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The White House on Sunday released text of an executive order that aims to tie Medicare payments for outpatient and pharmacy drugs to the lowest price offered in comparable developed countries.The order revokes a similar order that only would have applied to outpatient drugs, which the White House refused to release for more than seven how much does ventolin cost in canada ventolin hfa drug test weeks as the administration tried to force drugmakers to the negotiating table. "Negotiations did not produce an acceptable alternative, so how much does ventolin cost in canada the President is moving forward," White House spokesman Judd Deere said.The most-favored-nation policy cannot be implemented by executive order alone, and would have to be followed up with regulatory action. However, the expansion to include drugs in Medicare Part D in some sort of international reference pricing plan was a big fear for drugmakers, as Part D makes up a larger share of drug spending. Pharmaceutical Research and Manufacturers of America in a statement called the policy "irresponsible and unworkable.""What's worse is that they are now expanding the policy to include medicines in both Medicare Part B and Part D, an overreach that further threatens America's innovation leadership and puts access to medicines for tens of millions of seniors at risk," PhRMA President and CEO Stephen Ubl said in a written statement how much does ventolin cost in canada. President Donald Trump announced signing the new order Sunday afternoon."Just signed a new Executive Order to LOWER how much does ventolin cost in canada DRUG PRICES!.

My Most Favored Nation order will ensure that our Country gets the same low price Big Pharma gives to other countries. The days of global freeriding at America's expense are over…" Trump tweeted.Trump has campaigned as a foe of the pharmaceutical industry, though many of his how much does ventolin cost in canada drug-pricing policies have stalled or been stopped in the courts. Trump is bucking some conservatives who dislike international reference pricing, as they view it as importing foreign price controls from countries with "socialized" health systems. "Importing price controls from foreign countries is flawed how much does ventolin cost in canada and dangerous policy that will result in a substantial reduction in investment in new cures and drugs at the worst possible time," U.S. Chamber of Commerce Executive Vice President and Chief Policy Officer Neil Bradley said.The 2020 Democratic platform states that if elected, "Democrats will take aggressive action to ensure that Americans do not pay more for prescription how much does ventolin cost in canada drugs than people in other advanced economies."The described "most-favored-nation" payment methodology would guarantee that Medicare would pay the lowest price of any Organisation for Economic Co-operation and Development member country that has a comparable per-capita gross domestic product, adjusted for volume and differences in national gross domestic product.

"When the Federal Government purchases a drug covered by Medicare — the cost of which is shared by American seniors who take the drug and American taxpayers — it should insist on, at a minimum, the lowest price at which the manufacturer sells that drug to any other developed nation," the order states.The order directs the HHS secretary to pursue rulemaking to create a demonstration of a payment model to ensure Medicare Part B pays the most-favored-nation prices for some high-cost outpatient drugs. A proposed rule to implement that policy has been under review since June 2019.The HHS secretary is also directed to develop rulemaking to how much does ventolin cost in canada create a Center for Medicare and Medicaid Innovation demonstration for Medicare to pay the most-favored-nation price for Part D drugs with "insufficient" competition and that have prices higher in the United States than other comparable developed countries. The White House has not previously included how much does ventolin cost in canada Part D in international reference pricing proposals. Johns Hopkins University Professor Gerard Anderson, who has advised the administration and congressional leaders on international reference pricing issues, said he met with CMS leadership last week and discussed some drug pricing issues, but implementing international reference pricing in Medicare Part D did not come up in the conversation. Drugmakers have indicated they may pursue legal action if payments in Medicare tied to foreign countries are how much does ventolin cost in canada implemented.

Dr. Michelle McMurry-Heath, president and CEO of the Biotechnology Innovation Organization, called the White House's most-favored-nation pricing policy a "reckless scheme." "We will use every tool available – including legal action if necessary – to how much does ventolin cost in canada fight this risky foreign price control scheme," McMurry-Heath said.Health systems for years have been talking about patient- and consumer-centered care, trying to figure out new ways to meet patients where they are, make their hospitals stays more enjoyable and more strongly engage them in clinical decisions.But as asthma treatment led more people to seek care from home and decreased touch points with patients even inside of hospitals, health systems needed new strategies to keep patients involved in care and provide them with resources—two core components of patient-centered care, according to Modern Healthcare’s Power Panel, a survey of top healthcare CEOs—even when providers couldn’t see them face-to-face.While asthma treatment created a new reality for healthcare in just a few months, it hasn’t sidetracked health systems from projects focused on patient-centered care and experience, according to their CEOs. In fact, for many, it accelerated digital efforts how much does ventolin cost in canada focused on patients.Roughly 87% of CEOs who participated in the Power Panel survey said their organization had implemented new digital tools related to consumerism during asthma treatment.“A lot of what we do in the consumer experience is in person,” said David Entwistle, CEO of Stanford Health Care. €œBut despite all of that, I still think what we’ve been able to focus on and do has probably propelled us further than what we gave up, so to speak.”When asthma treatment hit, executives at Scripps Health knew they needed to figure out how care teams could reduce contact with patients who had the highly infectious disease, without losing the personal touch.“We wanted to be customer service-oriented and patient-centered, but we also wanted to protect our employees from going in and out of the rooms a lot,” said Chris Van Gorder, CEO of the San Diego-based health system.Their solution?. Installing baby monitors in patient rooms.It proved to be a low-cost way to let nurses communicate with asthma treatment patients—and have patients talk back—without necessarily having to go inside the patient’s room, Van Gorder said.It’s one example of how systems have developed new processes to keep patients engaged and employees safe.For ambulatory visits, health systems are overhauling entrenched processes, keeping patients outside of the facility as much as possible.Scripps Health recently how much does ventolin cost in canada rolled out an option for patients to automatically get checked in when they arrive at a clinic by enabling location tracking on their patient portal app.

Then, patients get a text message when the exam room is prepped and the provider is ready to see them—meaning they can go directly to the exam room, bypassing registration and other steps.Sometimes, patients don’t even have to step foot into the hospital. Dartmouth-Hitchcock Health in Lebanon, N.H., has started drawing some labs while patients sit in their cars.These how much does ventolin cost in canada types of programs are part of a growing trend that Paddy Padmanabhan, founder and CEO of Damo Consulting, refers to as the “drive-through experience.”He compared the process to ordering a coffee from Starbucks. Patients schedule appointments, check in from the parking lot and then pay for services online, similar to how customers can place an order for coffee through an app and pick it up at a drive-through window.“If you have to go into a clinic for something, you go in and you go how much does ventolin cost in canada in for exactly what you need,” Padmanabhan explained, adding that the trend is still just emerging.But with health systems implementing whole new sets of processes—often with a quick rollout amid asthma treatment—organizations are still assessing how well they’re working.Froedtert Health in Milwaukee launched a project during the ventolin to get feedback from patients about their experiences at the health system. Most data is collected through calling patients and sending emails, said Cathy Jacobson, Froedtert Health’s CEO. There’s a pretty quick turnaround, so executives and managers get that feedback on a weekly basis.Froedtert had planned to roll out the customer experience project a few months earlier but delayed it and retooled some questions to focus how much does ventolin cost in canada on patients’ perception of control and safety—such as getting patient feedback on masking policies.“We get that (feedback) back to our managers immediately,” Jacobson said.

€œWe’re just now starting to tap the insights from that.”Carilion Clinic in Roanoke, Va., had how much does ventolin cost in canada been planning to roll out a multipronged digital front door strategy over the next 24 months. But as asthma treatment cases mounted in the spring, executives realized they needed to move faster.Executives in healthcare for years have been discussing the so-called “digital front door,” wanting to use new technologies to engage patients outside a facility’s walls. But with many health systems compelled how much does ventolin cost in canada to restrict patients from walking into their actual physical front doors at the height of the asthma treatment ventolin, executives had to revisit those plans, pushing out new chatbot symptom checkers and at-home virtual visits.asthma treatment “hasn’t changed our thinking” about patient-centered care, said Nancy Agee, Carilion Clinic’s CEO. But it has accelerated “how far and how fast” the system moved toward implementing tasks already on its to-do list.Agee is in good company. Seventy-three percent of CEOs in Modern Healthcare’s Power Panel survey said their focus on consumerism increased amid asthma treatment, with the remaining 27% saying their focus stayed the same.At how much does ventolin cost in canada Carilion Clinic, that included expanding the roster of tools that patients use to connect with the system online, such as rolling out options to self-schedule appointments and pay bills.

And Carilion is developing an app, dubbed MyCarilion, which will centralize where how much does ventolin cost in canada patients access those services as well as educational videos, directions to facilities and on-demand telehealth.Across the board, telehealth has played a major role in how health systems are keeping patients outside of the hospital, but still connected to their care team.All CEOs who responded to Modern Healthcare’s Power Panel survey indicated they’d increased their telehealth investments during the ventolin. CEOs are chosen to participate in the survey.Dartmouth-Hitchcock Health in Lebanon, N.H., was averaging just three telehealth visits per week before asthma treatment hit. At the how much does ventolin cost in canada height of the ventolin, it was conducting up to 2,000 virtual visits a day. To make sure patients were prepared for a telehealth visit, medical assistants how much does ventolin cost in canada called patients the day before their appointment to walk them through the process and how to use the technology.Even if telehealth use slows as the ventolin subsides, as some experts predict will happen, it’ll still be a powerful option for patients, said Dr. Joanne Conroy, Dartmouth-Hitchcock Health’s CEO.

In the health system’s territory in New Hampshire and Vermont, telehealth could prove a useful tool how much does ventolin cost in canada to avoid missed patient appointments during snow storms, she said.“People appreciated the importance of virtual everything during the ventolin,” she said. €œI don’t think all of that is going to go away.”Moving forward, Dartmouth-Hitchcock sees telehealth as a market opportunity. The health system is working to how much does ventolin cost in canada create a direct-to-consumer urgent-care telehealth program, which could help to attract new patients, according to Conroy. The program, which is still being developed, will initially roll out to the health system’s employees, who will provide feedback.As telehealth use soared this past spring, health systems how much does ventolin cost in canada were confronted with a problem. Not all patients have access to high-quality internet.It’s not a new problem, but it took on newfound importance as health systems were forced to shift more and more patient appointments online.It’s frustrating to be “in the middle of a telehealth visit and it drops or you can’t hear someone,” said David Entwistle, CEO of Palo Alto, Calif.-based Stanford Health Care.

For some patient populations, that could go beyond frustration and become an issue of access to care.“What I do worry about is that there’s some socio-economic demographics that are not going to have access to (this) technology,” Entwistle added.Health systems are still grappling with how to address that challenge.During the ventolin, clinicians have how much does ventolin cost in canada been able to replace some appointments with audio-only telephone visits. However, payment for those services from CMS might expire with the public health emergency.Dr. R. Lawrence Moss, CEO of Jacksonville, Fla.-based Nemours Children’s Health System, suggested that internet access could be the next social determinant of health that health systems target. All CEOs in Modern Healthcare’s Power Panel survey said their organizations need to address patient issues beyond traditional healthcare, including social determinants.

That typically includes addressing access to food or transportation, but not internet.Internet access is one of many social factors that Nemours is considering, Moss said.“Just like I believe the health system needs to play a role with partners in ensuring that every child has access to high-quality food, every child also needs access to high-quality digital connectivity,” Moss said. €œA decade ago we wouldn’t have said that, but it’s a different world now.”Roughly 6.5% of Americans lacked access to wired broadband that met the Federal Communications Commission’s speed benchmark in 2017, according to a report the agency released last year. About 26.4% of rural Americans lack that access, an issue that HHS, the FCC and the Agriculture Department said they’ll tackle as part of a new Rural Telehealth Initiative.Even if patients do have internet access, they might need help learning to use health systems’ emerging digital tools.Carilion Clinic in Roanoke, Va., is working to stand up Apple Genius Bar-style technology support stations in its surrounding community, as part of a program to better answer patients’ questions about using the health system’s tech tools and encourage them to adopt the capabilities, said Nancy Agee, Carilion’s CEO. The system hopes to open the first station in a few months.Given asthma treatment, Agee said Carilion is working on possibilities for creating a “virtual” tech bar. The health system is planning to use a new patient education program, which it’s already using to let clinicians assign short educational videos to patients about some conditions and procedures.

A set of videos on how to use Carilion’s digital tools, such as its apps, could fit into that resource, Agee said.Patients know her as Wesley Reed, a psychiatric tech at Atrium Health Carolinas Medical Center in Charlotte, N.C. But to her colleagues, Reed is a star, winner of the 2020 “Atrium Health Has Talent” competition. Reed was one of 12 finalists in the recent 71-minute virtual grand finale, the first time the event wasn’t held in person.In all, 86 Atrium employees auditioned for the contest. Five local judges, including an actress/singer and two professional musicians, evaluated the finalists. Other top contestants were Tia Jackson, a patient services specialist at the Women’s Center for Pelvic Health, second place.

