferred generics, generics, preferred brands, non-preferred drugs, and specialty drugs. Among all PDPs, median standard cost sharing in 2021 is $0 for preferred generics and $5 for generics (an increase from $4 in 2020), $40 for preferred brands (a decrease from $42 in 2020), 40% coinsurance for non-preferred drugs (an increase from 38% in 2020. The maximum allowed is 50%), and buy ventolin over the counter nz 25% coinsurance for specialty drugs (the same as in 2020.

The maximum allowed is 33%).Among the 21 national PDPs, 13 PDPs, covering 9.3 million enrollees as of September 2020, are increasing cost-sharing amounts for drugs on at least one formulary tier between 2020 and 2021 (Table 3). Five PDPs are increasing copayments buy ventolin over the counter nz for generics, with increases ranging from $1 to $4. Six PDPs are increasing copayments for preferred brands, with increases ranging from $3 to $10.

And 10 PDPs are increasing coinsurance for non-preferred drugs, with increases ranging from 2 percentage points (e.g., from a 38% coinsurance rate to 40%) to buy ventolin over the counter nz 14 percentage points (e.g., from a 35% coinsurance rate to 49%).Low-Income Subsidy Plan AvailabilityIn 2021, 259 Part D Stand-Alone Drug Plans Will Be Premium-Free to Enrollees Receiving the Low-Income Subsidy (Benchmark Plans)Figure 8. In 2021, 259 Part D Stand-Alone Drug Plans Will Be Available Without a Premium to Enrollees Receiving the Low-Income Subsidy (“Benchmark” Plans)​In 2021, a larger number of PDPs will be premium-free benchmark plans—that is, PDPs available for no monthly premium to Medicare Part D enrollees receiving the Low-Income Subsidy (LIS)—than in recent years, with 259 premium-free benchmark plans, or roughly a quarter of all PDPs in 2021 (Figure 8). Through the Part D LIS program, enrollees with low incomes and modest assets are eligible for assistance with Part D plan premiums and cost sharing.

As of 2020, approximately 13 million Part D enrollees are receiving LIS, including 6.7 million (52%) in PDPs and 6.1 million (48%) in MA-PDs.On average (weighted by Medicare enrollment), LIS beneficiaries have eight benchmark plans available to them for 2021, or about one-fourth the average number of PDP buy ventolin over the counter nz choices available overall. All LIS enrollees can select any plan offered in their area, but if they enroll in a non-benchmark plan, they must pay some portion of their chosen plan’s monthly premium. In 2021, 10% of all LIS PDP enrollees who are eligible for premium-free Part D coverage (0.6 million LIS enrollees) buy ventolin over the counter nz will pay Part D premiums averaging $33 per month unless they switch or are reassigned by CMS to premium-free plans.The number of benchmark plans available in 2021 will vary by region, from five to 10 (see map).

In 2020, 89% of the 6.6 million LIS PDP enrollees are projected to be in PDPs operated by five firms. CVS Health, buy ventolin over the counter nz Centene, Humana, UnitedHealth, and Cigna (based on 2020 enrollment). DiscussionOur analysis of the Medicare Part D stand-alone drug plan landscape for 2021 shows that millions of Part D enrollees without low-income subsidies will face premium and other cost increases in 2021 if they stay in their current stand-alone drug plan.

There are more plans available nationwide in 2021, with Medicare beneficiaries having 30 PDP choices during this year’s open buy ventolin over the counter nz enrollment period, plus 27 Medicare Advantage drug plan options. Most Part D PDP enrollees who remain in the same plan in 2021 will be in a plan with the standard $445 deductible and will face much higher cost sharing for brands than for generic drugs, including as much as 50% coinsurance for non-preferred drugs.Some Part D enrollees who choose to stay in their current plans may see lower premiums and other costs for their drug coverage, but nearly 8 in 10 non-LIS enrollees will face higher premiums if they remain in their current plan, and many will also face higher deductibles and cost sharing for covered drugs. Some beneficiaries might find the best coverage and costs for their specific medications in a plan buy ventolin over the counter nz with a relatively low premium, while for other beneficiaries, a higher-premium plan might be more suitable.

