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Over the last few years, there have been buy kamagra online canada many articles detailing how bad sitting can be for the body. You may have even seen the phrase, “Sitting is the new smoking.” But how bad is sitting down, really?. As a physical therapist, I see many people who come into my office and sheepishly admit that buy kamagra online canada they sit all day long for their jobs.

As our reliance on technology for our jobs increases, this becomes more and more of the norm for society. Personally, I think sitting has gotten a bad rap, and what we really need to do is look at our buy kamagra online canada lack of physical activity overall. When we sit every day for our job, it can have a negative impact on the body, but an overall lack of physical activity is much more concerning than sitting itself.

When we sit, our bodies adapt to that position. There are several things that occur, such as a tightening of buy kamagra online canada the hamstrings and a forward head and rounded shoulder posture. We don’t use our core muscles when we sit, because our body is supported, so there can be a weakening of those muscles as well.

Our body gets used to not buy kamagra online canada having to use these muscle groups. Then, when you do try to get out and be active, or work in the yard, you might be more susceptible to injury or pain because your body isn’t used to that kind of stress. In short, you don’t need to quit your buy kamagra online canada day job to pursue a career that involves standing all day.

What you really need to do is increase your activity level outside of work and incorporate some regular exercises that combat the negative effects of sitting. These exercises can include core strengthening, stretching of the hips and chest and exercises to reverse your forward posture. If you are experiencing pain related to sitting for long periods of time, a physical therapist can help you identify a more buy kamagra online canada targeted exercise program.

Physical Therapist Kyle Stevenson, D.P.T., sees patients at MidMichigan’s Rehabilitation Services location in Greater Midland North-End Fitness Center. He has a buy kamagra online canada special interest in sports medicine, and enjoys working with athletes of all ages. He has completed specialized coursework and training for the throwing athletes.

New patients are welcome with a physician buy kamagra online canada referral by calling (989) 832-5913. Those who would like more information about MidMichigan’s Rehabilitation Services may visit www.midmichigan.org/rehabilitation.W-sitting is a normal developmental position that babies usually discover when they sit back straight from their hands and knees. Their legs will then form a “W.” Often, babies also transition back to a single hip, toward a side sitting position.

When a baby varies his or her sitting position, W-sitting is buy kamagra online canada rarely a problem. However, when a baby sits back straight to a W-sit consistently, they don’t get the opportunity to elongate and activate lateral trunk muscles to develop their core muscles. W-sitting is a very stable position that children find useful, however, it allows them to play without developing muscle that provide the buy kamagra online canada ability for kids to reach out to their sides or rotate across their midline, leading to underdevelopment of lower trunk muscles, which stabilize the pelvis.

When a child uses this position as their preference without the normal variety in movements, it can affect development. They may demonstrate an in-toeing gait, core weakness buy kamagra online canada or balance difficulties. The hips are positioned in extreme internal rotation, placing stress on the hips and the knee joints.

This can lead to hip and knee orthopedic issues as the child develops. So, what can buy kamagra online canada you do to prevent any development issues?. Encourage your child to alternate sitting positions, such as side sitting (alternating sides), ring sitting, or, with older children, sitting in a chair or on a ball.

This might be challenging initially, but once your child gets used to it, they may just need reminders buy kamagra online canada. If it’s difficult for your child to sit in alternate positions or they begin to show other developmental concerns, a referral to a physical therapist may be helpful to facilitate trunk muscle development. Eileen McMahon, M.S.P.T., is a physical therapist at MidMichigan Health..

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With specificity down to the colours you were to wear, buy kamagra online canada you’d think choosing an outfit would be pretty simple. You’d be wrong.It's buy kamagra online canada one week prior to the event. I'm in Melbourne’s Chadstone Shopping Centre spending ludicrous amounts of money, I don't have. Returning home buy kamagra online canada with several outfit and accessory options.

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She shares buy kamagra online canada her top tips with Body + Soul:PlanKeep note of any events, holidays or special occasions that you have coming up. Keep track of your shopping needs by listing the items in the notes on your phone, then tick off as you manage buy kamagra online canada to buy each item. Set yourself reminders too – so you don’t forget/avoid what you need to buy.Break it downSometimes the thought of everything needed to create an outfit can be totally overwhelming. The best thing buy kamagra online canada is to break it down and section the list – such as accessories/shoes/dress/makeup.Also, don’t put yourself under the pressure of buying everything in one go.

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For example, if you’re after a special event outfit, local shopping centres often don’t have the buy kamagra online canada widest selection and local shopping strips, or the CBD have more extensive options.Take with your second opinionIf you tend to get overwhelmed in stores and know you’re challenged making decisions, take someone with you whose opinion you trust.Set your budget and stick to itWhen you are a desperate shopper, you are shopping under pressure which is when you take what you can and when budgets are often blown.Be in the moodOnly shop when you’re feeling good, positive, and never shop when you’re hungry!. Your heart and head need to be in it!. Engage a personal stylistIf you want to bypass all the shopping stress and anxiety, you can always use a personal stylist who will do buy kamagra online canada the planning and research for you. If I had only had these tips back in 2017.Shona Hendley is a freelance buy kamagra online canada writer and ex-secondary school teacher.

You can follow her on Instagram. @shonamarion.Sarah Singer runs dressyu Melbourne, a Personal Styling Consultancy based in Melbourne offering a range of styling services to individual clients, groups, and buy kamagra online canada businesses. Contact her buy kamagra online canada at www.dressyu.com.au , sarah@dressyu.com.au, t 0422 033 071. Instagram dressyu_melbourne.

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Funding Will Help Communities, Hospitals, Health Clinics Respond to the kamagra and Support http://www.sunsoakedcreative.com/language-courses/ Local Efforts to Increase treatment Confidence and Uptake in Rural CommunitiesToday, thanks to the American Rescue Plan, the can i get kamagra over the counter U.S. Department of Health and Human Services (HHS) is announcing the availability of nearly $1 billion to strengthen erectile dysfunction treatment response efforts and increase vaccinations in rural communities. As part of the Biden Administration's commitment to expanding access to treatments and can i get kamagra over the counter ensuring equity in the erectile dysfunction treatment response, the Health Resources and Services Administration, a part of HHS, will increase the number of treatments sent to rural communities, expand testing and other erectile dysfunction treatment prevention services, and work to increase treatment confidence by empowering trusted local voices with additional funding for outreach efforts in underserved communities. "Rural health providers are vital to ensure equity in erectile dysfunction treatment testing, vaccinations and in making sure rural residents have the information about treatment safety, especially for populations who are at an increased risk for erectile dysfunction treatment or severe illness due to systemic health and social inequities and geographic isolation," said HHS Secretary Xavier Becerra. "Support to Rural Health Clinics and small rural hospitals for erectile dysfunction treatment testing, strengthening treatment allocation and confidence, and treatment outreach will help rural residents make informed health decisions about erectile dysfunction treatment to protect themselves and their communities." HRSA's Rural Health Clinic erectile dysfunction treatment Testing and Mitigation Program will provide $460 million to more than 4,600 rural health clinics (RHCs) across the country.

RHCs will use the funds to maintain and increase erectile dysfunction treatment testing, expand access to testing for rural residents, and broaden efforts to mitigate the spread can i get kamagra over the counter of the kamagra in ways tailored to their local communities. RHCs are a special certification given to health care practices in underserved rural areas by the Centers for Medicare and Medicaid Services (CMS) to help ensure access to care for rural residents. HRSA will provide up to $100,000 per RHC-certified clinic site and will can i get kamagra over the counter issue the funds this summer. To further support erectile dysfunction treatment testing in rural areas, HRSA will provide $398 million to existing grantees of the Small Rural Hospital Improvement Program (SHIP) to work with approximately 1,730 small rural hospitals – those with fewer than 50 beds – and Critical Access Hospitals on erectile dysfunction treatment testing and mitigation. SHIP state grantees will use the funding to support all eligible rural hospitals, up to $230,000 per hospital, and will issue the funds later in the year.

"Addressing the health care challenges rural areas face requires a targeted approach that's tailored to can i get kamagra over the counter the needs of local communities," said HRSA Acting Administrator Diana Espinosa. "This critical funding strengthens our ability to deliver on President Biden's commitment to ensure that the nation's underserved communities and those who are disproportionately affected by erectile dysfunction treatment get the help they need." HRSA will also support RHCs to increase the availability of erectile dysfunction treatments in rural communities and expand outreach to build treatment confidence. Working in partnership with the Centers for Disease Control and Prevention (CDC), HRSA is inviting Medicare-certified RHCs to join the new Rural can i get kamagra over the counter Health Clinic erectile dysfunction treatment Distribution (RHCVD) Program to directly receive treatments from the Biden Administration. HRSA and CDC will continue to enroll interested RHCs to receive erectile dysfunction treatments, the allocation for which is separate from jurisdictions' weekly allocations. In addition, through the Rural Health Clinic treatment Confidence (RHCVC) Program, HRSA will make nearly $100 million available in grants to eligible RHCs nationwide to address health equity gaps by offering support and resources to medically underserved rural communities where erectile dysfunction treatment uptake lags in comparison to more populated areas.

HRSA will can i get kamagra over the counter fund all eligible RHCs that apply. The RHCVC Program is the first targeted RHC grant since the passage of the Rural Health Clinic Service Act in 1977. RHCs will be able to use the funds to increase treatment confidence, improve health care in can i get kamagra over the counter rural areas, and reinforce key messages about prevention and treatment of erectile dysfunction treatment and other infectious diseases. Implementation efforts in rural communities will include disseminating information to rural residents about how and where to get vaccinated, and coordinating with existing vaccination sites and public health partners to identify strategies to increase treatment confidence among key populations. RHCs may also use funding to promote vaccination and bolster patient literacy in rural areas on the benefits of broad vaccination and treatment safety in support of continued efforts to return to a more normal lifestyle.

For more information about HRSA's rural programs, visit the Federal Office of Rural Health can i get kamagra over the counter Policy website. Https://www.hrsa.gov/rural-health/index.html To learn more about HRSA's allocation to Rural Health Clinics for erectile dysfunction treatment testing visit. Https://www.hrsa.gov/rural-health/erectile dysfunction/rural-health-clinics-erectile dysfunction treatment-testing-fy20-awards To learn more about the Small Rural Hospital Improvement Program can i get kamagra over the counter (SHIP), visit https://www.hrsa.gov/rural-health/rural-hospitals.Enlarge this image Medical workers with Delta Health Center prepare to vaccinate people in Leland, Miss., last week. In some places, rural hospital workers have been slow to get the treatment themselves. Spencer Platt/Getty Images hide caption toggle caption Spencer Platt/Getty Images President Biden on Tuesday is set to announce new steps to reach rural Americans in the push to get as many people as possible vaccinated for the erectile dysfunction, a White House official tells NPR.

This emphasis comes as rural hospitals are raising alarms about the pace of vaccination — even among their own employees can i get kamagra over the counter. The Biden administration is moving into a new phase of its vaccination campaign, one where it knows doctors and health care professionals are often more persuasive than the government. It has can i get kamagra over the counter prioritized a list of doctors enrolled in the treatment system based on a "social vulnerability index" used by the Centers for Disease Control and Prevention — including doctors in many rural communities — and has been asking state government to send treatment doses to those doctors, the official said. The administration also plans to work with states to enroll more pediatricians and family doctors in their treatment systems so they can begin giving people treatments, a step that becomes "particularly critical" if the Food and Drug Administration gives emergency authorization for adolescents ages 12-15 to start getting the Pfizer treatment, the official said. The administration also is working with provider groups to encourage their members to sign up to give the treatments and will be providing technical assistance to help practices get ready for vaccination, the official said.

"Tremendously problematic" The new steps come as some rural hospitals are finding can i get kamagra over the counter that their own staff members are reluctant to get the shot. A new survey conducted by the National Rural Health Association and Chartis Center for Rural Health showed that 30% of the 160 rural hospital executives who responded said less than half of their employees had been vaccinated — even though health care workers have been eligible for months now. Only about a third said that 70% or more of can i get kamagra over the counter their staff were vaccinated. "These survey results match what we are hearing from our members and that is tremendously problematic," said Alan Morgan, chief executive of the National Rural Health Association. "At a federal level, every effort to overcome treatment hesitancy has health care professionals front and center," Morgan said.

"So if you've got a quarter of the nation's rural hospitals having less than 50% of their staff vaccinated, you have a problem that needs to can i get kamagra over the counter be fixed now." This survey also lines up with a poll done earlier this year by the Kaiser Family Foundation and The Washington Post that found 29% of health care workers in rural areas didn't plan to get the erectile dysfunction treatment. That's a greater well of hesitancy than the poll found among health care workers in urban and suburban areas. Michael Topchik at Chartis said the hospitals they work with have high vaccination rates every year for can i get kamagra over the counter the flu shot. It's required. "We were surprised at how many rural hospitals were telling us their vaccination rates for erectile dysfunction treatment were significantly lower," Topchik said.

"It's too early" In Carrollton, Mo., Jeff Tindle, the chief executive at Carroll County Memorial Hospital, is beside himself can i get kamagra over the counter about the low rate of vaccination among his staff. Only 59% are vaccinated for erectile dysfunction treatment and at this point he doesn't have much hope of that number growing dramatically. Tindle, who describes himself as conservative, like most people in his town, can i get kamagra over the counter said he had assumed that health care workers would understand the importance of the treatment. "I'm disappointed that we built in so many safeguards ... First and foremost to protect our employees, and yet we had almost 40% who chose not to help themselves," he said.

The hospital had a treatment clinic but shut it down, turning its attention to helping can i get kamagra over the counter the public health department. Most of the people who wanted to get vaccinated in the town of 4,000 have already done so, he said. "We're worried about always wasting treatment because we just don't have enough arms," he can i get kamagra over the counter said. Talking to friends, Tindle says some have told him they are afraid of being implanted with microchips, a false conspiracy theory alive and well on the internet. "Employees that I talk to, health care employees, will be a little more rational in their irrational behavior by saying, 'Well Jeff, we don't have enough studies.

It's too early,' can i get kamagra over the counter " he said. "I know that swayed people" Some rural hospitals have had better luck getting employees vaccinated. Memorial Hospital in New Hampshire's Mount Washington Valley region can i get kamagra over the counter is currently at 78%. Will Owen, who is running the hospital's community vaccination clinic, said education was key. In December, a highly respected local physician named Victor Lazaron sent a letter to staff.

"I am keen to be vaccinated as soon as possible," Lazaron said can i get kamagra over the counter in the letter. He cited studies showing treatments were effective and that the worst side effects were comparable to the treatment for shingles, which is widely used. "I hope you all will choose to be vaccinated as soon can i get kamagra over the counter as the treatment is available to you. In my judgment it is the best way forward. It is safe and effective.

And it will can i get kamagra over the counter help us get back to our core mission. Protecting the health of our friends and neighbors in the Mount Washington Valley," Lazaron wrote. That letter opened people's can i get kamagra over the counter minds to the treatment, Owen said. "I know that [letter] swayed people, because I had people tell me that," he said. There were also Zoom sessions for staff, led by doctors, leaving plenty of time for questions.

Having trusted doctors and nurses vaccinated has been reassuring to others can i get kamagra over the counter in the broader community, said chief nursing officer Kris Dascoulias, whose roots in the community are so deep that she was born in Memorial Hospital, where she now works. "I've gotten lots of text messages, questions. I think people relied on the hospital community that they knew and trusted to guide them a can i get kamagra over the counter little bit in this," Dascoulias said. She said she has encouraged people, telling them, "I know it's a little scary, it's a little bit of a leap of faith, but you know it's better than the alternatives." White House looks to local doctors The White House knows that doctors and other trusted local leaders will be the way to break through pockets of hesitancy in rural communities, said Bechara Choucair, the White House vaccinations coordinator. Choucair also pointed to a different Kaiser Family Foundation poll that found a majority of rural residents had been vaccinated or planned to get vaccinated, although it also shows a much smaller share of urban and suburban residents would "definitely not" get the shot than those in rural areas.

"Luckily we know that the overwhelming majority of health care providers are very supportive of [the] treatment. Ninety percent of doctors and master's-prepared nurses have either gotten the treatment or are in the process of getting vaccinated," Choucair told NPR, citing national data about doctors and highly trained nurses. "We need to do that across the board for health care professionals and non-health care professionals and will continue to do that," he said..

Funding Will Help Communities, Hospitals, Health Clinics Respond to the buy kamagra online canada kamagra and Support Local Efforts to Increase treatment Confidence and Uptake in Rural CommunitiesToday, thanks generic kamagra cost to the American Rescue Plan, the U.S. Department of Health and Human Services (HHS) is announcing the availability of nearly $1 billion to strengthen erectile dysfunction treatment response efforts and increase vaccinations in rural communities. As part of the Biden Administration's commitment to expanding access to buy kamagra online canada treatments and ensuring equity in the erectile dysfunction treatment response, the Health Resources and Services Administration, a part of HHS, will increase the number of treatments sent to rural communities, expand testing and other erectile dysfunction treatment prevention services, and work to increase treatment confidence by empowering trusted local voices with additional funding for outreach efforts in underserved communities. "Rural health providers are vital to ensure equity in erectile dysfunction treatment testing, vaccinations and in making sure rural residents have the information about treatment safety, especially for populations who are at an increased risk for erectile dysfunction treatment or severe illness due to systemic health and social inequities and geographic isolation," said HHS Secretary Xavier Becerra. "Support to Rural Health Clinics and small rural hospitals for erectile dysfunction treatment testing, strengthening treatment allocation and confidence, and treatment outreach will help rural residents make informed health decisions about erectile dysfunction treatment to protect themselves and their communities." HRSA's Rural Health Clinic erectile dysfunction treatment Testing and Mitigation Program will provide $460 million to more than 4,600 rural health clinics (RHCs) across the country.