Chara Reese, team leader for patient access at Navicent Health, third place and the People’s Choice Award. And Andrea Nielsen, a clinical nurse I at Atrium Health Carolinas Medical Center, the Executive Council Award.Reed, 24, who says she was “making music before I could talk,” gave a soulful rendering of her composition “Over It.” The grand finale program also included a 6-minute video produced by Atrium CEO Gene Woods of him singing and playing guitar on his own bluesy tune “Not Enuff Joy,” accompanied by professional musicians. He said it’s one of the first songs he ever wrote, and introduced it by urging his colleagues “to do everything in our collective power to bring more joy, more health, more hope and more healing into this world.”On HCA Healthcare’s second-quarter investor call, an analyst asked the for-profit chain’s chief financial officer an intriguing question. What’s the profitability of asthma treatment patients?. Posed to most other health systems, such a query would have sounded absurd.

But the Nashville-based hospital giant had just posted $1.1 billion in profit, up 38% from the prior-year period, even as elective procedures were largely shut down.Finance chief Bill Rutherford responded that asthma tends to prompt longer lengths of stay and higher acuity than typical hospitalized patients. €œIt’s too early to convert that to profitability,” he said. €œOur focus is making sure we’ve got all the resources we need to care for those patients.” Examples of wealthy health systems reporting higher 2020 profits, anecdotes of sky-high bills for asthma treatment and billions in federal grants have raised the question of whether a subset of well-performing hospitals are making money on their asthma treatment books of business.Most hospitals, though, appear to be losing money on asthma treatment care, and that’s not counting the ventolin’s most detrimental effect. The plunge in profitable elective procedures. Hospitals’ divergent reimbursement experiences underscore the ventolin’s role in deepening the split between wealthy systems and their financially vulnerable peers.

Now, as the country heads into an expected second wave of the ventolin, hospital administrators need to keep trimming expenses while revenue lags and the federal government makes tough decisions about how to allocate aid with little information to go on. Some experts are hoping HHS will consider financial need when allocating the remaining $57 billion in federal asthma Aid, Relief, and Economic Security Act grants. So far, a little over half the Provider Relief Fund grants distributed have been based on prior revenue, with large, financially secure systems amassing hundreds of millions in aid.“There is clear evidence that many hospitals that have done financially well historically, have good overall margins and hundreds of days cash on hand are getting millions in cash disbursements due to the revenue-based formula,” said William Schpero, an assistant professor of health policy and economics at Weill Cornell Medical College. €œThat money might be better used elsewhere, whether among hospitals that have been particularly hard-hit or that are financially vulnerable.”A hospital’s true margin on asthma treatment care will probably remain a mystery, experts say. That’s because the ventolin, unlike any other crisis that’s hit the industry, has come with a number of confounding factors that make it impossible to isolate the margin on treating seriously ill asthma patients.

Most importantly, hospitals’ biggest source of revenue—nonurgent procedures—dropped out from under them, and there’s no telling when, if ever, it will completely return. The crisis has sunk the margins of large systems like Mass General Brigham in Boston and Sutter Health in Northern California, but others, like Kaiser Permanente in Oakland, Calif., and ProMedica in Toledo, Ohio, are doing better than ever.Aside from the grants, CMS is tacking on an additional 20% to its reimbursement for treating hospitalized Medicare patients with asthma treatment. Medicare-age adults have seen the highest rates of asthma treatment hospitalization. The bump has prompted conspiracy theories about hospitals wanting more asthma treatment cases on their books to increase Medicare reimbursement.“The asthma treatment-specific impact is very, very difficult to quantify,” said Ge Bai, an associate professor of accounting and health policy and management at Johns Hopkins University.One factor that makes determining margins so tricky is that so much of hospitals’ costs are tied up in fixed overhead expenses that would be difficult to allocate to a specific patient. Almost half—48%—of hospitals’ total operating expenses were overhead and capital costs in 2018, according to a recent Journal of General Internal Medicine study of about 3,500 hospitals.Health systems prefer to discuss the ventolin’s effects in aggregate, without isolating the asthma treatment book of business.“They’re all unprofitable because we lost so much elective business and we have such a high fixed-cost infrastructure,” said Robin Damschroder, CFO of Detroit-based Henry Ford Health System.

€œYou really have to look at the totality of the clinical operations of any health system.”In normal times, there would be enough reimbursement to cover a hospital’s high overhead costs. But during the ventolin, the loss of volume and the added supply and labor costs associated with responding to the crisis has created “stranded overhead” that has nowhere to be liquidated, said Rob DeMichiei, a strategic adviser with data and analytics technology provider Health Catalyst and former CFO of UPMC.“With that volume gone, there is all that overhead with very few cases to cover it,” he said. €œThere is really no amount of reimbursement on an individual case that’s going to be able to cover the direct costs, which it does cover, but also all this overhead.”Experts are divided on the question of whether hospitals are generating a margin on their asthma treatment patients. The point they agree on, though, is that no one can know for sure except maybe the hospital CFO, and even then, there’s a good chance he or she can’t be certain.For Kevin Holloran, who covers not-for-profit hospitals at Fitch Ratings, the answer is an easy no. asthma treatment is a “completely different animal” from other conditions, with some patients hospitalized for weeks or months.

€œI can’t see a way that anyone would say, ‘asthma treatment patients are profitable for me’ in any way, shape or form,” he said.When it comes to treating asthma treatment patients who are uninsured or who rely on Medicaid, hospitals are unlikely to make money, as is their typical experience with those payers, said Dr. Ross Nelson, the head of KPMG’s healthcare strategy group.Medicare’s 20% add-on payment for asthma treatment patients could bump that margin into the black, Nelson said. But since Medicare pays a flat case rate per DRG, length of stay will be a big determinant of profitability. €œMy hypothesis is that the asthma treatment patients that come in and stay for a week to a week and a half, at least on the Medicare and commercial side, they probably make some money on,” Nelson said. €œAs length of stay starts to extend beyond a week and a half or so, I think it’s too early to tell on that.”Maimonides Medical Center, the largest hospital in Brooklyn, has treated north of 2,300 asthma treatment patients.

Leaders believe they broke even on commercial patients, using an estimated cost per patient, CEO Kenneth Gibbs said. Even with the 20% add-on, Medicare reimbursement covered about 90% of the cost of care. Medicaid covered about two-thirds the cost of asthma treatment care, he said.Gibbs said the struggle is just as much in front of providers as it is behind them. That’s because there will continue to be volume declines, and patients will still need to be isolated according to status. Basically, the cost per patient will be higher for the foreseeable future.

€œI think the challenges are unknown because the hit is ongoing,” Gibbs said. €œThe stress on the system may actually sort of be building, even though we’re past what feels like the core surge.”For Henry Ford, the 20% Medicare add-on culminated in an additional $8 million on its Medicare claims related to asthma treatment. Of the more than 10,000 asthma treatment patients Henry Ford treated, 32% were covered by Medicare, including Medicare Advantage. But the bigger impact from Medicare was waiving the 2% sequestration, a reduction that usually happens annually, and postponing cuts to disproportionate-share hospital payments.All told, that amounted to roughly $40 million for the health system, in addition to $328 million in federal relief grants in the first half of 2020. €œIs it compensating for everything related to the cost of asthma treatment?.

That’s a question yet to be answered,” Damschroder said.Henry Ford reported $224 million in operating income in the first half of 2020, a 165% increase from the prior year and a strong 7% operating margin.Private insurance payment rates are more than twice Medicare rates for the services most likely to be used by patients hospitalized with asthma treatment, although Medicare’s 20% add-on payment will narrow that gap, a July analysis from the Kaiser Family Foundation found. With the 20% add-on, the average Medicare reimbursement for patients on a ventilator for more than 96 hours would have increased from $40,218—the average payment in 2017—to $48,262. Private rates would be roughly double that even with the 20% add-on, ranging from 1.8 to 2.1 times those of Medicare.Of the $175 billion originally allocated for Provider Relief Fund grants, a little over half has been distributed according to prior total patient revenue, suggesting HHS tried to replace revenue lost from suspending procedures. Another $22 billion went to hospitals that saw large numbers of asthma treatment patients. Smaller amounts were targeted at safety-net hospitals, rural hospitals, skilled-nursing facilities and children’s hospitals.Karyn Schwartz, a senior fellow with the Kaiser Family Foundation, said she agrees that knowing whether hospitals’ reimbursement for asthma treatment covers their costs could be helpful information for policymakers in determining how the remaining roughly $57 billion in Provider Relief Fund grants would be best allocated.

€œI think knowing how costly it is to treat these patients is important in terms of understanding how important it is to allocate the money that way versus something else,” she said.Matt Hutt, an accountant who heads AAFCPAs’ healthcare division, said by his estimation, in order for Medicare’s 20% add-on payment to cover the cost of asthma treatment care, it would have needed to be a 35% add-on. Going forward, he said it’s important to tie Provider Relief Fund grants to the losses providers are seeing on asthma treatment care.“That’s really what the funds should be used for. The impact that asthma treatment had on your business,” he said.The problem with that, however, is the numbers used to calculate margin can be “warped,” Johns Hopkins associate professor Bai said. While revenue from asthma treatment is clear-cut, the cost component is open to interpretation. Large, well-connected providers would likely hire savvy consultants to make their margins look worse than they are, she said.

Instead, Bai said the decline in charges or outpatient claims would be a more objective way to distribute the money.Even if, hypothetically, systems were making money on asthma treatment patients but still losing money in every other aspect of their business due to lower demand, that would put the healthcare system in jeopardy, said Rick Kes, healthcare industry senior analyst with RSM. €œThe sustainability of our healthcare system is maybe the overriding issue.”Opinions abound on how the remaining federal aid should be allocated. Michael Abrams, managing partner and co-founder of healthcare consultancy Numerof &. Associates, said tying the disbursement to fee-for-service revenue, as has been done with much of the money so far, rewards providers who haven’t shifted toward value-based payment models. He thinks HHS should offer incentives for value-based payment with the remaining money.“I just hate the idea of bailing out an industry that is increasingly on a course that departs from what the country needs,” Abrams said..

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A Westchester school district located inside one of the state’s precautionary asthma treatment micro-cluster “yellow zones” has completed its mandatory testing to remain open for in-person learning.Last month, parts of New Rochelle were designated https://www.feuerwehr-oespel-kley.de/buy-real-viagra-online/ as a “yellow zone” asthma treatment hotspot, which required four of the district’s schools to comply with asthma treatment testing for 20 percent of the in-person population to remain open.Schools located within a yellow or orange zone are required to randomly select does ventolin contain alcohol 20 percent of the in-person students, faculty, and staff to be voluntarily tested for surveillance of the school community’s positivity rate. A school in does ventolin contain alcohol a red zone has to test 30 percent of students and staffers.The schools located in the “yellow zone” in New Rochelle are Isaac E. Young Middle School, Columbus, Trinity, and Webster elementary schools.On Friday, interim Schools Superintendent Alex Marrero announced that as of Wednesday, Dec.

9, testing was completed, and a total of 40 of the 41 tests collected were negative for asthma treatment, with the only positive coming from Trinity Elementary School.With no positive tests in the elementary school, they’ve been given the green light at does ventolin contain alcohol Isaac E. Young, Columbus, and Webster to does ventolin contain alcohol remain open and to stop mass testing. Trinity will be required to continue testing for an additional two weeks before re-evaluating the school’s circumstances.“The district is committed to providing in-person instruction for students when health and safety conditions permit,” Marrero said in a notice to parents on Friday.

€œThere is nothing more valuable to children's academic and social-emotional growth than being in a class with their teachers and peers, does ventolin contain alcohol and receiving vital support services as needed.“Students and staff are safe in our school buildings because of our continuing mitigation measures,” Marrero continued. €œThese include completing your student’s health screening as directed and temperature checks before and upon school arrival, face-covering requirements, social distancing, and the ongoing cleaning of school facilities.” Click here to sign up for Daily Voice's free daily emails and news alerts..

A Westchester school district located inside one of the state’s how much does ventolin cost in canada precautionary asthma treatment micro-cluster “yellow zones” has completed its mandatory testing to remain open for in-person learning.Last month, Buy real viagra online parts of New Rochelle were designated as a “yellow zone” asthma treatment hotspot, which required four of the district’s schools to comply with asthma treatment testing for 20 percent of the in-person population to remain open.Schools located within a yellow or orange zone are required to randomly select 20 percent of the in-person students, faculty, and staff to be voluntarily tested for surveillance of the school community’s positivity rate. A school in a red zone has to test 30 percent of students and staffers.The schools located in the “yellow zone” in New Rochelle are Isaac how much does ventolin cost in canada E. Young Middle School, Columbus, Trinity, and Webster elementary schools.On Friday, interim Schools Superintendent Alex Marrero announced that as of Wednesday, Dec. 9, testing was completed, and a total of 40 of the 41 tests collected were negative for asthma treatment, with how much does ventolin cost in canada the only positive coming from Trinity Elementary School.With no positive tests in the elementary school, they’ve been given the green light at Isaac E.

Young, Columbus, and Webster to remain how much does ventolin cost in canada open and to stop mass testing. Trinity will be required to continue testing for an additional two weeks before re-evaluating the school’s circumstances.“The district is committed to providing in-person instruction for students when health and safety conditions permit,” Marrero said in a notice to parents on Friday. €œThere is nothing more valuable to children's academic and social-emotional growth than being in a class with their teachers and peers, and receiving vital support services as needed.“Students and staff are safe how much does ventolin cost in canada in our school buildings because of our continuing mitigation measures,” Marrero continued. €œThese include completing your student’s health screening as directed and temperature checks before and upon school arrival, face-covering requirements, social distancing, and the ongoing cleaning of school facilities.” Click here to sign up for Daily Voice's free daily emails and news alerts..

