Menu
FRUKDE
société des amis de Pasteur
" Jeunes gens ! Ne vous laissez pas atteindre par le scepticisme dénigrant et stérile, ne vous laissez pas décourager par les tristesses de certaines heures qui passent sur une nation ! "
  • Generic accupril prices

    Où rencontrer Pasteur dans Arbois

    Après les monuments dolois à l'effigie de Louis Pasteur, c'est au tour des sites arboisiens !
    Avec quelques anecdotes historiques en prime, Alain Marchal nous présente les statues, médaillons ou encore portraits qui honorent la mémoire de Louis Pasteur...

    > LIRE LA SUITE

  • [

    Accupril street price

    SOBRE NOTICIAS EN ESPAÑOLNoticias en español es accupril street price una sección de Kaiser Health News que contiene traducciones de artículos de gran interés para la comunidad hispanohablante, y contenido original can i get accupril over the counter enfocado en la población hispana que vive en los Estados Unidos. Use Nuestro Contenido Este contenido puede usarse de manera accupril street price gratuita (detalles). La temporada de influenza se verá diferente este año, ya que los Estados Unidos se enfrentan a una pandemia de coronavirus que ya ha matado a más de 176.000 personas.Muchos estadounidenses son reacios a ir al médico y los funcionarios de salud pública temen que las personas eviten vacunarse. Aunque a veces se considera incorrectamente como un resfriado, la gripe también mata a decenas de accupril street price miles de personas en el país cada año. Los más vulnerables son los niños pequeños, los adultos mayores y las personas con enfermedades subyacentes.

    Cuando se combina con los efectos de COVID-19, los expertos en salud pública dicen que es más importante que nunca vacunarse contra la gripe.Si una cantidad suficiente de la población se vacuna, más del 45% lo hizo la temporada de gripe pasada, podría ayudar a evitar un escenario de pesadilla este invierno, con hospitales llenos de pacientes con COVID-19 y los que sufren los efectos graves de la influenza.Además de la posible carga para los hospitales, existe la posibilidad de que las personas contraigan ambos virus y “nadie sabe qué sucede si se contrae influenza y COVID simultáneamente porque nunca sucedió antes”, dijo la doctora Rachel Levine, secretaria de Salud accupril street price de Pennsylvania, a reporteros.En respuesta, este año los fabricantes están produciendo más suministros de vacunas, entre 194 y 198 millones de dosis, unas 20 millones más de las que se distribuyeron la temporada pasada, según los Centros para el Control y Prevención de Enfermedades (CDC).Mientras se acerca la temporada de gripe, aquí hay algunas respuestas a preguntas frecuentes:P. ¿Cuándo debo vacunarme contra la gripe?. La publicidad ya ha comenzado accupril street price y algunas farmacias y clínicas ya tienen sus suministros. Pero, debido a que la efectividad de la vacuna puede disminuir con el tiempo, los CDC recomiendan no recibir la dosis en agosto.Muchas farmacias y clínicas comenzarán las inmunizaciones a principios de septiembre. Generalmente, los virus de la influenza comienzan a circular accupril street price a mediados o fines de octubre, pero se expanden masivamente más tarde, en el invierno.

    Se necesitan aproximadamente dos semanas después de recibir la inyección para que los anticuerpos, que circulan en la sangre y frustran las infecciones, se acumulen.“Las personas jóvenes y sanas pueden comenzar a vacunarse contra la gripe en septiembre, y las personas mayores y otras poblaciones vulnerables pueden hacerlo en octubre”, dijo el doctor Steve Miller, director clínico de la aseguradora Cigna.Los CDC recomiendan que las personas “se vacunen contra la influenza a fines de octubre”, pero señalaron que se puede recibir la vacuna más tarde porque “aún puede ser beneficiosas y la vacunación debe ofrecerse a lo largo de toda la temporada de influenza”.Aun así, algunos expertos recomiendan no esperar demasiado este año, no solo por COVID-19, sino también en caso de que haya escasez debido a la abrumadora demanda.P. ¿Cuáles son las razones por las que las que debería ofrecer mi brazo para vacunarme? accupril street price. Hay que vacunarse porque brinda protección contra la gripe y, por lo tanto, contra la propagación a otras personas, lo que puede ayudar a disminuir la carga para los hospitales y el personal médico.Y hay otro mensaje que puede resonar en estos tiempos extraños.“Le da a la gente la sensación de que hay algunas cosas que pueden controlar”, dijo Eduardo Sánchez, director médico de prevención de la American Heart Association.Si bien una vacuna contra la gripe no evitará COVID-19, recibirla podría ayudar al médico a diferenciar entre las dos enfermedades si se desarrolla algún síntoma (fiebre, tos, dolor de garganta) que ambas infecciones comparten, explicó Sánchez.Y aunque las vacunas contra la gripe no evitarán todos los casos de gripe, vacunarse puede reducir la gravedad si la persona se enferma, dijo.Todas las personas elegibles, especialmente los trabajadores esenciales, los que sufren de afecciones subyacentes y aquellos en mayor riesgo, incluidos los niños muy pequeños y las mujeres embarazadas, deben buscar protección, dijeron los CDC. La entidad accupril street price recomienda la vacunación a partir de los 6 meses.P. ¿Qué sabemos sobre la efectividad de la vacuna de este año?.

    Se deben producir nuevas vacunas contra la gripe cada año, porque el virus muta y la efectividad de la vacuna varía, dependiendo de qué tan bien coincida con el virus circulante.Se calculó que la formulación del año pasado tuvo una eficacia de aproximadamente un 45% para prevenir la gripe accupril street price en general, con una efectividad de aproximadamente un 55% en los niños. Las vacunas disponibles en el país este año tienen como objetivo prevenir al menos tres cepas diferentes del virus, y la mayoría cubre cuatro.Todavía no se sabe qué tan bien coincidirá el suministro de este año con las cepas que circularán en los Estados Unidos. Las primeras indicaciones del hemisferio sur, que atraviesa su temporada de gripe durante nuestro verano, son accupril street price alentadoras. Allí, las personas practicaron el distanciamiento social, usaron máscaras y se vacunaron en mayor número este año, y los niveles mundiales de gripe son más bajos de lo esperado. Sin embargo, expertos advierten que no se debe contar con una temporada igual de suave en los Estados Unidos, en parte porque accupril street price los esfuerzos por usar mascara facial y de distanciamiento social varían ampliamente.P.

    ¿Qué están haciendo diferente los seguros y sistemas de salud este año?. Las aseguradoras y los sistemas de salud contactados por KHN dicen que seguirán las pautas de los CDC, que exigen limitar accupril street price y espaciar la cantidad de personas que esperan en las filas y las áreas de vacunación. Algunos están programando citas para vacunas contra la gripe para ayudar a controlar el flujo.Health Fitness Concepts, una compañía que trabaja con UnitedHealth Group y otras empresas para establecer clínicas de vacunación contra la gripe en el noreste del país, dijo que está “fomentando eventos más pequeños y frecuentes para apoyar el distanciamiento social” y “exigiendo que se completen todos los formularios y arremangarse las camisas antes de entrar al área de vacunación contra la influenza”.Se requerirá que todos usen máscaras.Además, a nivel nacional, algunos grupos médicos contratados por UnitedHealth instalarán carpas, para que las inyecciones se puedan administrar al aire libre, dijo un vocero.Kaiser Permanente planifica las vacunas directamente en autos en algunos de sus centros médicos y está probando los procedimientos de detección y registro sin contacto en algunos lugares.Geisinger Health, un proveedor de salud regional en Pennsylvania y Nueva Jersey, dijo que también tendría programas de vacunación contra la influenza al aire libre en sus instalaciones.Además, “Geisinger exige que todos los empleados reciban la vacuna contra la influenza este año”, dijo Mark Shelly, director de prevención y control de infecciones del sistema. €œAl dar este paso, esperamos accupril street price transmitir a nuestros vecinos la importancia de la vacuna contra la influenza para todos”.P. Por lo general, me vacunan contra la gripe en el trabajo.

    ¿Seguirá siendo una accupril street price opción este año?. Con el objetivo de evitar riesgosas reuniones en interiores, muchos empleadores se muestran reacios a patrocinar las clínicas de gripe en oficinas como han ofrecido en años anteriores. Y con tanta gente que sigue trabajando desde casa, hay menos necesidad de llevar las vacunas contra la gripe al accupril street price lugar de trabajo. En cambio, muchos empleadores están alentando a los trabajadores a que reciban vacunas de sus médicos de atención primaria, en farmacias u otros entornos comunitarios. El seguro generalmente cubrirá el costo de la vacuna.Algunos empleadores están considerando ofrecer cupones para vacunas contra la gripe a sus trabajadores sin accupril street price seguro o a aquellos que no participan en el plan médico de la compañía, dijo Julie Stone, directora general de salud y beneficios de Willis Towers Watson, una firma consultora.Estos cupones podrían, por ejemplo, permitir a los trabajadores obtener la vacuna en un laboratorio en particular sin costo.Algunos empleadores están comenzando a pensar en cómo podrían usar sus estacionamientos para administrar vacunas contra la gripe enlos autos, dijo el doctor David Zieg, líder de servicios clínicos para el consultor de beneficios Mercer.Aunque la ley federal permite a los empleadores exigir a los empleados que se vacunen contra la gripe, ese paso generalmente lo toman solo los centros de atención médica y algunas universidades donde las personas viven y trabajan en estrecha colaboración, dijo Zieg.Pero sucede.

    El mes pasado, el sistema de la Universidad de California emitió una orden ejecutiva que requiere que todos los estudiantes, profesores y personal se vacunen contra la gripe antes del accupril street price 1 de noviembre, con limitadas excepciones.P. ¿Qué están haciendo las farmacias para alentar a las personas a vacunarse contra la gripe?. Algunas farmacias están haciendo un esfuerzo adicional para salir a la comunidad y ofrecer vacunas contra la gripe.Walgreens, que tiene casi 9,100 farmacias en todo el accupril street price país, continúa una asociación iniciada en 2015 con organizaciones comunitarias, iglesias y empleadores que ha ofrecido alrededor de 150,000 clínicas de gripe móviles hasta la fecha.El programa pone especial énfasis en trabajar con poblaciones vulnerables y en áreas desatendidas, dijo el doctor Kevin Ban, director médico de la cadena de farmacias.Walgreens comenzó a ofrecer vacunas contra la gripe a mediados de agosto y está animando a las personas a no demorar en vacunarse.Tanto Walgreens como CVS están estimulando a las personas a programar citas y hacer trámites en línea este año para minimizar el tiempo que pasan en los locales.En los CVS MinuteClinic, una vez que los pacientes se han registrado para recibir la vacuna contra la gripe, deben esperar afuera o en su automóvil, ya que las áreas de espera interiores ahora están cerradas.“No tenemos un arsenal contra COVID”, dijo Ban, de Walgreens. €œPero quitar la presión del sistema de atención médica proporcionando vacunas por adelantado es algo que sí podemos hacer”. Julie Appleby accupril street price.

    jappleby@kff.org, @Julie_Appleby Michelle Andrews. andrews.khn@gmail.com, @mandrews110 Related Topics Insurance Noticias En Español Public Health CDC COVID-19 Insurers VaccinesThis story was produced in partnership with PolitiFact accupril street price. This story can be republished for free (details). President Donald Trump accepted the Republican Party’s nomination for president in a 70-minute speech from the South Lawn of the White House on Thursday night.Speaking to a friendly crowd that didn’t appear to be observing social distancing conventions, and with few participants wearing masks, he touched on a range of topics, including many related to the COVID pandemic and health care in general.Throughout, the partisan crowd applauded and chanted “Four more years!. € And, accupril street price even as the nation’s COVID-19 death toll exceeded 180,000, Trump was upbeat. €œIn recent months, our nation and the entire planet has been struck by a new and powerful invisible enemy,” he said.

    €œLike those brave Americans before us, we are meeting this accupril street price challenge.”At the end of the event, there were fireworks.Our partners at PolitiFact did an in-depth fact check on Trump’s entire acceptance speech. Here are the highlights related to the administration’s COVID-19 response and other health policy issues:“We developed, from scratch, the largest and most advanced testing system in the world.” This is partially right, but it needs context.It’s accurate that the U.S. Developed its accupril street price COVID-19 testing system from scratch, because the government didn’t accept the World Health Organization’s testing recipe. But whether the system is the “largest” or “most advanced” is subject to debate.The U.S. Has tested more accupril street price individuals than any other country.

    But experts told us a more meaningful metric would be the percentage of positive tests out of all tests, indicating that not only sick people were getting tested. Another useful accupril street price metric would be the percentage of the population that has been tested. The U.S. Is one of the most populous countries but has tested a lower percentage of its population accupril street price than other countries. Don't Miss A Story Subscribe to KHN’s free Weekly Edition newsletter.

    The accupril street price U.S. Was also slower than other countries in rolling out tests and amping up testing capacity. Even now, many states are experiencing delays in reporting test results to positive individuals.As for “the most advanced,” Trump may be referring to new testing investments and systems, like Abbott’s recently announced $5, 15-minute rapid antigen test, which the company says will be about the size of a credit card, needs no instrumentation and comes with a phone app through which people can accupril street price view their results. But Trump’s comment makes it sound as if these testing systems are already in place when they haven’t been distributed to the public.“The United States has among the lowest [COVID-19] case fatality rates of any major country in the world. The European Union’s case fatality rate is accupril street price nearly three times higher than ours.”The case fatality rate measures the known number of cases against the known number of deaths.

    The European Union has a rate that’s about 2½ times greater than the United States.But the source of that data, Oxford University’s Our World in Data project, reports that “during an outbreak of a pandemic, the case fatality rate is a poor measure of the mortality risk of the disease.”A better way to measure the threat of the virus, experts say, is to look at the number of deaths per 100,000 residents. Viewed that way, the accupril street price U.S. Has the 10th-highest death rate in the world.“We will produce a vaccine before the end of the year, or maybe even sooner.”It’s far from guaranteed that a coronavirus vaccine will be ready before the end of the year.While researchers are making rapid strides, it’s not yet known precisely when the vaccine will be available to the public, which is what’s most important. Six vaccines are in the third phase of testing, which involves thousands accupril street price of patients. Like earlier phases, this one looks at the safety of a vaccine but also accupril street price examines its effectiveness and collects more data on side effects.

    Results of the third phase will be submitted to the Food and Drug Administration for approval.The government website Operation Warp Speed seems less optimistic than Trump, announcing it “aims to deliver 300 million doses of a safe, effective vaccine for COVID-19 by January 2021.”And federal health officials and other experts have generally predicted a vaccine will be available in early 2021. Federal committees are working on recommendations for vaccine distribution, including which groups should accupril street price get it first. €œFrom everything we’ve seen now — in the animal data, as well as the human data — we feel cautiously optimistic that we will have a vaccine by the end of this year and as we go into 2021,” said Dr. Anthony Fauci, the nation’s top accupril street price infectious diseases expert. €œI don’t think it’s dreaming.”“Last month, I took on Big Pharma.

    You think that is easy? accupril street price. I signed orders that would massively lower the cost of your prescription drugs.”Quite misleading. Trump signed four executive orders on July 24 aimed at lowering prescription drug accupril street price prices. But those orders haven’t taken effect yet — the text of one hasn’t even been made publicly available — and experts told us that, if implemented, the measures would be unlikely to result in significant drug price reductions for the majority of Americans.“We will always and very strongly protect patients with preexisting conditions, and that is a pledge from the entire Republican Party.”Trump’s pledge is undermined by his efforts to overturn the Affordable Care Act, the only law that guarantees people with preexisting conditions both receive health coverage and do not have to pay more for it than others do. In 2017, Trump supported congressional efforts to repeal the accupril street price ACA.

    The Trump administration is now backing GOP-led efforts to overturn the ACA through a court case. And Trump accupril street price has also expanded short-term health plans that don’t have to comply with the ACA.“Joe Biden recently raised his hand on the debate stage and promised he was going to give it away, your health care dollars to illegal immigrants, which is going to bring a massive number of immigrants into our country.”This is misleading. During a June 2019 Democratic primary debate, candidates were asked. €œRaise your hand if your government plan would provide coverage for undocumented immigrants.” All candidates on accupril street price stage, including Biden, raised their hands. They were not asked if that coverage would be free or subsidized.Biden supports extending health care access to all immigrants, regardless of immigration status.

    A task force recommended that he allow immigrants who are in the country illegally to buy health insurance, without federal subsidies.“Joe Biden claims he has empathy for the vulnerable, yet accupril street price the party he leads supports the extreme late-term abortion of defenseless babies right up to the moment of birth.”This mischaracterizes the Democratic Party’s stance on abortion and Biden’s position.Biden has said he would codify the Supreme Court’s ruling in Roe v. Wade and related precedents. This would generally limit abortions accupril street price to the first 20 to 24 weeks of gestation. States are allowed under court rulings to ban abortion after the point at which a fetus can sustain life, usually considered to be between 24 and 28 weeks from the mother’s last menstrual period — and 43 states do. But the accupril street price rulings require states to make exceptions “to preserve the life or health of the mother.” Late-term abortions are very rare, about 1%.The Democratic Party platform holds that “every woman should have access to quality reproductive health care services, including safe and legal abortion — regardless of where she lives, how much money she makes, or how she is insured.” It does not address late-term abortion.PolitiFact’s Daniel Funke, Jon Greenberg, Louis Jacobson, Noah Y.

    Kim, Bill McCarthy, Samantha Putterman, Amy Sherman, Miriam Valverde and KHN reporter Victoria Knight contributed to this report. Related Topics Elections Health Industry Pharmaceuticals Public Health The Health Law Abortion COVID-19 Immigrants KHN accupril street price &. PolitiFact HealthCheck Preexisting Conditions Trump Administration VaccinesThis story also ran on CNN. This story can be republished for free (details). Flu season will look different this year, as the country grapples with a coronavirus pandemic that has killed more than 172,000 people. Many Americans are reluctant to visit a doctor’s office and public health officials worry people will accupril street price shy away from being immunized.Although sometimes incorrectly regarded as just another bad cold, flu also kills tens of thousands of people in the U.S. Each year, with the very young, the elderly and those with underlying conditions the most vulnerable.

    When coupled with the effects of COVID-19, public health experts say it’s more accupril street price important than ever to get a flu shot.If enough of the U.S. Population gets vaccinated — more than the 45% who did last flu season — it could help head off a nightmare scenario in the coming winter of hospitals stuffed with both COVID-19 patients and those suffering from severe effects of influenza.Aside from the potential burden on hospitals, there’s the possibility people could get both viruses — and “no one knows what happens if you get influenza and COVID [simultaneously] because it’s never happened before,” Dr. Rachel Levine, Pennsylvania’s secretary of health, told reporters this month.In response, manufacturers are producing accupril street price more vaccine supply this year, between 194 million and 198 million doses, or about 20 million more than they distributed last season, according to the Centers for Disease Control and Prevention. Email Sign-Up Subscribe accupril street price to KHN’s free Morning Briefing. As flu season approaches, here are some answers to a few common questions:Q.

    When should accupril street price I get my flu shot?. Advertising has already begun, and some pharmacies and clinics have their supplies now. But, because the effectiveness of the vaccine can wane over time, the CDC recommends against a shot in August.Many pharmacies and clinics will start immunizations in early September accupril street price. Generally, influenza viruses start circulating in mid- to late October but become more widespread later, in the winter. It takes about two weeks after getting a shot accupril street price for antibodies — which circulate in the blood and thwart infections — to build up.