Because Part D plans vary in a number of ways that can have a significant effect on an enrollee’s out-of-pocket spending, beyond the monthly premium, all Part D enrollees could benefit from the opportunity to compare plans during open enrollment.Juliette Cubanski is with KFF.Anthony Damico is an independent consultant. This analysis buy ventolin over the counter nz focuses on the Medicare Part D stand-alone prescription drug plan marketplace in 2021 and trends over time. The analysis includes 20.2 million enrollees in stand-alone PDPs, as of March 2020.

The analysis excludes 17.4 million MA-PD enrollees (non-employer), and another 4.6 million enrollees in employer-group only PDPs and 2.3 million in employer-group only MA-PDs for whom plan premium and benefits data are unavailable.Data on Part D plan availability, enrollment, and premiums were collected from a set of data files released by the Centers for buy ventolin over the counter nz Medicare &. Medicaid Services (CMS):– Part D plan landscape files, released each fall prior to the annual enrollment period– Part D plan and premium files, released each fall– Part D plan crosswalk files, released each fall– Part D contract/plan/state/county level enrollment files, released on a monthly basis– Part D Low-Income Subsidy enrollment files, released each spring– Medicare plan benefit package files, released each fallIn this analysis, premium estimates are weighted by September 2020 enrollment unless otherwise noted. Percentage increases are calculated based on non-rounded estimates and in some cases differ from percentage calculations calculated based on rounded estimates presented in the text..

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Submission Milestone Date 4 What follow-up measures will you can find out more the company take?. 5 What post-authorization activity has taken place for ?. 6 What other information is available about drugs?.

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Post-Authorization Activity Table (PAAT) for Post-Authorization Activity Table (PAAT) RowNum Activity/submission type, control number Date submitted Decision and date Summary of activities Summary Basis of Decision (SBD) for Date SBD issued. The following information relates to the new drug submission for. Drug Identification Number (DIN).

1 What was approved?. 2 Why was approved?. 3 What steps led to the approval of ?.

PAATs will Where to buy cheap viagra be updated buy ventolin over the counter nz regularly with post-authorization activity throughout the product's life cycle. Post-Authorization Activity Table (PAAT) for Post-Authorization Activity Table (PAAT) RowNum Activity/submission type, control number Date submitted Decision and date Summary of activities Summary Basis of Decision (SBD) for Date SBD issued. The following information relates to the new drug submission for.

Drug Identification Number (DIN) buy ventolin over the counter nz. 1 What was approved?. 2 Why was approved?.

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5 buy ventolin over the counter nz What post-authorization activity has taken place for ?. 6 What other information is available about drugs?. Summary Basis of Decision (SBD) documents provide information related to the original authorization of a product.

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Myeloproliferative neoplasms (MPNs) are a group of blood cancers that ventolin hfa aerosol solution 108 mcg act are maintained by stem cell populations. In this issue of JEM, Dagher et al. (https://doi.org/10.1084/jem.20201268) combine arsenic and interferon α to deliver a ventolin hfa aerosol solution 108 mcg act knockout punch to MPN stem cells and provide new hope to cure patients with MPNs. Myeloproliferative neoplasms (MPNs) are a group of clonal hematological disorders characterized by excessive production of mature myeloid cells including granulocytes, erythrocytes, and platelets. MPNs are ventolin hfa aerosol solution 108 mcg act driven by mutations arising in hematopoietic stem cells.