What should I tell my health care providers before I take Ventolin?

They need to know if you have any of the following conditions:

  • diabetes
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  • high blood pressure
  • pheochromocytoma
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  • an unusual or allergic reaction to albuterol, levalbuterol, sulfites, other medicines, foods, dyes, or preservatives
  • pregnant or trying to get pregnant
  • breast-feeding

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In 2018, Where to buy antabuse in canada the cvs ventolin price U.S. Maternal mortality rate stood at 17 for every 100,000 births -- more than double the rate of most other countries. Those figures capture deaths during pregnancy and within 42 days of the end of pregnancy. But many women die later in the so-called cvs ventolin price "fourth trimester," or the year after giving birth.

And of all pregnancy-related deaths in the United States, 52% happened after childbirth, the report found. When women died within a week of childbirth, it was often related to severe bleeding, s or high blood pressure. Later in the postpartum cvs ventolin price period, the leading cause of death was cardiomyopathy, a weakening of the heart muscle. "Even though the U.S.

Spends more on health care than anywhere else in the world, it has higher rates of these preventable deaths," said report co-author Roosa Tikkanen, a senior research associate at the Commonwealth Fund. The United States has long held that dubious cvs ventolin price distinction. And maternal mortality is yet another area where racial disparities are stark. Black women have more than double the death rate of white women in the United States.

The new report adds a cvs ventolin price layer, Tikkanen said -- looking at differences in countries' health care systems that may illuminate why the United States fares so poorly. One key difference is the supply of maternal care providers, including obstetricians/gynecologists and midwives. Nearly all other wealthy nations, except for Canada, have far more providers relative to population. In the United States, there are 15 providers for every 1,000 births, while Sweden has cvs ventolin price 78 per 1,000, according to the report.By Alan Mozes HealthDay Reporter TUESDAY, Nov.

17, 2020 (HealthDay News) -- In the face of ventolin-mandated gym closings and significant limits on movement outside the home, a new survey suggests that Americans are spending more time exercising while dialing back the intensity of their workouts. The survey of nearly 900 Americans across the country, conducted between May and June, used as its benchmark World Health Organization (WHO) recommendations that all adults between 18 and 64 get a minimum of 150 minutes of moderate-intensity exercise a week. "The asthma treatment restrictions imposed early in the ventolin created a unique, unprecedented environment, including restricted access to resources and, in some cases, increased unstructured time," said study author Mary cvs ventolin price Stenson, an associate professor of exercise science and sport studies at College of Saint Benedict/Saint John's University in St. Joseph, Minn.

"We were curious how these changes might impact physical activity patterns in the U.S. During the shutdowns, but also if these shifts would remain in the long term." In Stenson's study, more than 85% of cvs ventolin price those polled were women and nearly 90% were white, with an average age of almost 39. The findings. By June, just over 60% of those surveyed said they were meeting the WHO threshold, representing a nearly 8% jump from pre-ventolin routines.

Investigators also found a more than 11% jump in the cvs ventolin price number of people who were actually exceeding that threshold. The number of days per week spent exercising also went up notably, from 3.75 days to more than 4.25 days. Time spent per exercise session, however, stayed more or less stable, at just under an hour. And exercise intensity decreased "significantly," the researchers found, with respondents attributing the cvs ventolin price drop to an inability to access gym equipment and classes and a shift to more outdoor walking.

"The increased activity and lower intensity were in line with what we expected," said Stenson, who said the findings likely reflect the loss of performance "accountability" that comes with the cancellation of group exercise, organized sports and trainer sessions. But Stenson said she was surprised by an additional observation that nearly three-quarters of those surveyed said they were likely or very likely to stick with their ventolin exercise habits post-ventolin. And nearly 94% of those who had increased their activity levels since March said they planned to continue with their new routines cvs ventolin price over the coming year.By Amy Norton HealthDay Reporter TUESDAY, Nov. 17, 2020 (HealthDay News) -- A procedure that freezes bits of heart tissue may be a better option than medication for people with atrial fibrillation (a-fib, or AF), two clinical trials have found.

A-fib is a common heart arrhythmia in which the organ's upper chambers (the atria) beat erratically. Though it is not immediately life-threatening, over time it can lead to complications like cvs ventolin price heart failure, or blood clots that cause a stroke. Right now, the standard first-line treatment is medication, said Dr. Jason Andrade, lead researcher on one of the new studies.

Those drugs help control the heart's rate cvs ventolin price and rhythm. If they fail to do that, patients may move on to another option called ablation. It's a minimally invasive procedure in which doctors use heat or cold to destroy bits of heart tissue that are generating the faulty electrical signal causing the arrhythmia. The two new trials challenged the notion that ablation should only be a cvs ventolin price second option.

"The approach with medications is largely treating a symptom," said Andrade, who directs the Atrial Fibrillation Clinic at Vancouver General Hospital in British Columbia, Canada. "If we start with an ablation, we may be able to fix atrial fibrillation early in its course, which potentially means reducing the risk of stroke and other heart problems down the road." His team found that ablation was, in fact, a better first-line treatment. A-fib patients who cvs ventolin price underwent ablation were half as likely to have an arrhythmia episode in the following year compared to patients on medication. And they were 61% less likely to have an episode that caused symptoms.

The findings were simultaneously published Nov. 16 in the New England Journal of Medicine and reported at an online meeting of the American Heart Association cvs ventolin price. "Ablation is more successful than medication for AF, though neither is 100%," said Dr. Nieca Goldberg, an AHA spokeswoman and cardiologist at NYU Langone Health in New York City.

She noted that longer-term results are cvs ventolin price still needed, since trial patients were followed for only a year. "But I don't think medication will become any more effective over time," Goldberg added.Barry Fox, MD, clinical professor of infectious disease, University of Wisconsin School of Medicine and Public Health. Harri Hemilä, MD, PhD, adjunct professor, Department of Public Health, University of Helsinki, Finland. Simin Nikbin Meydani, DVM, PhD, senior cvs ventolin price scientist and director, Nutritional Immunology Lab, Human Nutrition Research Center on Aging , Tufts University.

Tracey J. Smith, PhD. John P cvs ventolin price. Richie Jr., PhD, professor of public health sciences and pharmacology, Penn State University College of Medicine, Hershey, PA.

Harvard T.H. Chan School of cvs ventolin price Public Health. €œNutrition and Immunity.” Annals of Internal Medicine. €œAssociation Among Dietary Supplement Use, Nutrient Intake, and Mortality Among U.S.

Adults.” Cochrane Database of Systematic cvs ventolin price Reviews. €œVitamin C for preventing and treating the common cold.” American Journal of Clinical Nutrition. €œVitamins E and C are safe across a broad range of intakes.” American Journal of Clinical Nutrition. €œVitamin C cvs ventolin price supplements and the risk of age-related cataract.

A population-based prospective cohort study in women.” The Journal of the American Medical Association. €œVitamin E and respiratory tract s in elderly nursing home residents. A randomized controlled cvs ventolin price trial.” British Medical Journal. €œVitamin D supplementation to prevent acute respiratory tract s.

Systematic review and meta-analysis of individual participant data.” The Journal of Clinical Endocrinology and Metabolism. €œVitamin D Status in Hospitalized cvs ventolin price Patients with asthma .” Horticultural Science. €œPatterns of Variation in Alkamides and Cichoric Acid in Roots and Aboveground Parts of Echinacea purpurea (L.) Moench.” Evidence-Based Complementary and Alternative Medicine. €œSafety and Efficacy Profile of Echinacea purpurea to Prevent Common Cold Episodes.

A Randomized, Double-Blind, Placebo-Controlled Trial.” Journal cvs ventolin price of the Royal Medical Society. €œZinc lozenges and the common cold. A meta-analysis comparing zinc acetate and zinc gluconate, and the role of zinc dosage.” British Medical Journal. €œEffect of Lactobacillus rhamnosus LGG and Bifidobacterium animalis cvs ventolin price ssp.

Lactis BB-12 on health-related quality of life in college students affected by upper respiratory s.” European Journal of Clinical Nutrition. €œOral supplementation with liposomal glutathione elevates body stores of glutathione and markers of immune function.” Journal of International Medical Research. €œRandomized Study of the Efficacy and Safety of Oral Elderberry Extract in the Treatment of Influenza A and B ventolin s.” Journal of General Internal Medicine cvs ventolin price. €œElderberry Extract Outpatient Influenza Treatment for Emergency Room Patients Ages 5 and Above.

A Randomized, Double-Blind, Placebo-Controlled Trial.” European Cytokine Network. €œThe effect cvs ventolin price of Sambucol, a black elderberry-based, natural product, on the production of human cytokines. I. Inflammatory cytokines.” Therapeutic Advances in Respiratory Disease.

€œLung under attack cvs ventolin price by asthma treatment-induced cytokine storm. Pathogenic mechanisms and therapeutic implications.” Planta Medica. €œImmunmodulatory and Antiproliferative Properties of Rhodiola Species.” European Journal of Clinical Microbiology &. Infectious Diseases cvs ventolin price.

€œProbiotics in respiratory ventolin s.” The Journal of the American Medical Association. €œEchinacea for preventing and treating the common cold.” National Kidney Foundation. €œFamily History of cvs ventolin price Kidney Stones?. Watch Those Megadoses of Vitamin C.” Mayo Clinic.

€œWhat is vitamin D toxicity?. Should cvs ventolin price I be worried about taking supplements?. € ScienceDaily. €œAdequate zinc eases pneumonia in elderly, study finds,” “Zinc.”By Robert Preidt HealthDay Reporter MONDAY, Nov.

16, 2020 (HealthDay News) -- Despite skyrocketing asthma rates, many Americans plan to attend large holiday gatherings, a nationwide survey finds cvs ventolin price. Nearly two in five respondents said they will likely gather with more than 10 people, according to the Ohio State University Wexner Medical Center poll. And while many plan to take precautions -- such as social distancing and asking those with asthma treatment symptoms not to attend holiday gatherings -- one-third of respondents said they won't ask guests to wear masks. The United States is seeing record cvs ventolin price numbers of asthma s, and colder weather is leading to more get-togethers indoors, where the ventolin can more easily spread.

"We're going to look back at what happened during this holiday season and ask ourselves, 'Were we part of the solution or were we part of the problem?. '" said Dr. Iahn Gonsenhauser, chief quality and cvs ventolin price patient safety officer at the Wexner Medical Center. "When you're gathered together around the table, engaged in conversation, sitting less than six feet apart with your masks down, even in a small group, that's when the spread of this ventolin can really happen," he warned in a university news release.

The safest way to mark the holidays is to cancel in-person plans with family and friends, and connect virtually instead, Gonsenhauser advised. If you do decide to host a gathering, it's crucial to create a safety plan and cvs ventolin price outline it to all your guests, he added. Measures could include having everyone wear masks at all times. Separating seating arrangements by household.

And assigning one or two people to serve cvs ventolin price the food. The same precautions should be used even if your holiday event is held outdoors, Gonsenhauser said. If you plan to travel or host out-of-town guests, monitor asthma treatment rates and restrictions in both locations. "If you have someone in your household who's high risk and you're in a low-incidence area, you're going to want to think twice about having a celebration where people are coming from an area where there's a lot of ventolin in the community," Gonsenhauser said.

More information For more on asthma treatment, go to the U.S. Centers for Disease Control and Prevention. SOURCE. Ohio State University, news release, Nov.

Those are some of the findings from a new report on maternal mortality by how much does ventolin cost in canada the nonprofit Commonwealth Fund, which compared the blog here United States with 10 other high-income nations. It found what the researchers called "unacceptable" numbers. In 2018, the U.S.

Maternal mortality rate stood at 17 for every 100,000 births -- how much does ventolin cost in canada more than double the rate of most other countries. Those figures capture deaths during pregnancy and within 42 days of the end of pregnancy. But many women die later in the so-called "fourth trimester," or the year after giving birth.

And of all pregnancy-related deaths in the United States, 52% happened after childbirth, how much does ventolin cost in canada the report found. When women died within a week of childbirth, it was often related to severe bleeding, s or high blood pressure. Later in the postpartum period, the leading cause of death was cardiomyopathy, a weakening of the heart muscle.

"Even though how much does ventolin cost in canada the U.S. Spends more on health care than anywhere else in the world, it has higher rates of these preventable deaths," said report co-author Roosa Tikkanen, a senior research associate at the Commonwealth Fund. The United States has long held that dubious distinction.

And maternal mortality is yet another how much does ventolin cost in canada area where racial disparities are stark. Black women have more than double the death rate of white women in the United States. The new report adds a layer, Tikkanen said -- looking at differences in countries' health care systems that may illuminate why the United States fares so poorly.

One key difference is the supply of maternal care providers, including obstetricians/gynecologists and how much does ventolin cost in canada midwives. Nearly all other wealthy nations, except for Canada, have far more providers relative to population. In the United States, there are 15 providers for every 1,000 births, while Sweden has 78 per 1,000, according to the report.By Alan Mozes HealthDay Reporter TUESDAY, Nov.