RHCs will use the funds to maintain and increase erectile dysfunction treatment testing, expand access to testing for rural residents, and broaden efforts to mitigate the spread of the kamagra in ways buy kamagra online canada tailored to their local communities. RHCs are a special certification given to health care practices in underserved rural areas by the Centers for Medicare and Medicaid Services (CMS) to help ensure access to care for rural residents. HRSA will provide up to $100,000 per buy kamagra online canada RHC-certified clinic site and will issue the funds this summer. To further support erectile dysfunction treatment testing in rural areas, HRSA will provide $398 million to existing grantees of the Small Rural Hospital Improvement Program (SHIP) to work with approximately 1,730 small rural hospitals – those with fewer than 50 beds – and Critical Access Hospitals on erectile dysfunction treatment testing and mitigation. SHIP state grantees will use the funding to support all eligible rural hospitals, up to $230,000 per hospital, and will issue the funds later in the year.

"Addressing the health care challenges rural areas face requires a targeted approach buy kamagra online canada that's tailored to the needs of local communities," said HRSA Acting Administrator Diana Espinosa. "This critical funding strengthens our ability to deliver on President Biden's commitment to ensure that the nation's underserved communities and those who are disproportionately affected by erectile dysfunction treatment get the help they need." HRSA will also support RHCs to increase the availability of erectile dysfunction treatments in rural communities and expand outreach to build treatment confidence. Working in partnership buy kamagra online canada with the Centers for Disease Control and Prevention (CDC), HRSA is inviting Medicare-certified RHCs to join the new Rural Health Clinic erectile dysfunction treatment Distribution (RHCVD) Program to directly receive treatments from the Biden Administration. HRSA and CDC will continue to enroll interested RHCs to receive erectile dysfunction treatments, the allocation for which is separate from jurisdictions' weekly allocations. In addition, through the Rural Health Clinic treatment Confidence (RHCVC) Program, HRSA will make nearly $100 million available in grants to eligible RHCs nationwide to address health equity gaps by offering support and resources to medically underserved rural communities where erectile dysfunction treatment uptake lags in comparison to more populated areas.

HRSA will buy kamagra online canada fund all eligible RHCs that apply. The RHCVC Program is the first targeted RHC grant since the passage of the Rural Health Clinic Service Act in 1977. RHCs will be able to use the funds to increase treatment confidence, improve health care in rural areas, and reinforce key messages about prevention and treatment of erectile dysfunction treatment and other infectious diseases buy kamagra online canada. Implementation efforts in rural communities will include disseminating information to rural residents about how and where to get vaccinated, and coordinating with existing vaccination sites and public health partners to identify strategies to increase treatment confidence among key populations. RHCs may also use funding to promote vaccination and bolster patient literacy in rural areas on the benefits of broad vaccination and treatment safety in support of continued efforts to return to a more normal lifestyle.

For more buy kamagra online canada information about HRSA's rural programs, visit the Federal Office of Rural Health Policy website. Https://www.hrsa.gov/rural-health/index.html To learn more about HRSA's allocation to Rural Health Clinics for erectile dysfunction treatment testing visit. Https://www.hrsa.gov/rural-health/erectile dysfunction/rural-health-clinics-erectile dysfunction treatment-testing-fy20-awards To learn more about the Small Rural Hospital Improvement Program (SHIP), visit https://www.hrsa.gov/rural-health/rural-hospitals.Enlarge this image Medical workers with Delta Health Center prepare buy kamagra online canada to vaccinate people in Leland, Miss., last week. In some places, rural hospital workers have been slow to get the treatment themselves. Spencer Platt/Getty Images hide caption toggle caption Spencer Platt/Getty Images President Biden on Tuesday is set to announce new steps to reach rural Americans in the push to get as many people as possible vaccinated for the erectile dysfunction, a White House official tells NPR.

This emphasis comes as rural hospitals are raising alarms about the pace of vaccination — even among their buy kamagra online canada own employees. The Biden administration is moving into a new phase of its vaccination campaign, one where it knows doctors and health care professionals are often more persuasive than the government. It has prioritized a list of doctors enrolled in the treatment system based on a buy kamagra online canada "social vulnerability index" used by the Centers for Disease Control and Prevention — including doctors in many rural communities — and has been asking state government to send treatment doses to those doctors, the official said. The administration also plans to work with states to enroll more pediatricians and family doctors in their treatment systems so they can begin giving people treatments, a step that becomes "particularly critical" if the Food and Drug Administration gives emergency authorization for adolescents ages 12-15 to start getting the Pfizer treatment, the official said. The administration also is working with provider groups to encourage their members to sign up to give the treatments and will be providing technical assistance to help practices get ready for vaccination, the official said.

"Tremendously problematic" The buy kamagra online canada new steps come as some rural hospitals are finding that their own staff members are reluctant to get the shot. A new survey conducted by the National Rural Health Association and Chartis Center for Rural Health showed that 30% of the 160 rural hospital executives who responded said less than half of their employees had been vaccinated — even though health care workers have been eligible for months now. Only about a third said that 70% or more of buy kamagra online canada their staff were vaccinated. "These survey results match what we are hearing from our members and that is tremendously problematic," said Alan Morgan, chief executive of the National Rural Health Association. "At a federal level, every effort to overcome treatment hesitancy has health care professionals front and center," Morgan said.

"So if you've got a quarter of the nation's rural hospitals having less than 50% of their staff vaccinated, you have a problem that needs to be fixed now." This survey also lines up with a poll done earlier this year by the Kaiser Family Foundation and The Washington Post that found 29% of health buy kamagra online canada care workers in rural areas didn't plan to get the erectile dysfunction treatment. That's a greater well of hesitancy than the poll found among health care workers in urban and suburban areas. Michael Topchik at Chartis said the hospitals buy kamagra online canada they work with have high vaccination rates every year for the flu shot. It's required. "We were surprised at how many rural hospitals were telling us their vaccination rates for erectile dysfunction treatment were significantly lower," Topchik said.

"It's too early" In Carrollton, Mo., Jeff Tindle, the chief executive at Carroll County Memorial Hospital, is beside himself buy kamagra online canada about the low rate of vaccination among his staff. Only 59% are vaccinated for erectile dysfunction treatment and at this point he doesn't have much hope of that number growing dramatically. Tindle, who describes himself as conservative, like most people in his town, said he had assumed buy kamagra online canada that health care workers would understand the importance of the treatment. "I'm disappointed that we built in so many safeguards ... First and foremost to protect our employees, and yet we had almost 40% who chose not to help themselves," he said.

The hospital had a treatment clinic but shut it down, turning its attention to helping the public health department buy kamagra online canada. Most of the people who wanted to get vaccinated in the town of 4,000 have already done so, he said. "We're worried about always wasting treatment because we just don't have enough arms," buy kamagra online canada he said. Talking to friends, Tindle says some have told him they are afraid of being implanted with microchips, a false conspiracy theory alive and well on the internet. "Employees that I talk to, health care employees, will be a little more rational in their irrational behavior by saying, 'Well Jeff, we don't have enough studies.

It's too buy kamagra online canada early,' " he said. "I know that swayed people" Some rural hospitals have had better luck getting employees vaccinated. Memorial Hospital in New Hampshire's Mount Washington Valley region is buy kamagra online canada currently at 78%. Will Owen, who is running the hospital's community vaccination clinic, said education was key. In December, a highly respected local physician named Victor Lazaron sent a letter to staff.

"I am keen to be vaccinated as soon as buy kamagra online canada possible," Lazaron said in the letter. He cited studies showing treatments were effective and that the worst side effects were comparable to the treatment for shingles, which is widely used. "I hope you all will choose buy kamagra online canada to be vaccinated as soon as the treatment is available to you. In my judgment it is the best way forward. It is safe and effective.

And it buy kamagra online canada will help us get back to our core mission. Protecting the health of our friends and neighbors in the Mount Washington Valley," Lazaron wrote. That letter opened buy kamagra online canada people's minds to the treatment, Owen said. "I know that [letter] swayed people, because I had people tell me that," he said. There were also Zoom sessions for staff, led by doctors, leaving plenty of time for questions.

Having trusted doctors and nurses vaccinated has been reassuring to others in the broader community, said chief nursing officer Kris Dascoulias, whose roots in the buy kamagra online canada community are so deep that she was born in Memorial Hospital, where she now works. "I've gotten lots of text messages, questions. I think people relied on buy kamagra online canada the hospital community that they knew and trusted to guide them a little bit in this," Dascoulias said. She said she has encouraged people, telling them, "I know it's a little scary, it's a little bit of a leap of faith, but you know it's better than the alternatives." White House looks to local doctors The White House knows that doctors and other trusted local leaders will be the way to break through pockets of hesitancy in rural communities, said Bechara Choucair, the White House vaccinations coordinator. Choucair also pointed to a different Kaiser Family Foundation poll that found a majority of rural residents had been vaccinated or planned to get vaccinated, although it also shows a much smaller share of urban and suburban residents would "definitely not" get the shot than those in rural areas.

"Luckily we know that the overwhelming majority of health care providers are very supportive of [the] treatment. Ninety percent of doctors and master's-prepared nurses have either gotten the treatment or are in the process of getting vaccinated," Choucair told NPR, citing national data about doctors and highly trained nurses. "We need to do that across the board for health care professionals and non-health care professionals and will continue to do that," he said..

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"Undocumented" immigrants are, you can try these out with some exceptions for pregnant women and Child Health Plus, only eligible for "emergency Medicaid."NYS announced the 2020 Income and Resource levels in GIS 19 MA/12 – 2020 Medicaid Levels and Other how good is kamagra Updates ) and levels based on the Federal Poverty Level are in GIS 20 MA/02 – 2020 Federal Poverty Levels Here is the 2020 HRA Income and Resources Level Chart Non-MAGI - 2020 Disabled, 65+ or Blind ("DAB" or SSI-Related) and have Medicare MAGI (2020) (<. 65, Does not have Medicare)(OR has Medicare and has dependent child <. 18 or <. 19 in school) 138% FPL*** Children < how good is kamagra. 5 and pregnant women have HIGHER LIMITS than shown ESSENTIAL PLAN For MAGI-eligible people over MAGI income limit up to 200% FPL No long term care.

See info here 1 2 1 2 3 1 2 Income $875 (up from $859 in 201) $1284 (up from $1,267 in 2019) $1,468 $1,983 $2,498 $2,127 $2,873 Resources $15,750 (up from $15,450 in 2019) $23,100 (up from $22,800 in 2019) NO LIMIT** NO LIMIT SOURCE for 2019 figures is GIS 18 MA/015 - 2019 Medicaid Levels and Other Updates (PDF). All of the attachments with the various levels are posted here how good is kamagra. NEED TO KNOW PAST MEDICAID INCOME AND RESOURCE LEVELS?. Which household size applies?. The how good is kamagra rules are complicated.

See rules here. On the HRA Medicaid Levels chart - Boxes 1 and 2 are NON-MAGI Income and Resource levels -- Age 65+, Blind or Disabled and other adults who need to use "spend-down" because they are over the MAGI income levels. Box 10 on page 3 are the MAGI income levels -- The Affordable Care Act changed the rules for how good is kamagra Medicaid income eligibility for many BUT NOT ALL New Yorkers. People in the "MAGI" category - those NOT on Medicare -- have expanded eligibility up to 138% of the Federal Poverty Line, so may now qualify for Medicaid even if they were not eligible before, or may now be eligible for Medicaid without a "spend-down." They have NO resource limit. Box 3 on page 1 is Spousal Impoverishment levels for Managed Long Term Care &.

Nursing Homes and Box 8 has the Transfer Penalty rates for nursing home eligibility Box 4 has Medicaid Buy-In for Working People with Disabilities Under Age 65 (still 2017 levels til April 2018) Box 6 are Medicare Savings Program levels (will be updated in April 2018) MAGI INCOME LEVEL of 138% FPL applies to most adults who are not disabled how good is kamagra and who do not have Medicare, AND can also apply to adults with Medicare if they have a dependent child/relative under age 18 or under 19 if in school. 42 C.F.R. § 435.4. Certain populations have an even higher income limit - 224% how good is kamagra FPL for pregnant women and babies <. Age 1, 154% FPL for children age 1 - 19.

CAUTION. What how good is kamagra is counted as income may not be what you think. For the NON-MAGI Disabled/Aged 65+/Blind, income will still be determined by the same rules as before, explained in this outline and these charts on income disregards. However, for the MAGI population - which is virtually everyone under age 65 who is not on Medicare - their income will now be determined under new rules, based on federal income tax concepts - called "Modifed Adjusted Gross Income" (MAGI). There are good changes and bad how good is kamagra changes.

GOOD. Veteran's benefits, Workers compensation, and gifts from family or others no longer count as income. BAD how good is kamagra. There is no more "spousal" or parental refusal for this population (but there still is for the Disabled/Aged/Blind.) and some other rules. For all of the rules see.

ALSO SEE 2018 Manual on Lump Sums and Impact on Public Benefits - with resource rules The income limits increase with the "household size." In other words, the income limit for a family of 5 may be higher than the income limit for a single person. HOWEVER, Medicaid rules about how to calculate the household size are not intuitive or how good is kamagra even logical. There are different rules depending on the "category" of the person seeking Medicaid. Here are the 2 basic categories and the rules for calculating their household size. People how good is kamagra who are Disabled, Aged 65+ or Blind - "DAB" or "SSI-Related" Category -- NON-MAGI - See this chart for their household size.

These same rules apply to the Medicare Savings Program, with some exceptions explained in this article. Everyone else -- MAGI - All children and adults under age 65, including people with disabilities who are not yet on Medicare -- this is the new "MAGI" population. Their household size will be determined using federal income tax rules, which are very how good is kamagra complicated. New rule is explained in State's directive 13 ADM-03 - Medicaid Eligibility Changes under the Affordable Care Act (ACA) of 2010 (PDF) pp. 8-10 of the PDF, This PowerPoint by NYLAG on MAGI Budgeting attempts to explain the new MAGI budgeting, including how to determine the Household Size.

See how good is kamagra slides 28-49. Also seeLegal Aid Society and Empire Justice Center materials OLD RULE used until end of 2013 -- Count the person(s) applying for Medicaid who live together, plus any of their legally responsible relatives who do not receive SNA, ADC, or SSI and reside with an applicant/recipient. Spouses or legally responsible for one another, and parents are legally responsible for their children under age 21 (though if the child is disabled, use the rule in the 1st "DAB" category. Under this rule, a child may be excluded from the household if that child's income causes other family members to lose Medicaid how good is kamagra eligibility. See 18 NYCRR 360-4.2, MRG p.

573, NYS GIS 2000 MA-007 CAUTION. Different people in the same household may be in different "categories" and hence have different household sizes AND Medicaid income and how good is kamagra resource limits. If a man is age 67 and has Medicare and his wife is age 62 and not disabled or blind, the husband's household size for Medicaid is determined under Category 1/ Non-MAGI above and his wife's is under Category 2/MAGI. The following programs were available prior to 2014, but are now discontinued because they are folded into MAGI Medicaid. Prenatal Care Assistance Program (PCAP) was Medicaid for pregnant women and children under age 19, with higher income limits for pregnant woman and infants under one year (200% FPL how good is kamagra for pregnant women receiving perinatal coverage only not full Medicaid) than for children ages 1-18 (133% FPL).

Medicaid for adults between ages 21-65 who are not disabled and without children under 21 in the household. It was sometimes known as "S/CC" category for Singles and Childless Couples. This category had lower income limits than DAB/ADC-related, but had no asset limits. It did not allow "spend down" of excess income. This category has now been subsumed under the new MAGI adult group whose limit is now raised to 138% FPL.

Family Health Plus - this was an expansion of Medicaid to families with income up to 150% FPL and for childless adults up to 100% FPL. This has now been folded into the new MAGI adult group whose limit is 138% FPL. For applicants between 138%-150% FPL, they will be eligible for a new program where Medicaid will subsidize their purchase of Qualified Health Plans on the Exchange. PAST INCOME &.

The Empire Justice Center published a report in May, 2013 exploring the policies that guide immigrant access to health care and making recommendations for improving buy kamagra online canada immigrant our website access through New York's Health Insurance Exchange. New York's Exchange Portal. A Gateway to Coverage for Immigrants The report includes a new tool -- Immigrant Eligibility Crosswalk -- Eligibility by Immigration Status-- designed to help advocates and policymakers sort through the tangle of immigrant eligibility categories to determine who is eligible for which health care programs in 2014 and beyond.

The report was made possible with support from the United buy kamagra online canada Hospital Fund and benefited from the advice and input from many of our national partners in the effort to ensure maximum participation of immigrants in the nation's healthcare system as well as experts from the New York State Department of Health and the Centers for Medicare and Medicaid Services. SEE more about "PRUCOL" immigrant eligibility for Medicaid in this article. "Undocumented" immigrants are, with some exceptions for pregnant women and Child Health Plus, only eligible for "emergency Medicaid."NYS announced the 2020 Income and Resource levels in GIS 19 MA/12 – 2020 Medicaid Levels and Other Updates ) and levels based on the Federal Poverty Level are in GIS 20 MA/02 – 2020 Federal Poverty Levels Here is the 2020 HRA Income and Resources Level Chart Non-MAGI - 2020 Disabled, 65+ or Blind ("DAB" or SSI-Related) and have Medicare MAGI (2020) (<.

65, Does not have Medicare)(OR has Medicare and buy kamagra online canada has dependent child <. 18 or <. 19 in school) 138% FPL*** Children <.

5 and pregnant women have HIGHER LIMITS than shown ESSENTIAL PLAN buy kamagra online canada For MAGI-eligible people over MAGI income limit up to 200% FPL No long term care. See info here 1 2 1 2 3 1 2 Income $875 (up from $859 in 201) $1284 (up from $1,267 in 2019) $1,468 $1,983 $2,498 $2,127 $2,873 Resources $15,750 (up from $15,450 in 2019) $23,100 (up from $22,800 in 2019) NO LIMIT** NO LIMIT SOURCE for 2019 figures is GIS 18 MA/015 - 2019 Medicaid Levels and Other Updates (PDF). All of the attachments with the various levels are posted here.