Excluding chronic myeloid leukemia, which is pathogenomonically associated with the BCR-ABL translocation, the classical MPNs include polycythemia vera, essential thrombocythemia, and primary myelofibrosis. These BCR-ABL–negative ventolin hfa aerosol solution 108 mcg act MPNs are primarily caused by driver mutations in JAK2, myeloproliferative leukemia ventolin (the thrombopoietin receptor), and Calreticulin. Mechanistically, these mutations all serve to constitutively activate JAK-STAT signaling, leading to the expansion of lineage committed progenitor cells and the corresponding disease phenotype (Vainchenker and Kralovics, 2017. Mullally et al., 2010). Insights from ventolin hfa aerosol solution 108 mcg act Megan Bywater and Steven W.

Lane. Current therapies used in the management of MPNs include combinations of phlebotomy, aspirin, and cytoreductive therapy, most ventolin hfa aerosol solution 108 mcg act commonly hydroxyurea (Spivak, 2019). More recently, inhibitors of JAK2 signaling such as ruxolitinib have shown efficacy in controlling blood counts and treating symptoms, including splenomegaly, in patients (Harrison et al., 2012. Verstovsek et ventolin hfa aerosol solution 108 mcg act al., 2012). However, they are unable to eradicate the disease initiating MPN clone (Austin et al., 2020).

Determining vulnerabilities that will allow the selective targeting of MPN-driver mutation–carrying stem cells is of key clinical importance, as it is likely to facilitate long-term disease control in patients and potentially also may reduce the incidence of transformation to secondary myelofibrosis or acute myeloid leukemia, a devastating complication of MPN associated with very poor long-term survival. IFNα therapy has shown efficacy in the treatment of MPNs for ventolin hfa aerosol solution 108 mcg act many years. However, clinical use has been limited by the requirement for frequent injections and relatively high rates of toxicity. More recently, longer-acting pegylated versions of IFNα ventolin hfa aerosol solution 108 mcg act have become available with increased efficacy and reduced toxicity compared with the historical short-acting forms. In contrast to other agents, such as the Jak1/2 inhibitors, pegylated IFNα has been shown to induce reduction in the molecular burden of disease, in some cases leading to complete molecular remission, thought to represent a reduction in the frequency of MPN mutation–bearing cells (Kiladjian et al., 2008).

These clinical responses are supported by data showing that ventolin hfa aerosol solution 108 mcg act IFNα is able to preferentially reduce the maintenance of Jak2V617F stem cells in murine models of disease (Austin et al., 2020. Mullally et al., 2013. Hasan et al., 2013). The mechanism behind this selective response to IFNα is not well understood, although it may be linked to increased DNA damage or failure to repair these processes ventolin hfa aerosol solution 108 mcg act (Austin et al., 2020). Molecular remissions appear to require prolonged treatment over a protracted time frame, and, therefore, it would be advantageous to determine combination strategies to further enhance this process in order to accelerate clinical responses.

Importantly, Dagher ventolin hfa aerosol solution 108 mcg act et al. Now demonstrate that arsenic trioxide (ATO) enhances the effect of IFNα in the treatment of MPN by depleting Jak2V617F mutant stem cell populations (Dagher et al., 2020). ATO ventolin hfa aerosol solution 108 mcg act has a long therapeutic history related to its use in traditional Chinese medicine. In modern medicine, it has shown marked clinical efficacy in the treatment of de novo and all-trans retinoic acid–resistant acute promyelocytic leukemia (APL). De Thé and colleagues had previously shown that this effect was mediated by its ability to facilitate the degradation of the APL oncogenic fusion protein, PML-RARΑ (Zhu et al., 1997).

Mechanistically, ATO can directly bind to PML ventolin hfa aerosol solution 108 mcg act and enhance nuclear body (NB) formation (Zhang et al., 2010). These PML-NBs facilitate the recruitment of proteins that both catalyze and interact with posttranslational modifications. Of note, activation of p53 can occur via its direct recruitment to NBs through ventolin hfa aerosol solution 108 mcg act posttranslational modifications that alter its transcriptional activity and increased stability via the sequestration of Mdm2 (Bernardi et al., 2004). Increased PML-NB formation has also been shown to attenuate E2F transcriptional programs, most likely through direct recruitment and enhanced hypo-phosphorylation of Rb, resulting in growth arrest and senescence (Vernier et al., 2011). Consequently, PML-NB formation has been ventolin hfa aerosol solution 108 mcg act shown to have a tumor-suppressive role in a number of cancer models.