17, 2020 (HealthDay News) -- In the how much does ventolin cost in canada face of ventolin-mandated gym closings and significant limits on movement outside the home, a new survey suggests that Americans are spending more time exercising while dialing back the intensity of their workouts. The survey of nearly 900 Americans across the country, conducted between May and June, used as its benchmark World Health Organization (WHO) recommendations that all adults between 18 and 64 get a minimum of 150 minutes of moderate-intensity exercise a week. "The asthma treatment restrictions imposed early in the ventolin created a unique, unprecedented environment, including restricted access to resources and, in some cases, increased unstructured time," said study author Mary Stenson, an associate professor of exercise science and sport studies at College of Saint Benedict/Saint John's University in St.

Joseph, Minn how much does ventolin cost in canada. "We were curious how these changes might impact physical activity patterns in the U.S. During the shutdowns, but also if these shifts would remain in the long term." In Stenson's study, more than 85% of those polled were women and nearly 90% were white, with an average age of almost 39.

The findings how much does ventolin cost in canada. By June, just over 60% of those surveyed said they were meeting the WHO threshold, representing a nearly 8% jump from pre-ventolin routines. Investigators also found a more than 11% jump in the number of people who were actually exceeding that threshold.

The number of days per week spent exercising also went up how much does ventolin cost in canada notably, from 3.75 days to more than 4.25 days. Time spent per exercise session, however, stayed more or less stable, at just under an hour. And exercise intensity decreased "significantly," the researchers found, with respondents attributing the drop to an inability to access gym equipment and classes and a shift to more outdoor walking.

"The increased activity and lower intensity were in line with what we expected," said Stenson, who said the findings likely reflect the loss of performance "accountability" how much does ventolin cost in canada that comes with the cancellation of group exercise, organized sports and trainer sessions. But Stenson said she was surprised by an additional observation that nearly three-quarters of those surveyed said they were likely or very likely to stick with their ventolin exercise habits post-ventolin. And nearly 94% of those who had increased their activity levels since March said they planned to continue with their new routines over the coming year.By Amy Norton HealthDay Reporter TUESDAY, Nov.

17, 2020 (HealthDay News) -- A procedure that freezes bits of heart tissue may be a better option than medication for people with atrial fibrillation (a-fib, or AF), two clinical trials have found how much does ventolin cost in canada. A-fib is a common heart arrhythmia in which the organ's upper chambers (the atria) beat erratically. Though it is not immediately life-threatening, over time it can lead to complications like heart failure, or blood clots that cause a stroke.

Right now, how much does ventolin cost in canada the standard first-line treatment is medication, said Dr. Jason Andrade, lead researcher on one of the new studies. Those drugs help control the heart's rate and rhythm.

If they fail to do that, patients may how much does ventolin cost in canada move on to another option called ablation. It's a minimally invasive procedure in which doctors use heat or cold to destroy bits of heart tissue that are generating the faulty electrical signal causing the arrhythmia. The two new trials challenged the notion that ablation should only be a second option.

"The approach with medications is largely treating a symptom," said Andrade, who directs the Atrial Fibrillation Clinic at Vancouver how much does ventolin cost in canada General Hospital in British Columbia, Canada. "If we start with an ablation, we may be able to fix atrial fibrillation early in its course, which potentially means reducing the risk of stroke and other heart problems down the road." His team found that ablation was, in fact, a better first-line treatment. A-fib patients who underwent ablation were half as likely to have an arrhythmia episode in the following year compared to patients on medication.

And they were how much does ventolin cost in canada 61% less likely to have an episode that caused symptoms. The findings were simultaneously published Nov. 16 in the New England Journal of Medicine and reported at an online meeting of the American Heart Association.

"Ablation is more successful than medication for AF, though neither how much does ventolin cost in canada is 100%," said Dr. Nieca Goldberg, an AHA spokeswoman and cardiologist at NYU Langone Health in New York City. She noted that longer-term results are still needed, since trial patients were followed for only a year.

"But I don't think medication will become any more effective over time," Goldberg added.Barry Fox, MD, clinical professor of infectious disease, University of Wisconsin School of Medicine and Public Health how much does ventolin cost in canada. Harri Hemilä, MD, PhD, adjunct professor, Department of Public Health, University of Helsinki, Finland. Simin Nikbin Meydani, DVM, PhD, senior scientist and director, Nutritional Immunology Lab, Human Nutrition Research Center on Aging , Tufts University.

Tracey J how much does ventolin cost in canada. Smith, PhD. John P.

Richie Jr., PhD, professor of public health sciences and how much does ventolin cost in canada pharmacology, Penn State University College of Medicine, Hershey, PA. Harvard T.H. Chan School of Public Health.

€œNutrition and how much does ventolin cost in canada Immunity.” Annals of Internal Medicine. €œAssociation Among Dietary Supplement Use, Nutrient Intake, and Mortality Among U.S. Adults.” Cochrane Database of Systematic Reviews.

€œVitamin C for preventing and treating the common cold.” American Journal how much does ventolin cost in canada of Clinical Nutrition. €œVitamins E and C are safe across a broad range of intakes.” American Journal of Clinical Nutrition. €œVitamin C supplements and the risk of age-related cataract.

A population-based prospective cohort study in how much does ventolin cost in canada women.” The Journal of the American Medical Association. €œVitamin E and respiratory tract s in elderly nursing home residents. A randomized controlled trial.” British Medical Journal.

€œVitamin D supplementation to prevent how much does ventolin cost in canada acute respiratory tract s. Systematic review and meta-analysis of individual participant data.” The Journal of Clinical Endocrinology and Metabolism. €œVitamin D Status in Hospitalized Patients with asthma .” Horticultural Science.

€œPatterns of Variation in Alkamides and Cichoric Acid in Roots and Aboveground Parts of Echinacea how much does ventolin cost in canada purpurea (L.) Moench.” Evidence-Based Complementary and Alternative Medicine. €œSafety and Efficacy Profile of Echinacea purpurea to Prevent Common Cold Episodes. A Randomized, Double-Blind, Placebo-Controlled Trial.” Journal of the Royal Medical Society.

€œZinc lozenges and the common how much does ventolin cost in canada cold. A meta-analysis comparing zinc acetate and zinc gluconate, and the role of zinc dosage.” British Medical Journal. €œEffect of Lactobacillus rhamnosus LGG and Bifidobacterium animalis ssp.

Lactis BB-12 on health-related how much does ventolin cost in canada quality of life in college students affected by upper respiratory s.” European Journal of Clinical Nutrition. €œOral supplementation with liposomal glutathione elevates body stores of glutathione and markers of immune function.” Journal of International Medical Research. €œRandomized Study of the Efficacy and Safety of Oral Elderberry Extract in the Treatment of Influenza A and B ventolin s.” Journal of General Internal Medicine.

€œElderberry Extract Outpatient Influenza Treatment for Emergency Room Patients Ages 5 how much does ventolin cost in canada and Above. A Randomized, Double-Blind, Placebo-Controlled Trial.” European Cytokine Network. €œThe effect of Sambucol, a black elderberry-based, natural product, on the production of human cytokines.

I. Inflammatory cytokines.” Therapeutic Advances in Respiratory Disease. €œLung under attack by asthma treatment-induced cytokine storm.

Pathogenic mechanisms and therapeutic implications.” Planta Medica. €œImmunmodulatory and Antiproliferative Properties of Rhodiola Species.” European Journal of Clinical Microbiology &. Infectious Diseases.

€œProbiotics in respiratory ventolin s.” The Journal of the American Medical Association. €œEchinacea for preventing and treating the common cold.” National Kidney Foundation. €œFamily History of Kidney Stones?.

Watch Those Megadoses of Vitamin C.” Mayo Clinic. €œWhat is vitamin D toxicity?. Should I be worried about taking supplements?.

€ ScienceDaily. €œAdequate zinc eases pneumonia in elderly, study finds,” “Zinc.”By Robert Preidt HealthDay Reporter MONDAY, Nov. 16, 2020 (HealthDay News) -- Despite skyrocketing asthma rates, many Americans plan to attend large holiday gatherings, a nationwide survey finds.

Nearly two in five respondents said they will likely gather with more than 10 people, according to the Ohio State University Wexner Medical Center poll. And while many plan to take precautions -- such as social distancing and asking those with asthma treatment symptoms not to attend holiday gatherings -- one-third of respondents said they won't ask guests to wear masks. The United States is seeing record numbers of asthma s, and colder weather is leading to more get-togethers indoors, where the ventolin can more easily spread.

"We're going to look back at what happened during this holiday season and ask ourselves, 'Were we part of the solution or were we part of the problem?. '" said Dr. Iahn Gonsenhauser, chief quality and patient safety officer at the Wexner Medical Center.

"When you're gathered together around the table, engaged in conversation, sitting less than six feet apart with your masks down, even in a small group, that's when the spread of this ventolin can really happen," he warned in a university news release. The safest way to mark the holidays is to cancel in-person plans with family and friends, and connect virtually instead, Gonsenhauser advised. If you do decide to host a gathering, it's crucial to create a safety plan and outline it to all your guests, he added.

Measures could include having everyone wear masks at all times. Separating seating arrangements by household. And assigning one or two people to serve the food.

The same precautions should be used even if your holiday event is held outdoors, Gonsenhauser said. If you plan to travel or host out-of-town guests, monitor asthma treatment rates and restrictions in both locations. "If you have someone in your household who's high risk and you're in a low-incidence area, you're going to want to think twice about having a celebration where people are coming from an area where there's a lot of ventolin in the community," Gonsenhauser said.

More information For more on asthma treatment, go to the U.S. Centers for Disease Control and Prevention. SOURCE.

Symbicort vs ventolin for bronchitis

Aug. 29, 2020 -- Chadwick Boseman, the star of the 2018 Marvel Studios megahit Black Panther, died of colon cancer Friday. He was 43. Boseman, who was diagnosed 4 years ago, had kept his condition a secret. He filmed his recent movies ''during and between countless surgeries and chemotherapy," according to a statement issued on his Twitter account.

When the actor was diagnosed in 2016, the cancer was at stage III -- meaning it had already grown through the colon wall -- but then progressed to the more lethal stage IV, meaning it had spread beyond his colon. Messages of condolences and the hashtag #Wakandaforever, referring to the fictional African nation in the Black Panther film, flooded social media Friday evening. Oprah tweeted. "What a gentle gifted SOUL. Showing us all that Greatness in between surgeries and chemo.

The courage, the strength, the Power it takes to do that. This is what Dignity looks like. " Marvel Studios tweeted. "Your legacy will live on forever." Boseman was also known for his role as Jackie Robinson in the movie 42. Coincidentally, Friday was Major League Baseball's Jackie Robinson Day, where every player on every team wears Robinson's number 42 on their jerseys.

Boseman's other starring roles include portraying James Brown in Get on Up and U.S. Supreme Court Justice Thurgood Marshall in Marshall. But his role as King T'Challa in Black Panther, the super hero protagonist, made him an icon and an inspiration. About Colon Cancer Boseman's death reflects a troubling recent trend, says Mark Hanna, MD, a colorectal surgeon at City of Hope, a comprehensive cancer center near Los Angeles. "We have noticed an increasing incidence of colorectal cancer in young adults," says Hanna, who did not treat Boseman.

"I've seen patients as young as their early 20s." About 104,000 cases of colon cancer will be diagnosed this year, according to American Cancer Society estimates, and another 43,000 cases of rectal cancer will be diagnosed. About 12% of those, or 18,000 cases, will be in people under age 50. As the rates have declined in older adults due to screening, rates in young adults have steadily risen. Younger patients are often diagnosed at a later stage than older adults, Hanna says, because patients and even their doctors don't think about the possibility of colon cancer. Because it is considered a cancer affecting older adults, many younger people may brush off the symptoms or delay getting medical attention, Hanna says.

In a survey of 885 colorectal cancer patients conducted by Colorectal Cancer Alliance earlier this year, 75% said they visited two or more doctors before getting their diagnosis, and 11% went to 10 or more before finding out. If found early, colon cancer is curable, Hanna says. About 50% of those with colon cancer will be diagnosed at stage I or II, which is considered localized disease, he says. "The majority have a very good prognosis." The 5-year survival rate is about 90% for both stage I and II. But when it progresses to stage III, the cancer has begun to grow into surrounding tissues and the lymph nodes, Hanna says, and the survival rate for 5 years drops to 75%.

About 25% of patients are diagnosed at stage III, he says. If the diagnosis is made at stage IV, the 5-year survival rate drops to about 10% or 15%, he says. Experts have been trying to figure out why more young adults are getting colon cancer and why some do so poorly. "Traditionally we thought that patients who are older would have a worse outlook," Hanna says, partly because they tend to have other medical conditions too. Some experts say that younger patients might have more ''genetically aggressive disease," Hanna says.

"Our understanding of colorectal cancer is becoming more nuanced, and we know that not all forms are the same." For instance, he says, testing is done for specific genetic mutations that have been tied to colon cancer. "It's not just about finding the mutations, but finding the drug that targets [that form] best." Paying Attention to Red Flags "If you have any of what we call the red flag signs, do not ignore your symptoms no matter what your age is," Hanna says. Those are. In 2018, the American Cancer Society changed its guidelines for screening, recommending those at average risk start at age 45, not 50. The screening can be stool-based testing, such as a fecal occult blood test, or visual, such as a colonoscopy.