    €œYoung, healthy people can begin getting their flu shots in September, and elderly people and other vulnerable populations can begin in October,” said Dr. Steve Miller, chief clinical officer for insurer Cigna.The CDC has recommended that people “get a accupril street price flu vaccine by the end of October,” but noted it’s not too late to get one after that because shots “can still be beneficial and vaccination should be offered throughout the flu season.”Even so, some experts say not to wait too long this year — not only because of COVID-19, but also in case a shortage develops because of overwhelming demand.Q. What are the reasons I should roll up my sleeve for this?. Get a shot because it protects you from catching the flu and spreading it to others, which may help lessen the burden on hospitals and medical staffs.And there’s another message that may resonate in this strange time.“It gives people a sense that there are some things you can control,” said Eduardo Sanchez, chief medical officer for prevention at the American Heart Association.While a flu shot won’t prevent accupril street price COVID-19, he said, getting one could help your doctors differentiate between the diseases if you develop any symptoms — fever, cough, sore throat — they share.And even though flu shots won’t prevent all cases of the flu, getting vaccinated can lessen the severity if you do fall ill, he said.You cannot get influenza from having a flu vaccine.All eligible people, especially essential workers, those with underlying conditions and those at higher risk — including very young children and pregnant women — should seek protection, the CDC said. It recommends that children over 6 months old get vaccinated.Q.

    What do we accupril street price know about the effectiveness of this year’s vaccine?. Flu vaccines — which must be developed anew each year because influenza viruses mutate — range in effectiveness annually, depending on how well they match the circulating virus. Last year’s formulation was estimated to be about 45% accupril street price effective in preventing the flu overall, with about a 55% effectiveness in children. The vaccines available in the U.S. This year are aimed accupril street price at preventing at least three strains of the virus, and most cover four.It isn’t yet known how well this year’s supply will match the strains that will circulate in the U.S.

    Early indications from the Southern Hemisphere, which goes through its flu season during our summer, are encouraging. There, people accupril street price practiced social distancing, wore masks and got vaccinated in greater numbers this year — and global flu levels are lower than expected. Experts caution, however, not to count on a similarly mild season in the U.S., in part because masking and social distancing efforts vary widely.Q. What are insurance plans and health systems doing accupril street price differently this year?. Insurers and health systems contacted by KHN say they will follow CDC guidelines, which call for limiting and spacing out the number of people waiting in lines and vaccination areas.

    Some are setting appointments for flu shots to help manage the flow.Health Fitness Concepts, a company that works with UnitedHealth Group and other businesses to set up flu shot clinics in the Northeast, said it is “encouraging smaller, more frequent events to support social distancing” and “requiring all forms to be completed and shirtsleeves rolled up before entering the flu shot area.” Everyone will be required to wear masks.Also, nationally, some physician groups contracted with UnitedHealth will set up tent areas so shots can be given outdoors, a spokesperson said.Kaiser Permanente plans drive-thru vaccinations at some of its medical accupril street price facilities and is testing touch-free screening and check-in procedures at some locations. (KHN is not affiliated with Kaiser Permanente.)Geisinger Health, a regional health provider in Pennsylvania and New Jersey, said it, too, would have outdoor flu vaccination programs at its facilities.Additionally, “Geisinger is making it mandatory for all employees to receive the flu vaccine this year,” said Mark Shelly, the system’s director of infection prevention and control. €œBy taking accupril street price this step, we hope to convey to our neighbors the importance of the flu vaccine for everyone.”Q. Usually I get a flu shot at work. Will that accupril street price be an option this year?.

    Aiming to avoid risky indoor gatherings, many employers are reluctant to sponsor the on-site flu clinics they’ve offered in years past. And with so many people continuing to work from home, accupril street price there’s less need to bring flu shots to employees on the job. Instead, many employers are encouraging workers to get shots from their primary care doctors, at accupril street price pharmacies or in other community settings. Insurance will generally cover the cost of the vaccine.Some employers are considering offering vouchers for flu shots to their uninsured workers or those who don’t participate in the company plan, said Julie Stone, managing director for health and benefits at Willis Towers Watson, a consulting firm. The vouchers could allow workers to get the shot at a particular lab at no cost, for example.Some employers are starting to think about how they might use their parking lots for administering accupril street price drive-thru flu shots, said Dr.

    David Zieg, clinical services leader for benefits consultant Mercer.Although federal law allows employers to require employees to get flu shots, that step is typically taken only by health care facilities and some universities where people live and work closely together, Zieg said.Q. What are pharmacies accupril street price doing to encourage people to get flu shots?. Some pharmacies are making an extra push to get out into the community to offer flu shots.Walgreens, which has nearly 9,100 pharmacies nationwide, is continuing a partnership begun in 2015 with community organizations, churches and employers that has offered about 150,000 off-site and mobile flu clinics to date.The program places a special emphasis on working with vulnerable populations and in underserved areas, said Dr. Kevin Ban, chief medical officer for the drugstore chain.Walgreens began offering flu shots in mid-August and is encouraging people not accupril street price to delay getting vaccinated.Both Walgreens and CVS are encouraging people to schedule appointments and do paperwork online this year to minimize time spent in the stores.At CVS MinuteClinic locations, once patients have checked in for their flu shot, they must wait outside or in their car, since the indoor waiting areas are now closed.“We don’t have tons of arrows in our quiver against COVID,” Walgreens’ Ban said. €œTaking pressure off the health care system by providing vaccines in advance is one thing we can do.” Julie Appleby.

    jappleby@kff.org, @Julie_Appleby Michelle accupril street price Andrews. andrews.khn@gmail.com, @mandrews110 Related Topics Insurance Public Health CDC COVID-19 Insurers VaccinesUse Our Content This story can be republished for free (details). As the smoke thickened near her home in Santa Cruz, California, last week, Amanda Smith kept asking herself the same questions. Should we accupril street price leave?. And where would we go?. The wildfire accupril street price evacuation zone, at the time, ended a few blocks from her house.

    But she worried about what the air quality — which had reached the second-highest warning level, purple for “very unhealthy” — would do to her children’s lungs. Her 4-year-old twins had spent time in the neonatal accupril street price intensive care unit. One was later diagnosed with asthma, and last year was hospitalized with pneumonia.By Tuesday, said Smith, “we all had headaches, the kids were coughing a little bit, and it was raining ash.” The family had been conscientiously isolating at home because of the COVID pandemic, and leaving meant potential exposures. But on Wednesday, Smith said, “I looked at my partner and said, maybe we should leave.”She called a friend in Orange County, about 380 miles south, who accupril street price offered her parents’ empty condo. But the next day, the friend’s child spiked a fever — a possible case of COVID-19 — and the plan fell through amid the distraction.Amanda Smith takes a selfie of herself and her twin children in Santa Cruz, California, in April.

    (Amanda Smith)So Smith looked on Airbnb, careful to seek out hosts who detailed their COVID accupril street price precautions, and found an apartment in San Bruno, about an hour’s drive north. She stuffed photos and documents into a suitcase, grabbed the go-bags, and her family headed out.“It’s coming out of our savings to stay here,” Smith said from the safety of her apartment rental, which runs about $1,150 a week. €œIt was accupril street price a really fraught decision to leave, but as soon as we got over the hill and the sky was blue, I took a big sigh of relief and knew that it had been a good decision.”As the twin disasters of COVID-19 and fire season sweep through California, thousands of residents like Smith are weighing difficult options, pitting risk against risk as they decide where to evacuate, whether from imminent flames or the toxic air. Amid a virulent pandemic, which is safest?. Doubling up at a friend’s accupril street price home?.

    A hotel?. An accupril street price evacuation center?. And when do the risks of smoke inhalation outweigh the risk of a deadly infection?. €œObviously the most important thing is for people to do what they can to protect their lives, not only from the fire, but also accupril street price from COVID,” said Detective Rosemerry Blankswade, public information officer for the San Mateo County Sheriff’s Office, which is helping coordinate response to the massive CZU Lightning Complex fires.“You have to evaluate the big picture here. If fire is your most imminent danger, maybe take the COVID risk.

    But if you can avoid both accupril street price of them, that’s obviously going to be the best option. It’s kind accupril street price of a little bit of triage that we’re asking for people to do in their own lives right now.” Email Sign-Up Subscribe to KHN’s free Morning Briefing. In San Mateo, one of two counties where the CZU Lightning Complex fires are blazing, officials are advising people to head to an evacuation center, where county workers will assist them in finding a hotel room. Meanwhile, in neighboring Santa Cruz, where tens of thousands of residents have evacuated and shelters have limited space, officials are asking those under orders to leave accupril street price to stay with family and friends whenever possible.What’s the right choice when all options pose additional risks?. We spoke with several experts to help guide your thought process.You have to evacuate.

    Where should you accupril street price go?. If your region is under an evacuation order, do not hesitate. Leave immediately accupril street price. If you can afford it, booking a room at a hotel or motel outside the evacuation zones may be the best option, said Dr. Michael Wilkes, a professor at the University of California-Davis School accupril street price of Medicine.

    They almost always have air-conditioning units, which help filter the air from both smoke and virus. Many hotels accupril street price are implementing new cleaning processes. Ask staffers to detail what they’re doing to sanitize rooms, and consider skipping the daily cleaning service during your stay. You might also check review sites such as TripAdvisor to accupril street price see what other guests report. When possible, avoid the lobby and other shared spaces, and opt for contactless check-in.Amanda Smith at home in Santa Cruz, California, with her twin children.

    Smith and her accupril street price family decided to voluntarily evacuate their home on Aug. 20, due to heavy smoke in the area from the CZU Lightning Complex fires in the nearby Santa Cruz Mountains. (Anna Maria Barry-Jester/KHN)With so many accupril street price people in Northern California fleeing the fires, many hotels are already full, especially in more remote areas. So what about staying with family or friends?. After months of being shut in and avoiding close contact beyond immediate family, moving into someone else’s accupril street price home means a host of potential exposures.

    Consider whether you or anyone else in the home is at high risk from COVID-19 because of age or a preexisting condition.“If so, that’s a reason to think twice before going to someone’s home,” said Dr. Gina Solomon, a program director at the Oakland-based Public Health Institute.Consider, too, what precautions your friends or family have accupril street price been taking. Sheltering with someone whose job brings them into frequent contact with other people may not be as safe as sheltering with people who largely have been staying home. Another question accupril street price is how crowded the home is. If you have your own room and, preferably, your own bathroom, that makes staying with friends a better option.

    If a separate bedroom is not available and smoky skies are not a problem, you might consider pitching a tent in their backyard.For those with an RV or tent, camping can present another good option — although, with hundreds of wildfires burning across accupril street price California, it may be challenging to drive far enough away to avoid fire and smoke. If you do camp, try to find a site away from wooded areas. And think accupril street price twice before using group bathrooms.Is an evacuation center safe?. Many counties have implemented new precautions at emergency shelters to prevent the spread of the coronavirus. In Santa Cruz, for example, officials are scaling back the capacity in each shelter to allow for social distancing, providing tents for people to use accupril street price as shielding inside and allowing camping in the parking lots.Still, staying in a shelter should probably not be your first choice.

    In terms of COVID risk, deciding between a accupril street price hotel and a friend’s house is “nipping at the edges,” said Dr. John Swartzberg, a clinical professor emeritus at the UC-Berkeley School of Public Health, while “being in a congregate setting is only better than being completely exposed to the elements.”If an evacuation shelter is your best immediate option, again, do not hesitate. €œYou have these standards you want to practice for yourselves,” Swartzberg said, “but when something worse comes along, it trumps how careful we can be with COVID because the need for shelter is greater.” You can lower your risk of infection by wearing a mask, washing hands frequently and sanitizing surfaces.Smith’s partner, Grant Whipple, walks with their children in Big Sur accupril street price on March 7. That was their last camping trip before the COVID-19 pandemic hit, Smith says. That area is now under threat from accupril street price wildfire.

    (Amanda Smith)If you aren’t in a fire zone, should you invite friends and family to stay with you?. Deciding whether to open your home to friends who are evacuating is an intensely personal decision and may depend on whether anyone in your family has a preexisting condition.“I accupril street price guess it depends on how good a friend they are and how desperate they are,” said Swartzberg. It may also depend on how much space you have. If your guests can have their own bedroom and bathroom, it might be safer.If you do offer your home, experts advise accupril street price against simply considering yourself a new pod with your guests. Instead, take steps to lower your chances of infection.“It might not be pleasant, but wearing a mask anytime you’re not in your own bedroom is the safest way to go,” said Solomon.

    Stay outside as much as possible, she added, and consider eating meals outdoors or eating in shifts to avoid being maskless with those outside your accupril street price family unit. Sanitize surfaces and wash hands frequently. If air quality permits, keep the windows open to improve airflow.If you’re in a region with accupril street price hazardous smoke conditions, should you leave?. If your area has dense smoke but no imminent fire risk, the thought of heading somewhere else may be appealing, especially if you have respiratory issues. But in most cases, Wilkes said, it accupril street price would be safer not to leave your COVID bubble.

    And given the expanse of California’s fires, anywhere you flee could end up having lousy air quality by the time you arrive.“The better part of rationality,” Wilkes said, “would be to stay at home, not exercise [outdoors], stay inside as much as you can, turn on the air conditioning.”California Healthline senior correspondent Anna Maria Barry-Jester contributed to this report. Jenny accupril street price Gold. jgold@kff.org, @JennyAGold Related Topics California Public Health States COVID-19 Environmental Health Natural DisastersIn the 2014 elections, Republicans rode a wave of anti-Affordable Care Act sentiment to pick up nine Senate seats, the largest gain for either party since 1980. Newly elected Republicans such as Cory Gardner in Colorado accupril street price and Steve Daines in Montana had hammered their Democratic opponents over the health care law during the campaign and promised to repeal it.Six years later, those senators are up for reelection. Not only is the law still around, but it’s gaining in popularity.

    What was once a winning strategy has become a political liability.Public sentiment about the ACA, accupril street price also known as Obamacare, has shifted considerably during the Trump administration after Republicans tried but failed to repeal it. Now, in the midst of the COVID-19 pandemic and the ensuing economic crisis, which has led to the loss of jobs and health insurance for millions of people, health care again looks poised to be a key issue for voters this election. Don't Miss A Story Subscribe accupril street price to KHN’s free Weekly Edition newsletter. With competitive races in Colorado, Montana, Arizona, North Carolina and Iowa pitting Republican incumbents who voted to repeal the ACA against Democratic challengers promising to protect it, attitudes surrounding the health law could help determine control of the Senate. Republicans hold a slim three-vote majority in the Senate but are defending 23 seats in accupril street price the Nov.

    3 election. Only one Democratic Senate seat — in Alabama, where incumbent Doug Jones is up against former Auburn University football coach Tommy Tuberville — is considered in play for Republicans.“The fall election will significantly revolve around people’s belief about what [candidates] will do for their health coverage,” accupril street price said Dr. Daniel Derksen, a professor of public health at the University of Arizona.The Affordable Care Act has been a wedge issue since it was signed into law in 2010. Because it then took four years to enact, its opponents talked for years accupril street price about how bad the not-yet-created marketplace for insurance would be, said Joe Hanel, spokesperson for the Colorado Health Institute, a nonpartisan nonprofit focused on health policy analysis. And they continued to attack the law as it took full effect in 2014.Gardner, for example, ran numerous campaign ads that year criticizing the ACA and, in particular, President Barack Obama’s assertion that “if you like your health care plan, you’ll be able to keep your health care plan.”But now, Hanel said, the ACA’s policies have become much more popular in accupril street price Colorado as the costs of health exchange plans have dropped.

    Thus, political messaging has changed, too.“This time it’s the opposite,” Hanel said. €œThe people bringing up the Affordable Care Act are the Democrats.”Despite Gardner’s multiple votes to repeal the accupril street price ACA, he has largely avoided talking about the measure during the 2020 campaign. He even removed his pro-repeal position from his campaign website.Democratic attack ads in July blasted Gardner for repeatedly dodging questions in an interview with Colorado Public Radio about his stance on a lawsuit challenging the ACA.His opponent, Democrat John Hickenlooper, fully embraced the law when he was Colorado governor, using the measure to expand Medicaid eligibility to more low-income people and to create a state health insurance exchange. Now, he’s campaigning on that record, with promises to expand health care access even further.Polling DataPolling conducted by KFF for the past 10 years shows a shift in public opinion has occurred nationwide accupril street price. (KHN is an editorially independent program of KFF, the Kaiser Family Foundation.)“Since Trump won the election in 2016, we now have consistently found that a larger share of the public holds favorable views” of the health law, said Ashley Kirzinger, associate director of public opinion and survey research for the foundation.

    €œThis really solidified in 2017 after the failed accupril street price repeal in the Senate.”The foundation’s polling found that, in July 2014, 55% of voters opposed the law, while 36% favored it. By July 2020, that had flipped, with 51% favoring the law and 38% opposing it. A shift was seen across all political groups, though 74% of Republicans still viewed it unfavorably in the latest poll.Public accupril street price support for individual provisions of the ACA — such as protections for people with preexisting conditions or allowing young adults to stay on their parents’ health plans until age 26 — have proved even more popular than the law as a whole. And the provision that consistently polled unfavorably — the mandate that those without insurance must pay a fine — was eliminated in 2017.“We’re 10 years along and the sky hasn’t caved in,” said Sabrina Corlette, a health policy professor at Georgetown University.Political MessagingFollowing the passage of the ACA, Democrats didn’t reference the law in their campaigns, said Erika Franklin Fowler, a government professor at Wesleyan University and the director of the Wesleyan Media Project, which tracks political advertising.“They ran on any other issue they could find,” Fowler said.Republicans, she said, kept promising to “repeal and replace” but weren’t able to do so.Then, in the 2018 election, Democrats seized on the shift in public opinion, touting the effects of the law and criticizing Republicans for their attempts to overturn it.“In the decade I have been tracking political advertising, there wasn’t a single-issue topic that was as prominent as health care was in 2018,” she said.As the global health crisis rages, health care concerns again dominate political ads in the 2020 races, Fowler said, although most ads haven’t explicitly focused on the ACA. Many highlight accupril street price Republicans’ support for the lawsuit challenging preexisting condition protections or specific provisions of the ACA that their votes would have overturned.

    Republicans say they, too, will protect people with preexisting conditions but otherwise have largely avoided talking about the ACA.“Cory Gardner has been running a lot on his environmental bills and conservation funding,” Fowler said. €œIt’s not difficult to figure out why he’s doing that. It’s easier for him to tout that in a state like Colorado than it is to talk about health care.”Similar dynamics are playing out in other key Senate races. In Arizona, Republican Sen. Martha McSally was one of the more vocal advocates of repealing the ACA while she served in the House of Representatives.

    She publicly acknowledged those votes may have hurt her 2018 Senate bid.“I did vote to repeal and replace Obamacare,” McSally said on conservative pundit Sean Hannity’s radio show during the 2018 campaign. €œI’m getting my ass kicked for it right now.”She indeed lost but was appointed to fill the seat of Sen. Jon Kyl after he resigned at the end of 2018. Now McSally is in a tight race with Democratic challenger Mark Kelly, an astronaut and the husband of former Rep. Gabby Giffords.“Kelly doesn’t have a track record of voting one way or another, but certainly in his campaign this is one of his top speaking points.

    What he would do to expand coverage and reassure people that coverage won’t be taken away,” said Derksen, the University of Arizona professor.The ACA has proved a stumbling block for Republican Sens. Thom Tillis of North Carolina and Joni Ernst of Iowa. In Maine, GOP Sen. Susan Collins cast a key vote that prevented the repeal of the law but cast other votes that weakened it. She now also appears vulnerable — but more for her vote to confirm Brett Kavanaugh’s nomination to the Supreme Court and for not doing more to oppose President Donald Trump.In Montana, Daines, who voted to repeal the ACA, is trying to hold on to his seat against Democratic Gov.

    Steve Bullock, who used the law to expand the state’s Medicaid enrollment in 2015. At its peak, nearly 1 in 10 Montanans were covered through the expansion.As more Montanans now face the high cost of paying for health care on their own amid pandemic-related job losses, Montana State University political science professor David Parker said he expects Democrats to talk about Daines’ votes to repeal cost-saving provisions of the ACA.“People are losing jobs, and their jobs bring health care with them,” Parker said. €œI don’t think it’s a good space for Daines to be right now.” Markian Hawryluk. MarkianH@kff.org, @MarkianHawryluk Related Topics Elections Health Care Costs Health Care Reform Insurance States Arizona Colorado Montana North Carolina Obamacare Plans.