Interestingly, PML has also been characterized as an IFN-stimulated gene (ISG. Stadler et al., 1995). These preliminary findings led Dagher ventolin hfa aerosol solution 108 mcg act et al. (2020) to ask whether increased PML-NB formation may contribute to the efficacy of IFNα therapy in the treatment of MPN and, furthermore, whether this effect could be enhanced by combining IFNα with ATO. Dagher et ventolin hfa aerosol solution 108 mcg act al.

(2020) were able to show that IFNα treatment increased the number of PML-NBs in primary human MPN CD34+ cells and JAK2V617F mutant human cell lines. Interestingly, JAK2 mutant CD34+ ventolin hfa aerosol solution 108 mcg act cells isolated from MPN patients demonstrated an increased number of PML-NBs at baseline in comparison to wild type. As PML has been identified as an ISG, this finding is consistent with the JAK2V617F mutation driving sensitization to IFN signaling, as inferred from the previous observation of higher basal transcriptional activation of Stat1 (Austin et al., 2020). Moreover, this also suggests that strategies to enhance PML-NB formation may be an effective way to selectively target Jak2 mutant stem cells. In support of this hypothesis, the combined administration of both ATO and IFNα was more effective at increasing PML-NB ventolin hfa aerosol solution 108 mcg act formation in comparison to either treatment alone and, importantly, was most effective in Jak2 mutant cells.

To functionally determine whether increased PML-NB formation was able to impact the long-term disease maintaining stem cell population, the authors next examined the effect of IFNα combination on the survival of JAK2V617F mutant stem and progenitor cell populations. Here, combined IFNα+ATO was effective in reducing the colony formation capacity of both primary Jak2 mutant MPN patient samples and primary murine cells with the Jak2V617F mutation ventolin hfa aerosol solution 108 mcg act knocked in to the endogenous locus. Impressively, the combination therapy proved effective in reducing not only MPN disease parameters in Jak2V617F chimeric mice, including leukocyte counts, platelet counts, hematocrit, and splenomegaly, but most importantly in reducing the frequency of both mature myeloid cells and stem and progenitor cells expressing the Jak2V617F mutation. Functionally, MPN stem cell populations were unable to transplant MPN into irradiated secondary recipients, an assay considered a gold standard ventolin hfa aerosol solution 108 mcg act of leukemia stem cell function. Additionally, after IFNα+ATO treatment was withdrawn, primary mice were monitored for the reemergence of disease.

In >50% of the IFNα+ATO combination–treated mice, the MPN did not recur after treatment was stopped, demonstrating long-term treatment-free remission and potentially a cure of the MPN. Next, to determine whether this selectivity was really dependent on PML-NB ventolin hfa aerosol solution 108 mcg act formation, the authors used shRNA targeting PML in Jak2 mutant CD34+ MPN patient cells. Here, loss of PML reversed the effect of the IFNα+ATO combination to reduce colony formation in vitro. Next, to validate this in a genetically engineered murine model, murine Jak2V617F mutant MPN stem cells were ventolin hfa aerosol solution 108 mcg act generated on either a wild-type or PML−/− background. In this context, the PML−/− mutant cells were preferentially selected during IFNα+ATO combination therapy, showing selective resistance to the effect of IFNα+ATO therapy.

Finally, they provide preliminary evidence that enhanced PML-NB formation may lead to an eradication of MPN stem ventolin hfa aerosol solution 108 mcg act cells through the induction of senescence (see figure). This is shown through the accumulation of senescence-associated β-galactosidase and through increased transcription of senescence-associated genes. JAK2V617F MPN stem cells are eradicated by ATO and IFNα. IFNα drives transcriptional expression ventolin hfa aerosol solution 108 mcg act of PML. ATO stabilizes PML-NBs.