Hanna says he orders a colonoscopy if the symptoms suggest colon cancer, regardless of a patient's age. Family history of colorectal cancer is a risk factor, as are being obese or overweight, being sedentary, and eating lots of red meat. Sources Mark Hanna, MD, colorectal surgeon and assistant clinical professor of surgery, City of Hope, Los Angeles. American Cancer Society. "Key Statistics for Colorectal Cancer." Twitter statement.

Chadwick Boseman. American Cancer Society. "Colorectal Cancer Risk Factors." American Cancer Society. '"Colorectal Cancer Rates Rise in Younger Adults." American Society of Clinical Oncology annual meeting, May 29-31, 2020. American Cancer Society "Survival Rates for Colorectal Cancer." American Cancer Society.

"Colorectal Cancer Facts &. Figures. 2017-2019." © 2020 WebMD, LLC. All rights reserved..

Aug https://gaileylawgroup.com/how-to-order-viagra/ how much does ventolin cost in canada. 29, 2020 -- Chadwick Boseman, the star of the 2018 Marvel Studios megahit Black Panther, died of colon cancer Friday. He was 43. Boseman, who was diagnosed 4 years ago, had kept his how much does ventolin cost in canada condition a secret.

He filmed his recent movies ''during and between countless surgeries and chemotherapy," according to a statement issued on his Twitter account. When the actor was diagnosed in 2016, the cancer was at stage III -- meaning it had already grown through the colon wall -- but then progressed to the more lethal stage IV, meaning it had spread beyond his colon. Messages of condolences and the hashtag how much does ventolin cost in canada #Wakandaforever, referring to the fictional African nation in the Black Panther film, flooded social media Friday evening. Oprah tweeted.

"What a gentle gifted SOUL. Showing us all that Greatness in between surgeries and how much does ventolin cost in canada chemo. The courage, the strength, the Power it takes to do that. This is what Dignity looks like.

" Marvel Studios how much does ventolin cost in canada tweeted. "Your legacy will live on forever." Boseman was also known for his role as Jackie Robinson in the movie 42. Coincidentally, Friday was Major League Baseball's Jackie Robinson Day, where every player on every team wears Robinson's number 42 on their jerseys. Boseman's other starring roles include portraying James Brown in Get how much does ventolin cost in canada on Up and U.S.

Supreme Court Justice Thurgood Marshall in Marshall. But his role as King T'Challa in Black Panther, the super hero protagonist, made him an icon and an inspiration. About Colon Cancer Boseman's death reflects a troubling recent trend, says Mark Hanna, MD, a colorectal surgeon how much does ventolin cost in canada at City of Hope, a comprehensive cancer center near Los Angeles. "We have noticed an increasing incidence of colorectal cancer in young adults," says Hanna, who did not treat Boseman.

"I've seen patients as young as their early 20s." About 104,000 cases of colon cancer will be diagnosed this year, according to American Cancer Society estimates, and another 43,000 cases of rectal cancer will be diagnosed. About 12% of those, or 18,000 cases, will be in people under age how much does ventolin cost in canada 50. As the rates have declined in older adults due to screening, rates in young adults have steadily risen. Younger patients are often diagnosed at a later stage than older adults, Hanna says, because patients and even their doctors don't think about the possibility of colon cancer.

Because it is considered a cancer affecting older adults, how much does ventolin cost in canada many younger people may brush off the symptoms or delay getting medical attention, Hanna says. In a survey of 885 colorectal cancer patients conducted by Colorectal Cancer Alliance earlier this year, 75% said they visited two or more doctors before getting their diagnosis, and 11% went to 10 or more before finding out. If found early, colon cancer is curable, Hanna says. About 50% of those with colon cancer will be diagnosed at stage I or II, which is considered how much does ventolin cost in canada localized disease, he says.

"The majority have a very good prognosis." The 5-year survival rate is about 90% for both stage I and II. But when it progresses to stage III, the cancer has begun to grow into surrounding tissues and the lymph nodes, Hanna says, and the survival rate for 5 years drops to 75%. About 25% of patients how much does ventolin cost in canada are diagnosed at stage III, he says. If the diagnosis is made at stage IV, the 5-year survival rate drops to about 10% or 15%, he says.

Experts have been trying to figure out why more young adults are getting colon cancer and why some do so poorly. "Traditionally we thought that patients who are older would have a worse outlook," Hanna says, how much does ventolin cost in canada partly because they tend to have other medical conditions too. Some experts say that younger patients might have more ''genetically aggressive disease," Hanna says. "Our understanding of colorectal cancer is becoming more nuanced, and we know that not all forms are the same." For instance, he says, testing is done for specific genetic mutations that have been tied to colon cancer.

"It's not just about finding the mutations, but finding the drug that targets [that how much does ventolin cost in canada form] best." Paying Attention to Red Flags "If you have any of what we call the red flag signs, do not ignore your symptoms no matter what your age is," Hanna says. Those are. In 2018, the American Cancer Society changed its guidelines for screening, recommending those at average risk start at age 45, not 50. The screening can be stool-based testing, such as a fecal occult how much does ventolin cost in canada blood test, or visual, such as a colonoscopy.

Hanna says he orders a colonoscopy if the symptoms suggest colon cancer, regardless of a patient's age. Family history of colorectal cancer is a risk factor, as are being obese or overweight, being sedentary, and eating lots of red meat. Sources Mark Hanna, MD, colorectal surgeon and assistant clinical professor of surgery, City of Hope, Los Angeles. American Cancer Society.

"Key Statistics for Colorectal Cancer." Twitter statement. Chadwick Boseman. American Cancer Society. "Colorectal Cancer Risk Factors." American Cancer Society.

'"Colorectal Cancer Rates Rise in Younger Adults." American Society of Clinical Oncology annual meeting, May 29-31, 2020. American Cancer Society "Survival Rates for Colorectal Cancer." American Cancer Society. "Colorectal Cancer Facts &. Figures.

2017-2019." © 2020 WebMD, LLC. All rights reserved..

Natural ventolin substitute

Participants Figure natural ventolin substitute 1 http://cz.keimfarben.de/where-can-i-buy-cialis-over-the-counter-usa/. Figure 1. Enrollment and natural ventolin substitute Randomization.

The diagram represents all enrolled participants through November 14, 2020. The safety subset (those with a median of 2 months of follow-up, in accordance with application requirements for Emergency Use Authorization) is based on an October 9, 2020, data cut-off date. The further procedures that natural ventolin substitute one participant in the placebo group declined after dose 2 (lower right corner of the diagram) were those involving collection of blood and nasal swab samples.Table 1.

Table 1. Demographic Characteristics of the Participants in the Main Safety Population. Between July 27, 2020, and November 14, 2020, a total of 44,820 persons were screened, and 43,548 persons 16 years natural ventolin substitute of age or older underwent randomization at 152 sites worldwide (United States, 130 sites.

Argentina, 1. Brazil, 2 natural ventolin substitute. South Africa, 4.

Germany, 6. And Turkey, 9) in the phase 2/3 portion natural ventolin substitute of the trial. A total of 43,448 participants received injections.

21,720 received BNT162b2 and 21,728 received placebo (Figure 1). At the data natural ventolin substitute cut-off date of October 9, a total of 37,706 participants had a median of at least 2 months of safety data available after the second dose and contributed to the main safety data set. Among these 37,706 participants, 49% were female, 83% were White, 9% were Black or African American, 28% were Hispanic or Latinx, 35% were obese (body mass index [the weight in kilograms divided by the square of the height in meters] of at least 30.0), and 21% had at least one coexisting condition.

The median age was 52 years, and 42% of participants were older than 55 years of age (Table 1 and Table S2). Safety Local natural ventolin substitute Reactogenicity Figure 2. Figure 2.

Local and Systemic Reactions Reported within 7 Days after Injection natural ventolin substitute of BNT162b2 or Placebo, According to Age Group. Data on local and systemic reactions and use of medication were collected with electronic diaries from participants in the reactogenicity subset (8,183 participants) for 7 days after each vaccination. Solicited injection-site (local) reactions are shown in Panel A.

Pain at natural ventolin substitute the injection site was assessed according to the following scale. Mild, does not interfere with activity. Moderate, interferes with activity.

Severe, prevents natural ventolin substitute daily activity. And grade 4, emergency department visit or hospitalization. Redness and natural ventolin substitute swelling were measured according to the following scale.

Mild, 2.0 to 5.0 cm in diameter. Moderate, >5.0 to 10.0 cm in diameter. Severe, >10.0 natural ventolin substitute cm in diameter.

And grade 4, necrosis or exfoliative dermatitis (for redness) and necrosis (for swelling). Systemic events and medication use are shown in Panel B. Fever categories are designated natural ventolin substitute in the key.

Medication use was not graded. Additional scales were as follows. Fatigue, headache, chills, new or worsened muscle pain, new or worsened joint natural ventolin substitute pain (mild.

Does not interfere with activity. Moderate. Some interference with activity.

Or severe. Prevents daily activity), vomiting (mild. 1 to 2 times in 24 hours.

Moderate. >2 times in 24 hours. Or severe.

Requires intravenous hydration), and diarrhea (mild. 2 to 3 loose stools in 24 hours. Moderate.

4 to 5 loose stools in 24 hours. Or severe. 6 or more loose stools in 24 hours).

Grade 4 for all events indicated an emergency department visit or hospitalization. Н™¸ bars represent 95% confidence intervals, and numbers above the 𝙸 bars are the percentage of participants who reported the specified reaction.The reactogenicity subset included 8183 participants. Overall, BNT162b2 recipients reported more local reactions than placebo recipients.

Among BNT162b2 recipients, mild-to-moderate pain at the injection site within 7 days after an injection was the most commonly reported local reaction, with less than 1% of participants across all age groups reporting severe pain (Figure 2). Pain was reported less frequently among participants older than 55 years of age (71% reported pain after the first dose. 66% after the second dose) than among younger participants (83% after the first dose.

78% after the second dose). A noticeably lower percentage of participants reported injection-site redness or swelling. The proportion of participants reporting local reactions did not increase after the second dose (Figure 2A), and no participant reported a grade 4 local reaction.

In general, local reactions were mostly mild-to-moderate in severity and resolved within 1 to 2 days. Systemic Reactogenicity Systemic events were reported more often by younger treatment recipients (16 to 55 years of age) than by older treatment recipients (more than 55 years of age) in the reactogenicity subset and more often after dose 2 than dose 1 (Figure 2B). The most commonly reported systemic events were fatigue and headache (59% and 52%, respectively, after the second dose, among younger treatment recipients.

51% and 39% among older recipients), although fatigue and headache were also reported by many placebo recipients (23% and 24%, respectively, after the second dose, among younger treatment recipients. 17% and 14% among older recipients). The frequency of any severe systemic event after the first dose was 0.9% or less.

Severe systemic events were reported in less than 2% of treatment recipients after either dose, except for fatigue (in 3.8%) and headache (in 2.0%) after the second dose. Fever (temperature, ≥38°C) was reported after the second dose by 16% of younger treatment recipients and by 11% of older recipients. Only 0.2% of treatment recipients and 0.1% of placebo recipients reported fever (temperature, 38.9 to 40°C) after the first dose, as compared with 0.8% and 0.1%, respectively, after the second dose.

Two participants each in the treatment and placebo groups reported temperatures above 40.0°C. Younger treatment recipients were more likely to use antipyretic or pain medication (28% after dose 1. 45% after dose 2) than older treatment recipients (20% after dose 1.

38% after dose 2), and placebo recipients were less likely (10 to 14%) than treatment recipients to use the medications, regardless of age or dose. Systemic events including fever and chills were observed within the first 1 to 2 days after vaccination and resolved shortly thereafter. Daily use of the electronic diary ranged from 90 to 93% for each day after the first dose and from 75 to 83% for each day after the second dose.

No difference was noted between the BNT162b2 group and the placebo group. Adverse Events Adverse event analyses are provided for all enrolled 43,252 participants, with variable follow-up time after dose 1 (Table S3). More BNT162b2 recipients than placebo recipients reported any adverse event (27% and 12%, respectively) or a related adverse event (21% and 5%).

This distribution largely reflects the inclusion of transient reactogenicity events, which were reported as adverse events more commonly by treatment recipients than by placebo recipients. Sixty-four treatment recipients (0.3%) and 6 placebo recipients (<0.1%) reported lymphadenopathy. Few participants in either group had severe adverse events, serious adverse events, or adverse events leading to withdrawal from the trial.

Four related serious adverse events were reported among BNT162b2 recipients (shoulder injury related to treatment administration, right axillary lymphadenopathy, paroxysmal ventricular arrhythmia, and right leg paresthesia). Two BNT162b2 recipients died (one from arteriosclerosis, one from cardiac arrest), as did four placebo recipients (two from unknown causes, one from hemorrhagic stroke, and one from myocardial infarction). No deaths were considered by the investigators to be related to the treatment or placebo.

No asthma treatment–associated deaths were observed. No stopping rules were met during the reporting period. Safety monitoring will continue for 2 years after administration of the second dose of treatment.

Efficacy Table 2. Table 2. treatment Efficacy against asthma treatment at Least 7 days after the Second Dose.

Table 3. Table 3. treatment Efficacy Overall and by Subgroup in Participants without Evidence of before 7 Days after Dose 2.

Figure 3. Figure 3. Efficacy of BNT162b2 against asthma treatment after the First Dose.