    Generic accupril prices

    Accupril
    Co amoxiclav
    Retrovir
    Baycip
    Septra
    Buy with visa
    Consultation
    Ask your Doctor
    Ask your Doctor
    Australia pharmacy price
    $
    $
    300mg 20 tablet $135.00
    $
    $
    Where can you buy
    Yes
    Online
    No
    Yes
    No
    Cheapest price
    Ask your Doctor
    You need consultation
    Ask your Doctor
    You need consultation
    You need consultation

    Publisher. PLOS ONE Oct 15, 2020 Authors Keith Kranker, Sarah Bardin, So O’Neil, and Dara Lee Luca ObjectivesUnintended (mistimed or unwanted) pregnancies occur frequently in the United States and have negative effects. When designing prevention programs and intervention strategies for the provision of comprehensive birth control methods, it is necessary to identify (1) populations at high risk of unintended pregnancy, and (2) geographic areas with a concentration of need.MethodsTo estimate the proportion and incidence of unintended births and pregnancies for regions in Missouri, two machine-learning prediction models were developed using data from the National Survey of Family Growth and the Missouri Pregnancy Risk Assessment Monitoring System. Each model was applied to Missouri birth certificate data from 2014 to 2016 to estimate the number of unintended births and pregnancies across regions in Missouri. Population sizes from the American Community Survey were incorporated to estimate the incidence of unintended births and pregnancies.ResultsAbout 24,500 (34.0%) of the live births in Missouri each year were estimated to have resulted from unintended pregnancies.

    About 25 per 1,000 women (ages 15 to 45) annually. Further, 40,000 pregnancies (39.7%) were unintended each year. About 41 per 1,000 women annually. Unintended pregnancy was concentrated in Missouri’s largest urban areas, and annual incidence varied substantially across regions.ConclusionsOur proposed methodology was feasible to implement. Random forest modeling identified factors in the data that best predicted unintended birth and pregnancy and outperformed other approaches.

    Maternal age, marital status, health insurance status, parity, and month that prenatal care began predict unintended pregnancy among women with a recent live birth. Using this approach to estimate the rates of unintended births and pregnancies across regions within Missouri revealed substantial within-state variation in the proportion and incidence of unintended pregnancy. States and other agencies could use this study’s results or methods to better target interventions to reduce unintended pregnancy or address other public health needs..

    Publisher. PLOS ONE Oct 15, 2020 Authors Keith Kranker, Sarah Bardin, So O’Neil, and Dara Lee Luca ObjectivesUnintended (mistimed or unwanted) pregnancies occur frequently in the United States and have negative effects. When designing prevention programs and intervention strategies for the provision of comprehensive birth control methods, it is necessary to identify (1) populations at high risk of unintended pregnancy, and (2) geographic areas with a concentration of need.MethodsTo estimate the proportion and incidence of unintended births and pregnancies for regions in Missouri, two machine-learning prediction models were developed using data from the National Survey of Family Growth and the Missouri Pregnancy Risk Assessment Monitoring System. Each model was applied to Missouri birth certificate data from 2014 to 2016 to estimate the number of unintended births and pregnancies across regions in Missouri.

    Population sizes from the American Community Survey were incorporated to estimate the incidence of unintended births and pregnancies.ResultsAbout 24,500 (34.0%) of the live births in Missouri each year were estimated to have resulted from unintended pregnancies. About 25 per 1,000 women (ages 15 to 45) annually. Further, 40,000 pregnancies (39.7%) were unintended each year. About 41 per 1,000 women annually.

    Unintended pregnancy was concentrated in Missouri’s largest urban areas, and annual incidence varied substantially across regions.ConclusionsOur proposed methodology was feasible to implement. Random forest modeling identified factors in the data that best predicted unintended birth and pregnancy and outperformed other approaches. Maternal age, marital status, health insurance status, parity, and month that prenatal care began predict unintended pregnancy among women with a recent live birth. Using this approach to estimate the rates of unintended births and pregnancies across regions within Missouri revealed substantial within-state variation in the proportion and incidence of unintended pregnancy.

    States and other agencies could use this study’s results or methods to better target interventions to reduce unintended pregnancy or address other public health needs..

    Can you buy over the counter accupril

    To the can you buy over the counter accupril web link Editor. Rapid and accurate diagnostic tests are essential for controlling the ongoing can you buy over the counter accupril Covid-19 pandemic. Although the current standard involves testing of nasopharyngeal swab specimens by quantitative reverse-transcriptase polymerase chain reaction (RT-qPCR) to detect SARS-CoV-2, saliva specimens may be an alternative diagnostic sample.1-4 Rigorous evaluation is needed to determine how saliva specimens compare with nasopharyngeal swab specimens with respect to sensitivity in detection of SARS-CoV-2 during the course of infection. A total of 70 inpatients with Covid-19 provided written informed consent to participate in our study (see the Methods section in Supplementary Appendix 1, available with the can you buy over the counter accupril full text of this letter at NEJM.org).

    After Covid-19 was confirmed with a positive nasopharyngeal swab specimen at hospital admission, we obtained additional samples from the patients during hospitalization. We tested saliva specimens collected by the patients themselves and nasopharyngeal swabs collected from the patients at the same time point by health can you buy over the counter accupril care workers. Figure 1 can you buy over the counter accupril. Figure 1.

    SARS-CoV-2 RNA Titers in Saliva can you buy over the counter accupril Specimens and Nasopharyngeal Swab Specimens. Samples were obtained from 70 hospital inpatients who had a diagnosis of Covid-19. Panel A shows SARS-CoV-2 RNA titers in the first available nasopharyngeal and can you buy over the counter accupril saliva samples. The lines indicate samples from the same patient.

    Results were compared can you buy over the counter accupril with the use of a Wilcoxon signed-rank test (P<0.001). Panel B shows percentages of positivity for SARS-CoV-2 in tests of the first matched nasopharyngeal and saliva samples at 1 to 5 days, 6 to 10 days, and can you buy over the counter accupril 11 or more days (maximum, 53 days) after the diagnosis of Covid-19. Panel C shows longitudinal SARS-CoV-2 RNA copies per milliliter in 97 saliva samples, according to days since symptom onset. Each circle represents a separate sample can you buy over the counter accupril.

    Dashed lines indicate additional samples from the same patient. The red line indicates a negative saliva sample that was followed by a positive sample at the next collection of a specimen can you buy over the counter accupril. Panel D shows longitudinal SARS-CoV-2 RNA copies per milliliter in 97 nasopharyngeal swab specimens, according to can you buy over the counter accupril days since symptom onset. The red lines indicate negative nasopharyngeal swab specimens there were followed by a positive swab at the next collection of a specimen.

    The gray area in Panels C and D indicates samples that were below the lower limit of detection of 5610 virus RNA copies per milliliter can you buy over the counter accupril of sample, which is at cycle threshold 38 of our quantitative reverse-transcriptase polymerase chain reaction assay targeting the SARS-CoV-2 N1 sequence recommended by the Centers for Disease Control and Prevention. To analyze these data, we used a linear mixed-effects regression model (see Supplementary Appendix 1) that accounts for the correlation between samples collected from the same person at a single time point (i.e., multivariate response) and the correlation between samples collected across time from the same patient (i.e., repeated measures). All the data used to generate this figure, including the raw cycle thresholds, are provided in Supplementary Data 1 in Supplementary Appendix 2.Using primer sequences from the Centers can you buy over the counter accupril for Disease Control and Prevention, we detected more SARS-CoV-2 RNA copies in the saliva specimens (mean log copies per milliliter, 5.58. 95% confidence interval [CI], 5.09 to 6.07) than in the nasopharyngeal swab specimens (mean log copies per milliliter, 4.93.

    95% CI, 4.53 to can you buy over the counter accupril 5.33) (Figure 1A, and Fig. S1 in can you buy over the counter accupril Supplementary Appendix 1). In addition, a higher percentage of saliva samples than nasopharyngeal swab samples were positive up to 10 days after the Covid-19 diagnosis (Figure 1B). At 1 to can you buy over the counter accupril 5 days after diagnosis, 81% (95% CI, 71 to 96) of the saliva samples were positive, as compared with 71% (95% CI, 67 to 94) of the nasopharyngeal swab specimens.

    These findings suggest that saliva specimens and nasopharyngeal swab specimens have at least similar sensitivity in the detection of SARS-CoV-2 during the course of hospitalization. Because the results of testing of nasopharyngeal swab specimens to detect SARS-CoV-2 may vary with repeated sampling in individual patients,5 we evaluated viral detection in matched samples can you buy over the counter accupril over time. The level of SARS-CoV-2 RNA decreased after symptom onset in both saliva specimens (estimated slope, −0.11. 95% credible interval, −0.15 to −0.06) (Figure 1C) and nasopharyngeal can you buy over the counter accupril swab specimens (estimated slope, −0.09.

    95% credible interval, −0.13 can you buy over the counter accupril to −0.05) (Figure 1D). In three instances, a negative nasopharyngeal swab specimen was followed by a positive swab at the next collection of a specimen (Figure 1D). This phenomenon occurred only once with the saliva can you buy over the counter accupril specimens (Figure 1C). During the clinical course, we observed less variation in levels of SARS-CoV-2 RNA in the saliva specimens (standard deviation, 0.98 virus RNA copies per milliliter.

    95% credible interval, 0.08 to 1.98) than in the nasopharyngeal swab specimens (standard deviation, 2.01 virus RNA can you buy over the counter accupril copies per milliliter. 95% credible interval, 1.29 to 2.70) (see Supplementary Appendix can you buy over the counter accupril 1). Recent studies have shown that SARS-CoV-2 can be detected in the saliva of asymptomatic persons and outpatients.1-3 We therefore screened 495 asymptomatic health care workers who provided written informed consent to participate in our prospective study, and we used RT-qPCR to test both saliva and nasopharyngeal samples obtained from these persons. We detected SARS-CoV-2 RNA in saliva specimens obtained from 13 persons who did not report any symptoms at or before the time of can you buy over the counter accupril sample collection.

    Of these 13 health care workers, 9 had collected matched nasopharyngeal swab specimens by themselves on the same day, and 7 of these specimens tested negative (Fig. S2). The diagnosis in the 13 health care workers with positive saliva specimens was later confirmed in diagnostic testing of additional nasopharyngeal samples by a CLIA (Clinical Laboratory Improvement Amendments of 1988)–certified laboratory. Variation in nasopharyngeal sampling may be an explanation for false negative results, so monitoring an internal control for proper sample collection may provide an alternative evaluation technique.

    In specimens collected from inpatients by health care workers, we found greater variation in human RNase P cycle threshold (Ct) values in nasopharyngeal swab specimens (standard deviation, 2.89 Ct. 95% CI, 26.53 to 27.69) than in saliva specimens (standard deviation, 2.49 Ct. 95% CI, 23.35 to 24.35). When health care workers collected their own specimens, we also found greater variation in RNase P Ct values in nasopharyngeal swab specimens (standard deviation, 2.26 Ct.

    95% CI, 28.39 to 28.56) than in saliva specimens (standard deviation , 1.65 Ct. 95% CI, 24.14 to 24.26) (Fig. S3). Collection of saliva samples by patients themselves negates the need for direct interaction between health care workers and patients.

    This interaction is a source of major testing bottlenecks and presents a risk of nosocomial infection. Collection of saliva samples by patients themselves also alleviates demands for supplies of swabs and personal protective equipment. Given the growing need for testing, our findings provide support for the potential of saliva specimens in the diagnosis of SARS-CoV-2 infection. Anne L.

    Wyllie, Ph.D.Yale School of Public Health, New Haven, CT [email protected]John Fournier, M.D.Yale School of Medicine, New Haven, CTArnau Casanovas-Massana, Ph.D.Yale School of Public Health, New Haven, CTMelissa Campbell, M.D.Maria Tokuyama, Ph.D.Pavithra Vijayakumar, B.A.Yale School of Medicine, New Haven, CTJoshua L. Warren, Ph.D.Yale School of Public Health, New Haven, CTBertie Geng, M.D.Yale School of Medicine, New Haven, CTM. Catherine Muenker, M.S.Adam J. Moore, M.P.H.Chantal B.F.

    Vogels, Ph.D.Mary E. Petrone, B.S.Isabel M. Ott, B.S.Yale School of Public Health, New Haven, CTPeiwen Lu, Ph.D.Arvind Venkataraman, B.S.Alice Lu-Culligan, B.S.Jonathan Klein, B.S.Yale School of Medicine, New Haven, CTRebecca Earnest, M.P.H.Yale School of Public Health, New Haven, CTMichael Simonov, M.D.Rupak Datta, M.D., Ph.D.Ryan Handoko, M.D.Nida Naushad, B.S.Lorenzo R. Sewanan, M.Phil.Jordan Valdez, B.S.Yale School of Medicine, New Haven, CTElizabeth B.

    White, A.B.Sarah Lapidus, M.S.Chaney C. Kalinich, M.P.H.Yale School of Public Health, New Haven, CTXiaodong Jiang, M.D., Ph.D.Daniel J. Kim, A.B.Eriko Kudo, Ph.D.Melissa Linehan, M.S.Tianyang Mao, B.S.Miyu Moriyama, Ph.D.Ji E. Oh, M.D., Ph.D.Annsea Park, B.A.Julio Silva, B.S.Eric Song, M.S.Takehiro Takahashi, M.D., Ph.D.Manabu Taura, Ph.D.Orr-El Weizman, B.A.Patrick Wong, M.S.Yexin Yang, B.S.Santos Bermejo, B.S.Yale School of Medicine, New Haven, CTCamila D.

    Odio, M.D.Yale New Haven Health, New Haven, CTSaad B. Omer, M.B., B.S., Ph.D.Yale Institute for Global Health, New Haven, CTCharles S. Dela Cruz, M.D., Ph.D.Shelli Farhadian, M.D., Ph.D.Richard A. Martinello, M.D.Akiko Iwasaki, Ph.D.Yale School of Medicine, New Haven, CTNathan D.

    Grubaugh, Ph.D.Albert I. Ko, M.D.Yale School of Public Health, New Haven, CT [email protected], [email protected] Supported by the Huffman Family Donor Advised Fund, a Fast Grant from Emergent Ventures at the Mercatus Center at George Mason University, the Yale Institute for Global Health, the Yale School of Medicine, a grant (U19 AI08992, to Dr. Ko) from the National Institute of Allergy and Infectious Diseases, the Beatrice Kleinberg Neuwirth Fund, and a grant (Rubicon 019.181EN.004, to Dr. Vogel) from the Dutch Research Council (NWO).

    Disclosure forms provided by the authors are available with the full text of this letter at NEJM.org. This letter was published on August 28, 2020, at NEJM.org. Drs. Grubaugh and Ko contributed equally to this letter.

    5 References1. Kojima N, Turner F, Slepnev V, et al. Self-collected oral fluid and nasal swabs demonstrate comparable sensitivity to clinician collected nasopharyngeal swabs for Covid-19 detection. April 15, 2020 (https://www.medrxiv.org/content/10.1101/2020.04.11.20062372v1).

    Preprint.Google Scholar2. Williams E, Bond K, Zhang B, Putland M, Williamson DA. Saliva as a non-invasive specimen for detection of SARS-CoV-2. J Clin Microbiol 2020;58(8):e00776-20-e00776-20.3.

    Pasomsub E, Watcharananan SP, Boonyawat K, et al. Saliva sample as a non-invasive specimen for the diagnosis of coronavirus disease 2019. A cross-sectional study. Clin Microbiol Infect 2020 May 15 (Epub ahead of print).4.

    Vogels CBF, Brackney D, Wang J, et al. SalivaDirect. Simple and sensitive molecular diagnostic test for SARS-CoV-2 surveillance. August 4, 2020 (https://www.medrxiv.org/content/10.1101/2020.08.03.20167791v1).

    Preprint.Google Scholar5. Zou L, Ruan F, Huang M, et al. SARS-CoV-2 viral load in upper respiratory specimens of infected patients. N Engl J Med 2020;382:1177-1179.Trial Population Table 1.

    Table 1. Characteristics of the Participants in the mRNA-1273 Trial at Enrollment. The 45 enrolled participants received their first vaccination between March 16 and April 14, 2020 (Fig. S1).

    Three participants did not receive the second vaccination, including one in the 25-μg group who had urticaria on both legs, with onset 5 days after the first vaccination, and two (one in the 25-μg group and one in the 250-μg group) who missed the second vaccination window owing to isolation for suspected Covid-19 while the test results, ultimately negative, were pending. All continued to attend scheduled trial visits. The demographic characteristics of participants at enrollment are provided in Table 1. Vaccine Safety No serious adverse events were noted, and no prespecified trial halting rules were met.

    As noted above, one participant in the 25-μg group was withdrawn because of an unsolicited adverse event, transient urticaria, judged to be related to the first vaccination. Figure 1. Figure 1. Systemic and Local Adverse Events.

    The severity of solicited adverse events was graded as mild, moderate, or severe (see Table S1).After the first vaccination, solicited systemic adverse events were reported by 5 participants (33%) in the 25-μg group, 10 (67%) in the 100-μg group, and 8 (53%) in the 250-μg group. All were mild or moderate in severity (Figure 1 and Table S2). Solicited systemic adverse events were more common after the second vaccination and occurred in 7 of 13 participants (54%) in the 25-μg group, all 15 in the 100-μg group, and all 14 in the 250-μg group, with 3 of those participants (21%) reporting one or more severe events. None of the participants had fever after the first vaccination.

    After the second vaccination, no participants in the 25-μg group, 6 (40%) in the 100-μg group, and 8 (57%) in the 250-μg group reported fever. One of the events (maximum temperature, 39.6°C) in the 250-μg group was graded severe. (Additional details regarding adverse events for that participant are provided in the Supplementary Appendix.) Local adverse events, when present, were nearly all mild or moderate, and pain at the injection site was common. Across both vaccinations, solicited systemic and local adverse events that occurred in more than half the participants included fatigue, chills, headache, myalgia, and pain at the injection site.

    Evaluation of safety clinical laboratory values of grade 2 or higher and unsolicited adverse events revealed no patterns of concern (Supplementary Appendix and Table S3). SARS-CoV-2 Binding Antibody Responses Table 2. Table 2. Geometric Mean Humoral Immunogenicity Assay Responses to mRNA-1273 in Participants and in Convalescent Serum Specimens.

    Figure 2. Figure 2. SARS-CoV-2 Antibody and Neutralization Responses. Shown are geometric mean reciprocal end-point enzyme-linked immunosorbent assay (ELISA) IgG titers to S-2P (Panel A) and receptor-binding domain (Panel B), PsVNA ID50 responses (Panel C), and live virus PRNT80 responses (Panel D).

    In Panel A and Panel B, boxes and horizontal bars denote interquartile range (IQR) and median area under the curve (AUC), respectively. Whisker endpoints are equal to the maximum and minimum values below or above the median ±1.5 times the IQR. The convalescent serum panel includes specimens from 41 participants. Red dots indicate the 3 specimens that were also tested in the PRNT assay.

    The other 38 specimens were used to calculate summary statistics for the box plot in the convalescent serum panel. In Panel C, boxes and horizontal bars denote IQR and median ID50, respectively. Whisker end points are equal to the maximum and minimum values below or above the median ±1.5 times the IQR. In the convalescent serum panel, red dots indicate the 3 specimens that were also tested in the PRNT assay.

    The other 38 specimens were used to calculate summary statistics for the box plot in the convalescent panel. In Panel D, boxes and horizontal bars denote IQR and median PRNT80, respectively. Whisker end points are equal to the maximum and minimum values below or above the median ±1.5 times the IQR. The three convalescent serum specimens were also tested in ELISA and PsVNA assays.