NEED buy kamagra online canada TO KNOW PAST MEDICAID INCOME AND RESOURCE LEVELS?. Which household size applies?. The rules are complicated.

See buy kamagra online canada rules here. On the HRA Medicaid Levels chart - Boxes 1 and 2 are NON-MAGI Income and Resource levels -- Age 65+, Blind or Disabled and other adults who need to use "spend-down" because they are over the MAGI income levels. Box 10 on page 3 are the MAGI income levels -- The Affordable Care Act changed the rules for Medicaid income eligibility for many BUT NOT ALL New Yorkers.

People in the "MAGI" category - those NOT on Medicare -- have expanded eligibility up to 138% of the Federal Poverty Line, so may now qualify for Medicaid even if they were not eligible buy kamagra online canada before, or may now be eligible for Medicaid without a "spend-down." They have NO resource limit. Box 3 on page 1 is Spousal Impoverishment levels for Managed Long Term Care &. Nursing Homes and Box 8 has the Transfer Penalty rates for nursing home eligibility Box 4 has Medicaid Buy-In for Working People with Disabilities Under Age 65 (still 2017 levels til April 2018) Box 6 are Medicare Savings Program levels (will be updated in April 2018) MAGI INCOME LEVEL of 138% FPL applies to most adults who are not disabled and who do not have Medicare, AND can also apply to adults with Medicare if they have a dependent child/relative under age 18 or under 19 if in school.

42 C.F.R buy kamagra online canada. § 435.4. Certain populations have an even higher income limit - 224% FPL for pregnant women and babies <.

Age 1, 154% FPL for children age 1 buy kamagra online canada - 19. CAUTION. What is counted as income may not be what you think.

For the NON-MAGI Disabled/Aged 65+/Blind, income will buy kamagra online canada still be determined by the same rules as before, explained in this outline and these charts on income disregards. However, for the MAGI population - which is virtually everyone under age 65 who is not on Medicare - their income will now be determined under new rules, based on federal income tax concepts - called "Modifed Adjusted Gross Income" (MAGI). There are good changes and bad changes.

GOOD. Veteran's benefits, Workers compensation, and gifts from family or others no longer count buy kamagra online canada as income. BAD.

There is no more "spousal" or parental refusal for this population (but there still is for the Disabled/Aged/Blind.) and some other rules. For all buy kamagra online canada of the rules see. ALSO SEE 2018 Manual on Lump Sums and Impact on Public Benefits - with resource rules The income limits increase with the "household size." In other words, the income limit for a family of 5 may be higher than the income limit for a single person.

HOWEVER, Medicaid rules about how to calculate the household size are not intuitive or even logical. There buy kamagra online canada are different rules depending on the "category" of the person seeking Medicaid. Here are the 2 basic categories and the rules for calculating their household size.

People who are Disabled, Aged 65+ or Blind - "DAB" or "SSI-Related" Category -- NON-MAGI - See this chart for their household size. These same rules apply to the Medicare Savings Program, with some exceptions buy kamagra online canada explained in this article. Everyone else -- MAGI - All children and adults under age 65, including people with disabilities who are not yet on Medicare -- this is the new "MAGI" population.

Their household size will be determined using federal income tax rules, which are very complicated. New rule is explained in State's directive 13 ADM-03 - Medicaid Eligibility Changes under the Affordable Care Act (ACA) of buy kamagra online canada 2010 (PDF) pp. 8-10 of the PDF, This PowerPoint by NYLAG on MAGI Budgeting attempts to explain the new MAGI budgeting, including how to determine the Household Size.

See slides 28-49. Also seeLegal Aid Society and Empire Justice Center materials OLD RULE used until end of 2013 -- Count the person(s) applying for Medicaid who live together, plus any of their legally responsible relatives who do not receive SNA, ADC, or SSI and buy kamagra online canada reside with an applicant/recipient. Spouses or legally responsible for one another, and parents are legally responsible for their children under age 21 (though if the child is disabled, use the rule in the 1st "DAB" category.

Under this rule, a child may be excluded from the household if that child's income causes other family members to lose Medicaid eligibility. See 18 NYCRR buy kamagra online canada 360-4.2, MRG p. 573, NYS GIS 2000 MA-007 CAUTION.

Different people in the same household may be in different "categories" and hence have different household sizes AND Medicaid income and resource limits. If a man buy kamagra online canada is age 67 and has Medicare and his wife is age 62 and not disabled or blind, the husband's household size for Medicaid is determined under Category 1/ Non-MAGI above and his wife's is under Category 2/MAGI. The following programs were available prior to 2014, but are now discontinued because they are folded into MAGI Medicaid.

Prenatal Care Assistance Program (PCAP) was Medicaid for pregnant women and children under age 19, with higher income limits for pregnant woman and infants under one year (200% FPL for pregnant women receiving perinatal coverage only not full Medicaid) than for children ages 1-18 (133% FPL). Medicaid for adults between ages 21-65 who are buy kamagra online canada not disabled and without children under 21 in the household. It was sometimes known as "S/CC" category for Singles and Childless Couples.

This category had lower income limits than DAB/ADC-related, but had no asset limits. It did not allow "spend down" of excess income.

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Date published kamagra oral jelly walmart What is the cost of lasix. August 26, 2020On this page Backgrounderectile dysfunction treatment is an infectious disease caused by the erectile dysfunction erectile dysfunction. The World Health Organization declared a global kamagra in March 2020, and the Minister of Health signed the Interim Order Respecting the Importation and Sale of Medical Devices for Use in Relation to erectile dysfunction treatment on kamagra oral jelly walmart March 18, 2020. The Interim Order (IO) allows us to quickly address large-scale public health emergencies.This IO allows for faster authorization of Class I-IV medical devices for erectile dysfunction treatment.This document presents the criteria for safety and effectiveness that apply to test swabs used for erectile dysfunction treatment sampling.

It also provides guidance on how to meet these criteria in an application under the IO pathway. Diagnostic testing kamagra oral jelly walmart is a key element in both. identifying cases of preventing the spread of the erectile dysfunction A test swab may be used to collect a sample for either Polymerase Chain Reaction (PCR) laboratory testing or point-of-care testing. Point-of-care testing can be done directly in a hospital or doctor’s office.

Once the sample has been taken, the swab is either placed in a preserving liquid and sent to a kamagra oral jelly walmart laboratory for testing, or placed directly in a testing device (point-of-care).Swabs may be packaged in a variety of kamagra transport media (VTM). Specifications for individual VTMs are beyond the scope of this document. Swabs play a role in the accuracy of erectile dysfunction treatment diagnostic testing. For example, false negatives kamagra oral jelly walmart can occur in PCR tests if.

the swab material inhibits the test reaction or the swab design doesn’t provide enough surface area to obtain a sufficient sample Test swabs that are not safe and effective may cause or lead to harm. For example. A swab that breaks during kamagra oral jelly walmart sample collection can cause physical injury a non-sterile swab that produces an incorrect test result can lead to harmHealth Canada has published a guidance document to support the preparation of applications submitted under the IO. It should be read in conjunction with this document.

We are processing applications as quickly as possible. To avoid delays, please ensure you have completed your application properly.Medical Devices Regulations (MDR) classification In the Canadian regulatory framework, Class I devices present the kamagra oral jelly walmart lowest potential risk and Class IV the highest. Swabs are classified according to their labelling and intended use. For example, if a swab is labelled for nasopharyngeal (NP) or oropharyngeal (OP) use only, it will be classified as a Class I medical device according to Classification Rule 2(2) of the MDR.

If a swab is not exclusively for use in oral or nasal cavities, or its use is not explicitly stated, it will be classified as a kamagra oral jelly walmart Class II device by Rule 2(1). These swabs belong to a higher risk class because their use in other body orifices for the collection of tissue samples (for example, to test for chlamydia or ureaplasma) is associated with greater risk. Rule 2 Subject to subrules (2) to (4), all invasive devices kamagra oral jelly walmart that penetrate the body through a body orifice or that come into contact with the surface of the eye are classified as Class II. A device described in subrule (1) that is intended to be placed in the oral or nasal cavities as far as the pharynx or in the ear canal up to the ear drum is classified as Class I.Regulatory pathways for erectile dysfunction treatment devicesManufacturers of Class I swabs may seek authorization to import and sell their products under either.

A Medical Device Establishment Licence (MDEL) MDEL is an establishment oversight framework that is not product-specific and not designed to assess safety and effectiveness an IO authorization information on safety and effectiveness are required as part of the application Health Canada is encouraging a sub-group of swab manufacturers to use the IO authorization pathway for Class I swabs, especially if they are. New to the manufacturing of swabs and manufacturing in Canada (such as a company that has re-tooled to manufacture), or using a new manufacturing process or design for swabs (such as 3D printing or honeycomb design)IO applications for swabs should include kamagra oral jelly walmart the following information.Device description The device description should include. A picture and/or engineering drawing identification of all materials used in the production of the swab the intended use(s) (for example, NP swabs)Quality manufacturingManufacturers must either. demonstrate compliance with Quality Manufacturing Systems (for example, ISO 13485 certificate) applicable to the swab, or provide a clear description of the planned quality manufacturing systems that are consistent with similar existing manufacturing systemsDesign verificationProvide swab design verification (bench testing) data in a summary report.

It should kamagra oral jelly walmart show that the essential minimum design characteristics are met. These data should be based on test samples representative of finished swabs that have undergone sterilization prior to bench testing.Dimensions Swabs should have minimum length specifications and minimum and maximum head diameter specifications in order to be safe and effective. Minimum length specification for example, adult NP swabs require ≥14 cm to reach the posterior nasopharynx minimum and maximum head diameter specification for example, adult NP swabs require 1–4 mm to pass into the mid-inferior portion of the inferior turbinate and maneuver well FlexibilitySwab flexibility is assessed through. Durability for example, tolerate 20 rough repeated insertions into a 4 mm inner diameter clear plastic tube curved back on itself with a curve radius of 3 cm bendability for example, bend tip and neck 90º without breaking ability to maintain initial form for example, restore to initial form kamagra oral jelly walmart following 45º bending Manufacturers may describe the test performed, the number of samples, and a summary of the results.Strength/Breakpoint (failure) To limit the potential for patient harm, the minimum breakpoint distance should be approximately 8 to 9 cm from the nasopharynx.

However, no breaks or fractures should occur following reasonable manipulation. Applicants should submit a rationale for the design of the breakpoint distance from the swab tip. It should demonstrate kamagra oral jelly walmart that the breakpoint length can be accommodated by commercially available swab/media tubes.Surface propertiesThe swab surface should be free of. processing aids (such as disinfectants) foreign materials degreasers mold release agents For injection molded swabs, no burrs, flashing, or sharp edges should be present.

Design validationProvide swab validation (performance) data in a summary report that demonstrates that the swab. can acquire samples comparable to a commercially available swab control, and will not inhibit the PCR reactionThese data should be based on test samples representative of finished swabs that have undergone sterilization prior to testing.Comparable sample acquisition to a control, and PCR compatibilityThe manufacturer should demonstrate test swab cycle threshold (Ct) kamagra oral jelly walmart recovery values (RT-PCR) that are statistically comparable to those obtained from a commercially available swab control using erectile dysfunction (or a scientifically justified surrogate).Pass/Fail criteria. Values ≥ 2Cts indicate significantly less efficient ribonucleic acid collection and/or elution.Clinical feasibility/suitability simulationManufacturers should submit either. A clinical test report or previous clinical data Clinical test reportThe clinical test report should describe the use of the proposed finished swab (sterilized) in a sufficient number of individuals by trained healthcare professionals in a minimum of 30 patients that have tested positive for erectile dysfunction, or a scientifically justified surrogate kamagra.

Include comparisons of the proposed swab against kamagra oral jelly walmart a flocked swab commercially available in Canada with respect to. flexibility fit ability to navigate to the nasopharynx (or other areas specified in the indications) ability to collect a specimen/respiratory epithelial cells for example, using the RNase P housekeeping gene test results agreement for example, ≥ 90% positive % agreement using a composite control (positive % agreement calculation that includes all positive findings from control and test swabs) Clinical testing considerations A scientifically justified surrogate kamagra may be used if erectile dysfunction treatment-positive patients are not available. Positive % agreement should not be determined using high Ct samples. One-half (1/2) to two-thirds (2/3) of kamagra oral jelly walmart erectile dysfunction treatment-positive samples should have a high viral loads (Cts <.

30). Report agreement between control and test kamagra oral jelly walmart swabs in terms of quantitative (Ct) and qualitative (+/- test) values with appropriate descriptive statistics. Include patient symptomatology for samples. For example, days from symptom onset, known vs.

Suspected erectile dysfunction treatment status kamagra oral jelly walmart. Use of different VTM/universal transport media (V/UTM) across erectile dysfunction treatment-positive samples may contribute to Ct variability. Ensure consistency by using the same media/tubes for each specimen within a clinical evaluation. Validate the chosen V/UTM media/tubes to show they kamagra oral jelly walmart will not interfere with the PCR test results.

For example, allowing 7 days of swab positive specimen incubation with the chosen media/vial is considered a worst-case transportation scenario to evaluate maximal leaching/interaction potential). Use a single PCR test platform throughout each clinical evaluation. The platform should have been previously authorized kamagra oral jelly walmart by HC or another jurisdiction. Location (for example, left vs right nostril) and order of sampling (for example, control vs.

Test swab) can affect specimen quality and results variability. Location and swab sampling order should be randomized.For additional information on collecting, handling, and testing erectile dysfunction treatment specimens, please refer to the Centers for Disease Control and Prevention (CDC) Interim Guidelines for Collecting, Handling, and Testing Clinical Specimens for erectile dysfunction treatment.Previous clinical kamagra oral jelly walmart dataPreviously obtained clinical data may be submitted in lieu of clinical testing. Those data should demonstrate the safe and effective use of a swab of identical design and materials in human subjects. The proposed swab should be compared against a flocked swab commercially available in Canada with respect to.

flexibility fit ability to kamagra oral jelly walmart navigate to the nasopharynx (or other areas specified in the indications) ability to collect a specimen/respiratory epithelial cells for example, using the RNase P housekeeping gene test results agreement for example, ≥ 90% positive % agreement) using a composite control (positive % agreement calculation that includes all positive findings from control and test swabs) Sterility Provide sterilization validation data in a summary report. It should demonstrate that the chosen sterilization method will achieve a minimum Sterility Assurance Level (SAL) of 10-6 for the proposed swab, using an appropriate biological indicator (BI) organism (see below). If the swab will be sterilized using an ethylene oxide (EtO) method, you should demonstrate that EtO and ethylene chlorohydrin (ECH) residuals meet the tolerable contact limits (TCL) specified in ISO 10993-7. Commonly used swab kamagra oral jelly walmart materials, compatible sterilization methods, and appropriate biological indicators are described below.

Sterilization Method Swab Materials EtO(for example, ISO 11135) Gamma Irradiation(ISO 11137) Polystyrene handle, polyester bicomponent fiber tipFootnote * X(for example, Puritan 25-3316-H/U) Not applicable Polystyrene handle, nylon flocked fiber tipFootnote * X(for example, Copan 503CS01) X(for example, BD 220252) Footnote * The CDC provides guidance on the types of swabs that should be used for optimal specimen collection for PCR testing. They include swabs that are made of polyester (for example, Dacron), rayon, or nylon-flocked. Cotton-tipped or kamagra oral jelly walmart calcium alginate swabs are not acceptable because residues present in those materials inhibit the PCR reaction. Return to footnote * referrer Appropriate BIIf ionizing radiation will be used to sterilize the swab.

Bacillus pumilus spores are recommended for doses of 25 kGy Bacillus cereus or Bacillus sphaericus spores are recommended for doses kamagra oral jelly walmart of >. 25 kGy (World Health Organization, The International Pharmacopoeia, 9th Ed., 2019) Sterilization Process Spore (Indicator Organism) Steam Geobacillus stearothermophilus(formerly Bacillus stearothermophilus) Dry Heat Bacillus atrophaeus (formerly Bacillus subtilis var. Niger) Ethlylene Oxide Bacillus atrophaeus (formerly Bacillus subtilis var. Niger) Hydrogen kamagra oral jelly walmart Peroxide Geobacillus stearothermophilus(formerly Bacillus stearothermophilus) Source.

US Food and Drug Administration, "Biological Indicator (BI) Premarket Notification [510(k)] Submissions," October 2007. [Online].Packaging validation Provide packaging validation data in a summary report. It should demonstrate that the swab packaging system will maintain a sterile kamagra oral jelly walmart environment across the labelled shelf life (for example, ASTM F1980). without leakage (for example, ASTM D3078-02) with adequate seal strength (for example, ASTM F88/EN 868-5)Test packaging samples should be representative of finished swab packages that have undergone sterilization prior to testing.Biocompatibility Provide biocompatibility data in a summary report.

It should demonstrate compliance with biocompatibility tests recommended for devices in limited contact (≤24 hrs) with mucosal membranes, as per ISO 10993-1. These include kamagra oral jelly walmart. cytotoxicity sensitization irritation/intracutaneous reactivityThese data should be based on test samples representative of finished swabs that have undergone sterilization prior to testing.LabellingSwabs should be individually packaged and labelled. The application must include the swab label, which must include.

The name and model number of the device the term ‘sterile’, along with the sterilization method (EtO kamagra oral jelly walmart = ethylene oxide. R = gamma irradiation), if the swab is intended to be sold in a sterile condition the name and address of the manufacturer manufacturing and expiry datesIf swabs are not sterile but must be sterilized at the user facility, then the sterilization parameters and method should be clearly described in accompanying instructions for use documentation.Post-market requirementsAs stated in Section 12 of the IO, within 10 days of becoming aware of an incident in Canada, all IO authorization holders must. report the incident specify the nature of the incident specify the circumstances surrounding the incidentOn this page About face shields Personal protective equipment (PPE) can help prevent potential exposure to infectious disease. They are considered medical devices in Canada and therefore must follow the requirements kamagra oral jelly walmart outlined in the Medical Devices Regulations.