Shown is the cumulative incidence of asthma treatment after the first dose (modified intention-to-treat population). Each symbol represents asthma treatment cases starting on a given day. Filled symbols represent severe asthma treatment cases.

Some symbols represent more than one case, owing to overlapping dates. The inset shows the same data on an enlarged y axis, through 21 days. Surveillance time is the total time in 1000 person-years for the given end point across all participants within each group at risk for the end point.

The time period for asthma treatment case accrual is from the first dose to the end of the surveillance period. The confidence interval (CI) for treatment efficacy (VE) is derived according to the Clopper–Pearson method.Among 36,523 participants who had no evidence of existing or prior asthma , 8 cases of asthma treatment with onset at least 7 days after the second dose were observed among treatment recipients and 162 among placebo recipients. This case split corresponds to 95.0% treatment efficacy (95% confidence interval [CI], 90.3 to 97.6.

Table 2). Among participants with and those without evidence of prior SARS CoV-2 , 9 cases of asthma treatment at least 7 days after the second dose were observed among treatment recipients and 169 among placebo recipients, corresponding to 94.6% treatment efficacy (95% CI, 89.9 to 97.3). Supplemental analyses indicated that treatment efficacy among subgroups defined by age, sex, race, ethnicity, obesity, and presence of a coexisting condition was generally consistent with that observed in the overall population (Table 3 and Table S4).

treatment efficacy among participants with hypertension was analyzed separately but was consistent with the other subgroup analyses (treatment efficacy, 94.6%. 95% CI, 68.7 to 99.9. Case split.

BNT162b2, 2 cases. Placebo, 44 cases). Figure 3 shows cases of asthma treatment or severe asthma treatment with onset at any time after the first dose (mITT population) (additional data on severe asthma treatment are available in Table S5).

Between the first dose and the second dose, 39 cases in the BNT162b2 group and 82 cases in the placebo group were observed, resulting in a treatment efficacy of 52% (95% CI, 29.5 to 68.4) during this interval and indicating early protection by the treatment, starting as soon as 12 days after the first dose.V-safe Surveillance. Local and Systemic Reactogenicity in Pregnant Persons Table 1. Table 1.

Characteristics of Persons Who Identified as Pregnant in the V-safe Surveillance System and Received an mRNA asthma treatment. Table 2. Table 2.

Frequency of Local and Systemic Reactions Reported on the Day after mRNA asthma treatment Vaccination in Pregnant Persons. From December 14, 2020, to February 28, 2021, a total of 35,691 v-safe participants identified as pregnant. Age distributions were similar among the participants who received the Pfizer–BioNTech treatment and those who received the Moderna treatment, with the majority of the participants being 25 to 34 years of age (61.9% and 60.6% for each treatment, respectively) and non-Hispanic White (76.2% and 75.4%, respectively).

Most participants (85.8% and 87.4%, respectively) reported being pregnant at the time of vaccination (Table 1). Solicited reports of injection-site pain, fatigue, headache, and myalgia were the most frequent local and systemic reactions after either dose for both treatments (Table 2) and were reported more frequently after dose 2 for both treatments. Participant-measured temperature at or above 38°C was reported by less than 1% of the participants on day 1 after dose 1 and by 8.0% after dose 2 for both treatments.

Figure 1. Figure 1. Most Frequent Local and Systemic Reactions Reported in the V-safe Surveillance System on the Day after mRNA asthma treatment Vaccination.

Shown are solicited reactions in pregnant persons and nonpregnant women 16 to 54 years of age who received a messenger RNA (mRNA) asthma disease 2019 (asthma treatment) treatment — BNT162b2 (Pfizer–BioNTech) or mRNA-1273 (Moderna) — from December 14, 2020, to February 28, 2021. The percentage of respondents was calculated among those who completed a day 1 survey, with the top events shown of injection-site pain (pain), fatigue or tiredness (fatigue), headache, muscle or body aches (myalgia), chills, and fever or felt feverish (fever).These patterns of reporting, with respect to both most frequently reported solicited reactions and the higher reporting of reactogenicity after dose 2, were similar to patterns observed among nonpregnant women (Figure 1). Small differences in reporting frequency between pregnant persons and nonpregnant women were observed for specific reactions (injection-site pain was reported more frequently among pregnant persons, and other systemic reactions were reported more frequently among nonpregnant women), but the overall reactogenicity profile was similar.

Pregnant persons did not report having severe reactions more frequently than nonpregnant women, except for nausea and vomiting, which were reported slightly more frequently only after dose 2 (Table S3). V-safe Pregnancy Registry. Pregnancy Outcomes and Neonatal Outcomes Table 3.

Table 3. Characteristics of V-safe Pregnancy Registry Participants. As of March 30, 2021, the v-safe pregnancy registry call center attempted to contact 5230 persons who were vaccinated through February 28, 2021, and who identified during a v-safe survey as pregnant at or shortly after asthma treatment vaccination.

Of these, 912 were unreachable, 86 declined to participate, and 274 did not meet inclusion criteria (e.g., were never pregnant, were pregnant but received vaccination more than 30 days before the last menstrual period, or did not provide enough information to determine eligibility). The registry enrolled 3958 participants with vaccination from December 14, 2020, to February 28, 2021, of whom 3719 (94.0%) identified as health care personnel. Among enrolled participants, most were 25 to 44 years of age (98.8%), non-Hispanic White (79.0%), and, at the time of interview, did not report a asthma treatment diagnosis during pregnancy (97.6%) (Table 3).

Receipt of a first dose of treatment meeting registry-eligibility criteria was reported by 92 participants (2.3%) during the periconception period, by 1132 (28.6%) in the first trimester of pregnancy, by 1714 (43.3%) in the second trimester, and by 1019 (25.7%) in the third trimester (1 participant was missing information to determine the timing of vaccination) (Table 3). Among 1040 participants (91.9%) who received a treatment in the first trimester and 1700 (99.2%) who received a treatment in the second trimester, initial data had been collected and follow-up scheduled at designated time points approximately 10 to 12 weeks apart. Limited follow-up calls had been made at the time of this analysis.

Table 4. Table 4. Pregnancy Loss and Neonatal Outcomes in Published Studies and V-safe Pregnancy Registry Participants.

Among 827 participants who had a completed pregnancy, the pregnancy resulted in a live birth in 712 (86.1%), in a spontaneous abortion in 104 (12.6%), in stillbirth in 1 (0.1%), and in other outcomes (induced abortion and ectopic pregnancy) in 10 (1.2%). A total of 96 of 104 spontaneous abortions (92.3%) occurred before 13 weeks of gestation (Table 4), and 700 of 712 pregnancies that resulted in a live birth (98.3%) were among persons who received their first eligible treatment dose in the third trimester. Adverse outcomes among 724 live-born infants — including 12 sets of multiple gestation — were preterm birth (60 of 636 among those vaccinated before 37 weeks [9.4%]), small size for gestational age (23 of 724 [3.2%]), and major congenital anomalies (16 of 724 [2.2%]).

No neonatal deaths were reported at the time of interview. Among the participants with completed pregnancies who reported congenital anomalies, none had received asthma treatment in the first trimester or periconception period, and no specific pattern of congenital anomalies was observed. Calculated proportions of pregnancy and neonatal outcomes appeared similar to incidences published in the peer-reviewed literature (Table 4).

Adverse-Event Findings on the VAERS During the analysis period, the VAERS received and processed 221 reports involving asthma treatment vaccination among pregnant persons. 155 (70.1%) involved nonpregnancy-specific adverse events, and 66 (29.9%) involved pregnancy- or neonatal-specific adverse events (Table S4). The most frequently reported pregnancy-related adverse events were spontaneous abortion (46 cases.

37 in the first trimester, 2 in the second trimester, and 7 in which the trimester was unknown or not reported), followed by stillbirth, premature rupture of membranes, and vaginal bleeding, with 3 reports for each. No congenital anomalies were reported to the VAERS, a requirement under the EUAs.Trial Design and Oversight The Applying Wolbachia to Eliminate Dengue (AWED) trial was supported by the Tahija Foundation and was hosted by Universitas Gadjah Mada, Indonesia. The protocol was published previously20,21 and is available with the full text of this article at NEJM.org.

Community approval for wMel releases was obtained from the leaders of 37 urban villages after a campaign of community engagement and mass communication. Written informed consent for participation in the clinical component of the trial was obtained from all the participants or from a guardian if the participant was a minor. In addition, participants 13 to 17 years of age gave written informed assent.

The trial was conducted in accordance with the International Council for Harmonisation guidelines for Good Clinical Practice and was approved by the human research ethics committees at Universitas Gadjah Mada and Monash University. The trial data were analyzed by the independent trial statisticians. The funders had no role in the analysis of the data, in the preparation or approval of the manuscript, or in the decision to submit the manuscript for publication.

Randomization Figure 1. Figure 1. Map of the Trial Location and Clusters.

A map of Indonesia is shown at the top, with the location of Yogyakarta Province shaded in dark blue. The enlarged area at the bottom shows the trial area in Yogyakarta City, which includes a small area of neighboring Bantul District (clusters 23 and 24). Intervention clusters (which received deployments of Aedes aegypti mosquitoes infected with the wMel strain of Wolbachia pipientis) are shaded in dark blue, and control clusters (which received no deployments) are shaded in light blue.

Red crosses indicate the locations of the primary care clinics where enrollment was conducted.The baseline characteristics of the trial clusters are described in Table S1 in the Supplementary Appendix, available at NEJM.org. In brief, the trial site was a contiguous urban area of 26 km2 with a population of approximately 311,700. The trial site was subdivided into 24 clusters, each approximately 1 km2 in size, and where possible, having geographic borders that would slow the dispersal of mosquitoes between clusters.

Of the 24 clusters, 12 were randomly assigned to receive deployments of open-label wolbachia-infected mosquitoes (intervention clusters), and 12 clusters were assigned to receive no deployments (control clusters, termed “untreated clusters” in the protocol) (Figure 1 and Fig. S1). In intervention clusters, most community members were unaware of the cluster assignment because release containers were placed discretely in a minority of residential properties for a limited time.

No placebo was used in the control clusters. Constrained randomization was used to prevent a chance imbalance in the baseline characteristics or in the spatial distribution of the intervention and control clusters (see the Supplementary Appendix). Wolbachia Deployment and Entomologic Monitoring A.

Aegypti infected with the wMel strain of wolbachia were sourced from an outcrossed colony, as described previously.14 In 2013, we found that this wMel-infected Indonesian mosquito line was less likely than wild-type A. Aegypti to transmit DENV (Figs. S2 and S3).

Mosquito eggs were placed in intervention clusters from March through December 2017. Each cluster received between 9 and 14 rounds of deployments (Table S2). Details regarding mosquito releases and monitoring of wMel in the mosquito populations are provided in the Supplementary Appendix.

Monitoring was performed with the use of a network of 348 adult mosquito traps (BG-Sentinel, BioGents). Participant Enrollment Participants were recruited from a network of 18 government-run primary care clinics in Yogyakarta and the adjacent Bantul District. Eligible participants were 3 to 45 years of age, had fever (either reported by the participant or measured in the clinic and defined as a forehead or axillary temperature of >37.5°C) with onset 1 to 4 days before presentation, and had resided in the trial area every night for the 10 days preceding the onset of illness.

Participants were not eligible if they had localizing symptoms suggestive of a specific diagnosis other than an arboviral (e.g., severe diarrhea, otitis, and pneumonia) or were enrolled in the trial within the previous 4 weeks. Procedures Participants provided demographic information, a geolocated residential address, and a detailed travel history for the 3 to 10 days before the onset of illness. A 3-ml venous blood sample was obtained for arboventolin diagnostic testing.

No other diagnostic investigations were performed. Participants were contacted 14 to 21 days after enrollment to obtain vital status and to determine whether they had been hospitalized since enrollment. No information on the clinical severity of VCD cases was collected, and no information on clinical diagnoses or severity of non-VCD cases was acquired.

Diagnostic Investigations and Classifications Trial participants were classified as having VCD if the plasma sample obtained at enrollment was positive for DENV in a multiplex (DENV, chikungunya ventolin, and Zika ventolin) reverse-transcriptase–polymerase-chain-reaction (RT-PCR) assay or in an enzyme-linked immunosorbent assay (ELISA) for DENV nonstructural protein 1 (NS1) antigen (Platelia dengue NS1 [Bio-Rad]). Participants were classified as test-negative controls if the plasma sample obtained at enrollment was negative by RT-PCR for DENV, chikungunya ventolin, and Zika ventolin and also negative by ELISA capture assay for DENV NS1 antigen and dengue IgM and IgG. The diagnostic algorithm is provided in Figure S4.

The DENV serotype was determined with the use of a separate RT-PCR assay (Simplexa) by an independent laboratory at the Eijkman Institute, Jakarta. Details of the diagnostic methods are provided in the Supplementary Appendix. Primary, Secondary, and Safety End Points The primary end point was symptomatic VCD of any severity caused by any DENV serotype.

The secondary end points reported here are symptomatic VCD caused by each of the four DENV serotypes (DENV-1, DENV-2, DENV-3, and DENV-4) and symptomatic, virologically confirmed chikungunya and Zika ventolin s. Safety end points included hospitalization or death within 21 days after enrollment. Statistical Analysis The sample size that was needed to show a 50% lower incidence of dengue in the intervention clusters than in the control clusters, which was considered the minimum effect size for public health value, evolved over time.