    Because of the time-intensive nature of the PRNT assay, for this preliminary report, PRNT results were available only for the 25-μg and 100-μg dose groups.Binding antibody IgG geometric mean titers (GMTs) to S-2P increased rapidly after the first vaccination, with seroconversion in all participants by day 15 (Table 2 and Figure 2A). Dose-dependent responses to the first and second vaccinations were evident. Receptor-binding domain–specific antibody responses were similar in pattern and magnitude (Figure 2B). For both assays, the median magnitude of antibody responses after the first vaccination in the 100-μg and 250-μg dose groups was similar to the median magnitude in convalescent serum specimens, and in all dose groups the median magnitude after the second vaccination was in the upper quartile of values in the convalescent serum specimens.

    The S-2P ELISA GMTs at day 57 (299,751 [95% confidence interval {CI}, 206,071 to 436,020] in the 25-μg group, 782,719 [95% CI, 619,310 to 989,244] in the 100-μg group, and 1,192,154 [95% CI, 924,878 to 1,536,669] in the 250-μg group) exceeded that in the convalescent serum specimens (142,140 [95% CI, 81,543 to 247,768]). SARS-CoV-2 Neutralization Responses No participant had detectable PsVNA responses before vaccination. After the first vaccination, PsVNA responses were detected in less than half the participants, and a dose effect was seen (50% inhibitory dilution [ID50]. Figure 2C, Fig.

    S8, and Table 2. 80% inhibitory dilution [ID80]. Fig. S2 and Table S6).

    However, after the second vaccination, PsVNA responses were identified in serum samples from all participants. The lowest responses were in the 25-μg dose group, with a geometric mean ID50 of 112.3 (95% CI, 71.2 to 177.1) at day 43. The higher responses in the 100-μg and 250-μg groups were similar in magnitude (geometric mean ID50, 343.8 [95% CI, 261.2 to 452.7] and 332.2 [95% CI, 266.3 to 414.5], respectively, at day 43). These responses were similar to values in the upper half of the distribution of values for convalescent serum specimens.

    Before vaccination, no participant had detectable 80% live-virus neutralization at the highest serum concentration tested (1:8 dilution) in the PRNT assay. At day 43, wild-type virus–neutralizing activity capable of reducing SARS-CoV-2 infectivity by 80% or more (PRNT80) was detected in all participants, with geometric mean PRNT80 responses of 339.7 (95% CI, 184.0 to 627.1) in the 25-μg group and 654.3 (95% CI, 460.1 to 930.5) in the 100-μg group (Figure 2D). Neutralizing PRNT80 average responses were generally at or above the values of the three convalescent serum specimens tested in this assay. Good agreement was noted within and between the values from binding assays for S-2P and receptor-binding domain and neutralizing activity measured by PsVNA and PRNT (Figs.

    S3 through S7), which provides orthogonal support for each assay in characterizing the humoral response induced by mRNA-1273. SARS-CoV-2 T-Cell Responses The 25-μg and 100-μg doses elicited CD4 T-cell responses (Figs. S9 and S10) that on stimulation by S-specific peptide pools were strongly biased toward expression of Th1 cytokines (tumor necrosis factor α >. Interleukin 2 >.

    Interferon γ), with minimal type 2 helper T-cell (Th2) cytokine expression (interleukin 4 and interleukin 13). CD8 T-cell responses to S-2P were detected at low levels after the second vaccination in the 100-μg dose group (Fig. S11).Announced on May 15, Operation Warp Speed (OWS) — a partnership of the Department of Health and Human Services (HHS), the Department of Defense (DOD), and the private sector — aims to accelerate control of the Covid-19 pandemic by advancing development, manufacturing, and distribution of vaccines, therapeutics, and diagnostics. OWS is providing support to promising candidates and enabling the expeditious, parallel execution of the necessary steps toward approval or authorization of safe products by the Food and Drug Administration (FDA).The partnership grew out of an acknowledged need to fundamentally restructure the way the U.S.

    Government typically supports product development and vaccine distribution. The initiative was premised on setting a “stretch goal” — one that initially seemed impossible but that is becoming increasingly achievable.The concept of an integrated structure for Covid-19 countermeasure research and development across the U.S. Government was based on experience with Zika and the Zika Leadership Group led by the National Institutes of Health (NIH) and the assistant secretary for preparedness and response (ASPR). One of us (M.S.) serves as OWS chief advisor.

    We are drawing on expertise from the NIH, ASPR, the Centers for Disease Control and Prevention (CDC), the Biomedical Advanced Research and Development Authority (BARDA), and the DOD, including the Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense and the Defense Advanced Research Projects Agency. OWS has engaged experts in all critical aspects of medical countermeasure research, development, manufacturing, and distribution to work in close coordination.The initiative set ambitious objectives. To deliver tens of millions of doses of a SARS-CoV-2 vaccine — with demonstrated safety and efficacy, and approved or authorized by the FDA for use in the U.S. Population — beginning at the end of 2020 and to have as many as 300 million doses of such vaccines available and deployed by mid-2021.

    The pace and scope of such a vaccine effort are unprecedented. The 2014 http://www.amisdepasteur.fr/where-to-get-accupril/ West African Ebola virus epidemic spurred rapid vaccine development, but though preclinical data existed before the outbreak, a period of 12 months was required to progress from phase 1 first-in-human trials to phase 3 efficacy trials. OWS aims to compress this time frame even further. SARS-CoV-2 vaccine development began in January, phase 1 clinical studies in March, and the first phase 3 trials in July.

    Our objectives are based on advances in vaccine platform technology, improved understanding of safe and efficacious vaccine design, and similarities between the SARS-CoV-1 and SARS-CoV-2 disease mechanisms.OWS’s role is to enable, accelerate, harmonize, and advise the companies developing the selected vaccines. The companies will execute the clinical or process development and manufacturing plans, while OWS leverages the full capacity of the U.S. Government to ensure that no technical, logistic, or financial hurdles hinder vaccine development or deployment.OWS selected vaccine candidates on the basis of four criteria. We required candidates to have robust preclinical data or early-stage clinical trial data supporting their potential for clinical safety and efficacy.

    Candidates had to have the potential, with our acceleration support, to enter large phase 3 field efficacy trials this summer or fall (July to November 2020) and, assuming continued active transmission of the virus, to deliver efficacy outcomes by the end of 2020 or the first half of 2021. Candidates had to be based on vaccine-platform technologies permitting fast and effective manufacturing, and their developers had to demonstrate the industrial process scalability, yields, and consistency necessary to reliably produce more than 100 million doses by mid-2021. Finally, candidates had to use one of four vaccine-platform technologies that we believe are the most likely to yield a safe and effective vaccine against Covid-19. The mRNA platform, the replication-defective live-vector platform, the recombinant-subunit-adjuvanted protein platform, or the attenuated replicating live-vector platform.OWS’s strategy relies on a few key principles.

    First, we sought to build a diverse project portfolio that includes two vaccine candidates based on each of the four platform technologies. Such diversification mitigates the risk of failure due to safety, efficacy, industrial manufacturability, or scheduling factors and may permit selection of the best vaccine platform for each subpopulation at risk for contracting or transmitting Covid-19, including older adults, frontline and essential workers, young adults, and pediatric populations. In addition, advancing eight vaccines in parallel will increase the chances of delivering 300 million doses in the first half of 2021.Second, we must accelerate vaccine program development without compromising safety, efficacy, or product quality. Clinical development, process development, and manufacturing scale-up can be substantially accelerated by running all streams, fully resourced, in parallel.

    Doing so requires taking on substantial financial risk, as compared with the conventional sequential development approach. OWS will maximize the size of phase 3 trials (30,000 to 50,000 participants each) and optimize trial-site location by consulting daily epidemiologic and disease-forecasting models to ensure the fastest path to an efficacy readout. Such large trials also increase the safety data set for each candidate vaccine.With heavy up-front investment, companies can conduct clinical operations and site preparation for these phase 3 efficacy trials even as they file their Investigational New Drug application (IND) for their phase 1 studies, thereby ensuring immediate initiation of phase 3 when they get a green light from the FDA. To permit appropriate comparisons among the vaccine candidates and to optimize vaccine utilization after approval by the FDA, the phase 3 trial end points and assay readouts have been harmonized through a collaborative effort involving the National Institute of Allergy and Infectious Diseases (NIAID), the Coronavirus Prevention Network, OWS, and the sponsor companies.Finally, OWS is supporting the companies financially and technically to commence process development and scale up manufacturing while their vaccines are in preclinical or very early clinical stages.

    To ensure that industrial processes are set, running, and validated for FDA inspection when phase 3 trials end, OWS is also supporting facility building or refurbishing, equipment fitting, staff hiring and training, raw-material sourcing, technology transfer and validation, bulk product processing into vials, and acquisition of ample vials, syringes, and needles for each vaccine candidate. We aim to have stockpiled, at OWS’s expense, a few tens of millions of vaccine doses that could be swiftly deployed once FDA approval is obtained.This strategy aims to accelerate vaccine development without curtailing the critical steps required by sound science and regulatory standards. The FDA recently reissued guidance and standards that will be used to assess each vaccine for a Biologics License Application (BLA). Alternatively, the agency could decide to issue an Emergency Use Authorization to permit vaccine administration before all BLA procedures are completed.Of the eight vaccines in OWS’s portfolio, six have been announced and partnerships executed with the companies.

    Moderna and Pfizer/BioNTech (both mRNA), AstraZeneca and Janssen (both replication-defective live-vector), and Novavax and Sanofi/GSK (both recombinant-subunit-adjuvanted protein). These candidates cover three of the four platform technologies and are currently in clinical trials. The remaining two candidates will enter trials soon.Moderna developed its RNA vaccine in collaboration with the NIAID, began its phase 1 trial in March, recently published encouraging safety and immunogenicity data,1 and entered phase 3 on July 27. Pfizer and BioNTech’s RNA vaccine also produced encouraging phase 1 results2 and started its phase 3 trial on July 27.

    The ChAdOx replication-defective live-vector vaccine developed by AstraZeneca and Oxford University is in phase 3 trials in the United Kingdom, Brazil, and South Africa, and it should enter U.S. Phase 3 trials in August.3 The Janssen Ad26 Covid-19 replication-defective live-vector vaccine has demonstrated excellent protection in nonhuman primate models and began its U.S. Phase 1 trial on July 27. It should be in phase 3 trials in mid-September.

    Novavax completed a phase 1 trial of its recombinant-subunit-adjuvanted protein vaccine in Australia and should enter phase 3 trials in the United States by the end of September.4 Sanofi/GSK is completing preclinical development steps and plans to commence a phase 1 trial in early September and to be well into phase 3 by year’s end.5On the process-development front, the RNA vaccines are already being manufactured at scale. The other candidates are well advanced in their scale-up development, and manufacturing sites are being refurbished.While development and manufacturing proceed, the HHS–DOD partnership is laying the groundwork for vaccine distribution, subpopulation prioritization, financing, and logistic support. We are working with bioethicists and experts from the NIH, the CDC, BARDA, and the Centers for Medicare and Medicaid Services to address these critical issues. We will receive recommendations from the CDC Advisory Committee on Immunization Practices, and we are working to ensure that the most vulnerable and at-risk persons will receive vaccine doses once they are ready.

    Prioritization will also depend on the relative performance of each vaccine and its suitability for particular populations. Because some technologies have limited previous data on safety in humans, the long-term safety of these vaccines will be carefully assessed using pharmacovigilance surveillance strategies.No scientific enterprise could guarantee success by January 2021, but the strategic decisions and choices we’ve made, the support the government has provided, and the accomplishments to date make us optimistic that we will succeed in this unprecedented endeavor.Patients Figure 1. Figure 1. Enrollment and Randomization.

    Of the 1107 patients who were assessed for eligibility, 1063 underwent randomization. 541 were assigned to the remdesivir group and 522 to the placebo group (Figure 1). Of those assigned to receive remdesivir, 531 patients (98.2%) received the treatment as assigned. Forty-nine patients had remdesivir treatment discontinued before day 10 because of an adverse event or a serious adverse event other than death (36 patients) or because the patient withdrew consent (13).

    Of those assigned to receive placebo, 518 patients (99.2%) received placebo as assigned. Fifty-three patients discontinued placebo before day 10 because of an adverse event or a serious adverse event other than death (36 patients), because the patient withdrew consent (15), or because the patient was found to be ineligible for trial enrollment (2). As of April 28, 2020, a total of 391 patients in the remdesivir group and 340 in the placebo group had completed the trial through day 29, recovered, or died. Eight patients who received remdesivir and 9 who received placebo terminated their participation in the trial before day 29.

    There were 132 patients in the remdesivir group and 169 in the placebo group who had not recovered and had not completed the day 29 follow-up visit. The analysis population included 1059 patients for whom we have at least some postbaseline data available (538 in the remdesivir group and 521 in the placebo group). Four of the 1063 patients were not included in the primary analysis because no postbaseline data were available at the time of the database freeze. Table 1.

    Table 1. Demographic and Clinical Characteristics at Baseline. The mean age of patients was 58.9 years, and 64.3% were male (Table 1). On the basis of the evolving epidemiology of Covid-19 during the trial, 79.8% of patients were enrolled at sites in North America, 15.3% in Europe, and 4.9% in Asia (Table S1).

    Overall, 53.2% of the patients were white, 20.6% were black, 12.6% were Asian, and 13.6% were designated as other or not reported. 249 (23.4%) were Hispanic or Latino. Most patients had either one (27.0%) or two or more (52.1%) of the prespecified coexisting conditions at enrollment, most commonly hypertension (49.6%), obesity (37.0%), and type 2 diabetes mellitus (29.7%). The median number of days between symptom onset and randomization was 9 (interquartile range, 6 to 12).

    Nine hundred forty-three (88.7%) patients had severe disease at enrollment as defined in the Supplementary Appendix. 272 (25.6%) patients met category 7 criteria on the ordinal scale, 197 (18.5%) category 6, 421 (39.6%) category 5, and 127 (11.9%) category 4. There were 46 (4.3%) patients who had missing ordinal scale data at enrollment. No substantial imbalances in baseline characteristics were observed between the remdesivir group and the placebo group.

    Primary Outcome Figure 2. Figure 2. Kaplan–Meier Estimates of Cumulative Recoveries. Cumulative recovery estimates are shown in the overall population (Panel A), in patients with a baseline score of 4 on the ordinal scale (not receiving oxygen.

    Panel B), in those with a baseline score of 5 (receiving oxygen. Panel C), in those with a baseline score of 6 (receiving high-flow oxygen or noninvasive mechanical ventilation. Panel D), and in those with a baseline score of 7 (receiving mechanical ventilation or ECMO. Panel E).

    Table 2. Table 2. Outcomes Overall and According to Score on the Ordinal Scale in the Intention-to-Treat Population. Figure 3.

    Figure 3. Time to Recovery According to Subgroup. The widths of the confidence intervals have not been adjusted for multiplicity and therefore cannot be used to infer treatment effects. Race and ethnic group were reported by the patients.

    Patients in the remdesivir group had a shorter time to recovery than patients in the placebo group (median, 11 days, as compared with 15 days. Rate ratio for recovery, 1.32. 95% confidence interval [CI], 1.12 to 1.55. P<0.001.

    1059 patients (Figure 2 and Table 2). Among patients with a baseline ordinal score of 5 (421 patients), the rate ratio for recovery was 1.47 (95% CI, 1.17 to 1.84). Among patients with a baseline score of 4 (127 patients) and those with a baseline score of 6 (197 patients), the rate ratio estimates for recovery were 1.38 (95% CI, 0.94 to 2.03) and 1.20 (95% CI, 0.79 to 1.81), respectively. For those receiving mechanical ventilation or ECMO at enrollment (baseline ordinal scores of 7.

    272 patients), the rate ratio for recovery was 0.95 (95% CI, 0.64 to 1.42). A test of interaction of treatment with baseline score on the ordinal scale was not significant. An analysis adjusting for baseline ordinal score as a stratification variable was conducted to evaluate the overall effect (of the percentage of patients in each ordinal score category at baseline) on the primary outcome. This adjusted analysis produced a similar treatment-effect estimate (rate ratio for recovery, 1.31.

    95% CI, 1.12 to 1.54. 1017 patients). Table S2 in the Supplementary Appendix shows results according to the baseline severity stratum of mild-to-moderate as compared with severe. Patients who underwent randomization during the first 10 days after the onset of symptoms had a rate ratio for recovery of 1.28 (95% CI, 1.05 to 1.57.

    664 patients), whereas patients who underwent randomization more than 10 days after the onset of symptoms had a rate ratio for recovery of 1.38 (95% CI, 1.05 to 1.81. 380 patients) (Figure 3). Key Secondary Outcome The odds of improvement in the ordinal scale score were higher in the remdesivir group, as determined by a proportional odds model at the day 15 visit, than in the placebo group (odds ratio for improvement, 1.50. 95% CI, 1.18 to 1.91.

    P=0.001. 844 patients) (Table 2 and Fig. S5). Mortality was numerically lower in the remdesivir group than in the placebo group, but the difference was not significant (hazard ratio for death, 0.70.

    95% CI, 0.47 to 1.04. 1059 patients). The Kaplan–Meier estimates of mortality by 14 days were 7.1% and 11.9% in the remdesivir and placebo groups, respectively (Table 2). The Kaplan–Meier estimates of mortality by 28 days are not reported in this preliminary analysis, given the large number of patients that had yet to complete day 29 visits.

    An analysis with adjustment for baseline ordinal score as a stratification variable showed a hazard ratio for death of 0.74 (95% CI, 0.50 to 1.10). Safety Outcomes Serious adverse events occurred in 114 patients (21.1%) in the remdesivir group and 141 patients (27.0%) in the placebo group (Table S3). 4 events (2 in each group) were judged by site investigators to be related to remdesivir or placebo. There were 28 serious respiratory failure adverse events in the remdesivir group (5.2% of patients) and 42 in the placebo group (8.0% of patients).

    Acute respiratory failure, hypotension, viral pneumonia, and acute kidney injury were slightly more common among patients in the placebo group. No deaths were considered to be related to treatment assignment, as judged by the site investigators. Grade 3 or 4 adverse events occurred in 156 patients (28.8%) in the remdesivir group and in 172 in the placebo group (33.0%) (Table S4). The most common adverse events in the remdesivir group were anemia or decreased hemoglobin (43 events [7.9%], as compared with 47 [9.0%] in the placebo group).

    Acute kidney injury, decreased estimated glomerular filtration rate or creatinine clearance, or increased blood creatinine (40 events [7.4%], as compared with 38 [7.3%]). Pyrexia (27 events [5.0%], as compared with 17 [3.3%]). Hyperglycemia or increased blood glucose level (22 events [4.1%], as compared with 17 [3.3%]). And increased aminotransferase levels including alanine aminotransferase, aspartate aminotransferase, or both (22 events [4.1%], as compared with 31 [5.9%]).

    Otherwise, the incidence of adverse events was not found to be significantly different between the remdesivir group and the placebo group.Trial Design and Oversight We conducted a randomized, double-blind, placebo-controlled trial to evaluate postexposure prophylaxis with hydroxychloroquine after exposure to Covid-19.12 We randomly assigned participants in a 1:1 ratio to receive either hydroxychloroquine or placebo. Participants had known exposure (by participant report) to a person with laboratory-confirmed Covid-19, whether as a household contact, a health care worker, or a person with other occupational exposures. Trial enrollment began on March 17, 2020, with an eligibility threshold to enroll within 3 days after exposure. The objective was to intervene before the median incubation period of 5 to 6 days.

    Because of limited access to prompt testing, health care workers could initially be enrolled on the basis of presumptive high-risk exposure to patients with pending tests. However, on March 23, eligibility was changed to exposure to a person with a positive polymerase-chain-reaction (PCR) assay for SARS-CoV-2, with the eligibility window extended to within 4 days after exposure. This trial was approved by the institutional review board at the University of Minnesota and conducted under a Food and Drug Administration Investigational New Drug application. In Canada, the trial was approved by Health Canada.