Medical devices are classified into 4 groups (Class I, II, III and IV) based on their risk to health and safety. Class I devices, such as gauze bandages, pose the lowest potential risk, while Class IV devices, such as pacemakers, pose the greatest potential risk. In Canada, face shields are kamagra oral jelly walmart Class I medical devices. A face shield has a transparent window or visor that shields the face and associated mucous membranes (eyes, nose and mouth).

It protects the wearer against exposure from splashes and sprays of body fluids. Face shields are made of shatterproof plastic, fit over the face and are held in place by head straps kamagra oral jelly walmart or caps. They may be made of polycarbonate, propionate, acetate, polyvinyl chloride, or polyethylene terephthalate. They are usually worn with kamagra oral jelly walmart other PPE, such as a medical mask, respirator or eyewear.

Health Canada strongly advises against the use of plastic bags as an alternative to face shields. Standards and requirements for face shields Organizations that are manufacturing face shields are advised to consult some or all of the following standards throughout the design and testing stages. ANSI/ISEA Z.87.1 (2015), American National Standard for Occupational and Educational Personal Eye and Face Protection Devices CSA Z94.3 (2020), Eye and Face Protectors CSA Z94.3.1 (2016), Guideline for Selection, Use, and Care of Eye and Face Protectors BS EN kamagra oral jelly walmart 166 (2002), Personal Eye Protection. Specifications.

Minimum specifications must be incorporated into the design and verification stages to ensure safe and effective face shields. Provide adequate coverage (CSA Z94.3 kamagra oral jelly walmart Sections 0.2.1/10.2.2/10.3/10.4). The size of the face shield is important because it must protect the face and front part of the head. This includes the eyes, forehead, cheeks, nose, mouth, and chin.

Protection may also need to extend to kamagra oral jelly walmart the front of the neck in situations with flying particles and sprays of hazardous liquids. Fit snugly to afford a good seal to the forehead area and to prevent slippage of the device Footnote 1. Be made of optically clear, distortion-free, lightweight materials (CSA Z94.3.1-16 and Footnote 1). Be free of visible kamagra oral jelly walmart defects or flaws that would impede vision (ANSI Z87.1 Section 9.4).

Be comfortable and easy to assemble, use and remove by health care professionals. Provide adequate space between the wearer’s face and the inner surface of the visor to allow for the use of ancillary equipment (for example, medical mask, respirator, eyewear) Footnote 1. The characteristics and performance requirements of face shields must not be altered when attaching shields kamagra oral jelly walmart to other protective equipment, such as hats or caps. Display anti-fog characteristics on inside and outside of shield (CSA Z94.3.1-16).

For face shields that are not fog resistant, anti-fog spray must be provided. Provide user-contacting materials that have adequate kamagra oral jelly walmart material biocompatibility (skin sensitivity and cytotoxic testing) (ISO 10993-5, 10). Other items to take note of include. Face shields used for protection in hospital settings do not have to be impact- or flame- resistant.

If the device is specifically designed to withstand impact from sharp or fast projectiles, kamagra oral jelly walmart it must comply with set-out standards (ANSI Z87.1, sections 9.2 and 9.3, CSA Z94.3, section 10.1). For reuse, manufacturers must provide validated cleaning instructions. Sterilization procedures must not compromise the shield in any way, kamagra oral jelly walmart such as deformation or cracking. Regulatory authorization Most PPE, including face shields, are Class I medical devices if they are manufactured, sold or represented for use for reducing the risk of or preventing the user from .

This includes erectile dysfunction treatment. Face shields may be authorized for sale or import kamagra oral jelly walmart into Canada through the following regulatory pathways. Pathway 1. Interim order authorization to import and sell medical devices related to erectile dysfunction treatment.

Pathway 2 kamagra oral jelly walmart. Expedited review and issuance of Medical Device Establishment Licences (MDEL) related to erectile dysfunction treatment. MDEL holders that import and sell face shields should take measures to ensure they are safe and effective. Pathway 3 kamagra oral jelly walmart.

Exceptional importation and sale of certain non-compliant medical devices related to erectile dysfunction treatment. Note that a sale generally requires the transfer of ownership of a device from one party to another and does not necessitate any transfer of money. Applicants should carefully kamagra oral jelly walmart review the pathways and select the most appropriate authorization route for their product. For more information, see Personal protective equipment (erectile dysfunction treatment).

How to get authorization. If you intend to kamagra oral jelly walmart manufacture 3D print face shields in response to the erectile dysfunction treatment crisis, see. 3D printing and other manufacturing of personal protective equipment in response to erectile dysfunction treatment Feedback If you have any questions or comments about this notice, contact the Medical Devices Directorate at hc.meddevices-instrumentsmed.sc@canada.ca R. J.

Roberge, "Face shields for kamagra oral jelly walmart control. A review," Journal of Occupational and Environmental Hygiene, pp. 235-242, 2016. Related links FootnotesFootnote 1 R kamagra oral jelly walmart.

J. Roberge, "Face shields for control kamagra oral jelly walmart. A review," Journal of Occupational and Environmental Hygiene, pp. 235-242, 2016.Return to footnote 1 referrerA three-year trial in Indonesia has produced encouraging results that show a significant reduction in the number of dengue cases.

It involved the release Wolbachia-infected Aedes aegypti mosquitoes kamagra oral jelly walmart in and around the dengue-endemic city of Yogyakarta. The study found that in the city and surrounding areas where the infected mosquitoes were released the number of cases of dengue decreased significantly compared with parts of the city where they were not.The trial – conducted by the World Mosquito Program in close collaboration with the Tahija Foundation and the Gadjah Mada University in Indonesia – tested Ae. Aegypti mosquitoes carrying Wolbachia for their capacity to inhibit transmission of dengue kamagra.The results will be submitted for evaluation during the next meeting of the WHO Vector Control Advisory Group in December for experts to formally assess the impact of the strategy based on the results of the trial and associated studies. As there are few effective sustainable tools available to combat Aedes-borne diseases, all new tools that demonstrate public health value against dengue and similar kamagraes will be a welcome addition to kamagra oral jelly walmart the vector control arsenal.

WolbachiaWolbachia are intercellular natural symbiotic bacteria in insects that are known to reduce the capacity of Ae. Aegypti to transmit dengue kamagra and related kamagraes under laboratory conditions. However, epidemiological evidence has been awaited to demonstrate kamagra oral jelly walmart the large‐scale deployment of Wolbachia-infected Ae. Aegypti in reducing the overall frequency of transmission of dengue kamagra within a population.

The results of the study from Indonesia are therefore of great interest.DengueDengue is a mosquito-borne viral disease that has rapidly spread in all regions of WHO in recent years. The incidence of dengue has grown kamagra oral jelly walmart dramatically worldwide in recent decades. The kamagra is transmitted by female mosquitoes mainly of the species Ae. Aegypti and, to a lesser extent, Ae.

Albopictus. The number of dengue cases reported to WHO increased more than 8-fold over the past two decades, and dengue is the only communicable disease that has increased exponentially with rapid urbanization and environmental changes. The vast majority of cases are asymptomatic or mild and self-managed. Hence, the actual numbers of dengue cases are under-reported.

The world relies heavily on vector control, and conventional methods have limited impact. Lack of funds for operational research and the paucity of strong evidence for sustained interventions continue to undermine global control efforts.A three-year trial in Indonesia has produced encouraging results that show a significant reduction in the number of dengue cases. It involved the release Wolbachia-infected Aedes aegypti mosquitoes in and around the dengue-endemic city of Yogyakarta. The study found that in the city and surrounding areas where the infected mosquitoes were released the number of cases of dengue decreased significantly compared with parts of the city where they were not.The trial – conducted by the World Mosquito Program in close collaboration with the Tahija Foundation and the Gadjah Mada University in Indonesia – tested Ae.

Aegypti mosquitoes carrying Wolbachia for their capacity to inhibit transmission of dengue kamagra.The results will be submitted for evaluation during the next meeting of the WHO Vector Control Advisory Group in December for experts to formally assess the impact of the strategy based on the results of the trial and associated studies. As there are few effective sustainable tools available to combat Aedes-borne diseases, all new tools that demonstrate public health value against dengue and similar kamagraes will be a welcome addition to the vector control arsenal. WolbachiaWolbachia are intercellular natural symbiotic bacteria in insects that are known to reduce the capacity of Ae. Aegypti to transmit dengue kamagra and related kamagraes under laboratory conditions.

However, epidemiological evidence has been awaited to demonstrate the large‐scale deployment of Wolbachia-infected Ae. Aegypti in reducing the overall frequency of transmission of dengue kamagra within a population. The results of the study from Indonesia are therefore of great interest.DengueDengue is a mosquito-borne viral disease that has rapidly spread in all regions of WHO in recent years. The incidence of dengue has grown dramatically worldwide in recent decades.

The kamagra is transmitted by female mosquitoes mainly of the species Ae. Aegypti and, to a lesser extent, Ae. Albopictus. The number of dengue cases reported to WHO increased more than 8-fold over the past two decades, and dengue is the only communicable disease that has increased exponentially with rapid urbanization and environmental changes.

The vast majority of cases are asymptomatic or mild and self-managed. Hence, the actual numbers of dengue cases are under-reported. The world relies heavily on vector control, and conventional methods have limited impact. Lack of funds for operational research and the paucity of strong evidence for sustained interventions continue to undermine global control efforts.How have country-based malaria experts adapted to the double challenge of malaria and erectile dysfunction treatment?.

What successes have they achieved, and where are the remaining gaps?. In a virtual forum on 3 September, 10 Ministry of Health representatives shared their experiences and reflections. You can watch their presentations below.On 4 September, participants heard from senior political and health leaders from 2 regions that are heavily impacted by malaria. You will find below the presentations of WHO’s Regional Director for Africa, India’s Health Secretary and the Ugandan Minister of Health.

See, also, our photo story with images and quotes from global health leaders participating in the forum.Prerecorded videos of the webinarVideo 1:Dr Matshidiso Moeti, WHO Regional Director for AfricaDr Rajesh Bhushan, Health Secretary, Ministry of Health and Family Welfare, IndiaDr Jane Ruth Aceng, Minister of Health, UgandaVideo 2:Dr Jimmy Opigo, Ministry of Health, UgandaDr Paola Marchesini, Ministry of Health, BrazilDr Sovannaroth Siv, Ministry of Health, CambodiaDr Dorothy Achu, Ministry of Health, CameroonDr Baltazar Candrinho, Ministry of Health, Mozambique Video 3:Dr Harriet Pasquale, Ministry of Health, South SudanDr Neeraj Dhingra, Ministry of Health, IndiaDr Mariam Adam, WHO, SudanDr Helene Hiwat, Ministry of Health, SurinameDr Olugbenga Mokuolu, Ministry of Health, Nigeria.

Date published buy kamagra online canada check this link right here now. August 26, 2020On this page Backgrounderectile dysfunction treatment is an infectious disease caused by the erectile dysfunction erectile dysfunction. The World Health Organization declared a global kamagra in March 2020, and the Minister of Health signed the Interim Order Respecting the Importation and Sale of Medical Devices for buy kamagra online canada Use in Relation to erectile dysfunction treatment on March 18, 2020.

The Interim Order (IO) allows us to quickly address large-scale public health emergencies.This IO allows for faster authorization of Class I-IV medical devices for erectile dysfunction treatment.This document presents the criteria for safety and effectiveness that apply to test swabs used for erectile dysfunction treatment sampling. It also provides guidance on how to meet these criteria in an application under the IO pathway. Diagnostic testing is a key element in both buy kamagra online canada.

identifying cases of preventing the spread of the erectile dysfunction A test swab may be used to collect a sample for either Polymerase Chain Reaction (PCR) laboratory testing or point-of-care testing. Point-of-care testing can be done directly in a hospital or doctor’s office. Once the sample has been taken, the buy kamagra online canada swab is either placed in a preserving liquid and sent to a laboratory for testing, or placed directly in a testing device (point-of-care).Swabs may be packaged in a variety of kamagra transport media (VTM).

Specifications for individual VTMs are beyond the scope of this document. Swabs play a role in the accuracy of erectile dysfunction treatment diagnostic testing. For example, false negatives can buy kamagra online canada occur in PCR tests if.

the swab material inhibits the test reaction or the swab design doesn’t provide enough surface area to obtain a sufficient sample Test swabs that are not safe and effective may cause or lead to harm. For example. A swab that breaks during sample collection can cause physical injury a non-sterile swab that produces an incorrect test result can lead to harmHealth buy kamagra online canada Canada has published a guidance document to support the preparation of applications submitted under the IO.

It should be read in conjunction with this document. We are processing applications as quickly as possible. To avoid delays, please ensure you have completed your application properly.Medical Devices Regulations (MDR) classification In the buy kamagra online canada Canadian regulatory framework, Class I devices present the lowest potential risk and Class IV the highest.

Swabs are classified according to their labelling and intended use. For example, if a swab is labelled for nasopharyngeal (NP) or oropharyngeal (OP) use only, it will be classified as a Class I medical device according to Classification Rule 2(2) of the MDR. If a swab buy kamagra online canada is not exclusively for use in oral or nasal cavities, or its use is not explicitly stated, it will be classified as a Class II device by Rule 2(1).

These swabs belong to a higher risk class because their use in other body orifices for the collection of tissue samples (for example, to test for chlamydia or ureaplasma) is associated with greater risk. Rule 2 Subject to subrules (2) to (4), all invasive devices that penetrate the body through a body orifice or that buy kamagra online canada come into contact with the surface of the eye are classified as Class II. A device described in subrule (1) that is intended to be placed in the oral or nasal cavities as far as the pharynx or in the ear canal up to the ear drum is classified as Class I.Regulatory pathways for erectile dysfunction treatment devicesManufacturers of Class I swabs may seek authorization to import and sell their products under either.

A Medical Device Establishment Licence (MDEL) MDEL is an establishment oversight framework that is not product-specific and not designed to assess safety and effectiveness an IO authorization information on safety and effectiveness are required as part of the application Health Canada is encouraging a sub-group of swab manufacturers to use the IO authorization pathway for Class I swabs, especially if they are. New to the manufacturing of swabs and manufacturing in Canada (such as a company that has re-tooled to manufacture), or using a new manufacturing buy kamagra online canada process or design for swabs (such as 3D printing or honeycomb design)IO applications for swabs should include the following information.Device description The device description should include. A picture and/or engineering drawing identification of all materials used in the production of the swab the intended use(s) (for example, NP swabs)Quality manufacturingManufacturers must either.

demonstrate compliance with Quality Manufacturing Systems (for example, ISO 13485 certificate) applicable to the swab, or provide a clear description of the planned quality manufacturing systems that are consistent with similar existing manufacturing systemsDesign verificationProvide swab design verification (bench testing) data in a summary report. It should buy kamagra online canada show that the essential minimum design characteristics are met. These data should be based on test samples representative of finished swabs that have undergone sterilization prior to bench testing.Dimensions Swabs should have minimum length specifications and minimum and maximum head diameter specifications in order to be safe and effective.

Minimum length specification for example, adult NP swabs require ≥14 cm to reach the posterior nasopharynx minimum and maximum head diameter specification for example, adult NP swabs require 1–4 mm to pass into the mid-inferior portion of the inferior turbinate and maneuver well FlexibilitySwab flexibility is assessed through. Durability for example, tolerate 20 rough repeated insertions into a 4 mm inner diameter clear plastic tube curved back on itself with a curve radius of 3 cm bendability for example, bend tip and neck 90º without breaking ability to maintain initial form for example, restore to initial form following 45º bending Manufacturers may describe the test performed, the number of samples, and a summary of the results.Strength/Breakpoint (failure) To limit the potential for patient harm, the minimum breakpoint distance should be approximately 8 to 9 cm from the buy kamagra online canada nasopharynx. However, no breaks or fractures should occur following reasonable manipulation.

Applicants should submit a rationale for the design of the breakpoint distance from the swab tip. It should demonstrate that the breakpoint length can be buy kamagra online canada accommodated by commercially available swab/media tubes.Surface propertiesThe swab surface should be free of. processing aids (such as disinfectants) foreign materials degreasers mold release agents For injection molded swabs, no burrs, flashing, or sharp edges should be present.

Design validationProvide swab validation (performance) data in a summary report that demonstrates that the swab. can acquire samples comparable to a commercially available swab control, and will not inhibit the PCR reactionThese data should be based on test samples representative of finished swabs that have undergone sterilization prior to testing.Comparable sample acquisition to a control, and PCR compatibilityThe manufacturer should demonstrate test swab cycle threshold (Ct) recovery values (RT-PCR) that are statistically comparable to those obtained from a commercially available swab control using buy kamagra online canada erectile dysfunction (or a scientifically justified surrogate).Pass/Fail criteria. Values ≥ 2Cts indicate significantly less efficient ribonucleic acid collection and/or elution.Clinical feasibility/suitability simulationManufacturers should submit either.

A clinical test report or previous clinical data Clinical test reportThe clinical test report should describe the use of the proposed finished swab (sterilized) in a sufficient number of individuals by trained healthcare professionals in a minimum of 30 patients that have tested positive for erectile dysfunction, or a scientifically justified surrogate kamagra. Include comparisons of the proposed swab against a flocked swab buy kamagra online canada commercially available in Canada with respect to. flexibility fit ability to navigate to the nasopharynx (or other areas specified in the indications) ability to collect a specimen/respiratory epithelial cells for example, using the RNase P housekeeping gene test results agreement for example, ≥ 90% positive % agreement using a composite control (positive % agreement calculation that includes all positive findings from control and test swabs) Clinical testing considerations A scientifically justified surrogate kamagra may be used if erectile dysfunction treatment-positive patients are not available.

Positive % agreement should not be determined using high Ct samples. One-half (1/2) to two-thirds (2/3) of erectile dysfunction treatment-positive samples should have a high viral loads (Cts < buy kamagra online canada. 30).

Report agreement between control and test swabs in terms buy kamagra online canada of quantitative (Ct) and qualitative (+/- test) values with appropriate descriptive statistics. Include patient symptomatology for samples. For example, days from symptom onset, known vs.