The full description of the sample-size calculations is provided in the Supplementary Appendix. In brief, we determined that 400 cases of VCD and 1600 test-negative controls would be needed to give the trial 80% power to detect a 50% lower incidence of VCD among participants in intervention clusters than among those in control clusters. The emergence of severe acute respiratory syndrome asthma 2 in Yogyakarta in March 2020 prevented the continued recruitment of participants in clinics, and enrollment ended on March 18, 2020.

On May 5, 2020, the trial steering committee endorsed the recommendation of the trial investigators to terminate the trial, at which time 385 participants with VCD had been enrolled. The statistical analysis plan was published previously22 and is available with the protocol. The trial population used in the efficacy analysis included all enrolled participants with VCD and all test-negative controls, excluding participants who had been enrolled before the establishment of wolbachia throughout the intervention clusters (i.e., 1 month after the last release in the last cluster) and excluding test-negative controls who had been enrolled in a calendar month in which no dengue cases were observed among participants.

The primary intention-to-treat analysis considered wolbachia exposure as a binary classification on the basis of residence in an intervention cluster or a control cluster. Residence was defined as the primary place of residence during the 10 days before illness onset. The intervention effect was estimated from an aggregate odds ratio comparing the exposure odds (residence in an intervention cluster) among participants with VCD with that among test-negative controls, with the use of the constrained permutation distribution as the foundation for inference.

The null hypothesis was that the odds of residence in an intervention cluster would be the same among participants with VCD as that among test-negative controls. The efficacy of the intervention was calculated as 100×(1−aggregate odds ratio). A prespecified exploratory analysis evaluated the efficacy of the intervention in preventing hospitalization with VCD.

An additional prespecified cluster-level intention-to-treat analysis was performed by calculating the proportion of participants with VCD in each cluster. The difference in the average proportions of participants with VCD between the intervention clusters and the control clusters was used to test the null hypothesis of no intervention effect (a t-test statistic) and to derive an estimate of the cluster-specific relative risk, with inference based on the constrained permutation distribution.23,24 The same methods used in the intention-to-treat analyses described above were used in the analyses for the secondary end point of serotype-specific efficacy. The analyses included participants with VCD caused by one of the four DENV serotypes and used the same control population as that used in the primary analysis.

There was no prespecified plan to control for multiple testing in the analysis of secondary end points. Per-protocol analyses considered exposure contamination by assigning a wolbachia exposure index to each participant on the basis of the wMel prevalence in their cluster of residence only, or by combining this frequency with the participant’s recent travel history. A generalized linear model was fitted, with balanced bootstrap resampling based on cluster residence, to estimate the relative risk of VCD and associated confidence interval in each quintile of wolbachia exposure, relative to the risk of VCD in participants in the bottom quintile of wolbachia exposure.

Details are provided in the Supplementary Appendix..

Participants Figure Where can i buy cialis over the counter usa 1 how much does ventolin cost in canada. Figure 1. Enrollment and Randomization how much does ventolin cost in canada. The diagram represents all enrolled participants through November 14, 2020.

The safety subset (those with a median of 2 months of follow-up, in accordance with application requirements for Emergency Use Authorization) is based on an October 9, 2020, data cut-off date. The further procedures that one how much does ventolin cost in canada participant in the placebo group declined after dose 2 (lower right corner of the diagram) were those involving collection of blood and nasal swab samples.Table 1. Table 1. Demographic Characteristics of the Participants in the Main Safety Population.

Between July 27, 2020, and November 14, 2020, a total of 44,820 persons were screened, and 43,548 persons 16 years of age or older underwent randomization how much does ventolin cost in canada at 152 sites worldwide (United States, 130 sites. Argentina, 1. Brazil, 2 how much does ventolin cost in canada. South Africa, 4.

Germany, 6. And Turkey, how much does ventolin cost in canada 9) in the phase 2/3 portion of the trial. A total of 43,448 participants received injections. 21,720 received BNT162b2 and 21,728 received placebo (Figure 1).

At the data cut-off date of October 9, a total of 37,706 how much does ventolin cost in canada participants had a median of at least 2 months of safety data available after the second dose and contributed to the main safety data set. Among these 37,706 participants, 49% were female, 83% were White, 9% were Black or African American, 28% were Hispanic or Latinx, 35% were obese (body mass index [the weight in kilograms divided by the square of the height in meters] of at least 30.0), and 21% had at least one coexisting condition. The median age was 52 years, and 42% of participants were older than 55 years of age (Table 1 and Table S2). Safety Local Reactogenicity how much does ventolin cost in canada Figure 2.

Figure 2. Local and Systemic Reactions Reported within 7 Days after Injection of BNT162b2 or Placebo, According to Age how much does ventolin cost in canada Group. Data on local and systemic reactions and use of medication were collected with electronic diaries from participants in the reactogenicity subset (8,183 participants) for 7 days after each vaccination. Solicited injection-site (local) reactions are shown in Panel A.

Pain at the injection how much does ventolin cost in canada site was assessed according to the following scale. Mild, does not interfere with activity. Moderate, interferes with activity. Severe, prevents daily activity how much does ventolin cost in canada.

And grade 4, emergency department visit or hospitalization. Redness and swelling were measured how much does ventolin cost in canada according to the following scale. Mild, 2.0 to 5.0 cm in diameter. Moderate, >5.0 to 10.0 cm in diameter.

Severe, >10.0 cm how much does ventolin cost in canada in diameter. And grade 4, necrosis or exfoliative dermatitis (for redness) and necrosis (for swelling). Systemic events and medication use are shown in Panel B. Fever categories are designated how much does ventolin cost in canada in the key.

Medication use was not graded. Additional scales were as follows. Fatigue, headache, chills, new or worsened muscle pain, new or how much does ventolin cost in canada worsened joint pain (mild. Does not interfere with activity.

Moderate. Some interference with activity. Or severe. Prevents daily activity), vomiting (mild.

1 to 2 times in 24 hours. Moderate. >2 times in 24 hours. Or severe.

Requires intravenous hydration), and diarrhea (mild. 2 to 3 loose stools in 24 hours. Moderate. 4 to 5 loose stools in 24 hours.

Or severe. 6 or more loose stools in 24 hours). Grade 4 for all events indicated an emergency department visit or hospitalization. Н™¸ bars represent 95% confidence intervals, and numbers above the 𝙸 bars are the percentage of participants who reported the specified reaction.The reactogenicity subset included 8183 participants.

Overall, BNT162b2 recipients reported more local reactions than placebo recipients. Among BNT162b2 recipients, mild-to-moderate pain at the injection site within 7 days after an injection was the most commonly reported local reaction, with less than 1% of participants across all age groups reporting severe pain (Figure 2). Pain was reported less frequently among participants older than 55 years of age (71% reported pain after the first dose. 66% after the second dose) than among younger participants (83% after the first dose.

78% after the second dose). A noticeably lower percentage of participants reported injection-site redness or swelling. The proportion of participants reporting local reactions did not increase after the second dose (Figure 2A), and no participant reported a grade 4 local reaction. In general, local reactions were mostly mild-to-moderate in severity and resolved within 1 to 2 days.

Systemic Reactogenicity Systemic events were reported more often by younger treatment recipients (16 to 55 years of age) than by older treatment recipients (more than 55 years of age) in the reactogenicity subset and more often after dose 2 than dose 1 (Figure 2B). The most commonly reported systemic events were fatigue and headache (59% and 52%, respectively, after the second dose, among younger treatment recipients. 51% and 39% among older recipients), although fatigue and headache were also reported by many placebo recipients (23% and 24%, respectively, after the second dose, among younger treatment recipients. 17% and 14% among older recipients).

The frequency of any severe systemic event after the first dose was 0.9% or less. Severe systemic events were reported in less than 2% of treatment recipients after either dose, except for fatigue (in 3.8%) and headache (in 2.0%) after the second dose. Fever (temperature, ≥38°C) was reported after the second dose by 16% of younger treatment recipients and by 11% of older recipients. Only 0.2% of treatment recipients and 0.1% of placebo recipients reported fever (temperature, 38.9 to 40°C) after the first dose, as compared with 0.8% and 0.1%, respectively, after the second dose.

Two participants each in the treatment and placebo groups reported temperatures above 40.0°C. Younger treatment recipients were more likely to use antipyretic or pain medication (28% after dose 1. 45% after dose 2) than older treatment recipients (20% after dose 1. 38% after dose 2), and placebo recipients were less likely (10 to 14%) than treatment recipients to use the medications, regardless of age or dose.

Systemic events including fever and chills were observed within the first 1 to 2 days after vaccination and resolved shortly thereafter. Daily use of the electronic diary ranged from 90 to 93% for each day after the first dose and from 75 to 83% for each day after the second dose. No difference was noted between the BNT162b2 group and the placebo group. Adverse Events Adverse event analyses are provided for all enrolled 43,252 participants, with variable follow-up time after dose 1 (Table S3).

More BNT162b2 recipients than placebo recipients reported any adverse event (27% and 12%, respectively) or a related adverse event (21% and 5%). This distribution largely reflects the inclusion of transient reactogenicity events, which were reported as adverse events more commonly by treatment recipients than by placebo recipients. Sixty-four treatment recipients (0.3%) and 6 placebo recipients (<0.1%) reported lymphadenopathy. Few participants in either group had severe adverse events, serious adverse events, or adverse events leading to withdrawal from the trial.

Four related serious adverse events were reported among BNT162b2 recipients (shoulder injury related to treatment administration, right axillary lymphadenopathy, paroxysmal ventricular arrhythmia, and right leg paresthesia). Two BNT162b2 recipients died (one from arteriosclerosis, one from cardiac arrest), as did four placebo recipients (two from unknown causes, one from hemorrhagic stroke, and one from myocardial infarction). No deaths were considered by the investigators to be related to the treatment or placebo. No asthma treatment–associated deaths were observed.

No stopping rules were met during the reporting period. Safety monitoring will continue for 2 years after administration of the second dose of treatment. Efficacy Table 2. Table 2.

treatment Efficacy against asthma treatment at Least 7 days after the Second Dose. Table 3. Table 3. treatment Efficacy Overall and by Subgroup in Participants without Evidence of before 7 Days after Dose 2.

Figure 3. Figure 3. Efficacy of BNT162b2 against asthma treatment after the First Dose. Shown is the cumulative incidence of asthma treatment after the first dose (modified intention-to-treat population).

Each symbol represents asthma treatment cases starting on a given day. Filled symbols represent severe asthma treatment cases. Some symbols represent more than one case, owing to overlapping dates. The inset shows the same data on an enlarged y axis, through 21 days.

Surveillance time is the total time in 1000 person-years for the given end point across all participants within each group at risk for the end point. The time period for asthma treatment case accrual is from the first dose to the end of the surveillance period. The confidence interval (CI) for treatment efficacy (VE) is derived according to the Clopper–Pearson method.Among 36,523 participants who had no evidence of existing or prior asthma , 8 cases of asthma treatment with onset at least 7 days after the second dose were observed among treatment recipients and 162 among placebo recipients. This case split corresponds to 95.0% treatment efficacy (95% confidence interval [CI], 90.3 to 97.6.

Table 2). Among participants with and those without evidence of prior SARS CoV-2 , 9 cases of asthma treatment at least 7 days after the second dose were observed among treatment recipients and 169 among placebo recipients, corresponding to 94.6% treatment efficacy (95% CI, 89.9 to 97.3). Supplemental analyses indicated that treatment efficacy among subgroups defined by age, sex, race, ethnicity, obesity, and presence of a coexisting condition was generally consistent with that observed in the overall population (Table 3 and Table S4). treatment efficacy among participants with hypertension was analyzed separately but was consistent with the other subgroup analyses (treatment efficacy, 94.6%.

95% CI, 68.7 to 99.9. Case split. BNT162b2, 2 cases. Placebo, 44 cases).

Figure 3 shows cases of asthma treatment or severe asthma treatment with onset at any time after the first dose (mITT population) (additional data on severe asthma treatment are available in Table S5). Between the first dose and the second dose, 39 cases in the BNT162b2 group and 82 cases in the placebo group were observed, resulting in a treatment efficacy of 52% (95% CI, 29.5 to 68.4) during this interval and indicating early protection by the treatment, starting as soon as 12 days after the first dose.V-safe Surveillance. Local and Systemic Reactogenicity in Pregnant Persons Table 1. Table 1.

Characteristics of Persons Who Identified as Pregnant in the V-safe Surveillance System and Received an mRNA asthma treatment. Table 2. Table 2. Frequency of Local and Systemic Reactions Reported on the Day after mRNA asthma treatment Vaccination in Pregnant Persons.

From December 14, 2020, to February 28, 2021, a total of 35,691 v-safe participants identified as pregnant. Age distributions were similar among the participants who received the Pfizer–BioNTech treatment and those who received the Moderna treatment, with the majority of the participants being 25 to 34 years of age (61.9% and 60.6% for each treatment, respectively) and non-Hispanic White (76.2% and 75.4%, respectively). Most participants (85.8% and 87.4%, respectively) reported being pregnant at the time of vaccination (Table 1). Solicited reports of injection-site pain, fatigue, headache, and myalgia were the most frequent local and systemic reactions after either dose for both treatments (Table 2) and were reported more frequently after dose 2 for both treatments.