    Ethics approvals were obtained from the Research Institute of the McGill University Health Centre, the University of Manitoba, and the University of Alberta. Participants We included participants who had household or occupational exposure to a person with confirmed Covid-19 at a distance of less than 6 ft for more than 10 minutes while wearing neither a face mask nor an eye shield (high-risk exposure) or while wearing a face mask but no eye shield (moderate-risk exposure). Participants were excluded if they were younger than 18 years of age, were hospitalized, or met other exclusion criteria (see the Supplementary Appendix, available with the full text of this article at NEJM.org). Persons with symptoms of Covid-19 or with PCR-proven SARS-CoV-2 infection were excluded from this prevention trial but were separately enrolled in a companion clinical trial to treat early infection.

    Setting Recruitment was performed primarily with the use of social media outreach as well as traditional media platforms. Participants were enrolled nationwide in the United States and in the Canadian provinces of Quebec, Manitoba, and Alberta. Participants enrolled themselves through a secure Internet-based survey using the Research Electronic Data Capture (REDCap) system.13 After participants read the consent form, their comprehension of its contents was assessed. Participants provided a digitally captured signature to indicate informed consent.

    We sent follow-up e-mail surveys on days 1, 5, 10, and 14. A survey at 4 to 6 weeks asked about any follow-up testing, illness, or hospitalizations. Participants who did not respond to follow-up surveys received text messages, e-mails, telephone calls, or a combination of these to ascertain their outcomes. When these methods were unsuccessful, the emergency contact provided by the enrollee was contacted to determine the participant’s illness and vital status.

    When all communication methods were exhausted, Internet searches for obituaries were performed to ascertain vital status. Interventions Randomization occurred at research pharmacies in Minneapolis and Montreal. The trial statisticians generated a permuted-block randomization sequence using variably sized blocks of 2, 4, or 8, with stratification according to country. A research pharmacist sequentially assigned participants.

    The assignments were concealed from investigators and participants. Only pharmacies had access to the randomization sequence. Hydroxychloroquine sulfate or placebo was dispensed and shipped overnight to participants by commercial courier. The dosing regimen for hydroxychloroquine was 800 mg (4 tablets) once, then 600 mg (3 tablets) 6 to 8 hours later, then 600 mg (3 tablets) daily for 4 more days for a total course of 5 days (19 tablets total).

    If participants had gastrointestinal upset, they were advised to divide the daily dose into two or three doses. We chose this hydroxychloroquine dosing regimen on the basis of pharmacokinetic simulations to achieve plasma concentrations above the SARS-CoV-2 in vitro half maximal effective concentration for 14 days.14 Placebo folate tablets, which were similar in appearance to the hydroxychloroquine tablets, were prescribed as an identical regimen for the control group. Rising Pharmaceuticals provided a donation of hydroxychloroquine, and some hydroxychloroquine was purchased. Outcomes The primary outcome was prespecified as symptomatic illness confirmed by a positive molecular assay or, if testing was unavailable, Covid-19–related symptoms.

    We assumed that health care workers would have access to Covid-19 testing if symptomatic. However, access to testing was limited throughout the trial period. Covid-19–related symptoms were based on U.S. Council for State and Territorial Epidemiologists criteria for confirmed cases (positivity for SARS-Cov-2 on PCR assay), probable cases (the presence of cough, shortness of breath, or difficulty breathing, or the presence of two or more symptoms of fever, chills, rigors, myalgia, headache, sore throat, and new olfactory and taste disorders), and possible cases (the presence of one or more compatible symptoms, which could include diarrhea).15 All the participants had epidemiologic linkage,15 per trial eligibility criteria.

    Four infectious disease physicians who were unaware of the trial-group assignments reviewed symptomatic participants to generate a consensus with respect to whether their condition met the case definition.15 Secondary outcomes included the incidence of hospitalization for Covid-19 or death, the incidence of PCR-confirmed SARS-CoV-2 infection, the incidence of Covid-19 symptoms, the incidence of discontinuation of the trial intervention owing to any cause, and the severity of symptoms (if any) at days 5 and 14 according to a visual analogue scale (scores ranged from 0 [no symptoms] to 10 [severe symptoms]). Data on adverse events were also collected with directed questioning for common side effects along with open-ended free text. Outcome data were measured within 14 days after trial enrollment. Outcome data including PCR testing results, possible Covid-19–related symptoms, adherence to the trial intervention, side effects, and hospitalizations were all collected through participant report.

    Details of trial conduct are provided in the protocol and statistical analysis plan, available at NEJM.org. Sample Size We anticipated that illness compatible with Covid-19 would develop in 10% of close contacts exposed to Covid-19.9 Using Fisher’s exact method with a 50% relative effect size to reduce new symptomatic infections, a two-sided alpha of 0.05, and 90% power, we estimated that 621 persons would need to be enrolled in each group. With a pragmatic, Internet-based, self-referral recruitment strategy, we planned for a 20% incidence of attrition by increasing the sample size to 750 participants per group. We specified a priori that participants who were already symptomatic on day 1 before receiving hydroxychloroquine or placebo would be excluded from the prophylaxis trial and would instead be separately enrolled in the companion symptomatic treatment trial.

    Because the estimates for both incident symptomatic Covid-19 after an exposure and loss to follow-up were relatively unknown in early March 2020,9 the protocol prespecified a sample-size reestimation at the second interim analysis. This reestimation, which used the incidence of new infections in the placebo group and the observed percentage of participants lost to follow-up, was aimed at maintaining the ability to detect an effect size of a 50% relative reduction in new symptomatic infections. Interim Analyses An independent data and safety monitoring board externally reviewed the data after 25% and 50% of the participants had completed 14 days of follow-up. Stopping guidelines were provided to the data and safety monitoring board with the use of a Lan–DeMets spending function analogue of the O’Brien–Fleming boundaries for the primary outcome.

    A conditional power analysis was performed at the second and third interim analysis with the option of early stopping for futility. At the second interim analysis on April 22, 2020, the sample size was reduced to 956 participants who could be evaluated with 90% power on the basis of the higher-than-expected event rate of infections in the control group. At the third interim analysis on May 6, the trial was halted on the basis of a conditional power of less than 1%, since it was deemed futile to continue. Statistical Analysis We assessed the incidence of Covid-19 disease by day 14 with Fisher’s exact test.

    Secondary outcomes with respect to percentage of patients were also compared with Fisher’s exact test. Among participants in whom incident illness compatible with Covid-19 developed, we summarized the symptom severity score at day 14 with the median and interquartile range and assessed the distributions with a Kruskal–Wallis test. We conducted all analyses with SAS software, version 9.4 (SAS Institute), according to the intention-to-treat principle, with two-sided type I error with an alpha of 0.05. For participants with missing outcome data, we conducted a sensitivity analysis with their outcomes excluded or included as an event.

    Subgroups that were specified a priori included type of contact (household vs. Health care), days from exposure to enrollment, age, and sex..

    To the accupril street price Editor. Rapid and accurate diagnostic tests are essential for controlling accupril street price the ongoing Covid-19 pandemic. Although the current standard involves testing of nasopharyngeal swab specimens by quantitative reverse-transcriptase polymerase chain reaction (RT-qPCR) to detect SARS-CoV-2, saliva specimens may be an alternative diagnostic sample.1-4 Rigorous evaluation is needed to determine how saliva specimens compare with nasopharyngeal swab specimens with respect to sensitivity in detection of SARS-CoV-2 during the course of infection. A total of 70 inpatients with Covid-19 provided written informed consent to participate in our study (see the Methods section in Supplementary accupril street price Appendix 1, available with the full text of this letter at NEJM.org). After Covid-19 was confirmed with a positive nasopharyngeal swab specimen at hospital admission, we obtained additional samples from the patients during hospitalization.

    We tested accupril street price saliva specimens collected by the patients themselves and nasopharyngeal swabs collected from the patients at the same time point by health care workers. Figure 1 accupril street price. Figure 1. SARS-CoV-2 RNA accupril street price Titers in Saliva Specimens and Nasopharyngeal Swab Specimens. Samples were obtained from 70 hospital inpatients who had a diagnosis of Covid-19.

    Panel A shows SARS-CoV-2 RNA accupril street price titers in the first available nasopharyngeal and saliva samples. The lines indicate samples from the same patient. Results were compared with the use of a Wilcoxon signed-rank test (P<0.001) accupril street price. Panel B shows percentages of positivity for SARS-CoV-2 in tests of the first accupril street price matched nasopharyngeal and saliva samples at 1 to 5 days, 6 to 10 days, and 11 or more days (maximum, 53 days) after the diagnosis of Covid-19. Panel C shows longitudinal SARS-CoV-2 RNA copies per milliliter in 97 saliva samples, according to days since symptom onset.

    Each circle represents a separate sample accupril street price. Dashed lines indicate additional samples from the same patient. The red line accupril street price indicates a negative saliva sample that was followed by a positive sample at the next collection of a specimen. Panel D shows longitudinal SARS-CoV-2 RNA copies per milliliter in 97 nasopharyngeal swab specimens, according to days since symptom accupril street price onset. The red lines indicate negative nasopharyngeal swab specimens there were followed by a positive swab at the next collection of a specimen.

    The gray area in Panels C and accupril street price D indicates samples that were below the lower limit of detection of 5610 virus RNA copies per milliliter of sample, which is at cycle threshold 38 of our quantitative reverse-transcriptase polymerase chain reaction assay targeting the SARS-CoV-2 N1 sequence recommended by the Centers for Disease Control and Prevention. To analyze these data, we used a linear mixed-effects regression model (see Supplementary Appendix 1) that accounts for the correlation between samples collected from the same person at a single time point (i.e., multivariate response) and the correlation between samples collected across time from the same patient (i.e., repeated measures). All the data accupril street price used to generate this figure, including the raw cycle thresholds, are provided in Supplementary Data 1 in Supplementary Appendix 2.Using primer sequences from the Centers for Disease Control and Prevention, we detected more SARS-CoV-2 RNA copies in the saliva specimens (mean log copies per milliliter, 5.58. 95% confidence interval [CI], 5.09 to 6.07) than in the nasopharyngeal swab specimens (mean log copies per milliliter, 4.93. 95% CI, 4.53 to 5.33) (Figure 1A, and accupril street price Fig.

    S1 in Supplementary accupril street price Appendix 1). In addition, a higher percentage of saliva samples than nasopharyngeal swab samples were positive up to 10 days after the Covid-19 diagnosis (Figure 1B). At 1 to 5 days after diagnosis, 81% (95% CI, 71 to 96) of the saliva samples were positive, as compared with 71% (95% CI, 67 to 94) of the accupril street price nasopharyngeal swab specimens. These findings suggest that saliva specimens and nasopharyngeal swab specimens have at least similar sensitivity in the detection of SARS-CoV-2 during the course of hospitalization. Because the results of testing of nasopharyngeal swab specimens to detect SARS-CoV-2 accupril street price may vary with repeated sampling in individual patients,5 we evaluated viral detection in matched samples over time.

    The level of SARS-CoV-2 RNA decreased after symptom onset in both saliva specimens (estimated slope, −0.11. 95% credible interval, −0.15 to accupril street price −0.06) (Figure 1C) and nasopharyngeal swab specimens (estimated slope, −0.09. 95% credible interval, accupril street price −0.13 to −0.05) (Figure 1D). In three instances, a negative nasopharyngeal swab specimen was followed by a positive swab at the next collection of a specimen (Figure 1D). This phenomenon accupril street price occurred only once with the saliva specimens (Figure 1C).

    During the clinical course, we observed less variation in levels of SARS-CoV-2 RNA in the saliva specimens (standard deviation, 0.98 virus RNA copies per milliliter. 95% credible interval, 0.08 to 1.98) than accupril street price in the nasopharyngeal swab specimens (standard deviation, 2.01 virus RNA copies per milliliter. 95% credible interval, 1.29 to 2.70) (see Supplementary Appendix 1) accupril street price. Recent studies have shown that SARS-CoV-2 can be detected in the saliva of asymptomatic persons and outpatients.1-3 We therefore screened 495 asymptomatic health care workers who provided written informed consent to participate in our prospective study, and we used RT-qPCR to test both saliva and nasopharyngeal samples obtained from these persons. We detected SARS-CoV-2 RNA in saliva specimens obtained from accupril street price 13 persons who did not report any symptoms at or before the time of sample collection.

    Of these 13 health care workers, 9 had collected matched nasopharyngeal swab specimens by themselves on the same day, and 7 of these specimens tested negative (Fig. S2). The diagnosis in the 13 health care workers with positive saliva specimens was later confirmed in diagnostic testing of additional nasopharyngeal samples by a CLIA (Clinical Laboratory Improvement Amendments of 1988)–certified laboratory. Variation in nasopharyngeal sampling may be an explanation for false negative results, so monitoring an internal control for proper sample collection may provide an alternative evaluation technique. In specimens collected from inpatients by health care workers, we found greater variation in human RNase P cycle threshold (Ct) values in nasopharyngeal swab specimens (standard deviation, 2.89 Ct.

    95% CI, 26.53 to 27.69) than in saliva specimens (standard deviation, 2.49 Ct. 95% CI, 23.35 to 24.35). When health care workers collected their own specimens, we also found greater variation in RNase P Ct values in nasopharyngeal swab specimens (standard deviation, 2.26 Ct. 95% CI, 28.39 to 28.56) than in saliva specimens (standard deviation , 1.65 Ct. 95% CI, 24.14 to 24.26) (Fig.

    S3). Collection of saliva samples by patients themselves negates the need for direct interaction between health care workers and patients. This interaction is a source of major testing bottlenecks and presents a risk of nosocomial infection. Collection of saliva samples by patients themselves also alleviates demands for supplies of swabs and personal protective equipment. Given the growing need for testing, our findings provide support for the potential of saliva specimens in the diagnosis of SARS-CoV-2 infection.

    Anne L. Wyllie, Ph.D.Yale School of Public Health, New Haven, CT [email protected]John Fournier, M.D.Yale School of Medicine, New Haven, CTArnau Casanovas-Massana, Ph.D.Yale School of Public Health, New Haven, CTMelissa Campbell, M.D.Maria Tokuyama, Ph.D.Pavithra Vijayakumar, B.A.Yale School of Medicine, New Haven, CTJoshua L. Warren, Ph.D.Yale School of Public Health, New Haven, CTBertie Geng, M.D.Yale School of Medicine, New Haven, CTM. Catherine Muenker, M.S.Adam J. Moore, M.P.H.Chantal B.F.

    Vogels, Ph.D.Mary E. Petrone, B.S.Isabel M. Ott, B.S.Yale School of Public Health, New Haven, CTPeiwen Lu, Ph.D.Arvind Venkataraman, B.S.Alice Lu-Culligan, B.S.Jonathan Klein, B.S.Yale School of Medicine, New Haven, CTRebecca Earnest, M.P.H.Yale School of Public Health, New Haven, CTMichael Simonov, M.D.Rupak Datta, M.D., Ph.D.Ryan Handoko, M.D.Nida Naushad, B.S.Lorenzo R. Sewanan, M.Phil.Jordan Valdez, B.S.Yale School of Medicine, New Haven, CTElizabeth B. White, A.B.Sarah Lapidus, M.S.Chaney C.

    Kalinich, M.P.H.Yale School of Public Health, New Haven, CTXiaodong Jiang, M.D., Ph.D.Daniel J. Kim, A.B.Eriko Kudo, Ph.D.Melissa Linehan, M.S.Tianyang Mao, B.S.Miyu Moriyama, Ph.D.Ji E. Oh, M.D., Ph.D.Annsea Park, B.A.Julio Silva, B.S.Eric Song, M.S.Takehiro Takahashi, M.D., Ph.D.Manabu Taura, Ph.D.Orr-El Weizman, B.A.Patrick Wong, M.S.Yexin Yang, B.S.Santos Bermejo, B.S.Yale School of Medicine, New Haven, CTCamila D. Odio, M.D.Yale New Haven Health, New Haven, CTSaad B. Omer, M.B., B.S., Ph.D.Yale Institute for Global Health, New Haven, CTCharles S.

    Dela Cruz, M.D., Ph.D.Shelli Farhadian, M.D., Ph.D.Richard A. Martinello, M.D.Akiko Iwasaki, Ph.D.Yale School of Medicine, New Haven, CTNathan D. Grubaugh, Ph.D.Albert I. Ko, M.D.Yale School of Public Health, New Haven, CT [email protected], [email protected] Supported by the Huffman Family Donor Advised Fund, a Fast Grant from Emergent Ventures at the Mercatus Center at George Mason University, the Yale Institute for Global Health, the Yale School of Medicine, a grant (U19 AI08992, to Dr. Ko) from the National Institute of Allergy and Infectious Diseases, the Beatrice Kleinberg Neuwirth Fund, and a grant (Rubicon 019.181EN.004, to Dr.

    Vogel) from the Dutch Research Council (NWO). Disclosure forms provided by the authors are available with the full text of this letter at NEJM.org. This letter was published on August 28, 2020, at NEJM.org. Drs. Grubaugh and Ko contributed equally to this letter.

    5 References1. Kojima N, Turner F, Slepnev V, et al. Self-collected oral fluid and nasal swabs demonstrate comparable sensitivity to clinician collected nasopharyngeal swabs for Covid-19 detection. April 15, 2020 (https://www.medrxiv.org/content/10.1101/2020.04.11.20062372v1). Preprint.Google Scholar2.

    Williams E, Bond K, Zhang B, Putland M, Williamson DA. Saliva as a non-invasive specimen for detection of SARS-CoV-2. J Clin Microbiol 2020;58(8):e00776-20-e00776-20.3. Pasomsub E, Watcharananan SP, Boonyawat K, et al. Saliva sample as a non-invasive specimen for the diagnosis of coronavirus disease 2019.

    A cross-sectional study. Clin Microbiol Infect 2020 May 15 (Epub ahead of print).4. Vogels CBF, Brackney D, Wang J, et al. SalivaDirect. Simple and sensitive molecular diagnostic test for SARS-CoV-2 surveillance.

    August 4, 2020 (https://www.medrxiv.org/content/10.1101/2020.08.03.20167791v1). Preprint.Google Scholar5. Zou L, Ruan F, Huang M, et al. SARS-CoV-2 viral load in upper respiratory specimens of infected patients. N Engl J Med 2020;382:1177-1179.Trial Population Table 1.

    Table 1. Characteristics of the Participants in the mRNA-1273 Trial at Enrollment. The 45 enrolled participants received their first vaccination between March 16 and April 14, 2020 (Fig. S1). Three participants did not receive the second vaccination, including one in the 25-μg group who had urticaria on both legs, with onset 5 days after the first vaccination, and two (one in the 25-μg group and one in the 250-μg group) who missed the second vaccination window owing to isolation for suspected Covid-19 while the test results, ultimately negative, were pending.

    All continued to attend scheduled trial visits. The demographic characteristics of participants at enrollment are provided in Table 1. Vaccine Safety No serious adverse events were noted, and no prespecified trial halting rules were met. As noted above, one participant in the 25-μg group was withdrawn because of an unsolicited adverse event, transient urticaria, judged to be related to the first vaccination. Figure 1.

    Figure 1. Systemic and Local Adverse Events. The severity of solicited adverse events was graded as mild, moderate, or severe (see Table S1).After the first vaccination, solicited systemic adverse events were reported by 5 participants (33%) in the 25-μg group, 10 (67%) in the 100-μg group, and 8 (53%) in the 250-μg group. All were mild or moderate in severity (Figure 1 and Table S2). Solicited systemic adverse events were more common after the second vaccination and occurred in 7 of 13 participants (54%) in the 25-μg group, all 15 in the 100-μg group, and all 14 in the 250-μg group, with 3 of those participants (21%) reporting one or more severe events.

    None of the participants had fever after the first vaccination. After the second vaccination, no participants in the 25-μg group, 6 (40%) in the 100-μg group, and 8 (57%) in the 250-μg group reported fever. One of the events (maximum temperature, 39.6°C) in the 250-μg group was graded severe. (Additional details regarding adverse events for that participant are provided in the Supplementary Appendix.) Local adverse events, when present, were nearly all mild or moderate, and pain at the injection site was common. Across both vaccinations, solicited systemic and local adverse events that occurred in more than half the participants included fatigue, chills, headache, myalgia, and pain at the injection site.