These processes lead to senescence and depletion of JAK2V617F MPN stem ventolin hfa aerosol solution 108 mcg act cells. In aggregate, this work provides a detailed mechanistic and functional validation of the effects of ATO in combination with IFNα in MPN stem cells. Specifically, this combination is able to ventolin hfa aerosol solution 108 mcg act deplete MPN stem cells, leading to reduced transplantation and even long-term treatment-free remission in disease control. Clinically, one would hope that these effects may manifest as molecular remissions and even cures. The findings in this paper ventolin hfa aerosol solution 108 mcg act are significant because they provide a very clear path to clinical translation.

ATO is well established as a treatment for APL and is widely available, although limited by the need for parenteral therapy. Oral forms of ATO are also being developed. The toxicities of each agent are ventolin hfa aerosol solution 108 mcg act nonoverlapping, and one would suspect that this combination might be well tolerated clinically, in addition to the proposed beneficial effects. Future clinical studies to combine these two agents should be pursued in patients with MPN to carefully assess the clinical safety and efficacy of combining IFNα+ATO in patients with classical MPN with the long-term goal of achieving long-term treatment-free remissions, prevention of secondary transformation to leukemia, and potentially cure of the MPN. References ReferencesAustin, ventolin hfa aerosol solution 108 mcg act R.J., et al.

2020. Leukemia. Bernardi, R., et al. 2004. Nat.

Kiladjian, J.J., et al. 2008.. Blood. Mullally, A., et al. 2010.

Cancer Cell. Mullally, A., et al. 2013. Blood. Spivak, J.L.

2019. Blood. Stadler, M., et al. 1995. Oncogene.

11:2565–2573.Vainchenker, W., and R. Kralovics. 2017. Blood. Vernier, M., et al.

2011. Genes Dev. Verstovsek, S., et al. 2012. N.

Acad. Sci. USA. © 2020 Bywater and Lane2020This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/)..

Myeloproliferative neoplasms (MPNs) buy ventolin over the counter nz are a group of blood cancers that are maintained by stem cell populations. In this issue of JEM, Dagher et al. (https://doi.org/10.1084/jem.20201268) combine buy ventolin over the counter nz arsenic and interferon α to deliver a knockout punch to MPN stem cells and provide new hope to cure patients with MPNs. Myeloproliferative neoplasms (MPNs) are a group of clonal hematological disorders characterized by excessive production of mature myeloid cells including granulocytes, erythrocytes, and platelets.

MPNs are driven buy ventolin over the counter nz by mutations arising in hematopoietic stem cells. Excluding chronic myeloid leukemia, which is pathogenomonically associated with the BCR-ABL translocation, the classical MPNs include polycythemia vera, essential thrombocythemia, and primary myelofibrosis. These BCR-ABL–negative MPNs are primarily caused by driver mutations in JAK2, myeloproliferative leukemia ventolin (the thrombopoietin receptor), and Calreticulin buy ventolin over the counter nz. Mechanistically, these mutations all serve to constitutively activate JAK-STAT signaling, leading to the expansion of lineage committed progenitor cells and the corresponding disease phenotype (Vainchenker and Kralovics, 2017.

Mullally et al., 2010). Insights from buy ventolin over the counter nz Megan Bywater and Steven W. Lane. Current therapies used in the management of MPNs include combinations of phlebotomy, buy ventolin over the counter nz aspirin, and cytoreductive therapy, most commonly hydroxyurea (Spivak, 2019).

More recently, inhibitors of JAK2 signaling such as ruxolitinib have shown efficacy in controlling blood counts and treating symptoms, including splenomegaly, in patients (Harrison et al., 2012. Verstovsek et al., buy ventolin over the counter nz 2012). However, they are unable to eradicate the disease initiating MPN clone (Austin et al., 2020). Determining vulnerabilities that will allow the selective targeting of MPN-driver mutation–carrying stem cells is of key clinical importance, as it is likely to facilitate long-term disease control in patients and potentially also may reduce the incidence of transformation to secondary myelofibrosis or acute myeloid leukemia, a devastating complication of MPN associated with very poor long-term survival.