Participant-measured temperature at or above 38°C was reported by less than 1% of the participants on day 1 after dose 1 and by 8.0% after dose 2 for both treatments. Figure 1. Figure 1. Most Frequent Local and Systemic Reactions Reported in the V-safe Surveillance System on the Day after mRNA asthma treatment Vaccination.

Shown are solicited reactions in pregnant persons and nonpregnant women 16 to 54 years of age who received a messenger RNA (mRNA) asthma disease 2019 (asthma treatment) treatment — BNT162b2 (Pfizer–BioNTech) or mRNA-1273 (Moderna) — from December 14, 2020, to February 28, 2021. The percentage of respondents was calculated among those who completed a day 1 survey, with the top events shown of injection-site pain (pain), fatigue or tiredness (fatigue), headache, muscle or body aches (myalgia), chills, and fever or felt feverish (fever).These patterns of reporting, with respect to both most frequently reported solicited reactions and the higher reporting of reactogenicity after dose 2, were similar to patterns observed among nonpregnant women (Figure 1). Small differences in reporting frequency between pregnant persons and nonpregnant women were observed for specific reactions (injection-site pain was reported more frequently among pregnant persons, and other systemic reactions were reported more frequently among nonpregnant women), but the overall reactogenicity profile was similar. Pregnant persons did not report having severe reactions more frequently than nonpregnant women, except for nausea and vomiting, which were reported slightly more frequently only after dose 2 (Table S3).

V-safe Pregnancy Registry. Pregnancy Outcomes and Neonatal Outcomes Table 3. Table 3. Characteristics of V-safe Pregnancy Registry Participants.

As of March 30, 2021, the v-safe pregnancy registry call center attempted to contact 5230 persons who were vaccinated through February 28, 2021, and who identified during a v-safe survey as pregnant at or shortly after asthma treatment vaccination. Of these, 912 were unreachable, 86 declined to participate, and 274 did not meet inclusion criteria (e.g., were never pregnant, were pregnant but received vaccination more than 30 days before the last menstrual period, or did not provide enough information to determine eligibility). The registry enrolled 3958 participants with vaccination from December 14, 2020, to February 28, 2021, of whom 3719 (94.0%) identified as health care personnel. Among enrolled participants, most were 25 to 44 years of age (98.8%), non-Hispanic White (79.0%), and, at the time of interview, did not report a asthma treatment diagnosis during pregnancy (97.6%) (Table 3).

Receipt of a first dose of treatment meeting registry-eligibility criteria was reported by 92 participants (2.3%) during the periconception period, by 1132 (28.6%) in the first trimester of pregnancy, by 1714 (43.3%) in the second trimester, and by 1019 (25.7%) in the third trimester (1 participant was missing information to determine the timing of vaccination) (Table 3). Among 1040 participants (91.9%) who received a treatment in the first trimester and 1700 (99.2%) who received a treatment in the second trimester, initial data had been collected and follow-up scheduled at designated time points approximately 10 to 12 weeks apart. Limited follow-up calls had been made at the time of this analysis. Table 4.

Table 4. Pregnancy Loss and Neonatal Outcomes in Published Studies and V-safe Pregnancy Registry Participants. Among 827 participants who had a completed pregnancy, the pregnancy resulted in a live birth in 712 (86.1%), in a spontaneous abortion in 104 (12.6%), in stillbirth in 1 (0.1%), and in other outcomes (induced abortion and ectopic pregnancy) in 10 (1.2%). A total of 96 of 104 spontaneous abortions (92.3%) occurred before 13 weeks of gestation (Table 4), and 700 of 712 pregnancies that resulted in a live birth (98.3%) were among persons who received their first eligible treatment dose in the third trimester.

Adverse outcomes among 724 live-born infants — including 12 sets of multiple gestation — were preterm birth (60 of 636 among those vaccinated before 37 weeks [9.4%]), small size for gestational age (23 of 724 [3.2%]), and major congenital anomalies (16 of 724 [2.2%]). No neonatal deaths were reported at the time of interview. Among the participants with completed pregnancies who reported congenital anomalies, none had received asthma treatment in the first trimester or periconception period, and no specific pattern of congenital anomalies was observed. Calculated proportions of pregnancy and neonatal outcomes appeared similar to incidences published in the peer-reviewed literature (Table 4).

Adverse-Event Findings on the VAERS During the analysis period, the VAERS received and processed 221 reports involving asthma treatment vaccination among pregnant persons. 155 (70.1%) involved nonpregnancy-specific adverse events, and 66 (29.9%) involved pregnancy- or neonatal-specific adverse events (Table S4). The most frequently reported pregnancy-related adverse events were spontaneous abortion (46 cases. 37 in the first trimester, 2 in the second trimester, and 7 in which the trimester was unknown or not reported), followed by stillbirth, premature rupture of membranes, and vaginal bleeding, with 3 reports for each.

No congenital anomalies were reported to the VAERS, a requirement under the EUAs.Trial Design and Oversight The Applying Wolbachia to Eliminate Dengue (AWED) trial was supported by the Tahija Foundation and was hosted by Universitas Gadjah Mada, Indonesia. The protocol was published previously20,21 and is available with the full text of this article at NEJM.org. Community approval for wMel releases was obtained from the leaders of 37 urban villages after a campaign of community engagement and mass communication. Written informed consent for participation in the clinical component of the trial was obtained from all the participants or from a guardian if the participant was a minor.

In addition, participants 13 to 17 years of age gave written informed assent. The trial was conducted in accordance with the International Council for Harmonisation guidelines for Good Clinical Practice and was approved by the human research ethics committees at Universitas Gadjah Mada and Monash University. The trial data were analyzed by the independent trial statisticians. The funders had no role in the analysis of the data, in the preparation or approval of the manuscript, or in the decision to submit the manuscript for publication.

Randomization Figure 1. Figure 1. Map of the Trial Location and Clusters. A map of Indonesia is shown at the top, with the location of Yogyakarta Province shaded in dark blue.

The enlarged area at the bottom shows the trial area in Yogyakarta City, which includes a small area of neighboring Bantul District (clusters 23 and 24). Intervention clusters (which received deployments of Aedes aegypti mosquitoes infected with the wMel strain of Wolbachia pipientis) are shaded in dark blue, and control clusters (which received no deployments) are shaded in light blue. Red crosses indicate the locations of the primary care clinics where enrollment was conducted.The baseline characteristics of the trial clusters are described in Table S1 in the Supplementary Appendix, available at NEJM.org. In brief, the trial site was a contiguous urban area of 26 km2 with a population of approximately 311,700.

The trial site was subdivided into 24 clusters, each approximately 1 km2 in size, and where possible, having geographic borders that would slow the dispersal of mosquitoes between clusters. Of the 24 clusters, 12 were randomly assigned to receive deployments of open-label wolbachia-infected mosquitoes (intervention clusters), and 12 clusters were assigned to receive no deployments (control clusters, termed “untreated clusters” in the protocol) (Figure 1 and Fig. S1). In intervention clusters, most community members were unaware of the cluster assignment because release containers were placed discretely in a minority of residential properties for a limited time.

No placebo was used in the control clusters. Constrained randomization was used to prevent a chance imbalance in the baseline characteristics or in the spatial distribution of the intervention and control clusters (see the Supplementary Appendix). Wolbachia Deployment and Entomologic Monitoring A. Aegypti infected with the wMel strain of wolbachia were sourced from an outcrossed colony, as described previously.14 In 2013, we found that this wMel-infected Indonesian mosquito line was less likely than wild-type A.

Aegypti to transmit DENV (Figs. S2 and S3). Mosquito eggs were placed in intervention clusters from March through December 2017. Each cluster received between 9 and 14 rounds of deployments (Table S2).

Details regarding mosquito releases and monitoring of wMel in the mosquito populations are provided in the Supplementary Appendix. Monitoring was performed with the use of a network of 348 adult mosquito traps (BG-Sentinel, BioGents). Participant Enrollment Participants were recruited from a network of 18 government-run primary care clinics in Yogyakarta and the adjacent Bantul District. Eligible participants were 3 to 45 years of age, had fever (either reported by the participant or measured in the clinic and defined as a forehead or axillary temperature of >37.5°C) with onset 1 to 4 days before presentation, and had resided in the trial area every night for the 10 days preceding the onset of illness.

Participants were not eligible if they had localizing symptoms suggestive of a specific diagnosis other than an arboviral (e.g., severe diarrhea, otitis, and pneumonia) or were enrolled in the trial within the previous 4 weeks. Procedures Participants provided demographic information, a geolocated residential address, and a detailed travel history for the 3 to 10 days before the onset of illness. A 3-ml venous blood sample was obtained for arboventolin diagnostic testing. No other diagnostic investigations were performed.

Participants were contacted 14 to 21 days after enrollment to obtain vital status and to determine whether they had been hospitalized since enrollment. No information on the clinical severity of VCD cases was collected, and no information on clinical diagnoses or severity of non-VCD cases was acquired. Diagnostic Investigations and Classifications Trial participants were classified as having VCD if the plasma sample obtained at enrollment was positive for DENV in a multiplex (DENV, chikungunya ventolin, and Zika ventolin) reverse-transcriptase–polymerase-chain-reaction (RT-PCR) assay or in an enzyme-linked immunosorbent assay (ELISA) for DENV nonstructural protein 1 (NS1) antigen (Platelia dengue NS1 [Bio-Rad]). Participants were classified as test-negative controls if the plasma sample obtained at enrollment was negative by RT-PCR for DENV, chikungunya ventolin, and Zika ventolin and also negative by ELISA capture assay for DENV NS1 antigen and dengue IgM and IgG.

The diagnostic algorithm is provided in Figure S4. The DENV serotype was determined with the use of a separate RT-PCR assay (Simplexa) by an independent laboratory at the Eijkman Institute, Jakarta. Details of the diagnostic methods are provided in the Supplementary Appendix. Primary, Secondary, and Safety End Points The primary end point was symptomatic VCD of any severity caused by any DENV serotype.

The secondary end points reported here are symptomatic VCD caused by each of the four DENV serotypes (DENV-1, DENV-2, DENV-3, and DENV-4) and symptomatic, virologically confirmed chikungunya and Zika ventolin s. Safety end points included hospitalization or death within 21 days after enrollment. Statistical Analysis The sample size that was needed to show a 50% lower incidence of dengue in the intervention clusters than in the control clusters, which was considered the minimum effect size for public health value, evolved over time. The full description of the sample-size calculations is provided in the Supplementary Appendix.

In brief, we determined that 400 cases of VCD and 1600 test-negative controls would be needed to give the trial 80% power to detect a 50% lower incidence of VCD among participants in intervention clusters than among those in control clusters. The emergence of severe acute respiratory syndrome asthma 2 in Yogyakarta in March 2020 prevented the continued recruitment of participants in clinics, and enrollment ended on March 18, 2020. On May 5, 2020, the trial steering committee endorsed the recommendation of the trial investigators to terminate the trial, at which time 385 participants with VCD had been enrolled. The statistical analysis plan was published previously22 and is available with the protocol.

The trial population used in the efficacy analysis included all enrolled participants with VCD and all test-negative controls, excluding participants who had been enrolled before the establishment of wolbachia throughout the intervention clusters (i.e., 1 month after the last release in the last cluster) and excluding test-negative controls who had been enrolled in a calendar month in which no dengue cases were observed among participants. The primary intention-to-treat analysis considered wolbachia exposure as a binary classification on the basis of residence in an intervention cluster or a control cluster. Residence was defined as the primary place of residence during the 10 days before illness onset. The intervention effect was estimated from an aggregate odds ratio comparing the exposure odds (residence in an intervention cluster) among participants with VCD with that among test-negative controls, with the use of the constrained permutation distribution as the foundation for inference.

The null hypothesis was that the odds of residence in an intervention cluster would be the same among participants with VCD as that among test-negative controls. The efficacy of the intervention was calculated as 100×(1−aggregate odds ratio). A prespecified exploratory analysis evaluated the efficacy of the intervention in preventing hospitalization with VCD. An additional prespecified cluster-level intention-to-treat analysis was performed by calculating the proportion of participants with VCD in each cluster.

The difference in the average proportions of participants with VCD between the intervention clusters and the control clusters was used to test the null hypothesis of no intervention effect (a t-test statistic) and to derive an estimate of the cluster-specific relative risk, with inference based on the constrained permutation distribution.23,24 The same methods used in the intention-to-treat analyses described above were used in the analyses for the secondary end point of serotype-specific efficacy. The analyses included participants with VCD caused by one of the four DENV serotypes and used the same control population as that used in the primary analysis. There was no prespecified plan to control for multiple testing in the analysis of secondary end points. Per-protocol analyses considered exposure contamination by assigning a wolbachia exposure index to each participant on the basis of the wMel prevalence in their cluster of residence only, or by combining this frequency with the participant’s recent travel history.

A generalized linear model was fitted, with balanced bootstrap resampling based on cluster residence, to estimate the relative risk of VCD and associated confidence interval in each quintile of wolbachia exposure, relative to the risk of VCD in participants in the bottom quintile of wolbachia exposure. Details are provided in the Supplementary Appendix..