    Evaluation of safety clinical laboratory values of grade 2 or higher and unsolicited adverse events revealed no patterns of concern (Supplementary Appendix and Table S3). SARS-CoV-2 Binding Antibody Responses Table 2. Table 2. Geometric Mean Humoral Immunogenicity Assay Responses to mRNA-1273 in Participants and in Convalescent Serum Specimens. Figure 2.

    Figure 2. SARS-CoV-2 Antibody and Neutralization Responses. Shown are geometric mean reciprocal end-point enzyme-linked immunosorbent assay (ELISA) IgG titers to S-2P (Panel A) and receptor-binding domain (Panel B), PsVNA ID50 responses (Panel C), and live virus PRNT80 responses (Panel D). In Panel A and Panel B, boxes and horizontal bars denote interquartile range (IQR) and median area under the curve (AUC), respectively. Whisker endpoints are equal to the maximum and minimum values below or above the median ±1.5 times the IQR.

    The convalescent serum panel includes specimens from 41 participants. Red dots indicate the 3 specimens that were also tested in the PRNT assay. The other 38 specimens were used to calculate summary statistics for the box plot in the convalescent serum panel. In Panel C, boxes and horizontal bars denote IQR and median ID50, respectively. Whisker end points are equal to the maximum and minimum values below or above the median ±1.5 times the IQR.

    In the convalescent serum panel, red dots indicate the 3 specimens that were also tested in the PRNT assay. The other 38 specimens were used to calculate summary statistics for the box plot in the convalescent panel. In Panel D, boxes and horizontal bars denote IQR and median PRNT80, respectively. Whisker end points are equal to the maximum and minimum values below or above the median ±1.5 times the IQR. The three convalescent serum specimens were also tested in ELISA and PsVNA assays.

    Because of the time-intensive nature of the PRNT assay, for this preliminary report, PRNT results were available only for the 25-μg and 100-μg dose groups.Binding antibody IgG geometric mean titers (GMTs) to S-2P increased rapidly after the first vaccination, with seroconversion in all participants by day 15 (Table 2 and Figure 2A). Dose-dependent responses to the first and second vaccinations were evident. Receptor-binding domain–specific antibody responses were similar in pattern and magnitude (Figure 2B). For both assays, the median magnitude of antibody responses after the first vaccination in the 100-μg and 250-μg dose groups was similar to the median magnitude in convalescent serum specimens, and in all dose groups the median magnitude after the second vaccination was in the upper quartile of values in the convalescent serum specimens. The S-2P ELISA GMTs at day 57 (299,751 [95% confidence interval {CI}, 206,071 to 436,020] in the 25-μg group, 782,719 [95% CI, 619,310 to 989,244] in the 100-μg group, and 1,192,154 [95% CI, 924,878 to 1,536,669] in the 250-μg group) exceeded that in the convalescent serum specimens (142,140 [95% CI, 81,543 to 247,768]).

    SARS-CoV-2 Neutralization Responses No participant had detectable PsVNA responses before vaccination. After the first vaccination, PsVNA responses were detected in less than half the participants, and a dose effect was seen (50% inhibitory dilution [ID50]. Figure 2C, Fig. S8, and Table 2. 80% inhibitory dilution [ID80].

    Fig. S2 and Table S6). However, after the second vaccination, PsVNA responses were identified in serum samples from all participants. The lowest responses were in the 25-μg dose group, with a geometric mean ID50 of 112.3 (95% CI, 71.2 to 177.1) at day 43. The higher responses in the 100-μg and 250-μg groups were similar in magnitude (geometric mean ID50, 343.8 [95% CI, 261.2 to 452.7] and 332.2 [95% CI, 266.3 to 414.5], respectively, at day 43).

    These responses were similar to values in the upper half of the distribution of values for convalescent serum specimens. Before vaccination, no participant had detectable 80% live-virus neutralization at the highest serum concentration tested (1:8 dilution) in the PRNT assay. At day 43, wild-type virus–neutralizing activity capable of reducing SARS-CoV-2 infectivity by 80% or more (PRNT80) was detected in all participants, with geometric mean PRNT80 responses of 339.7 (95% CI, 184.0 to 627.1) in the 25-μg group and 654.3 (95% CI, 460.1 to 930.5) in the 100-μg group (Figure 2D). Neutralizing PRNT80 average responses were generally at or above the values of the three convalescent serum specimens tested in this assay. Good agreement was noted within and between the values from binding assays for S-2P and receptor-binding domain and neutralizing activity measured by PsVNA and PRNT (Figs.

    S3 through S7), which provides orthogonal support for each assay in characterizing the humoral response induced by mRNA-1273. SARS-CoV-2 T-Cell Responses The 25-μg and 100-μg doses elicited CD4 T-cell responses (Figs. S9 and S10) that on stimulation by S-specific peptide pools were strongly biased toward expression of Th1 cytokines (tumor necrosis factor α >. Interleukin 2 >. Interferon γ), with minimal type 2 helper T-cell (Th2) cytokine expression (interleukin 4 and interleukin 13).

    CD8 T-cell responses to S-2P were detected at low levels after the second vaccination in the 100-μg dose group (Fig. S11).Announced on May 15, Operation Warp Speed (OWS) — a partnership of the Department of Health and Human Services (HHS), the Department of Defense (DOD), and the private sector — aims to accelerate control of the Covid-19 pandemic by advancing development, manufacturing, and distribution of vaccines, therapeutics, and diagnostics. OWS is providing support to promising candidates and enabling the expeditious, parallel execution of the necessary steps toward approval or authorization of safe products by the Food and Drug Administration (FDA).The partnership grew out of an acknowledged need to fundamentally restructure the way the U.S. Government typically supports product development and vaccine distribution. The initiative was premised on setting a “stretch goal” — one that initially seemed impossible but that is becoming increasingly achievable.The concept of an integrated structure for Covid-19 countermeasure research and development across the U.S.

    Government was based on experience with Zika and the Zika Leadership Group led by the National Institutes of Health (NIH) and the assistant secretary for preparedness and response (ASPR). One of us (M.S.) serves as OWS chief advisor. We are drawing on expertise from the NIH, ASPR, the Centers for Disease Control and Prevention (CDC), the Biomedical Advanced Research and Development Authority (BARDA), and the DOD, including the Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense and the Defense Advanced Research Projects Agency. OWS has engaged experts in all critical aspects of medical countermeasure research, development, manufacturing, and distribution to work in close coordination.The initiative set ambitious objectives. To deliver tens of millions of doses of a SARS-CoV-2 vaccine — with demonstrated safety and efficacy, and approved or authorized by the FDA for use in the U.S.

    Population — beginning at the end of 2020 and to have as many as 300 million doses of such vaccines available and deployed by mid-2021. The pace and scope of such a vaccine effort are unprecedented. The 2014 West African Ebola virus epidemic spurred rapid vaccine development, but though preclinical data existed before the outbreak, a period of 12 months was required to progress from phase 1 first-in-human trials to phase 3 efficacy trials. OWS aims to compress this time frame even further. SARS-CoV-2 vaccine development began in January, phase 1 clinical studies in March, and the first phase 3 trials in July.

    Our objectives are based on advances in vaccine platform technology, improved understanding of safe and efficacious vaccine design, and similarities between the SARS-CoV-1 and SARS-CoV-2 disease mechanisms.OWS’s role is to enable, accelerate, harmonize, and advise the companies developing the selected vaccines. The companies will execute the clinical or process development and manufacturing plans, while OWS leverages the full capacity of the U.S. Government to ensure that no technical, logistic, or financial hurdles hinder vaccine development or deployment.OWS selected vaccine candidates on the basis of four criteria. We required candidates to have robust preclinical data or early-stage clinical trial data supporting their potential for clinical safety and efficacy. Candidates had to have the potential, with our acceleration support, to enter large phase 3 field efficacy trials this summer or fall (July to November 2020) and, assuming continued active transmission of the virus, to deliver efficacy outcomes by the end of 2020 or the first half of 2021.

    Candidates had to be based on vaccine-platform technologies permitting fast and effective manufacturing, and their developers had to demonstrate the industrial process scalability, yields, and consistency necessary to reliably produce more than 100 million doses by mid-2021. Finally, candidates had to use one of four vaccine-platform technologies that we believe are the most likely to yield a safe and effective vaccine against Covid-19. The mRNA platform, the replication-defective live-vector platform, the recombinant-subunit-adjuvanted protein platform, or the attenuated replicating live-vector platform.OWS’s strategy relies on a few key principles. First, we sought to build a diverse project portfolio that includes two vaccine candidates based on each of the four platform technologies. Such diversification mitigates the risk of failure due to safety, efficacy, industrial manufacturability, or scheduling factors and may permit selection of the best vaccine platform for each subpopulation at risk for contracting or transmitting Covid-19, including older adults, frontline and essential workers, young adults, and pediatric populations.

    In addition, advancing eight vaccines in parallel will increase the chances of delivering 300 million doses in the first half of 2021.Second, we must accelerate vaccine program development without compromising safety, efficacy, or product quality. Clinical development, process development, and manufacturing scale-up can be substantially accelerated by running all streams, fully resourced, in parallel. Doing so requires taking on substantial financial risk, as compared with the conventional sequential development approach. OWS will maximize the size of phase 3 trials (30,000 to 50,000 participants each) and optimize trial-site location by consulting daily epidemiologic and disease-forecasting models to ensure the fastest path to an efficacy readout. Such large trials also increase the safety data set for each candidate vaccine.With heavy up-front investment, companies can conduct clinical operations and site preparation for these phase 3 efficacy trials even as they file their Investigational New Drug application (IND) for their phase 1 studies, thereby ensuring immediate initiation of phase 3 when they get a green light from the FDA.

    To permit appropriate comparisons among the vaccine candidates and to optimize vaccine utilization after approval by the FDA, the phase 3 trial end points and assay readouts have been harmonized through a collaborative effort involving the National Institute of Allergy and Infectious Diseases (NIAID), the Coronavirus Prevention Network, OWS, and the sponsor companies.Finally, OWS is supporting the companies financially and technically to commence process development and scale up manufacturing while their vaccines are in preclinical or very early clinical stages. To ensure that industrial processes are set, running, and validated for FDA inspection when phase 3 trials end, OWS is also supporting facility building or refurbishing, equipment fitting, staff hiring and training, raw-material sourcing, technology transfer and validation, bulk product processing into vials, and acquisition of ample vials, syringes, and needles for each vaccine candidate. We aim to have stockpiled, at OWS’s expense, a few tens of millions of vaccine doses that could be swiftly deployed once FDA approval is obtained.This strategy aims to accelerate vaccine development without curtailing the critical steps required by sound science and regulatory standards. The FDA recently reissued guidance and standards that will be used to assess each vaccine for a Biologics License Application (BLA). Alternatively, the agency could decide to issue an Emergency Use Authorization to permit vaccine administration before all BLA procedures are completed.Of the eight vaccines in OWS’s portfolio, six have been announced and partnerships executed with the companies.

    Moderna and Pfizer/BioNTech (both mRNA), AstraZeneca and Janssen (both replication-defective live-vector), and Novavax and Sanofi/GSK (both recombinant-subunit-adjuvanted protein). These candidates cover three of the four platform technologies and are currently in clinical trials. The remaining two candidates will enter trials soon.Moderna developed its RNA vaccine in collaboration with the NIAID, began its phase 1 trial in March, recently published encouraging safety and immunogenicity data,1 and entered phase 3 on July 27. Pfizer and BioNTech’s RNA vaccine also produced encouraging phase 1 results2 and started its phase 3 trial on July 27. The ChAdOx replication-defective live-vector vaccine developed by AstraZeneca and Oxford University is in phase 3 trials in the United Kingdom, Brazil, and South Africa, and it should enter U.S.

    Phase 3 trials in August.3 The Janssen Ad26 Covid-19 replication-defective live-vector vaccine has demonstrated excellent protection in nonhuman primate models and began its U.S. Phase 1 trial on July 27. It should be in phase 3 trials in mid-September. Novavax completed a phase 1 trial of its recombinant-subunit-adjuvanted protein vaccine in Australia and should enter phase 3 trials in the United States by the end of September.4 Sanofi/GSK is completing preclinical development steps and plans to commence a phase 1 trial in early September and to be well into phase 3 by year’s end.5On the process-development front, the RNA vaccines are already being manufactured at scale. The other candidates are well advanced in their scale-up development, and manufacturing sites are being refurbished.While development and manufacturing proceed, the HHS–DOD partnership is laying the groundwork for vaccine distribution, subpopulation prioritization, financing, and logistic support.

    We are working with bioethicists and experts from the NIH, the CDC, BARDA, and the Centers for Medicare and Medicaid Services to address these critical issues. We will receive recommendations from the CDC Advisory Committee on Immunization Practices, and we are working to ensure that the most vulnerable and at-risk persons will receive vaccine doses once they are ready. Prioritization will also depend on the relative performance of each vaccine and its suitability for particular populations. Because some technologies have limited previous data on safety in humans, the long-term safety of these vaccines will be carefully assessed using pharmacovigilance surveillance strategies.No scientific enterprise could guarantee success by January 2021, but the strategic decisions and choices we’ve made, the support the government has provided, and the accomplishments to date make us optimistic that we will succeed in this unprecedented endeavor.Patients Figure 1. Figure 1.

    Enrollment and Randomization. Of the 1107 patients who were assessed for eligibility, 1063 underwent randomization. 541 were assigned to the remdesivir group and 522 to the placebo group (Figure 1). Of those assigned to receive remdesivir, 531 patients (98.2%) received the treatment as assigned. Forty-nine patients had remdesivir treatment discontinued before day 10 because of an adverse event or a serious adverse event other than death (36 patients) or because the patient withdrew consent (13).

    Of those assigned to receive placebo, 518 patients (99.2%) received placebo as assigned. Fifty-three patients discontinued placebo before day 10 because of an adverse event or a serious adverse event other than death (36 patients), because the patient withdrew consent (15), or because the patient was found to be ineligible for trial enrollment (2). As of April 28, 2020, a total of 391 patients in the remdesivir group and 340 in the placebo group had completed the trial through day 29, recovered, or died. Eight patients who received remdesivir and 9 who received placebo terminated their participation in the trial before day 29. There were 132 patients in the remdesivir group and 169 in the placebo group who had not recovered and had not completed the day 29 follow-up visit.

    The analysis population included 1059 patients for whom we have at least some postbaseline data available (538 in the remdesivir group and 521 in the placebo group). Four of the 1063 patients were not included in the primary analysis because no postbaseline data were available at the time of the database freeze. Table 1. Table 1. Demographic and Clinical Characteristics at Baseline.

    The mean age of patients was 58.9 years, and 64.3% were male (Table 1). On the basis of the evolving epidemiology of Covid-19 during the trial, 79.8% of patients were enrolled at sites in North America, 15.3% in Europe, and 4.9% in Asia (Table S1). Overall, 53.2% of the patients were white, 20.6% were black, 12.6% were Asian, and 13.6% were designated as other or not reported. 249 (23.4%) were Hispanic or Latino. Most patients had either one (27.0%) or two or more (52.1%) of the prespecified coexisting conditions at enrollment, most commonly hypertension (49.6%), obesity (37.0%), and type 2 diabetes mellitus (29.7%).

    The median number of days between symptom onset and randomization was 9 (interquartile range, 6 to 12). Nine hundred forty-three (88.7%) patients had severe disease at enrollment as defined in the Supplementary Appendix. 272 (25.6%) patients met category 7 criteria on the ordinal scale, 197 (18.5%) category 6, 421 (39.6%) category 5, and 127 (11.9%) category 4. There were 46 (4.3%) patients who had missing ordinal scale data at enrollment. No substantial imbalances in baseline characteristics were observed between the remdesivir group and the placebo group.

    Primary Outcome Figure 2. Figure 2. Kaplan–Meier Estimates of Cumulative Recoveries. Cumulative recovery estimates are shown in the overall population (Panel A), in patients with a baseline score of 4 on the ordinal scale (not receiving oxygen. Panel B), in those with a baseline score of 5 (receiving oxygen.

    Panel C), in those with a baseline score of 6 (receiving high-flow oxygen or noninvasive mechanical ventilation. Panel D), and in those with a baseline score of 7 (receiving mechanical ventilation or ECMO. Panel E). Table 2. Table 2.

    Outcomes Overall and According to Score on the Ordinal Scale in the Intention-to-Treat Population. Figure 3. Figure 3. Time to Recovery According to Subgroup. The widths of the confidence intervals have not been adjusted for multiplicity and therefore cannot be used to infer treatment effects.

    Race and ethnic group were reported by the patients. Patients in the remdesivir group had a shorter time to recovery than patients in the placebo group (median, 11 days, as compared with 15 days. Rate ratio for recovery, 1.32. 95% confidence interval [CI], 1.12 to 1.55. P<0.001.

    1059 patients (Figure 2 and Table 2). Among patients with a baseline ordinal score of 5 (421 patients), the rate ratio for recovery was 1.47 (95% CI, 1.17 to 1.84). Among patients with a baseline score of 4 (127 patients) and those with a baseline score of 6 (197 patients), the rate ratio estimates for recovery were 1.38 (95% CI, 0.94 to 2.03) and 1.20 (95% CI, 0.79 to 1.81), respectively. For those receiving mechanical ventilation or ECMO at enrollment (baseline ordinal scores of 7. 272 patients), the rate ratio for recovery was 0.95 (95% CI, 0.64 to 1.42).

    A test of interaction of treatment with baseline score on the ordinal scale was not significant. An analysis adjusting for baseline ordinal score as a stratification variable was conducted to evaluate the overall effect (of the percentage of patients in each ordinal score category at baseline) on the primary outcome. This adjusted analysis produced a similar treatment-effect estimate (rate ratio for recovery, 1.31. 95% CI, 1.12 to 1.54. 1017 patients).

    Table S2 in the Supplementary Appendix shows results according to the baseline severity stratum of mild-to-moderate as compared with severe. Patients who underwent randomization during the first 10 days after the onset of symptoms had a rate ratio for recovery of 1.28 (95% CI, 1.05 to 1.57. 664 patients), whereas patients who underwent randomization more than 10 days after the onset of symptoms had a rate ratio for recovery of 1.38 (95% CI, 1.05 to 1.81. 380 patients) (Figure 3). Key Secondary Outcome The odds of improvement in the ordinal scale score were higher in the remdesivir group, as determined by a proportional odds model at the day 15 visit, than in the placebo group (odds ratio for improvement, 1.50.

    95% CI, 1.18 to 1.91. P=0.001. 844 patients) (Table 2 and Fig. S5). Mortality was numerically lower in the remdesivir group than in the placebo group, but the difference was not significant (hazard ratio for death, 0.70.

    95% CI, 0.47 to 1.04. 1059 patients). The Kaplan–Meier estimates of mortality by 14 days were 7.1% and 11.9% in the remdesivir and placebo groups, respectively (Table 2). The Kaplan–Meier estimates of mortality by 28 days are not reported in this preliminary analysis, given the large number of patients that had yet to complete day 29 visits. An analysis with adjustment for baseline ordinal score as a stratification variable showed a hazard ratio for death of 0.74 (95% CI, 0.50 to 1.10).

    Safety Outcomes Serious adverse events occurred in 114 patients (21.1%) in the remdesivir group and 141 patients (27.0%) in the placebo group (Table S3). 4 events (2 in each group) were judged by site investigators to be related to remdesivir or placebo. There were 28 serious respiratory failure adverse events in the remdesivir group (5.2% of patients) and 42 in the placebo group (8.0% of patients). Acute respiratory failure, hypotension, viral pneumonia, and acute kidney injury were slightly more common among patients in the placebo group. No deaths were considered to be related to treatment assignment, as judged by the site investigators.