IFNα therapy has shown efficacy in the treatment of MPNs for many buy ventolin over the counter nz years. However, clinical use has been limited by the requirement for frequent injections and relatively high rates of toxicity. More recently, longer-acting pegylated versions buy ventolin over the counter nz of IFNα have become available with increased efficacy and reduced toxicity compared with the historical short-acting forms. In contrast to other agents, such as the Jak1/2 inhibitors, pegylated IFNα has been shown to induce reduction in the molecular burden of disease, in some cases leading to complete molecular remission, thought to represent a reduction in the frequency of MPN mutation–bearing cells (Kiladjian et al., 2008).

These clinical responses are supported by data showing that IFNα is able to preferentially reduce the maintenance of Jak2V617F stem cells in murine models of disease (Austin et buy ventolin over the counter nz al., 2020. Mullally et al., 2013. Hasan et al., 2013). The mechanism behind this selective response to IFNα is not well understood, although it may be linked to increased DNA damage or buy ventolin over the counter nz failure to repair these processes (Austin et al., 2020).

Molecular remissions appear to require prolonged treatment over a protracted time frame, and, therefore, it would be advantageous to determine combination strategies to further enhance this process in order to accelerate clinical responses. Importantly, Dagher buy ventolin over the counter nz et al. Now demonstrate that arsenic trioxide (ATO) enhances the effect of IFNα in the treatment of MPN by depleting Jak2V617F mutant stem cell populations (Dagher et al., 2020). ATO has a long buy ventolin over the counter nz therapeutic history related to its use in traditional Chinese medicine.

In modern medicine, it has shown marked clinical efficacy in the treatment of de novo and all-trans retinoic acid–resistant acute promyelocytic leukemia (APL). De Thé and colleagues had previously shown that this effect was mediated by its ability to facilitate the degradation of the APL oncogenic fusion protein, PML-RARΑ (Zhu et al., 1997). Mechanistically, ATO can directly bind to PML and enhance nuclear body (NB) formation buy ventolin over the counter nz (Zhang et al., 2010). These PML-NBs facilitate the recruitment of proteins that both catalyze and interact with posttranslational modifications.

Of note, activation of p53 can occur via its direct recruitment to NBs through posttranslational modifications that alter its transcriptional activity and increased stability via buy ventolin over the counter nz the sequestration of Mdm2 (Bernardi et al., 2004). Increased PML-NB formation has also been shown to attenuate E2F transcriptional programs, most likely through direct recruitment and enhanced hypo-phosphorylation of Rb, resulting in growth arrest and senescence (Vernier et al., 2011). Consequently, PML-NB formation has been shown to have a tumor-suppressive role in a number of cancer buy ventolin over the counter nz models. Interestingly, PML has also been characterized as an IFN-stimulated gene (ISG.

Stadler et al., 1995). These preliminary buy ventolin over the counter nz findings led Dagher et al. (2020) to ask whether increased PML-NB formation may contribute to the efficacy of IFNα therapy in the treatment of MPN and, furthermore, whether this effect could be enhanced by combining IFNα with ATO. Dagher buy ventolin over the counter nz et al.

(2020) were able to show that IFNα treatment increased the number of PML-NBs in primary human MPN CD34+ cells and JAK2V617F mutant human cell lines. Interestingly, JAK2 mutant CD34+ cells isolated from MPN patients demonstrated an increased number of buy ventolin over the counter nz PML-NBs at baseline in comparison to wild type. As PML has been identified as an ISG, this finding is consistent with the JAK2V617F mutation driving sensitization to IFN signaling, as inferred from the previous observation of higher basal transcriptional activation of Stat1 (Austin et al., 2020). Moreover, this also suggests that strategies to enhance PML-NB formation may be an effective way to selectively target Jak2 mutant stem cells.