Suspected erectile dysfunction treatment status buy kamagra online canada. Use of different VTM/universal transport media (V/UTM) across erectile dysfunction treatment-positive samples may contribute to Ct variability. Ensure consistency by using the same media/tubes for each specimen within a clinical evaluation.

Validate the chosen V/UTM buy kamagra online canada media/tubes to show they will not interfere with the PCR test results. For example, allowing 7 days of swab positive specimen incubation with the chosen media/vial is considered a worst-case transportation scenario to evaluate maximal leaching/interaction potential). Use a single PCR test platform throughout each clinical evaluation.

The platform should have buy kamagra online canada been previously authorized by HC or another jurisdiction. Location (for example, left vs right nostril) and order of sampling (for example, control vs. Test swab) can affect specimen quality and results variability.

Location and swab sampling order should buy kamagra online canada be randomized.For additional information on collecting, handling, and testing erectile dysfunction treatment specimens, please refer to the Centers for Disease Control and Prevention (CDC) Interim Guidelines for Collecting, Handling, and Testing Clinical Specimens for erectile dysfunction treatment.Previous clinical dataPreviously obtained clinical data may be submitted in lieu of clinical testing. Those data should demonstrate the safe and effective use of a swab of identical design and materials in human subjects. The proposed swab should be compared against a flocked swab commercially available in Canada with respect to.

flexibility fit ability to navigate to the nasopharynx (or other areas specified in the indications) ability to collect a specimen/respiratory epithelial cells for example, using the RNase P housekeeping gene test results agreement for example, buy kamagra online canada ≥ 90% positive % agreement) using a composite control (positive % agreement calculation that includes all positive findings from control and test swabs) Sterility Provide sterilization validation data in a summary report. It should demonstrate that the chosen sterilization method will achieve a minimum Sterility Assurance Level (SAL) of 10-6 for the proposed swab, using an appropriate biological indicator (BI) organism (see below). If the swab will be sterilized using an ethylene oxide (EtO) method, you should demonstrate that EtO and ethylene chlorohydrin (ECH) residuals meet the tolerable contact limits (TCL) specified in ISO 10993-7.

Commonly used swab materials, compatible sterilization methods, and appropriate buy kamagra online canada biological indicators are described below. Sterilization Method Swab Materials EtO(for example, ISO 11135) Gamma Irradiation(ISO 11137) Polystyrene handle, polyester bicomponent fiber tipFootnote * X(for example, Puritan 25-3316-H/U) Not applicable Polystyrene handle, nylon flocked fiber tipFootnote * X(for example, Copan 503CS01) X(for example, BD 220252) Footnote * The CDC provides guidance on the types of swabs that should be used for optimal specimen collection for PCR testing. They include swabs that are made of polyester (for example, Dacron), rayon, or nylon-flocked.

Cotton-tipped or buy kamagra online canada calcium alginate swabs are not acceptable because residues present in those materials inhibit the PCR reaction. Return to footnote * referrer Appropriate BIIf ionizing radiation will be used to sterilize the swab. Bacillus pumilus spores are recommended for doses of 25 kGy Bacillus cereus or Bacillus buy kamagra online canada sphaericus spores are recommended for doses of >.

25 kGy (World Health Organization, The International Pharmacopoeia, 9th Ed., 2019) Sterilization Process Spore (Indicator Organism) Steam Geobacillus stearothermophilus(formerly Bacillus stearothermophilus) Dry Heat Bacillus atrophaeus (formerly Bacillus subtilis var. Niger) Ethlylene Oxide Bacillus atrophaeus (formerly Bacillus subtilis var. Niger) Hydrogen Peroxide Geobacillus stearothermophilus(formerly Bacillus stearothermophilus) Source buy kamagra online canada.

US Food and Drug Administration, "Biological Indicator (BI) Premarket Notification [510(k)] Submissions," October 2007. [Online].Packaging validation Provide packaging validation data in a summary report. It should demonstrate that the swab packaging system will maintain a sterile environment across the labelled shelf life (for example, ASTM F1980) buy kamagra online canada.

without leakage (for example, ASTM D3078-02) with adequate seal strength (for example, ASTM F88/EN 868-5)Test packaging samples should be representative of finished swab packages that have undergone sterilization prior to testing.Biocompatibility Provide biocompatibility data in a summary report. It should demonstrate compliance with biocompatibility tests recommended for devices in limited contact (≤24 hrs) with mucosal membranes, as per ISO 10993-1. These include buy kamagra online canada.

cytotoxicity sensitization irritation/intracutaneous reactivityThese data should be based on test samples representative of finished swabs that have undergone sterilization prior to testing.LabellingSwabs should be individually packaged and labelled. The application must include the swab label, which must include. The name and model number of the device the term ‘sterile’, along buy kamagra online canada with the sterilization method (EtO = ethylene oxide.

R = gamma irradiation), if the swab is intended to be sold in a sterile condition the name and address of the manufacturer manufacturing and expiry datesIf swabs are not sterile but must be sterilized at the user facility, then the sterilization parameters and method should be clearly described in accompanying instructions for use documentation.Post-market requirementsAs stated in Section 12 of the IO, within 10 days of becoming aware of an incident in Canada, all IO authorization holders must. report the incident specify the nature of the incident specify the circumstances surrounding the incidentOn this page About face shields Personal protective equipment (PPE) can help prevent potential exposure to infectious disease. They are considered medical devices in Canada and buy kamagra online canada therefore must follow the requirements outlined in the Medical Devices Regulations.

Medical devices are classified into 4 groups (Class I, II, III and IV) based on their risk to health and safety. Class I devices, such as gauze bandages, pose the lowest potential risk, while Class IV devices, such as pacemakers, pose the greatest potential risk. In Canada, face shields are buy kamagra online canada Class I medical devices.

A face shield has a transparent window or visor that shields the face and associated mucous membranes (eyes, nose and mouth). It protects the wearer against exposure from splashes and sprays of body fluids. Face shields are made of buy kamagra online canada shatterproof plastic, fit over the face and are held in place by head straps or caps.

They may be made of polycarbonate, propionate, acetate, polyvinyl chloride, or polyethylene terephthalate. They are usually worn with other PPE, such buy kamagra online canada as a medical mask, respirator or eyewear. Health Canada strongly advises against the use of plastic bags as an alternative to face shields.

Standards and requirements for face shields Organizations that are manufacturing face shields are advised to consult some or all of the following standards throughout the design and testing stages. ANSI/ISEA Z.87.1 (2015), American National Standard buy kamagra online canada for Occupational and Educational Personal Eye and Face Protection Devices CSA Z94.3 (2020), Eye and Face Protectors CSA Z94.3.1 (2016), Guideline for Selection, Use, and Care of Eye and Face Protectors BS EN 166 (2002), Personal Eye Protection. Specifications.

Minimum specifications must be incorporated into the design and verification stages to ensure safe and effective face shields. Provide adequate buy kamagra online canada coverage (CSA Z94.3 Sections 0.2.1/10.2.2/10.3/10.4). The size of the face shield is important because it must protect the face and front part of the head.

This includes the eyes, forehead, cheeks, nose, mouth, and chin. Protection may also need to extend to the front of the neck in buy kamagra online canada situations with flying particles and sprays of hazardous liquids. Fit snugly to afford a good seal to the forehead area and to prevent slippage of the device Footnote 1.

Be made of optically clear, distortion-free, lightweight materials (CSA Z94.3.1-16 and Footnote 1). Be free buy kamagra online canada of visible defects or flaws that would impede vision (ANSI Z87.1 Section 9.4). Be comfortable and easy to assemble, use and remove by health care professionals.

Provide adequate space between the wearer’s face and the inner surface of the visor to allow for the use of ancillary equipment (for example, medical mask, respirator, eyewear) Footnote 1. The characteristics and performance requirements of face shields must not be altered when attaching shields to other protective buy kamagra online canada equipment, such as hats or caps. Display anti-fog characteristics on inside and outside of shield (CSA Z94.3.1-16).

For face shields that are not fog resistant, anti-fog spray must be provided. Provide user-contacting materials that have adequate material biocompatibility (skin sensitivity and cytotoxic testing) buy kamagra online canada (ISO 10993-5, 10). Other items to take note of include.

Face shields used for protection in hospital settings do not have to be impact- or flame- resistant. If the device is specifically designed to withstand impact from sharp or fast projectiles, it buy kamagra online canada must comply with set-out standards (ANSI Z87.1, sections 9.2 and 9.3, CSA Z94.3, section 10.1). For reuse, manufacturers must provide validated cleaning instructions.

Sterilization procedures must not compromise the shield in any way, such as deformation or buy kamagra online canada cracking. Regulatory authorization Most PPE, including face shields, are Class I medical devices if they are manufactured, sold or represented for use for reducing the risk of or preventing the user from . This includes erectile dysfunction treatment.

Face shields may be authorized for buy kamagra online canada sale or import into Canada through the following regulatory pathways. Pathway 1. Interim order authorization to import and sell medical devices related to erectile dysfunction treatment.

Pathway 2 buy kamagra online canada. Expedited review and issuance of Medical Device Establishment Licences (MDEL) related to erectile dysfunction treatment. MDEL holders that import and sell face shields should take measures to ensure they are safe and effective.

Pathway 3 buy kamagra online canada. Exceptional importation and sale of certain non-compliant medical devices related to erectile dysfunction treatment. Note that a sale generally requires the transfer of ownership of a device from one party to another and does not necessitate any transfer of money.

Applicants should carefully review the pathways and select the buy kamagra online canada most appropriate authorization route for their product. For more information, see Personal protective equipment (erectile dysfunction treatment). How to get authorization.

If you intend to manufacture 3D print face shields in response to the erectile dysfunction treatment crisis, see buy kamagra online canada. 3D printing and other manufacturing of personal protective equipment in response to erectile dysfunction treatment Feedback If you have any questions or comments about this notice, contact the Medical Devices Directorate at hc.meddevices-instrumentsmed.sc@canada.ca R. J.

Roberge, "Face shields buy kamagra online canada for control. A review," Journal of Occupational and Environmental Hygiene, pp. 235-242, 2016.

Related links FootnotesFootnote buy kamagra online canada 1 R. J. Roberge, "Face shields for buy kamagra online canada control.

A review," Journal of Occupational and Environmental Hygiene, pp. 235-242, 2016.Return to footnote 1 referrerA three-year trial in Indonesia has produced encouraging results that show a significant reduction in the number of dengue cases. It involved the release Wolbachia-infected Aedes buy kamagra online canada aegypti mosquitoes in and around the dengue-endemic city of Yogyakarta.

The study found that in the city and surrounding areas where the infected mosquitoes were released the number of cases of dengue decreased significantly compared with parts of the city where they were not.The trial – conducted by the World Mosquito Program in close collaboration with the Tahija Foundation and the Gadjah Mada University in Indonesia – tested Ae. Aegypti mosquitoes carrying Wolbachia for their capacity to inhibit transmission of dengue kamagra.The results will be submitted for evaluation during the next meeting of the WHO Vector Control Advisory Group in December for experts to formally assess the impact of the strategy based on the results of the trial and associated studies. As there are few effective sustainable tools buy kamagra online canada available to combat Aedes-borne diseases, all new tools that demonstrate public health value against dengue and similar kamagraes will be a welcome addition to the vector control arsenal.

WolbachiaWolbachia are intercellular natural symbiotic bacteria in insects that are known to reduce the capacity of Ae. Aegypti to transmit dengue kamagra and related kamagraes under laboratory conditions. However, epidemiological evidence has been buy kamagra online canada awaited to demonstrate the large‐scale deployment of Wolbachia-infected Ae.

Aegypti in reducing the overall frequency of transmission of dengue kamagra within a population. The results of the study from Indonesia are therefore of great interest.DengueDengue is a mosquito-borne viral disease that has rapidly spread in all regions of WHO in recent years. The incidence of dengue has grown dramatically worldwide in buy kamagra online canada recent decades.

The kamagra is transmitted by female mosquitoes mainly of the species Ae. Aegypti and, to a lesser extent, Ae. Albopictus.

The number of dengue cases reported to WHO increased more than 8-fold over the past two decades, and dengue is the only communicable disease that has increased exponentially with rapid urbanization and environmental changes. The vast majority of cases are asymptomatic or mild and self-managed. Hence, the actual numbers of dengue cases are under-reported.

The world relies heavily on vector control, and conventional methods have limited impact. Lack of funds for operational research and the paucity of strong evidence for sustained interventions continue to undermine global control efforts.A three-year trial in Indonesia has produced encouraging results that show a significant reduction in the number of dengue cases. It involved the release Wolbachia-infected Aedes aegypti mosquitoes in and around the dengue-endemic city of Yogyakarta.

The study found that in the city and surrounding areas where the infected mosquitoes were released the number of cases of dengue decreased significantly compared with parts of the city where they were not.The trial – conducted by the World Mosquito Program in close collaboration with the Tahija Foundation and the Gadjah Mada University in Indonesia – tested Ae. Aegypti mosquitoes carrying Wolbachia for their capacity to inhibit transmission of dengue kamagra.The results will be submitted for evaluation during the next meeting of the WHO Vector Control Advisory Group in December for experts to formally assess the impact of the strategy based on the results of the trial and associated studies. As there are few effective sustainable tools available to combat Aedes-borne diseases, all new tools that demonstrate public health value against dengue and similar kamagraes will be a welcome addition to the vector control arsenal.

WolbachiaWolbachia are intercellular natural symbiotic bacteria in insects that are known to reduce the capacity of Ae. Aegypti to transmit dengue kamagra and related kamagraes under laboratory conditions. However, epidemiological evidence has been awaited to demonstrate the large‐scale deployment of Wolbachia-infected Ae.

Aegypti in reducing the overall frequency of transmission of dengue kamagra within a population. The results of the study from Indonesia are therefore of great interest.DengueDengue is a mosquito-borne viral disease that has rapidly spread in all regions of WHO in recent years. The incidence of dengue has grown dramatically worldwide in recent decades.

The kamagra is transmitted by female mosquitoes mainly of the species Ae. Aegypti and, to a lesser extent, Ae. Albopictus.

The number of dengue cases reported to WHO increased more than 8-fold over the past two decades, and dengue is the only communicable disease that has increased exponentially with rapid urbanization and environmental changes. The vast majority of cases are asymptomatic or mild and self-managed. Hence, the actual numbers of dengue cases are under-reported.

The world relies heavily on vector control, and conventional methods have limited impact. Lack of funds for operational research and the paucity of strong evidence for sustained interventions continue to undermine global control efforts.How have country-based malaria experts adapted to the double challenge of malaria and erectile dysfunction treatment?. What successes have they achieved, and where are the remaining gaps?.

In a virtual forum on 3 September, 10 Ministry of Health representatives shared their experiences and reflections. You can watch their presentations below.On 4 September, participants heard from senior political and health leaders from 2 regions that are heavily impacted by malaria. You will find below the presentations of WHO’s Regional Director for Africa, India’s Health Secretary and the Ugandan Minister of Health.

See, also, our photo story with images and quotes from global health leaders participating in the forum.Prerecorded videos of the webinarVideo 1:Dr Matshidiso Moeti, WHO Regional Director for AfricaDr Rajesh Bhushan, Health Secretary, Ministry of Health and Family Welfare, IndiaDr Jane Ruth Aceng, Minister of Health, UgandaVideo 2:Dr Jimmy Opigo, Ministry of Health, UgandaDr Paola Marchesini, Ministry of Health, BrazilDr Sovannaroth Siv, Ministry of Health, CambodiaDr Dorothy Achu, Ministry of Health, CameroonDr Baltazar Candrinho, Ministry of Health, Mozambique Video 3:Dr Harriet Pasquale, Ministry of Health, South SudanDr Neeraj Dhingra, Ministry of Health, IndiaDr Mariam Adam, WHO, SudanDr Helene Hiwat, Ministry of Health, SurinameDr Olugbenga Mokuolu, Ministry of Health, Nigeria.

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€‚ For the podcast associated with this article, please visit https://academic.oup.com/eurheartj/pages/Podcasts.This Focus Issue on vascular biology and medicine contains a clinical research article entitled ‘The association of amputations and peripheral artery disease in patients kamagra bestellen per nachnahme with type 2 diabetes mellitus receiving sodium–glucose co-transporter type-2 inhibitors. Real-world study’, authored by Sanjoy Paul from the University of Melbourne in Australia, and colleagues.1 Patients with peripheral artery disease (PAD) remain a challenging population to treat, in particular in the attempt to reduce the risk of amputation.2–4 Paul et al. Evaluated the temporal pattern of amputations in type kamagra bestellen per nachnahme 2 diabetes (T2DM) patients, the risk of amputations by new and older antidiabetic drugs (ADDs), and the interplay of PAD with therapy and amputation risk.

Using Centricity Electronic Medical Records from the USA, ∼3 300 000 patients with T2DM were identified. The proportion of incident amputations per 10 000 adults ranged between 4.7 and 6.8 during 2000–2008 and significantly increased to 12.3 in 2017. Patients with pre-existing PAD had a more than four-fold higher risk kamagra bestellen per nachnahme of lower limb amputation (LLA).

In propensity score-adjusted pair-wise analyses, the risk of LLA was similar in sodium–glucose co-transporter type-2 inhibitors (SGLT-2is) vs. Glucagon-like peptide 1 receptor agonists (GLP1-RAs), and lower in SGLT-2i vs. Dipeptidyl peptidase-4 inhibitor (DPP-4i) or other ADDs kamagra bestellen per nachnahme (hazard ratio 0.65 and 0.43, respectively) (Figure 1).

The rate of LLA was similar in patients treated with canagliflozin, empagliflozin, or dapagliflozin. Figure 1Adjusted risk of amputations and peripheral artery disease (from Paul kamagra bestellen per nachnahme SK, Bhatt DL, Montvida O. The association of amputations and peripheral artery disease in patients with type 2 diabetes mellitus receiving sodium–glucose co-transporter type-2 inhibitors.