    Grade 3 or 4 adverse events occurred in 156 patients (28.8%) in the remdesivir group and in 172 in the placebo group (33.0%) (Table S4). The most common adverse events in the remdesivir group were anemia or decreased hemoglobin (43 events [7.9%], as compared with 47 [9.0%] in the placebo group). Acute kidney injury, decreased estimated glomerular filtration rate or creatinine clearance, or increased blood creatinine (40 events [7.4%], as compared with 38 [7.3%]). Pyrexia (27 events [5.0%], as compared with 17 [3.3%]). Hyperglycemia or increased blood glucose level (22 events [4.1%], as compared with 17 [3.3%]).

    And increased aminotransferase levels including alanine aminotransferase, aspartate aminotransferase, or both (22 events [4.1%], as compared with 31 [5.9%]). Otherwise, the incidence of adverse events was not found to be significantly different between the remdesivir group and the placebo group.Trial Design and Oversight We conducted a randomized, double-blind, placebo-controlled trial to evaluate postexposure prophylaxis with hydroxychloroquine after exposure to Covid-19.12 We randomly assigned participants in a 1:1 ratio to receive either hydroxychloroquine or placebo. Participants had known exposure (by participant report) to a person with laboratory-confirmed Covid-19, whether as a household contact, a health care worker, or a person with other occupational exposures. Trial enrollment began on March 17, 2020, with an eligibility threshold to enroll within 3 days after exposure. The objective was to intervene before the median incubation period of 5 to 6 days.

    Because of limited access to prompt testing, health care workers could initially be enrolled on the basis of presumptive high-risk exposure to patients with pending tests. However, on March 23, eligibility was changed to exposure to a person with a positive polymerase-chain-reaction (PCR) assay for SARS-CoV-2, with the eligibility window extended to within 4 days after exposure. This trial was approved by the institutional review board at the University of Minnesota and conducted under a Food and Drug Administration Investigational New Drug application. In Canada, the trial was approved by Health Canada. Ethics approvals were obtained from the Research Institute of the McGill University Health Centre, the University of Manitoba, and the University of Alberta.

    Participants We included participants who had household or occupational exposure to a person with confirmed Covid-19 at a distance of less than 6 ft for more than 10 minutes while wearing neither a face mask nor an eye shield (high-risk exposure) or while wearing a face mask but no eye shield (moderate-risk exposure). Participants were excluded if they were younger than 18 years of age, were hospitalized, or met other exclusion criteria (see the Supplementary Appendix, available with the full text of this article at NEJM.org). Persons with symptoms of Covid-19 or with PCR-proven SARS-CoV-2 infection were excluded from this prevention trial but were separately enrolled in a companion clinical trial to treat early infection. Setting Recruitment was performed primarily with the use of social media outreach as well as traditional media platforms. Participants were enrolled nationwide in the United States and in the Canadian provinces of Quebec, Manitoba, and Alberta.

    Participants enrolled themselves through a secure Internet-based survey using the Research Electronic Data Capture (REDCap) system.13 After participants read the consent form, their comprehension of its contents was assessed. Participants provided a digitally captured signature to indicate informed consent. We sent follow-up e-mail surveys on days 1, 5, 10, and 14. A survey at 4 to 6 weeks asked about any follow-up testing, illness, or hospitalizations. Participants who did not respond to follow-up surveys received text messages, e-mails, telephone calls, or a combination of these to ascertain their outcomes.

    When these methods were unsuccessful, the emergency contact provided by the enrollee was contacted to determine the participant’s illness and vital status. When all communication methods were exhausted, Internet searches for obituaries were performed to ascertain vital status. Interventions Randomization occurred at research pharmacies in Minneapolis and Montreal. The trial statisticians generated a permuted-block randomization sequence using variably sized blocks of 2, 4, or 8, with stratification according to country. A research pharmacist sequentially assigned participants.

    The assignments were concealed from investigators and participants. Only pharmacies had access to the randomization sequence. Hydroxychloroquine sulfate or placebo was dispensed and shipped overnight to participants by commercial courier. The dosing regimen for hydroxychloroquine was 800 mg (4 tablets) once, then 600 mg (3 tablets) 6 to 8 hours later, then 600 mg (3 tablets) daily for 4 more days for a total course of 5 days (19 tablets total). If participants had gastrointestinal upset, they were advised to divide the daily dose into two or three doses.

    We chose this hydroxychloroquine dosing regimen on the basis of pharmacokinetic simulations to achieve plasma concentrations above the SARS-CoV-2 in vitro half maximal effective concentration for 14 days.14 Placebo folate tablets, which were similar in appearance to the hydroxychloroquine tablets, were prescribed as an identical regimen for the control group. Rising Pharmaceuticals provided a donation of hydroxychloroquine, and some hydroxychloroquine was purchased. Outcomes The primary outcome was prespecified as symptomatic illness confirmed by a positive molecular assay or, if testing was unavailable, Covid-19–related symptoms. We assumed that health care workers would have access to Covid-19 testing if symptomatic. However, access to testing was limited throughout the trial period.

    Covid-19–related symptoms were based on U.S. Council for State and Territorial Epidemiologists criteria for confirmed cases (positivity for SARS-Cov-2 on PCR assay), probable cases (the presence of cough, shortness of breath, or difficulty breathing, or the presence of two or more symptoms of fever, chills, rigors, myalgia, headache, sore throat, and new olfactory and taste disorders), and possible cases (the presence of one or more compatible symptoms, which could include diarrhea).15 All the participants had epidemiologic linkage,15 per trial eligibility criteria. Four infectious disease physicians who were unaware of the trial-group assignments reviewed symptomatic participants to generate a consensus with respect to whether their condition met the case definition.15 Secondary outcomes included the incidence of hospitalization for Covid-19 or death, the incidence of PCR-confirmed SARS-CoV-2 infection, the incidence of Covid-19 symptoms, the incidence of discontinuation of the trial intervention owing to any cause, and the severity of symptoms (if any) at days 5 and 14 according to a visual analogue scale (scores ranged from 0 [no symptoms] to 10 [severe symptoms]). Data on adverse events were also collected with directed questioning for common side effects along with open-ended free text. Outcome data were measured within 14 days after trial enrollment.

    Outcome data including PCR testing results, possible Covid-19–related symptoms, adherence to the trial intervention, side effects, and hospitalizations were all collected through participant report. Details of trial conduct are provided in the protocol and statistical analysis plan, available at NEJM.org. Sample Size We anticipated that illness compatible with Covid-19 would develop in 10% of close contacts exposed to Covid-19.9 Using Fisher’s exact method with a 50% relative effect size to reduce new symptomatic infections, a two-sided alpha of 0.05, and 90% power, we estimated that 621 persons would need to be enrolled in each group. With a pragmatic, Internet-based, self-referral recruitment strategy, we planned for a 20% incidence of attrition by increasing the sample size to 750 participants per group. We specified a priori that participants who were already symptomatic on day 1 before receiving hydroxychloroquine or placebo would be excluded from the prophylaxis trial and would instead be separately enrolled in the companion symptomatic treatment trial.

    Because the estimates for both incident symptomatic Covid-19 after an exposure and loss to follow-up were relatively unknown in early March 2020,9 the protocol prespecified a sample-size reestimation at the second interim analysis. This reestimation, which used the incidence of new infections in the placebo group and the observed percentage of participants lost to follow-up, was aimed at maintaining the ability to detect an effect size of a 50% relative reduction in new symptomatic infections. Interim Analyses An independent data and safety monitoring board externally reviewed the data after 25% and 50% of the participants had completed 14 days of follow-up. Stopping guidelines were provided to the data and safety monitoring board with the use of a Lan–DeMets spending function analogue of the O’Brien–Fleming boundaries for the primary outcome. A conditional power analysis was performed at the second and third interim analysis with the option of early stopping for futility.

    At the second interim analysis on April 22, 2020, the sample size was reduced to 956 participants who could be evaluated with 90% power on the basis of the higher-than-expected event rate of infections in the control group. At the third interim analysis on May 6, the trial was halted on the basis of a conditional power of less than 1%, since it was deemed futile to continue. Statistical Analysis We assessed the incidence of Covid-19 disease by day 14 with Fisher’s exact test. Secondary outcomes with respect to percentage of patients were also compared with Fisher’s exact test. Among participants in whom incident illness compatible with Covid-19 developed, we summarized the symptom severity score at day 14 with the median and interquartile range and assessed the distributions with a Kruskal–Wallis test.

    We conducted all analyses with SAS software, version 9.4 (SAS Institute), according to the intention-to-treat principle, with two-sided type I error with an alpha of 0.05. For participants with missing outcome data, we conducted a sensitivity analysis with their outcomes excluded or included as an event. Subgroups that were specified a priori included type of contact (household vs. Health care), days from exposure to enrollment, age, and sex..

    Buy accupril online without prescription

    Many athletes buy accupril online without prescription have had their baseball season http://www.amisdepasteur.fr/where-to-get-accupril/ shortened or cancelled due to COVID-19. This extra rest can be helpful in decreasing stress on the shoulder and elbow joints, but it can also lead to decreased strength and ROM. Overhead athletes need to keep their bodies buy accupril online without prescription strong, and a great way to achieve that is by performing a regular strengthening program. With many gyms remaining closed or limiting access during social distancing, that can be even more challenging.

    However, there are many exercises that can be done at home with minimal equipment buy accupril online without prescription needs. A great program to focus on during the off season is the Thrower’s Ten program that was developed with the overhead athlete in mind. These exercises focus on the muscle groups that matter most for the overhead athlete. We use our entire buy accupril online without prescription body to throw a ball and the stress on the shoulder to decelerate the arm is about twice our body weight.

    Most of this stress gets placed on the rotator cuff and scapular muscles that slow the arm down as we follow through with our throw. Weakness in buy accupril online without prescription these muscles can lead to problems with the shoulder and elbow joints. Common injuries can be Little League shoulder and elbow or strains to the ulnar collateral ligaments (Tommy John). If you have dealt with pain or injuries in the past, a comprehensive evaluation buy accupril online without prescription by a physical therapist (PT) who focuses on treating the overhead athlete can be extremely helpful in identifying areas of concern.

    Your PT will evaluate your strength with a dynamometer to look at any significant abnormalities between shoulders. They can also perform a video throwing analysis to look at ways to potentially reduce injury risk and improve performance. This can almost always be achieved with only a couple of visits, and the off season is a great time to start addressing areas of concern buy accupril online without prescription to be ready for next season or throwing during the winter. Your PT can help you develop a customized home exercise program based on your needs.

    Physical Therapist Kyle Stevenson, D.P.T., sees patients buy accupril online without prescription at MidMichigan’s Rehabilitation Services location in Greater Midland North-End Fitness Center. He has a special interest in sports medicine, and enjoys working with athletes of all ages. He has buy accupril online without prescription completed specialized coursework and training for the throwing athletes. New patients are welcome with a physician referral by calling (989) 832-5913.

    Those who would like more information about MidMichigan’s Rehabilitation Services may visit www.midmichigan.org/rehabilitation..

    Many athletes have had their baseball season shortened or cancelled accupril street price due to COVID-19. This extra rest can be helpful in decreasing stress on the shoulder and elbow joints, but it can also lead to decreased strength and ROM. Overhead athletes need to keep their bodies strong, and a great way to achieve that is by performing a regular accupril street price strengthening program. With many gyms remaining closed or limiting access during social distancing, that can be even more challenging.

    However, there are many accupril street price exercises that can be done at home with minimal equipment needs. A great program to focus on during the off season is the Thrower’s Ten program that was developed with the overhead athlete in mind. These exercises focus on the muscle groups that matter most for the overhead athlete. We use our entire body to throw a ball and the stress on the shoulder to decelerate accupril street price the arm is about twice our body weight.

    Most of this stress gets placed on the rotator cuff and scapular muscles that slow the arm down as we follow through with our throw. Weakness in these muscles can lead to problems with the shoulder and elbow joints accupril street price. Common injuries can be Little League shoulder and elbow or strains to the ulnar collateral ligaments (Tommy John). If you have dealt with pain or injuries in the accupril street price past, a comprehensive evaluation by a physical therapist (PT) who focuses on treating the overhead athlete can be extremely helpful in identifying areas of concern.

    Your PT will evaluate your strength with a dynamometer to look at any significant abnormalities between shoulders. They can also perform a video throwing analysis to look at ways to potentially reduce injury risk and improve performance. This can accupril street price almost always be achieved with only a couple of visits, and the off season is a great time to start addressing areas of concern to be ready for next season or throwing during the winter. Your PT can help you develop a customized home exercise program based on your needs.

    Physical Therapist Kyle Stevenson, D.P.T., sees patients at accupril street price MidMichigan’s Rehabilitation Services location in Greater Midland North-End Fitness Center. He has a special interest in sports medicine, and enjoys working with athletes of all ages. He has completed specialized coursework and training accupril street price for the throwing athletes. New patients are welcome with a physician referral by calling (989) 832-5913.

    Those who would like more information about MidMichigan’s Rehabilitation Services may visit www.midmichigan.org/rehabilitation..

    Accupril online without prescription

    NCHS Data accupril online without prescription Brief No. 286, September 2017PDF Versionpdf icon (374 KB)Anjel Vahratian, Ph.D.Key findingsData from the National Health Interview Survey, 2015Among those aged 40–59, perimenopausal women (56.0%) were more likely than postmenopausal (40.5%) and premenopausal (32.5%) women to sleep less than 7 hours, on average, in a 24-hour period.Postmenopausal women aged 40–59 were more likely than premenopausal women aged 40–59 to have trouble falling asleep (27.1% compared with 16.8%, respectively), and staying asleep (35.9% compared with 23.7%), four times or more in the past week.Postmenopausal women aged 40–59 (55.1%) were more likely than premenopausal women aged 40–59 (47.0%) to not wake up feeling well rested 4 days or more in the past week.Sleep duration and quality are important contributors to health and wellness. Insufficient sleep is associated with an increased risk for accupril online without prescription chronic conditions such as cardiovascular disease (1) and diabetes (2). Women may be particularly vulnerable to sleep problems during times of reproductive hormonal change, such as after the menopausal transition.

    Menopause is “the permanent cessation of menstruation that occurs after accupril online without prescription the loss of ovarian activity” (3). This data brief describes sleep duration and sleep quality among nonpregnant women aged 40–59 by menopausal status. The age range selected for this analysis reflects the focus on midlife sleep health. In this analysis, 74.2% of women are accupril online without prescription premenopausal, 3.7% are perimenopausal, and 22.1% are postmenopausal.

    Keywords. Insufficient sleep, menopause, National accupril online without prescription Health Interview Survey Perimenopausal women were more likely than premenopausal and postmenopausal women to sleep less than 7 hours, on average, in a 24-hour period.More than one in three nonpregnant women aged 40–59 slept less than 7 hours, on average, in a 24-hour period (35.1%) (Figure 1). Perimenopausal women were most likely to sleep less than 7 hours, on average, in a 24-hour period (56.0%), compared with 32.5% of premenopausal and 40.5% of postmenopausal women. Postmenopausal women were significantly more likely than premenopausal women to sleep less than 7 hours, on average, in a 24-hour period.

    Figure 1 accupril online without prescription. Percentage of nonpregnant women aged 40–59 who slept less than 7 hours, on average, in a 24-hour period, by menopausal status. United States, 2015image icon1Significant quadratic trend by menopausal status (p accupril online without prescription <. 0.05).NOTES.

    Women were postmenopausal if they had gone without a menstrual cycle for more than 1 year or were in surgical menopause after the removal of their ovaries. Women were perimenopausal if they no longer had a menstrual cycle and their accupril online without prescription last menstrual cycle was 1 year ago or less. Women were premenopausal if they still had a menstrual cycle. Access data table for Figure 1pdf icon.SOURCE accupril online without prescription.

    NCHS, National Health Interview Survey, 2015. The percentage of women aged 40–59 who had accupril online without prescription trouble falling asleep four times or more in the past week varied by menopausal status.Nearly one in five nonpregnant women aged 40–59 had trouble falling asleep four times or more in the past week (19.4%) (Figure 2). The percentage of women in this age group who had trouble falling asleep four times or more in the past week increased from 16.8% among premenopausal women to 24.7% among perimenopausal and 27.1% among postmenopausal women. Postmenopausal women were significantly more likely than premenopausal women to have trouble falling asleep four times or more in the past week.

    Figure 2 accupril online without prescription. Percentage of nonpregnant women aged 40–59 who had trouble falling asleep four times or more in the past week, by menopausal status. United States, accupril online without prescription 2015image icon1Significant linear trend by menopausal status (p <. 0.05).NOTES.

    Women were postmenopausal if they had gone without a menstrual cycle for more than 1 year or were in surgical menopause after the removal of their ovaries. Women were perimenopausal if they no longer had a menstrual cycle and their last menstrual accupril online without prescription cycle was 1 year ago or less. Women were premenopausal if they still had a menstrual cycle. Access data table accupril online without prescription for Figure 2pdf icon.SOURCE.

    NCHS, National Health Interview Survey, 2015. The percentage of women aged 40–59 who had trouble staying asleep four times or more in the past week varied by menopausal status.More than one in four nonpregnant women aged 40–59 had trouble staying asleep four times or more in the accupril online without prescription past week (26.7%) (Figure 3). The percentage of women aged 40–59 who had trouble staying asleep four times or more in the past week increased from 23.7% among premenopausal, to 30.8% among perimenopausal, and to 35.9% among postmenopausal women. Postmenopausal women were significantly more likely than premenopausal women to have trouble staying asleep four times or more in the past week.

    Figure 3 accupril online without prescription. Percentage of nonpregnant women aged 40–59 who had trouble staying asleep four times or more in the past week, by menopausal status. United States, 2015image icon1Significant linear trend by menopausal status (p accupril online without prescription <. 0.05).NOTES.

    Women were postmenopausal if they had gone without a menstrual cycle for more than 1 year or were in surgical menopause after the removal of their ovaries. Women were perimenopausal if they no accupril online without prescription longer had a menstrual cycle and their last menstrual cycle was 1 year ago or less. Women were premenopausal if they still had a menstrual cycle. Access data table for accupril online without prescription Figure 3pdf icon.SOURCE.

    NCHS, National Health Interview Survey, 2015. The percentage of women aged 40–59 who did not wake up feeling well rested 4 days or more in the past week varied by menopausal status.Nearly one in two nonpregnant women aged 40–59 did not wake up feeling well rested 4 days or more in the past week (48.9%) (Figure 4). The percentage of women in this age group who did not wake up feeling well rested 4 days accupril online without prescription or more in the past week increased from 47.0% among premenopausal women to 49.9% among perimenopausal and 55.1% among postmenopausal women. Postmenopausal women were significantly more likely than premenopausal women to not wake up feeling well rested 4 days or more in the past week.

    Figure 4 accupril online without prescription. Percentage of nonpregnant women aged 40–59 who did not wake up feeling well rested 4 days or more in the past week, by menopausal status. United States, 2015image icon1Significant linear trend by menopausal status (p <. 0.05).NOTES.

    Women were postmenopausal if they had gone without a menstrual cycle for more than 1 year or were in surgical menopause after the removal of their ovaries. Women were perimenopausal if they no longer had a menstrual cycle and their last menstrual cycle was 1 year ago or less. Women were premenopausal if they still had a menstrual cycle. Access data table for Figure 4pdf icon.SOURCE.

    NCHS, National Health Interview Survey, 2015. SummaryThis report describes sleep duration and sleep quality among U.S. Nonpregnant women aged 40–59 by menopausal status. Perimenopausal women were most likely to sleep less than 7 hours, on average, in a 24-hour period compared with premenopausal and postmenopausal women.

    In contrast, postmenopausal women were most likely to have poor-quality sleep. A greater percentage of postmenopausal women had frequent trouble falling asleep, staying asleep, and not waking well rested compared with premenopausal women. The percentage of perimenopausal women with poor-quality sleep was between the percentages for the other two groups in all three categories. Sleep duration changes with advancing age (4), but sleep duration and quality are also influenced by concurrent changes in women’s reproductive hormone levels (5).

    Because sleep is critical for optimal health and well-being (6), the findings in this report highlight areas for further research and targeted health promotion. DefinitionsMenopausal status. A three-level categorical variable was created from a series of questions that asked women. 1) “How old were you when your periods or menstrual cycles started?.