In support of this hypothesis, the combined administration of both ATO and IFNα was more effective at increasing PML-NB formation in comparison to either treatment alone and, buy ventolin over the counter nz importantly, was most effective in Jak2 mutant cells. To functionally determine whether increased PML-NB formation was able to impact the long-term disease maintaining stem cell population, the authors next examined the effect of IFNα combination on the survival of JAK2V617F mutant stem and progenitor cell populations. Here, combined IFNα+ATO was effective in reducing the colony formation capacity of both primary Jak2 mutant MPN patient samples and primary murine buy ventolin over the counter nz cells with the Jak2V617F mutation knocked in to the endogenous locus. Impressively, the combination therapy proved effective in reducing not only MPN disease parameters in Jak2V617F chimeric mice, including leukocyte counts, platelet counts, hematocrit, and splenomegaly, but most importantly in reducing the frequency of both mature myeloid cells and stem and progenitor cells expressing the Jak2V617F mutation.

Functionally, MPN stem cell populations were unable to transplant MPN into irradiated secondary recipients, buy ventolin over the counter nz an assay considered a gold standard of leukemia stem cell function. Additionally, after IFNα+ATO treatment was withdrawn, primary mice were monitored for the reemergence of disease. In >50% of the IFNα+ATO combination–treated mice, the MPN did not recur after treatment was stopped, demonstrating long-term treatment-free remission and potentially a cure of the MPN. Next, to determine whether this selectivity was really dependent on PML-NB formation, the authors used shRNA targeting PML in Jak2 mutant CD34+ MPN patient cells buy ventolin over the counter nz.

Here, loss of PML reversed the effect of the IFNα+ATO combination to reduce colony formation in vitro. Next, to validate this in a genetically engineered murine model, murine Jak2V617F mutant MPN stem cells were buy ventolin over the counter nz generated on either a wild-type or PML−/− background. In this context, the PML−/− mutant cells were preferentially selected during IFNα+ATO combination therapy, showing selective resistance to the effect of IFNα+ATO therapy. Finally, they provide preliminary evidence that enhanced PML-NB formation may lead to an eradication of MPN stem cells through the induction of senescence buy ventolin over the counter nz (see figure).

This is shown through the accumulation of senescence-associated β-galactosidase and through increased transcription of senescence-associated genes. JAK2V617F MPN stem cells are eradicated by ATO and IFNα. IFNα drives transcriptional expression of PML buy ventolin over the counter nz. ATO stabilizes PML-NBs.

These processes lead to senescence and depletion of JAK2V617F MPN stem buy ventolin over the counter nz cells. In aggregate, this work provides a detailed mechanistic and functional validation of the effects of ATO in combination with IFNα in MPN stem cells. Specifically, this combination is able to deplete MPN stem cells, leading to reduced transplantation and even long-term treatment-free remission in buy ventolin over the counter nz disease control. Clinically, one would hope that these effects may manifest as molecular remissions and even cures.

The findings in this buy ventolin over the counter nz paper are significant because they provide a very clear path to clinical translation. ATO is well established as a treatment for APL and is widely available, although limited by the need for parenteral therapy. Oral forms of ATO are also being developed. The toxicities of buy ventolin over the counter nz each agent are nonoverlapping, and one would suspect that this combination might be well tolerated clinically, in addition to the proposed beneficial effects.

Future clinical studies to combine these two agents should be pursued in patients with MPN to carefully assess the clinical safety and efficacy of combining IFNα+ATO in patients with classical MPN with the long-term goal of achieving long-term treatment-free remissions, prevention of secondary transformation to leukemia, and potentially cure of the MPN. References buy ventolin over the counter nz ReferencesAustin, R.J., et al. 2020. Leukemia.

Blood. Mullally, A., et al. 2010. Cancer Cell.

Mullally, A., et al. 2013. Blood. Spivak, J.L.

Oncogene. 11:2565–2573.Vainchenker, W., and R. Kralovics. 2017.

© 2020 Bywater and Lane2020This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/)..