Real-world study. See pages 1728–1738).Figure 1Adjusted risk of amputations and peripheral artery disease (from Paul SK, Bhatt DL, Montvida kamagra bestellen per nachnahme O. The association of amputations and peripheral artery disease in patients with type 2 diabetes mellitus receiving sodium–glucose co-transporter type-2 inhibitors.

Real-world study. See pages 1728–1738).The authors conclude that the risk of amputation kamagra bestellen per nachnahme in patients treated with SGLT-2is and incretins is not higher compared with other ADDs. In addition, and not surprisingly, pre-existing PAD is the greatest driver of amputation risk.

The manuscript is accompanied by an Editorial by Charalambos Vlachopoulos from the University of Athens Medical School in Greece, and colleagues.5 The authors conclude that a considerable number of original kamagra bestellen per nachnahme studies and analyses have been applied on the canvas of the risk of amputation by SGLT2is that as a whole reduce the contrast of the first randomized trials. While any risk appears to be related specifically to canagliflozin, recent large registries provide reassuring data on the safety of SGLT2is, as long as physicians are aware of this particular complication and monitor their patients closely. Undoubtedly, we are in need of more data, and the pursuit for proper evaluation of canagliflozin calls for ‘making haste slowly’.Inflammation plays an important role in development of cardiovascular disease (CVD).6–8 The NOD-like receptor protein-3 (NLRP3) inflammasome contributes to the development of atherosclerosis in animal models.

Components of the NLRP3 inflammasome pathway kamagra bestellen per nachnahme such as interleukin-1β (IL-1β) can be targeted therapeutically. In a clinical research article entitled ‘Genetically determined NLRP3 inflammasome activation associates with systemic inflammation and cardiovascular mortality’, Stefan Schunk from the Saarland University Hospital in Homburg/Saar, Germany, and colleagues note that associations of genetically determined inflammasome-mediated systemic inflammation with CVD and mortality in humans are unknown.9 The authors explored the association of genetic NLRP3 variants with prevalent CVD and cardiovascular mortality in 538 167 subjects on an individual participant level in an explorative gene-centric approach without performing multiple testing. The functional relevance of the single nucleotide polymorphism (SNP) for NLRP3 inflammasome activation was evaluated in monocyte-enriched peripheral blood mononuclear cells (PBMCs).

Genetic analyses identified the highly prevalent intronic NLRP3 variant rs10754555 as kamagra bestellen per nachnahme affecting NLRP3 gene expression. Rs10754555 carriers showed significantly higher C-reactive protein and serum amyloid A plasma levels. Carriers of the G allele showed higher NLRP3 inflammasome activation in kamagra bestellen per nachnahme isolated human PBMCs.

In carriers of the rs10754555 variant, the prevalence of coronary artery disease (CAD) was significantly higher as compared with non-carriers, with a significant interaction between rs10754555 and age. Importantly, rs10754555 carriers had significantly higher risk for cardiovascular mortality during follow-up. Inflammasome inducers (e.g kamagra bestellen per nachnahme.

Urate, triglycerides, and ApoC3) modulated the association between rs10754555 and mortality.The authors conclude that the NLRP3 intronic variant rs10754555 is associated with increased systemic inflammation, inflammasome activation, prevalent CAD, and mortality. This study provides evidence for a substantial role for genetically driven systemic inflammation in cardiovascular disease and highlights the NLRP3 inflammasome as a therapeutic target. The manuscript kamagra bestellen per nachnahme is accompanied by an Editorial by Christoph J.

Binder and Nikolina Papac-Milicevic from the Medical University of Vienna in Austria.10 The authors conclude that the findings of this study provide important evidence for the individual differences in the ability to develop chronic inflammation in the context of metabolic disturbances. This may kamagra bestellen per nachnahme open up the possibility for more personalized therapeutic approaches by enabling stratification of patients based on their genetically determined inflammatory risk before clinical manifestations occur.The aim of endovascular stent implantation at the time of coronary angioplasty is to prevent acute vessel closure and chronic negative arterial remodelling in patients affected by coronary disease. However, stents are sensed as a foreign body, leading to immune cell activation, resulting in chronic inflammation and, eventually, in-stent restenosis due to the local proliferation of arterial smooth muscle cells.

Mitigating the body’s reaction by improving stent biocompatibility thus represents a major challenge to increase the efficacy of arterial stents and hence the clinical outcome of patients affected by coronary disease.11,12 In a translational research article entitled ‘Coronary stent CD31-mimetic coating favours endothelialization and reduces local inflammation and neointimal development in vivo’, Sergio Diaz-Rodriguez from the Laval University, Québec, Canada, and colleagues evaluate the effect of CD31-mimetic metal stent coating on the in vitro adherence of endothelial cells (ECs) and blood elements, and the in vivo strut coverage and neointimal growth.13 The rapid endothelialization of bare metal stents (BMS) is counterbalanced by inflammation-induced neointimal growth. Drug-eluting stents (DES) prevent leucocyte activation kamagra bestellen per nachnahme but impair endothelialization, delaying effective device integration into arterial walls. Previously, it has been shown that engaging the vascular CD31 co-receptor is crucial for endothelial and leucocyte homeostasis and arterial healing.

Furthermore, it has been shown that a soluble synthetic peptide (known as P8RI) acts like a CD31 agonist. The authors produced cobalt chromium disks and stents coated with a CD31-mimetic peptide through two procedures, plasma amination or dip-coating, both yielding kamagra bestellen per nachnahme comparable results. They found that CD31-mimetic disks significantly reduced the extent of primary human coronary artery EC and blood platelet/leucocyte activation in vitro.

In vivo, CD31-mimetic stent kamagra bestellen per nachnahme properties were compared with those of DES and BMS by coronarography and microscopy at 7 and 28 days post-implantation in pig coronary arteries (n = 9 stents/group/time point). Seven days post-implantation, only CD31-mimetic struts were fully endothelialized, with no activated platelets/leucocytes. At day 28, neointima development over CD31-mimetic stents was significantly reduced compared with BMS, appearing as a normal arterial media with absence of thrombosis in contrast to DES.The authors conclude that CD31-mimetic coating favours vascular homeostasis and arterial wall healing, preventing in-stent stenosis and thrombosis.

Hence, such coatings seem to improve metal stent biocompatibility kamagra bestellen per nachnahme. The manuscript is accompanied by an Editorial by Alexandra Lansky from the Yale School of Medicine in New Haven, CT, USA and colleagues.14 The authors conclude that the effect of a CD31-mimetic stent in CAD patients may be blunted due to impaired function of CD31-expressing cells in this patient population. These will be critical benchmarks to more reliably predict whether this breakthrough combination stent technology can provide the incremental safety and effectiveness benefit needed to further advance the management options of our patients with obstructive coronary disease.In another translational research article entitled ‘A proteomic atlas of the neointima identifies novel druggable targets for preventive therapy’, Thorsten Kessler from the Deutsches Herzzentrum München in Germany, and colleagues sought to investigate the molecular processes underlying neointima formation and to identify new treatment and prevention targets.15 Neointima formation was induced by wire injury in mouse femoral arteries.

High-accuracy proteomic measurement of single femoral arteries to a depth of kamagra bestellen per nachnahme ∼5000 proteins revealed massive proteome remodelling, with more than half of all proteins exhibiting expression differences between injured and non-injured vessels. The authors observed major changes in the composition of the extracellular matrix and cell migration processes. Among the latter, they identified the classical transient receptor potential channel 6 (Trpc6) as kamagra bestellen per nachnahme driving neointima formation.

This was confirmed in an experimental model. Indeed, Trpc6–/– mice presented reduced neointima formation compared with wild-type mice. In addition, activating or repressing TRPC6 in human vascular smooth muscle cells resulted in increased or decreased migratory kamagra bestellen per nachnahme capacity, respectively.

Finally, in a cohort of individuals with angiographic follow-up in >3000 patients, homozygous carriers of a common genetic variant associated with elevated TRPC6 expression were at increased risk of restenosis after coronary stenting (adjusted odds ratio 1.49) during a mean follow-up of 217 days.The authors conclude that their study provides a proteomic atlas of the healthy and injured arterial wall that can be used to define novel factors for therapeutic targeting. They present TRPC6 as an actionable target to prevent neointima formation secondary to vascular injury and stent implantation. The manuscript is accompanied by an Editorial by Giuseppina Caligiuri from INSERM in Paris and Gregory Franck from the Hôpitaux Universitaires Paris Nord Val-de-Seine in France.16 The authors conclude that further studies are needed in order to specifically address the therapeutic potential of TRCP6 inhibitors in a kamagra bestellen per nachnahme clinical perspective.

If confirmed, a combo device eluting both mTOR inhibitors and TRCP blockers could select the right ‘channels’, affecting the broadest relevant targets and eventually reaching the ‘no-restenosis’ Holy Grail.‘Embolic stroke of undetermined source’ (ESUS) is used to describe patients with a non-lacunar ischaemic stroke without any identified embolic source from the heart or the arteries supplying the ischaemic territory, or any other apparent cause. In a kamagra bestellen per nachnahme State of the Art review article entitled ‘Supracardiac atherosclerosis in embolic stroke of undetermined source. The underestimated source’, George Ntaios from the University of Thessaly in Greece, and colleagues note that when the ESUS concept was introduced, covert atrial fibrillation was conceived to be the main underlying cause in the majority of ESUS patients.17 Yet another important embolic source in ESUS is the atherosclerotic plaque in the carotid, vertebrobasilar, and intracranial arteries, or the aortic arch—collectively described as supracardiac atherosclerosis.

There is emerging evidence showing that the role of supracardiac atherosclerosis is larger than was initially perceived. Advanced imaging methods are kamagra bestellen per nachnahme available to identify plaques which carry high embolic risk. The role of novel antithrombotic strategies in these patients needs to be assessed in randomized controlled trials.

This review presents the evidence which points towards a major aetiological association between atherosclerotic plaques and ESUS, summarizes the imaging features which may aid in identifying plaques more likely to be associated with ESUS, discusses strategies to reduce the associated stroke risk, and highlights the rationale for future research in this field.Unlike native LDL, modified LDLs such as oxidized, carbamylated, or acetylated LDLs are not recognized by the native LDL receptor (LDL-R). Rather, modified LDL binds to the lectin-like oxidized LDL receptor-1 (LOX-1).8,18,19 In a State of the Art kamagra bestellen per nachnahme review article entitled ‘Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1). A crucial driver of atherosclerotic cardiovascular disease’, Alexander Akhmedov from the University of Zurich in Switzerland, and colleagues note that LOX-1, a scavenger receptor that promotes endothelial dysfunction by inducing proatherogenic signalling and plaque formation via the endothelial uptake of oxidized LDL (oxLDL) and electronegative LDL, contributes to the initiation, progression, and destabilization of atheromatous plaques, eventually leading to the development of myocardial infarction and certain forms of stroke.20 In addition to its expression in endothelial cells, LOX-1 is expressed in macrophages, cardiomyocytes, fibroblasts, dendritic cells, lymphocytes, and neutrophils, further implicating this receptor in multiple aspects of atherosclerotic plaque formation.

LOX-1 holds promise as a novel diagnostic and therapeutic target for certain CVDs. Therefore, understanding kamagra bestellen per nachnahme the molecular structure and function of LOX-1 is of critical importance. In this review, the authors highlight the latest scientific findings related to LOX-1, its ligands, and their roles in the broad spectrum of CVDs.

They also describe recent findings from basic research, delineate their translational value, and discuss the potential of LOX-1 as a novel target for the prevention, diagnosis, and kamagra bestellen per nachnahme treatment of related CVDs (Figure 2). Figure 2Ligand–receptor interactions (left) and their potential role in various diseases (right). (A) Multiple ligands, including oxLDL, L5, and dysfunctional HDL, have been shown to induce full-length LOX-1 stimulation.

Depending on the cell type studied, LOX-1 stimulation activates subcellular signalling kamagra bestellen per nachnahme pathways that play major roles in the pathogenesis of various cardiovascular diseases. Notably, in human coronary endothelial cells exposed to oxLDL, Del-1 inhibits the LOX-1-dependent up-regulation of endothelial adhesion molecules, thereby representing an interesting endogenous molecule that—at least in part—curtails the detrimental effects mediated by LOX-1. (B) In recent years, the byproduct of LOX-1 cleavage (i.e.

SLOX-1) and kamagra bestellen per nachnahme the most electronegative LDL subfraction (i.e. L5) have emerged as novel biomarkers, specifically in atherosclerosis-related events, such as myocardial infarction and ischaemic stroke. Furthermore, enhanced LAB activity has kamagra bestellen per nachnahme been shown to be associated with the incidence of cardiovascular diseases, particularly ischaemic stroke.

AGEs, advanced glycation end-products. CRP, C-reactive protein. Del-1, developmental kamagra bestellen per nachnahme endothelial locus-1.

HSP70, heat shock protein 70. LAB, LOX-1 ligand containing apoB. LOX-1, lectin-like oxidized LDL receptor-1 kamagra bestellen per nachnahme.

L5, L5 LDL. NTF, N-terminal fragment kamagra bestellen per nachnahme. OxLDL, oxidized LDL.

SLOX-1, soluble LOX-1. VSMC, vascular smooth kamagra bestellen per nachnahme muscle cell (from Akhmedov A, Sawamura T, Chen CH, Kraler S, Vdovenko D, Lüscher TF. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1).

A crucial driver of atherosclerotic cardiovascular disease. See pages 1797–1807).Figure 2Ligand–receptor interactions (left) and kamagra bestellen per nachnahme their potential role in various diseases (right). (A) Multiple ligands, including oxLDL, L5, and dysfunctional HDL, have been shown to induce full-length LOX-1 stimulation.

Depending on the cell type studied, LOX-1 stimulation activates subcellular signalling pathways that play major roles kamagra bestellen per nachnahme in the pathogenesis of various cardiovascular diseases. Notably, in human coronary endothelial cells exposed to oxLDL, Del-1 inhibits the LOX-1-dependent up-regulation of endothelial adhesion molecules, thereby representing an interesting endogenous molecule that—at least in part—curtails the detrimental effects mediated by LOX-1. (B) In recent years, the byproduct of LOX-1 cleavage (i.e.

SLOX-1) and the most electronegative kamagra bestellen per nachnahme LDL subfraction (i.e. L5) have emerged as novel biomarkers, specifically in atherosclerosis-related events, such as myocardial infarction and ischaemic stroke. Furthermore, enhanced LAB activity has been shown to be associated with the incidence of cardiovascular diseases, particularly ischaemic stroke.

AGEs, advanced glycation end-products kamagra bestellen per nachnahme. CRP, C-reactive protein. Del-1, developmental kamagra bestellen per nachnahme endothelial locus-1.

HSP70, heat shock protein 70. LAB, LOX-1 ligand containing apoB. LOX-1, lectin-like oxidized LDL kamagra bestellen per nachnahme receptor-1.

L5, L5 LDL. NTF, N-terminal fragment. OxLDL, oxidized LDL kamagra bestellen per nachnahme.

SLOX-1, soluble LOX-1. VSMC, vascular smooth muscle cell (from Akhmedov A, Sawamura kamagra bestellen per nachnahme T, Chen CH, Kraler S, Vdovenko D, Lüscher TF. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1).

A crucial driver of atherosclerotic cardiovascular disease. See pages 1797–1807).The issue is complemented by two Discussion kamagra bestellen per nachnahme Forum articles. In a contribution entitled ‘Which biomarker to use, when to start, and how to improve adherence for reducing atherosclerotic cardiovascular disease risk?.

€™, Kwang Kon Koh from Gachon University in Korea comments on the contribution ‘2019 vs. 2016 ESC/EAS statin guidelines for primary prevention of atherosclerotic cardiovascular kamagra bestellen per nachnahme disease’ by Martin Bødtker Mortensen from the Aarhus University Hospital in Denmark, and colleagues.21,22 Mortensen et al. Respond in a separate comment.23The editors hope that readers of this issue of the European Heart Journal will find it of interest.With thanks to Amelia Meier-Batschelet, Johanna Huggler, and Martin Meyer for help with compilation of this article.

References1Paul SK, kamagra bestellen per nachnahme Bhatt DL, Montvida O. The association of amputations and peripheral artery disease in patients with type 2 diabetes mellitus receiving sodium–glucose co-transporter type-2 inhibitors. Real-world study.

Eur Heart J 2021;42:1728–1738.2Behrendt kamagra bestellen per nachnahme CA. Higher long-term mortality after endovascular vs. Open-surgical revascularization of peripheral artery disease in Australia and New Zealand?.

Eur kamagra bestellen per nachnahme Heart J 2021. Doi:10.1093/eurheartj/ehab143.3Parvar SL, Ngo L, Dawson J, Nicholls SJ, Fitridge R, Psaltis PJ, Ranasinghe I. Long-term outcomes following endovascular kamagra bestellen per nachnahme and surgical revascularization for peripheral artery disease.

A propensity score-matched analysis. Eur Heart J 2021. Doi.

10.1093/eurheartj/ehab116.4Tseng A, Bhatt S, Girardo M, Liedl D, Wennberg P, Shamoun F. Complex antithrombotic therapy and bleeding risk in patients with peripheral arterial disease. Eur Heart J 2020;41(Suppl_2):ehaa946.2396.5Vlachopoulos C, Terentes-Printzios D, Tsioufis K.

Do SGLT2 inhibitors increase the risk of amputation?. Make haste slowly. Eur Heart J 2021;42:1739–1741.6Lawler PR, Bhatt DL, Godoy LC, Lüscher TF, Bonow RO, Verma S, Ridker PM.

Targeting cardiovascular inflammation. Next steps in clinical translation. Eur Heart J 2021;42:113–131.7Liberale L, Montecucco F, Tardif JC, Libby P, Camici GG.

Inflamm-ageing. The role of inflammation in age-dependent cardiovascular disease. Eur Heart J 2020;41:2974–2982.8Stojanović SD, Fiedler J, Bauersachs J, Thum T, Sedding DG.