    €. 2) “Do you still have periods or menstrual cycles?. €. 3) “When did you have your last period or menstrual cycle?.

    €. And 4) “Have you ever had both ovaries removed, either as part of a hysterectomy or as one or more separate surgeries?. € Women were postmenopausal if they a) had gone without a menstrual cycle for more than 1 year or b) were in surgical menopause after the removal of their ovaries. Women were perimenopausal if they a) no longer had a menstrual cycle and b) their last menstrual cycle was 1 year ago or less.

    Premenopausal women still had a menstrual cycle.Not waking feeling well rested. Determined by respondents who answered 3 days or less on the questionnaire item asking, “In the past week, on how many days did you wake up feeling well rested?. €Short sleep duration. Determined by respondents who answered 6 hours or less on the questionnaire item asking, “On average, how many hours of sleep do you get in a 24-hour period?.

    €Trouble falling asleep. Determined by respondents who answered four times or more on the questionnaire item asking, “In the past week, how many times did you have trouble falling asleep?. €Trouble staying asleep. Determined by respondents who answered four times or more on the questionnaire item asking, “In the past week, how many times did you have trouble staying asleep?.

    € Data source and methodsData from the 2015 National Health Interview Survey (NHIS) were used for this analysis. NHIS is a multipurpose health survey conducted continuously throughout the year by the National Center for Health Statistics. Interviews are conducted in person in respondents’ homes, but follow-ups to complete interviews may be conducted over the telephone. Data for this analysis came from the Sample Adult core and cancer supplement sections of the 2015 NHIS.

    For more information about NHIS, including the questionnaire, visit the NHIS website.All analyses used weights to produce national estimates. Estimates on sleep duration and quality in this report are nationally representative of the civilian, noninstitutionalized nonpregnant female population aged 40–59 living in households across the United States. The sample design is described in more detail elsewhere (7). Point estimates and their estimated variances were calculated using SUDAAN software (8) to account for the complex sample design of NHIS.

    Linear and quadratic trend tests of the estimated proportions across menopausal status were tested in SUDAAN via PROC DESCRIPT using the POLY option. Differences between percentages were evaluated using two-sided significance tests at the 0.05 level. About the authorAnjel Vahratian is with the National Center for Health Statistics, Division of Health Interview Statistics. The author gratefully acknowledges the assistance of Lindsey Black in the preparation of this report.

    ReferencesFord ES. Habitual sleep duration and predicted 10-year cardiovascular risk using the pooled cohort risk equations among US adults. J Am Heart Assoc 3(6):e001454. 2014.Ford ES, Wheaton AG, Chapman DP, Li C, Perry GS, Croft JB.

    Associations between self-reported sleep duration and sleeping disorder with concentrations of fasting and 2-h glucose, insulin, and glycosylated hemoglobin among adults without diagnosed diabetes. J Diabetes 6(4):338–50. 2014.American College of Obstetrics and Gynecology. ACOG Practice Bulletin No.

    141. Management of menopausal symptoms. Obstet Gynecol 123(1):202–16. 2014.Black LI, Nugent CN, Adams PF.

    Tables of adult health behaviors, sleep. National Health Interview Survey, 2011–2014pdf icon. 2016.Santoro N. Perimenopause.

    From research to practice. J Women’s Health (Larchmt) 25(4):332–9. 2016.Watson NF, Badr MS, Belenky G, Bliwise DL, Buxton OM, Buysse D, et al. Recommended amount of sleep for a healthy adult.

    A joint consensus statement of the American Academy of Sleep Medicine and Sleep Research Society. J Clin Sleep Med 11(6):591–2. 2015.Parsons VL, Moriarity C, Jonas K, et al. Design and estimation for the National Health Interview Survey, 2006–2015.

    National Center for Health Statistics. Vital Health Stat 2(165). 2014.RTI International. SUDAAN (Release 11.0.0) [computer software].

    2012. Suggested citationVahratian A. Sleep duration and quality among women aged 40–59, by menopausal status. NCHS data brief, no 286.

    Hyattsville, MD. National Center for Health Statistics. 2017.Copyright informationAll material appearing in this report is in the public domain and may be reproduced or copied without permission. Citation as to source, however, is appreciated.National Center for Health StatisticsCharles J.

    Rothwell, M.S., M.B.A., DirectorJennifer H. Madans, Ph.D., Associate Director for ScienceDivision of Health Interview StatisticsMarcie L. Cynamon, DirectorStephen J. Blumberg, Ph.D., Associate Director for Science.

    NCHS Data Brief accupril street price No. 286, September 2017PDF Versionpdf icon (374 KB)Anjel Vahratian, Ph.D.Key findingsData from the National Health Interview Survey, 2015Among those aged 40–59, perimenopausal women (56.0%) were more likely than postmenopausal (40.5%) and premenopausal (32.5%) women to sleep less than 7 hours, on average, in a 24-hour period.Postmenopausal women aged 40–59 were more likely than premenopausal women aged 40–59 to have trouble falling asleep (27.1% compared with 16.8%, respectively), and staying asleep (35.9% compared with 23.7%), four times or more in the past week.Postmenopausal women aged 40–59 (55.1%) were more likely than premenopausal women aged 40–59 (47.0%) to not wake up feeling well rested 4 days or more in the past week.Sleep duration and quality are important contributors to health and wellness. Insufficient sleep is associated with an increased risk for chronic accupril street price conditions such as cardiovascular disease (1) and diabetes (2). Women may be particularly vulnerable to sleep problems during times of reproductive hormonal change, such as after the menopausal transition.

    Menopause is “the permanent cessation of menstruation that occurs after the accupril street price loss of ovarian activity” (3). This data brief describes sleep duration and sleep quality among nonpregnant women aged 40–59 by menopausal status. The age range selected for this analysis reflects the focus on midlife sleep health. In this analysis, accupril street price 74.2% of women are premenopausal, 3.7% are perimenopausal, and 22.1% are postmenopausal.

    Keywords. Insufficient sleep, menopause, National Health Interview Survey Perimenopausal women were more likely than premenopausal and postmenopausal women to sleep less than accupril street price 7 hours, on average, in a 24-hour period.More than one in three nonpregnant women aged 40–59 slept less than 7 hours, on average, in a 24-hour period (35.1%) (Figure 1). Perimenopausal women were most likely to sleep less than 7 hours, on average, in a 24-hour period (56.0%), compared with 32.5% of premenopausal and 40.5% of postmenopausal women. Postmenopausal women were significantly more likely than premenopausal women to sleep less than 7 hours, on average, in a 24-hour period.

    Figure 1 accupril street price. Percentage of nonpregnant women aged 40–59 who slept less than 7 hours, on average, in a 24-hour period, by menopausal status. United States, 2015image icon1Significant quadratic accupril street price trend by menopausal status (p <. 0.05).NOTES.

    Women were postmenopausal if they had gone without a menstrual cycle for more than 1 year or were in surgical menopause after the removal of their ovaries. Women were perimenopausal if accupril street price they no longer had a menstrual cycle and their last menstrual cycle was 1 year ago or less. Women were premenopausal if they still had a menstrual cycle. Access data table for Figure 1pdf accupril street price icon.SOURCE.

    NCHS, National Health Interview Survey, 2015. The percentage of women aged 40–59 who had trouble falling asleep four accupril street price times or more in the past week varied by menopausal status.Nearly one in five nonpregnant women aged 40–59 had trouble falling asleep four times or more in the past week (19.4%) (Figure 2). The percentage of women in this age group who had trouble falling asleep four times or more in the past week increased from 16.8% among premenopausal women to 24.7% among perimenopausal and 27.1% among postmenopausal women. Postmenopausal women were significantly more likely than premenopausal women to have trouble falling asleep four times or more in the past week.

    Figure 2 accupril street price. Percentage of nonpregnant women aged 40–59 who had trouble falling asleep four times or more in the past week, by menopausal status. United States, 2015image icon1Significant accupril street price linear trend by menopausal status (p <. 0.05).NOTES.

    Women were postmenopausal if they had gone without a menstrual cycle for more than 1 year or were in surgical menopause after the removal of their ovaries. Women were perimenopausal if they no longer accupril street price had a menstrual cycle and their last menstrual cycle was 1 year ago or less. Women were premenopausal if they still had a menstrual cycle. Access data table for Figure 2pdf accupril street price icon.SOURCE.

    NCHS, National Health Interview Survey, 2015. The percentage of women aged 40–59 who had trouble staying asleep four times or more in the past week varied by menopausal status.More accupril street price than one in four nonpregnant women aged 40–59 had trouble staying asleep four times or more in the past week (26.7%) (Figure 3). The percentage of women aged 40–59 who had trouble staying asleep four times or more in the past week increased from 23.7% among premenopausal, to 30.8% among perimenopausal, and to 35.9% among postmenopausal women. Postmenopausal women were significantly more likely than premenopausal women to have trouble staying asleep four times or more in the past week.

    Figure 3 accupril street price. Percentage of nonpregnant women aged 40–59 who had trouble staying asleep four times or more in the past week, by menopausal status. United States, 2015image icon1Significant linear trend by accupril street price menopausal status (p <. 0.05).NOTES.

    Women were postmenopausal if they had gone without a menstrual cycle for more than 1 year or were in surgical menopause after the removal of their ovaries. Women were perimenopausal if they no accupril street price longer had a menstrual cycle and their last menstrual cycle was 1 year ago or less. Women were premenopausal if they still had a menstrual cycle. Access data table accupril street price for Figure 3pdf icon.SOURCE.

    NCHS, National Health Interview Survey, 2015. The percentage of women aged 40–59 who did not wake up feeling well rested 4 days or more in the past week varied by menopausal status.Nearly one in two nonpregnant women aged 40–59 did not wake up feeling well rested 4 days or more in the past week (48.9%) (Figure 4). The percentage of women in this age group who did not wake up feeling well rested 4 days or more in the past week increased from 47.0% among premenopausal women to accupril street price 49.9% among perimenopausal and 55.1% among postmenopausal women. Postmenopausal women were significantly more likely than premenopausal women to not wake up feeling well rested 4 days or more in the past week.

    Figure 4 accupril street price. Percentage of nonpregnant women aged 40–59 who did not wake up feeling well rested 4 days or more in the past week, by menopausal status. United States, 2015image icon1Significant linear trend by menopausal status (p <. 0.05).NOTES.

    Women were postmenopausal if they had gone without a menstrual cycle for more than 1 year or were in surgical menopause after the removal of their ovaries. Women were perimenopausal if they no longer had a menstrual cycle and their last menstrual cycle was 1 year ago or less. Women were premenopausal if they still had a menstrual cycle. Access data table for Figure 4pdf icon.SOURCE.

    NCHS, National Health Interview Survey, 2015. SummaryThis report describes sleep duration and sleep quality among U.S. Nonpregnant women aged 40–59 by menopausal status. Perimenopausal women were most likely to sleep less than 7 hours, on average, in a 24-hour period compared with premenopausal and postmenopausal women.

    In contrast, postmenopausal women were most likely to have poor-quality sleep. A greater percentage of postmenopausal women had frequent trouble falling asleep, staying asleep, and not waking well rested compared with premenopausal women. The percentage of perimenopausal women with poor-quality sleep was between the percentages for the other two groups in all three categories. Sleep duration changes with advancing age (4), but sleep duration and quality are also influenced by concurrent changes in women’s reproductive hormone levels (5).

    Because sleep is critical for optimal health and well-being (6), the findings in this report highlight areas for further research and targeted health promotion. DefinitionsMenopausal status. A three-level categorical variable was created from a series of questions that asked women. 1) “How old were you when your periods or menstrual cycles started?.

    €. 2) “Do you still have periods or menstrual cycles?. €. 3) “When did you have your last period or menstrual cycle?.

    €. And 4) “Have you ever had both ovaries removed, either as part of a hysterectomy or as one or more separate surgeries?. € Women were postmenopausal if they a) had gone without a menstrual cycle for more than 1 year or b) were in surgical menopause after the removal of their ovaries. Women were perimenopausal if they a) no longer had a menstrual cycle and b) their last menstrual cycle was 1 year ago or less.

    Premenopausal women still had a menstrual cycle.Not waking feeling well rested. Determined by respondents who answered 3 days or less on the questionnaire item asking, “In the past week, on how many days did you wake up feeling well rested?. €Short sleep duration. Determined by respondents who answered 6 hours or less on the questionnaire item asking, “On average, how many hours of sleep do you get in a 24-hour period?.

    €Trouble falling asleep. Determined by respondents who answered four times or more on the questionnaire item asking, “In the past week, how many times did you have trouble falling asleep?. €Trouble staying asleep. Determined by respondents who answered four times or more on the questionnaire item asking, “In the past week, how many times did you have trouble staying asleep?.

    € Data source and methodsData from the 2015 National Health Interview Survey (NHIS) were used for this analysis. NHIS is a multipurpose health survey conducted continuously throughout the year by the National Center for Health Statistics. Interviews are conducted in person in respondents’ homes, but follow-ups to complete interviews may be conducted over the telephone. Data for this analysis came from the Sample Adult core and cancer supplement sections of the 2015 NHIS.

    For more information about NHIS, including the questionnaire, visit the NHIS website.All analyses used weights to produce national estimates. Estimates on sleep duration and quality in this report are nationally representative of the civilian, noninstitutionalized nonpregnant female population aged 40–59 living in households across the United States. The sample design is described in more detail elsewhere (7). Point estimates and their estimated variances were calculated using SUDAAN software (8) to account for the complex sample design of NHIS.

    Linear and quadratic trend tests of the estimated proportions across menopausal status were tested in SUDAAN via PROC DESCRIPT using the POLY option. Differences between percentages were evaluated using two-sided significance tests at the 0.05 level. About the authorAnjel Vahratian is with the National Center for Health Statistics, Division of Health Interview Statistics. The author gratefully acknowledges the assistance of Lindsey Black in the preparation of this report.

    ReferencesFord ES. Habitual sleep duration and predicted 10-year cardiovascular risk using the pooled cohort risk equations among US adults. J Am Heart Assoc 3(6):e001454. 2014.Ford ES, Wheaton AG, Chapman DP, Li C, Perry GS, Croft JB.

    Associations between self-reported sleep duration and sleeping disorder with concentrations of fasting and 2-h glucose, insulin, and glycosylated hemoglobin among adults without diagnosed diabetes. J Diabetes 6(4):338–50. 2014.American College of Obstetrics and Gynecology. ACOG Practice Bulletin No.

    141. Management of menopausal symptoms. Obstet Gynecol 123(1):202–16. 2014.Black LI, Nugent CN, Adams PF.

    Tables of adult health behaviors, sleep. National Health Interview Survey, 2011–2014pdf icon. 2016.Santoro N. Perimenopause.

    From research to practice. J Women’s Health (Larchmt) 25(4):332–9. 2016.Watson NF, Badr MS, Belenky G, Bliwise DL, Buxton OM, Buysse D, et al. Recommended amount of sleep for a healthy adult.

    A joint consensus statement of the American Academy of Sleep Medicine and Sleep Research Society. J Clin Sleep Med 11(6):591–2. 2015.Parsons VL, Moriarity C, Jonas K, et al. Design and estimation for the National Health Interview Survey, 2006–2015.

    National Center for Health Statistics. Vital Health Stat 2(165). 2014.RTI International. SUDAAN (Release 11.0.0) [computer software].

    2012. Suggested citationVahratian A. Sleep duration and quality among women aged 40–59, by menopausal status. NCHS data brief, no 286.

    Hyattsville, MD. National Center for Health Statistics. 2017.Copyright informationAll material appearing in this report is in the public domain and may be reproduced or copied without permission. Citation as to source, however, is appreciated.National Center for Health StatisticsCharles J.

    Rothwell, M.S., M.B.A., DirectorJennifer H. Madans, Ph.D., Associate Director for ScienceDivision of Health Interview StatisticsMarcie L. Cynamon, DirectorStephen J. Blumberg, Ph.D., Associate Director for Science.

    Can you get accupril over the counter

    A Northern Westchester man was struck by a can you get accupril over the counter bullet while traveling on the Long Island Expressway, police said.The victim, a 28-year-old Peekskill resident, whose name has not been released, was struck in the leg in a drive-by shooting at approximately 11:30 p.m. In Melville on Monday, can you get accupril over the counter Sept. 7 near Route 110 and Round Swamp Road.Suffolk County police investigators said that the alleged shooter was driving on the Expressway before speeding away after the shooting.The Peekskill man was transported to Nassau University Medical Center with non-life-threatening injuries, where he was treated and has since been released.It is believed that the driver of the SUV was targeted by the shooter. A second passenger in the vehicle was uninjured.No suspect has been identified as the investigation into the shooting can you get accupril over the counter continues.

    Anyone with information has been asked to contact Suffolk County Police Second Squad detectives by calling (631) can you get accupril over the counter 854-8252 or Crime Stoppers at 1-800-220-TIPS. Click here to sign up for Daily Voice's free daily emails and news alerts..

    A Northern Westchester man accupril street price was struck by a bullet while traveling on the Long Island Expressway, police said.The victim, a 28-year-old Peekskill resident, whose name has not been released, was struck in the leg in a drive-by shooting at approximately 11:30 p.m. In Melville on Monday, Sept accupril street price. 7 near Route 110 and Round Swamp Road.Suffolk County police investigators said that the alleged shooter was driving on the Expressway before speeding away after the shooting.The Peekskill man was transported to Nassau University Medical Center with non-life-threatening injuries, where he was treated and has since been released.It is believed that the driver of the SUV was targeted by the shooter.

    A second passenger in the vehicle was uninjured.No suspect has been accupril street price identified as the investigation into the shooting continues. Anyone with information has been asked to contact Suffolk County Police Second Squad detectives by calling accupril street price (631) 854-8252 or Crime Stoppers at 1-800-220-TIPS. Click here to sign up for Daily Voice's free daily emails and news alerts..

  • Generic accupril prices

    Où rencontrer Pasteur dans Dole

    A la façon du Circuit du Chat Perché qui permet de découvrir les sites les plus attractifs de Dole, Alain Marchal nous propose de déambuler dans certains lieux publics dolois...pour admirer statues, fresques trompe-l’œil, mosaïques ou bustes à l'effigie...

    > LIRE LA SUITE

  • Generic accupril prices

    Où rencontrer Pasteur dans Dole

    A la façon du Circuit du Chat Perché qui permet de découvrir les sites les plus attractifs de Dole, Alain Marchal nous propose de déambuler dans certains lieux publics dolois...pour admirer statues, fresques trompe-l’œil, mosaïques ou bustes à l'effigie...

    > LIRE LA SUITE

  • Generic accupril prices

    Visite passion

    Pendant les vacances , venez faire la connaissance de Louis PASTEUR, visitez sa maison natale à Dole et la salle scientifique exposant les découvertes de notre grand savant Jurassien.
    Les bénévoles des Amis de PASTEUR vous proposent une "visite passion...

    > LIRE LA SUITE

  • Generic accupril prices

    Visite passion

    Pendant les vacances , venez faire la connaissance de Louis PASTEUR, visitez sa maison natale à Dole et la salle scientifique exposant les découvertes de notre grand savant Jurassien.
    Les bénévoles des Amis de PASTEUR vous proposent une "visite passion...

    > LIRE LA SUITE

  • Generic accupril prices

    Louis Pasteur et le ver à soie :


    Une exposition présentera à la Maison natale des aspects actuels de l'utilisation de la soie, dans les domaines industriels et techniques, dans la création artistique, avec un clin d'oeil aux travaux de Pasteur sur les maladies des vers à soie en...

    > LIRE LA SUITE

  • Generic accupril prices

    Visite passion

    Pendant les vacances , venez faire la connaissance de Louis PASTEUR, visitez sa maison natale à Dole et la salle scientifique exposant les découvertes de notre grand savant Jurassien.
    Les bénévoles des Amis de PASTEUR vous proposent une "visite passion...

    > LIRE LA SUITE