Senescence-induced inflammation. An important player and key therapeutic target in atherosclerosis. Eur Heart J 2020;41:2983–2996.9Schunk SJ, Kleber ME, März W, Pang S, Zewinger S, Triem S, Ege P, Reichert MC, Krawczyk M, Weber SN, Jaumann I, Schmit D, Sarakpi T, Wagenpfeil S, Kramann R, Boerwinkle E, Ballantyne CM, Grove ML, Tragante V, Pilbrow AP, Richards AM, Cameron VA, Doughty RN, Dubé MP, Tardif JC, Feroz-Zada Y, Sun M, Liu C, Ko YA, Quyyumi AA, Hartiala JA, Tang WHW, Hazen SL, Allayee H, McDonough CW, Gong Y, Cooper-DeHoff RM, Johnson JA, Scholz M, Teren A, Burkhardt R, Martinsson A, Smith JG, Wallentin L, James SK, Eriksson N, White H, Held C, Waterworth D, Trompet S, Jukema JW, Ford I, Stott DJ, Sattar N, Cresci S, Spertus JA, Campbell H, Tierling S, Walter J, Ampofo E, Niemeyer BA, Lipp P, Schunkert H, Böhm M, Koenig W, Fliser D, Laufs U, Speer T.

Genetically determined NLRP3 inflammasome activation associates with systemic inflammation and cardiovascular mortality. Eur Heart J 2021;42:1742–1756.10Papac-Milicevic N, Binder CJ. Can a single genetic variant explain residual cardiovascular risk by modifying NLRP3 expression?.

Eur Heart J 2021;42:1757–1759.11Giacoppo D, Alfonso F, Xu B, Claessen B, Adriaenssens T, Jensen C, Pérez-Vizcayno MJ, Kang DY, Degenhardt R, Pleva L, Baan J, Cuesta J, Park DW, Schunkert H, Colleran R, Kukla P, Jiménez-Quevedo P, Unverdorben M, Gao R, Naber CK, Park SJ, Henriques JPS, Kastrati A, Byrne RA. Paclitaxel-coated balloon angioplasty vs. Drug-eluting stenting for the treatment of coronary in-stent restenosis.

A comprehensive, collaborative, individual patient data meta-analysis of 10 randomized clinical trials (DAEDALUS study). Eur Heart J 2020;41:3715–3728.12Byrne RA, Joner M, Kastrati A. Stent thrombosis and restenosis.

What have we learned and where are we going?. The Andreas Grüntzig Lecture ESC 2014. Eur Heart J 2015;36:3320–3331.13Diaz-Rodriguez S, Rasser C, Mesnier J, Chevallier P, Gallet R, Choqueux C, Even G, Sayah N, Chaubet F, Nicoletti A, Ghaleh B, Feldman LJ, Mantovani D, Caligiuri G.

Coronary stent CD31-mimetic coating favours endothelialization and reduces local inflammation and neointimal development in vivo. Eur Heart J 2021;42:1760–1769.14Lansky A, Chun H, Pietras C, Hussain Y. Refining drug-eluting stent technologies.

From engineering to basic science. Eur Heart J 2021;42:1770–1772.15Wierer M, Werner J, Wobst J, Kastrati A, Cepele G, Aherrahrou, Sager HB, Erdmann J, Dichgans M, Flockerzi V, Civelek M, Dietrich A, Mann M, Schunkert H, Kessler T. A proteomic atlas of the neointima identifies novel druggable targets for preventive therapy.

Eur Heart J 2021;42:1733–1785.16Caligiuri G, Frack G. Hitting the right channels to spread a ‘no-restenosis’ message to vascular wall cells. Eur Heart J 2021;42:1786–1788.17Ntaios G, Wintermark M, Michel P.

Supracardiac atherosclerosis in embolic stroke of undetermined source. The underestimated source. Eur Heart J 2021;42:1789–1796.18Borén J, Chapman MJ, Krauss RM, Packard CJ, Bentzon JF, Binder CJ, Daemen MJ, Demer LL, Hegele RA, Nicholls SJ, Nordestgaard BG, Watts GF, Bruckert E, Fazio S, Ference BA, Graham I, Horton JD, Landmesser U, Laufs U, Masana L, Pasterkamp G, Raal FJ, Ray KK, Schunkert H, Taskinen MR, van de Sluis B, Wiklund O, Tokgozoglu L, Catapano AL, Ginsberg HN.

Low-density lipoproteins cause atherosclerotic cardiovascular disease. Pathophysiological, genetic, and therapeutic insights. A consensus statement from the European Atherosclerosis Society Consensus Panel.

Eur Heart J 2020;41:2313–2330.19Lüscher TF. Understanding and preventing atherosclerosis. From bench to bedside.

Eur Heart J 2019;40:323–327.20Akhmedov A, Sawamura T, Chen CH, Kraler S, Vdovenko D, Lüscher TF. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1). A crucial driver of atherosclerotic cardiovascular disease.

Eur Heart J 2021;42:1797–1807.21Koh KK. Which biomarker to use, when to start, and how to improve adherence for reducing atherosclerotic cardiovascular disease risk?. Eur Heart J 2021;42:1808.22Mortensen MB, Nordestgaard BG.

2019 vs. 2016 ESC/EAS statin guidelines for primary prevention of atherosclerotic cardiovascular disease. Eur Heart J 2020;41:3005–3015.23Mortensen MB, Nordestgaard BG.

Examine low-density lipoprotein, remnants, and lipoprotein(a) in parallel in high risk patients. Eur Heart J 2021;42:1809–1810. Published on behalf of the European Society of Cardiology.

All rights reserved. © The Author(s) 2021. For permissions, please email.

Journals.permissions@oup.com.Comment on ‘Statin treatment and muscle symptoms. Series of randomised, placebo controlled n-of-1 trials’ published in the British Medical Journal (DOI. Http://dx.doi.org/10.1136/bmj.n135).Key pointsStatinWISE (Statin Web-based Investigation of Side Effects)1 was a series of institutionally funded, randomized, double-blind, placebo-controlled n-of-1 trials, recruiting 200 participants from general practices across 50 sites in the UK to establish the effect of statins on muscle symptoms.

Participants, who were taking any type of statin at any dose before trial enrolment, had recently stopped or were considering stopping treatment with statins because of muscle symptoms. Exclusion criteria were previously raised levels of serum alanine aminotransferase (≥3 times the upper limit of normal). Persistent, generalized, unexplained muscle pain.

Levels of creatine kinase ≥5 times the upper limit of normal. Any contraindication to atorvastatin treatment.The overall length of the trial was 1 year for each participant and comprised six 2-month treatment periods (three of placebo, three of atorvastatin 20 mg daily) in a randomly allocated order. At the end of each treatment period, participants rated their muscle symptoms on a visual analogue scale.

The primary outcome compared symptom scores (score 0 = no symptoms, 5 = moderate symptoms, and 10 = worst possible symptoms) in the statin and placebo periods. Three months after the end of the final treatment period, participants were asked whether they had, or intended to restart treatment with statins.Of the 200 participants, 151 (76%) provided one or more visual analogue scale measurements in both a statin and a placebo period and were included in the primary analysis. No statistically significant difference in muscle symptom scores was found between the statin and placebo periods [mean ± SD.

1.7 ± 2.6 vs. 1.8 ± 2.7. Mean difference statin minus placebo −0.1.

95% confidence interval (CI) −0.4 to 0.1. P = 0.40]. Atorvastatin showed no significant effect on development of muscle symptoms overall with an odds ratio (OR) of 1.11 (99% CI, 0.62–1.99).

Nor was there any effect on muscle symptoms that could not be attributed to another cause (OR, 1.22. 95% CI, 0.77–1.94).Of the 80 withdrawals during the study for any reason, 42% occurred when the patient was on the statin, 49% when the patient was on placebo, and 9% after randomization but before either statin or placebo had been initiated. Withdrawals because of intolerable muscle symptoms were 9% during a statin period and 7% during a placebo period.

Two-thirds of those completing the six treatment periods (74/113 participants) reported restarting long-term statin treatment. CommentThe European Atherosclerosis Society Consensus Panel and other groups established that there is evidence for causality for only three statin-related adverse effects. Muscle side effects, new-onset diabetes, and transient elevations of liver enzymes, with muscle symptoms being the most common complaint during statin treatment.2 Systematic reviews and meta-analyses of randomized controlled trials (RCTs) have confirmed the safety of statins, showing that the risk of myopathy and its progression to severe rhabdomyolysis are rare, and suggesting that symptomatic adverse events may be misattributed to statins.3–5 Indeed, the association between muscle symptoms and statins has suffered the bias of observational studies, reinforced by media reports.

Patients taking statins expect to experience adverse effects, and therefore reporting of symptoms in statin users may be higher than in a comparable population not on statins. This phenomenon, known as the ‘nocebo’ effect, often leads to patients discontinuing treatment, exposing them to an increased risk of cardiovascular events.6In the present study, patients who had previously faced severe muscle symptoms on a statin reported similar muscle symptom prevalence or severity during blinded statin or placebo periods. Also, there were no differences for the effect of muscle symptoms on several aspects of daily life between statin and placebo periods.

Thus, the study adds to the evidence from SAMSON,7 a recent trial with similar design, and from RCTs like ODYSSEY ALTERNATIVE8 and GAUSS-39 showing that a significant number of people who have problems with muscle pain associated with statins are experiencing a ‘nocebo’ effect, and that re-challenge with statins can be tolerated by most patients.StatinWISE, however, has several limitations. (i) the lack of creatine kinase measurement did not allow establishing what proportion of participants had symptoms associated with biochemical signs of muscle damage. (ii) the trial results may not apply to higher doses of atorvastatin or other statins, as only the effects of atorvastatin 20 mg were assessed.

(iii) most importantly, 86 of the original 200 participants did not complete the whole trial, 49 of whom did not provide sufficient data to contribute to the primary analysis. Furthermore, withdrawals due to intolerable muscle symptoms were not significantly different between statin (9%) and placebo (7%) periods, but StatinWISE was not powered to detect a difference in such withdrawals. (iv) the study participants may not be representative of all those who believe they experience side effects with statins.

On one hand, the study may have selected people who were less susceptible to the ‘nocebo’ effect. On the other hand, the majority (70%) of study participants had a history of cardiovascular disease, and they may have had a higher commitment to statin therapy than those in primary prevention. And (v) the 2-month treatment period should be long enough to allow washout between different treatments and avoid the carry-over of symptoms between statin and placebo periods.

However, while muscle pain/weakness typically occurs within 4–6 weeks after starting statin treatment, the onset may be delayed months or years.10Despite these limitations, these findings underscore the need for clinicians to acknowledge their patients’ muscle symptoms on statin therapy and, using a StatinWISE-like approach, ensure that as many as possible continue on a statin to reduce their cardiovascular risk.Conflict of interest. G.L. Received grant support (to the Institution) for investigator-initiated research from American Heart Association, Italian National Health Service and Italian Minister of Education, University and Research.

She is currently involved in the Research Programmes of the Italian Cardiovascular Network. C.P. Received consultant and speaker fees from Acticor Biotech, Amgen, Bayer, Eli Lilly, GlaxoSmithKline, Tremeau, Zambon, and grant support (to the Institution) for investigator-initiated research from AIFA (Italian Drug Agency), Bayer, Cancer Research UK, and European Commission.

He chairs the Scientific Advisory Board of the International Aspirin Foundation. References1Herrett E, Williamson E, Brack K, Beaumont D, Perkins A, Thayne A, Shakur-Still H, Roberts I, Prowse D, Goldacre B, van Staa T, MacDonald TM, Armitage J, Wimborne J, Melrose P, Singh J, Brooks L, Moore M, Hoffman M, Smeeth L, on behalf of the StatinWISE Trial Group. Statin treatment and muscle symptoms.

Series of randomised, placebo controlled n-of-1 trials. BMJ 2021;372:n135.2Stroes ES, Thompson PD, Corsini A, Vladutiu GD, Raal FJ, Ray KK, Roden M, Stein E, Tokgözoğlu L, Nordestgaard BG, Bruckert E, De Backer G, Krauss RM, Laufs U, Santos RD, Hegele RA, Hovingh GK, Leiter LA, Mach F, März W, Newman CB, Wiklund O, Jacobson TA, Catapano AL, Chapman MJ, Ginsberg HN, European Atherosclerosis Society Consensus Panel. Statin-associated muscle symptoms.

Impact on statin therapy-European Atherosclerosis Society Consensus Panel Statement on Assessment, Aetiology and Management. Eur Heart J 2015;36:1012–1022.3Collins R, Reith C, Emberson J, Armitage J, Baigent C, Blackwell L, Blumenthal R, Danesh J, Smith GD, DeMets D, Evans S, Law M, MacMahon S, Martin S, Neal B, Poulter N, Preiss D, Ridker P, Roberts I, Rodgers A, Sandercock P, Schulz K, Sever P, Simes J, Smeeth L, Wald N, Yusuf S, Peto R. Interpretation of the evidence for the efficacy and safety of statin therapy.

Lancet 2016;388:2532–2561.4Gupta A, Thompson D, Whitehouse A, Collier T, Dahlof B, Poulter N, Collins R, Sever P, ASCOT Investigators. Adverse events associated with unblinded, but not with blinded, statin therapy in the Anglo-Scandinavian Cardiac Outcomes Trial-Lipid-Lowering Arm (ASCOT-LLA). A randomised double-blind placebo-controlled trial and its non-randomised non-blind extension phase.

Lancet 2017;389:2473–2481.5Newman CB, Preiss D, Tobert JA, Jacobson TA, Page RL2nd, Goldstein LB, Chin C, Tannock LR, Miller M, Raghuveer G, Duell PB, Brinton EA, Pollak A, Braun LT, Welty FK, American Heart Association Clinical Lipidology, Lipoprotein, Metabolism and Thrombosis Committee, a Joint Committee of the Council on Atherosclerosis, Thrombosis and Vascular Biology and Council on Lifestyle and Cardiometabolic Health. Council on Cardiovascular Disease in the Young. Council on Clinical Cardiology.

Stroke Council. Statin safety and associated adverse events. A scientific statement from the American Heart Association.

Arterioscler Thromb Vasc Biol 2019;39:e38–e81.6Mach F, Baigent C, Catapano AL, Koskinas KC, Casula M, Badimon L, Chapman MJ, De Backer GG, Delgado V, Ference BA, Graham IM, Halliday A, Landmesser U, Mihaylova B, Pedersen TR, Riccardi G, Richter DJ, Sabatine MS, Taskinen MR, Tokgozoglu L, Wiklund O, ESC Scientific Document Group. 2019 ESC/EAS Guidelines for the management of dyslipidaemias. Lipid modification to reduce cardiovascular risk.

Eur Heart J 2020;41:111–188.7Wood FA, Howard JP, Finegold JA, Nowbar AN, Thompson DM, Arnold AD, Rajkumar CA, Connolly S, Cegla J, Stride C, Sever P, Norton C, Thom SAM, Shun-Shin MJ, Francis DP. N-of-1 trial of a statin, placebo, or no treatment to assess side effects. N Engl J Med 2020;383:2182–2184.8Moriarty PM, Jacobson TA, Bruckert E, Thompson PD, Guyton JR, Baccara-Dinet MT, Gipe D.

Efficacy and safety of alirocumab, a monoclonal antibody to PCSK9, in statin-intolerant patients. Design and rationale of ODYSSEY ALTERNATIVE, a randomized phase 3 trial. J Clin Lipidol 2014;8:554–561.9Nissen SE, Stroes E, Dent-Acosta RE, Rosenson RS, Lehman SJ, Sattar N, Preiss D, Bruckert E, Ceška R, Lepor N, Ballantyne CM, Gouni-Berthold I, Elliott M, Brennan DM, Wasserman SM, Somaratne R, Scott R, Stein EA, for the GAUSS-3 Investigators.

Efficacy and tolerability of evolocumab vs ezetimibe in patients with muscle-related statin intolerance. The GAUSS-3 randomized clinical trial. JAMA 2016;315:1580–1590.10Parker BA, Capizzi JA, Grimaldi AS, Clarkson PM, Cole SM, Keadle J, Chipkin S, Pescatello LS, Simpson K, White CM, Thompson PD.

Effect of statins on skeletal muscle function. Circulation 2013;127:96–103. Published on behalf of the European Society of Cardiology.

All rights reserved. © The Author(s) 2021. For permissions, please email.

€‚ For the podcast associated with this article, can u buy kamagra over the counter please buy kamagra online canada visit https://academic.oup.com/eurheartj/pages/Podcasts.This Focus Issue on vascular biology and medicine contains a clinical research article entitled ‘The association of amputations and peripheral artery disease in patients with type 2 diabetes mellitus receiving sodium–glucose co-transporter type-2 inhibitors. Real-world study’, authored by Sanjoy Paul from the University of Melbourne in Australia, and colleagues.1 Patients with peripheral artery disease (PAD) remain a challenging population to treat, in particular in the attempt to reduce the risk of amputation.2–4 Paul et al. Evaluated the temporal pattern of amputations in buy kamagra online canada type 2 diabetes (T2DM) patients, the risk of amputations by new and older antidiabetic drugs (ADDs), and the interplay of PAD with therapy and amputation risk. Using Centricity Electronic Medical Records from the USA, ∼3 300 000 patients with T2DM were identified. The proportion of incident amputations per 10 000 adults ranged between 4.7 and 6.8 during 2000–2008 and significantly increased to 12.3 in 2017.

Patients with pre-existing PAD had a more than four-fold higher risk of lower limb amputation buy kamagra online canada (LLA). In propensity score-adjusted pair-wise analyses, the risk of LLA was similar in sodium–glucose co-transporter type-2 inhibitors (SGLT-2is) vs. Glucagon-like peptide 1 receptor agonists (GLP1-RAs), and lower in SGLT-2i vs. Dipeptidyl peptidase-4 inhibitor (DPP-4i) or other ADDs (hazard ratio 0.65 and 0.43, respectively) (Figure 1) buy kamagra online canada. The rate of LLA was similar in patients treated with canagliflozin, empagliflozin, or dapagliflozin.

Figure 1Adjusted buy kamagra online canada risk of amputations and peripheral artery disease (from Paul SK, Bhatt DL, Montvida O. The association of amputations and peripheral artery disease in patients with type 2 diabetes mellitus receiving sodium–glucose co-transporter type-2 inhibitors. Real-world study. See pages 1728–1738).Figure 1Adjusted risk of amputations and peripheral artery disease (from buy kamagra online canada Paul SK, Bhatt DL, Montvida O. The association of amputations and peripheral artery disease in patients with type 2 diabetes mellitus receiving sodium–glucose co-transporter type-2 inhibitors.

Real-world study. See pages 1728–1738).The authors conclude that the risk buy kamagra online canada of amputation in patients treated with SGLT-2is and incretins is not higher compared with other ADDs. In addition, and not surprisingly, pre-existing PAD is the greatest driver of amputation risk. The manuscript is accompanied by an Editorial by Charalambos Vlachopoulos from the University of Athens Medical School in Greece, and colleagues.5 The authors conclude that a considerable number of original studies and analyses have been buy kamagra online canada applied on the canvas of the risk of amputation by SGLT2is that as a whole reduce the contrast of the first randomized trials. While any risk appears to be related specifically to canagliflozin, recent large registries provide reassuring data on the safety of SGLT2is, as long as physicians are aware of this particular complication and monitor their patients closely.

Undoubtedly, we are in need of more data, and the pursuit for proper evaluation of canagliflozin calls for ‘making haste slowly’.Inflammation plays an important role in development of cardiovascular disease (CVD).6–8 The NOD-like receptor protein-3 (NLRP3) inflammasome contributes to the development of atherosclerosis in animal models. Components of the NLRP3 inflammasome pathway such as interleukin-1β (IL-1β) buy kamagra online canada can be targeted therapeutically. In a clinical research article entitled ‘Genetically determined NLRP3 inflammasome activation associates with systemic inflammation and cardiovascular mortality’, Stefan Schunk from the Saarland University Hospital in Homburg/Saar, Germany, and colleagues note that associations of genetically determined inflammasome-mediated systemic inflammation with CVD and mortality in humans are unknown.9 The authors explored the association of genetic NLRP3 variants with prevalent CVD and cardiovascular mortality in 538 167 subjects on an individual participant level in an explorative gene-centric approach without performing multiple testing. The functional relevance of the single nucleotide polymorphism (SNP) for NLRP3 inflammasome activation was evaluated in monocyte-enriched peripheral blood mononuclear cells (PBMCs). Genetic analyses identified the highly prevalent buy kamagra online canada intronic NLRP3 variant rs10754555 as affecting NLRP3 gene expression.

Rs10754555 carriers showed significantly higher C-reactive protein and serum amyloid A plasma levels. Carriers of buy kamagra online canada the G allele showed higher NLRP3 inflammasome activation in isolated human PBMCs. In carriers of the rs10754555 variant, the prevalence of coronary artery disease (CAD) was significantly higher as compared with non-carriers, with a significant interaction between rs10754555 and age. Importantly, rs10754555 carriers had significantly higher risk for cardiovascular mortality during follow-up. Inflammasome inducers buy kamagra online canada (e.g.

Urate, triglycerides, and ApoC3) modulated the association between rs10754555 and mortality.The authors conclude that the NLRP3 intronic variant rs10754555 is associated with increased systemic inflammation, inflammasome activation, prevalent CAD, and mortality. This study provides evidence for a substantial role for genetically driven systemic inflammation in cardiovascular disease and highlights the NLRP3 inflammasome as a therapeutic target. The manuscript is accompanied by an Editorial by Christoph J buy kamagra online canada. Binder and Nikolina Papac-Milicevic from the Medical University of Vienna in Austria.10 The authors conclude that the findings of this study provide important evidence for the individual differences in the ability to develop chronic inflammation in the context of metabolic disturbances. This may open up the possibility buy kamagra online canada for more personalized therapeutic approaches by enabling stratification of patients based on their genetically determined inflammatory risk before clinical manifestations occur.The aim of endovascular stent implantation at the time of coronary angioplasty is to prevent acute vessel closure and chronic negative arterial remodelling in patients affected by coronary disease.

However, stents are sensed as a foreign body, leading to immune cell activation, resulting in chronic inflammation and, eventually, in-stent restenosis due to the local proliferation of arterial smooth muscle cells. Mitigating the body’s reaction by improving stent biocompatibility thus represents a major challenge to increase the efficacy of arterial stents and hence the clinical outcome of patients affected by coronary disease.11,12 In a translational research article entitled ‘Coronary stent CD31-mimetic coating favours endothelialization and reduces local inflammation and neointimal development in vivo’, Sergio Diaz-Rodriguez from the Laval University, Québec, Canada, and colleagues evaluate the effect of CD31-mimetic metal stent coating on the in vitro adherence of endothelial cells (ECs) and blood elements, and the in vivo strut coverage and neointimal growth.13 The rapid endothelialization of bare metal stents (BMS) is counterbalanced by inflammation-induced neointimal growth. Drug-eluting stents (DES) prevent leucocyte activation but impair endothelialization, delaying effective buy kamagra online canada device integration into arterial walls. Previously, it has been shown that engaging the vascular CD31 co-receptor is crucial for endothelial and leucocyte homeostasis and arterial healing. Furthermore, it has been shown that a soluble synthetic peptide (known as P8RI) acts like a CD31 agonist.

The authors produced cobalt chromium disks and stents coated with a CD31-mimetic peptide buy kamagra online canada through two procedures, plasma amination or dip-coating, both yielding comparable results. They found that CD31-mimetic disks significantly reduced the extent of primary human coronary artery EC and blood platelet/leucocyte activation in vitro. In vivo, CD31-mimetic stent properties were compared with those of DES and BMS by coronarography and microscopy at 7 and 28 days post-implantation in pig coronary buy kamagra online canada arteries (n = 9 stents/group/time point). Seven days post-implantation, only CD31-mimetic struts were fully endothelialized, with no activated platelets/leucocytes. At day 28, neointima development over CD31-mimetic stents was significantly reduced compared with BMS, appearing as a normal arterial media with absence of thrombosis in contrast to DES.The authors conclude that CD31-mimetic coating favours vascular homeostasis and arterial wall healing, preventing in-stent stenosis and thrombosis.

Hence, such coatings seem to buy kamagra online canada improve metal stent biocompatibility. The manuscript is accompanied by an Editorial by Alexandra Lansky from the Yale School of Medicine in New Haven, CT, USA and colleagues.14 The authors conclude that the effect of a CD31-mimetic stent in CAD patients may be blunted due to impaired function of CD31-expressing cells in this patient population. These will be critical benchmarks to more reliably predict whether this breakthrough combination stent technology can provide the incremental safety and effectiveness benefit needed to further advance the management options of our patients with obstructive coronary disease.In another translational research article entitled ‘A proteomic atlas of the neointima identifies novel druggable targets for preventive therapy’, Thorsten Kessler from the Deutsches Herzzentrum München in Germany, and colleagues sought to investigate the molecular processes underlying neointima formation and to identify new treatment and prevention targets.15 Neointima formation was induced by wire injury in mouse femoral arteries. High-accuracy proteomic measurement of single femoral arteries to a depth of ∼5000 proteins buy kamagra online canada revealed massive proteome remodelling, with more than half of all proteins exhibiting expression differences between injured and non-injured vessels. The authors observed major changes in the composition of the extracellular matrix and cell migration processes.

Among the latter, they identified the buy kamagra online canada classical transient receptor potential channel 6 (Trpc6) as driving neointima formation. This was confirmed in an experimental model. Indeed, Trpc6–/– mice presented reduced neointima formation compared with wild-type mice. In addition, activating or repressing TRPC6 in human vascular smooth muscle cells resulted in buy kamagra online canada increased or decreased migratory capacity, respectively. Finally, in a cohort of individuals with angiographic follow-up in >3000 patients, homozygous carriers of a common genetic variant associated with elevated TRPC6 expression were at increased risk of restenosis after coronary stenting (adjusted odds ratio 1.49) during a mean follow-up of 217 days.The authors conclude that their study provides a proteomic atlas of the healthy and injured arterial wall that can be used to define novel factors for therapeutic targeting.

They present TRPC6 as an actionable target to prevent neointima formation secondary to vascular injury and stent implantation. The manuscript is accompanied by an Editorial by Giuseppina Caligiuri from INSERM in Paris and Gregory Franck from the Hôpitaux Universitaires Paris Nord Val-de-Seine in France.16 buy kamagra online canada The authors conclude that further studies are needed in order to specifically address the therapeutic potential of TRCP6 inhibitors in a clinical perspective. If confirmed, a combo device eluting both mTOR inhibitors and TRCP blockers could select the right ‘channels’, affecting the broadest relevant targets and eventually reaching the ‘no-restenosis’ Holy Grail.‘Embolic stroke of undetermined source’ (ESUS) is used to describe patients with a non-lacunar ischaemic stroke without any identified embolic source from the heart or the arteries supplying the ischaemic territory, or any other apparent cause. In a State of the Art review article buy kamagra online canada entitled ‘Supracardiac atherosclerosis in embolic stroke of undetermined source. The underestimated source’, George Ntaios from the University of Thessaly in Greece, and colleagues note that when the ESUS concept was introduced, covert atrial fibrillation was conceived to be the main underlying cause in the majority of ESUS patients.17 Yet another important embolic source in ESUS is the atherosclerotic plaque in the carotid, vertebrobasilar, and intracranial arteries, or the aortic arch—collectively described as supracardiac atherosclerosis.

There is emerging evidence showing that the role of supracardiac atherosclerosis is larger than was initially perceived. Advanced imaging buy kamagra online canada methods are available to identify plaques which carry high embolic risk. The role of novel antithrombotic strategies in these patients needs to be assessed in randomized controlled trials. This review presents the evidence which points towards a major aetiological association between atherosclerotic plaques and ESUS, summarizes the imaging features which may aid in identifying plaques more likely to be associated with ESUS, discusses strategies to reduce the associated stroke risk, and highlights the rationale for future research in this field.Unlike native LDL, modified LDLs such as oxidized, carbamylated, or acetylated LDLs are not recognized by the native LDL receptor (LDL-R). Rather, modified LDL binds to the lectin-like oxidized LDL receptor-1 (LOX-1).8,18,19 In buy kamagra online canada a State of the Art review article entitled ‘Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1).

A crucial driver of atherosclerotic cardiovascular disease’, Alexander Akhmedov from the University of Zurich in Switzerland, and colleagues note that LOX-1, a scavenger receptor that promotes endothelial dysfunction by inducing proatherogenic signalling and plaque formation via the endothelial uptake of oxidized LDL (oxLDL) and electronegative LDL, contributes to the initiation, progression, and destabilization of atheromatous plaques, eventually leading to the development of myocardial infarction and certain forms of stroke.20 In addition to its expression in endothelial cells, LOX-1 is expressed in macrophages, cardiomyocytes, fibroblasts, dendritic cells, lymphocytes, and neutrophils, further implicating this receptor in multiple aspects of atherosclerotic plaque formation. LOX-1 holds promise as a novel diagnostic and therapeutic target for certain CVDs. Therefore, understanding the molecular structure buy kamagra online canada and function of LOX-1 is of critical importance. In this review, the authors highlight the latest scientific findings related to LOX-1, its ligands, and their roles in the broad spectrum of CVDs. They also describe recent findings from basic research, delineate their translational value, and discuss the potential of LOX-1 as a novel target for buy kamagra online canada the prevention, diagnosis, and treatment of related CVDs (Figure 2).

Figure 2Ligand–receptor interactions (left) and their potential role in various diseases (right). (A) Multiple ligands, including oxLDL, L5, and dysfunctional HDL, have been shown to induce full-length LOX-1 stimulation. Depending on the cell type studied, buy kamagra online canada LOX-1 stimulation activates subcellular signalling pathways that play major roles in the pathogenesis of various cardiovascular diseases. Notably, in human coronary endothelial cells exposed to oxLDL, Del-1 inhibits the LOX-1-dependent up-regulation of endothelial adhesion molecules, thereby representing an interesting endogenous molecule that—at least in part—curtails the detrimental effects mediated by LOX-1. (B) In recent years, the byproduct of LOX-1 cleavage (i.e.

SLOX-1) and the buy kamagra online canada most electronegative LDL subfraction (i.e. L5) have emerged as novel biomarkers, specifically in atherosclerosis-related events, such as myocardial infarction and ischaemic stroke. Furthermore, enhanced LAB activity has been shown to be associated with the incidence of buy kamagra online canada cardiovascular diseases, particularly ischaemic stroke. AGEs, advanced glycation end-products. CRP, C-reactive protein.

Del-1, developmental buy kamagra online canada endothelial locus-1. HSP70, heat shock protein 70. LAB, LOX-1 ligand containing apoB. LOX-1, lectin-like oxidized LDL buy kamagra online canada receptor-1. L5, L5 LDL.

NTF, N-terminal buy kamagra online canada fragment. OxLDL, oxidized LDL. SLOX-1, soluble LOX-1. VSMC, vascular smooth muscle cell (from Akhmedov A, Sawamura T, Chen CH, buy kamagra online canada Kraler S, Vdovenko D, Lüscher TF. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1).

A crucial driver of atherosclerotic cardiovascular disease. See pages 1797–1807).Figure 2Ligand–receptor interactions (left) buy kamagra online canada and their potential role in various diseases (right). (A) Multiple ligands, including oxLDL, L5, and dysfunctional HDL, have been shown to induce full-length LOX-1 stimulation. Depending on the cell type buy kamagra online canada studied, LOX-1 stimulation activates subcellular signalling pathways that play major roles in the pathogenesis of various cardiovascular diseases. Notably, in human coronary endothelial cells exposed to oxLDL, Del-1 inhibits the LOX-1-dependent up-regulation of endothelial adhesion molecules, thereby representing an interesting endogenous molecule that—at least in part—curtails the detrimental effects mediated by LOX-1.

(B) In recent years, the byproduct of LOX-1 cleavage (i.e. SLOX-1) and buy kamagra online canada the most electronegative LDL subfraction (i.e. L5) have emerged as novel biomarkers, specifically in atherosclerosis-related events, such as myocardial infarction and ischaemic stroke. Furthermore, enhanced LAB activity has been shown to be associated with the incidence of cardiovascular diseases, particularly ischaemic stroke. AGEs, advanced glycation buy kamagra online canada end-products.

CRP, C-reactive protein. Del-1, developmental endothelial locus-1 buy kamagra online canada. HSP70, heat shock protein 70. LAB, LOX-1 ligand containing apoB. LOX-1, lectin-like buy kamagra online canada oxidized LDL receptor-1.

L5, L5 LDL. NTF, N-terminal fragment. OxLDL, oxidized buy kamagra online canada LDL. SLOX-1, soluble LOX-1. VSMC, vascular buy kamagra online canada smooth muscle cell (from Akhmedov A, Sawamura T, Chen CH, Kraler S, Vdovenko D, Lüscher TF.

Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1). A crucial driver of atherosclerotic cardiovascular disease. See pages buy kamagra online canada 1797–1807).The issue is complemented by two Discussion Forum articles. In a contribution entitled ‘Which biomarker to use, when to start, and how to improve adherence for reducing atherosclerotic cardiovascular disease risk?. €™, Kwang Kon Koh from Gachon University in Korea comments on the contribution ‘2019 vs.

2016 ESC/EAS statin guidelines for primary prevention of atherosclerotic cardiovascular disease’ by Martin Bødtker Mortensen from the Aarhus University Hospital in buy kamagra online canada Denmark, and colleagues.21,22 Mortensen et al. Respond in a separate comment.23The editors hope that readers of this issue of the European Heart Journal will find it of interest.With thanks to Amelia Meier-Batschelet, Johanna Huggler, and Martin Meyer for help with compilation of this article. References1Paul SK, Bhatt DL, Montvida buy kamagra online canada O. The association of amputations and peripheral artery disease in patients with type 2 diabetes mellitus receiving sodium–glucose co-transporter type-2 inhibitors. Real-world study.

Eur Heart J 2021;42:1728–1738.2Behrendt CA buy kamagra online canada. Higher long-term mortality after endovascular vs. Open-surgical revascularization of peripheral artery disease in Australia and New Zealand?. Eur buy kamagra online canada Heart J 2021. Doi:10.1093/eurheartj/ehab143.3Parvar SL, Ngo L, Dawson J, Nicholls SJ, Fitridge R, Psaltis PJ, Ranasinghe I.

Long-term outcomes following endovascular and surgical revascularization for peripheral artery disease buy kamagra online canada. A propensity score-matched analysis. Eur Heart J 2021. Doi. 10.1093/eurheartj/ehab116.4Tseng A, Bhatt S, Girardo M, Liedl D, Wennberg P, Shamoun F.

Complex antithrombotic therapy and bleeding risk in patients with peripheral arterial disease. Eur Heart J 2020;41(Suppl_2):ehaa946.2396.5Vlachopoulos C, Terentes-Printzios D, Tsioufis K. Do SGLT2 inhibitors increase the risk of amputation?. Make haste slowly. Eur Heart J 2021;42:1739–1741.6Lawler PR, Bhatt DL, Godoy LC, Lüscher TF, Bonow RO, Verma S, Ridker PM kamagra for sale uk.

Targeting cardiovascular inflammation. Next steps in clinical translation. Eur Heart J 2021;42:113–131.7Liberale L, Montecucco F, Tardif JC, Libby P, Camici GG. Inflamm-ageing. The role of inflammation in age-dependent cardiovascular disease.

Eur Heart J 2020;41:2974–2982.8Stojanović SD, Fiedler J, Bauersachs J, Thum T, Sedding DG. Senescence-induced inflammation. An important player and key therapeutic target in atherosclerosis. Eur Heart J 2020;41:2983–2996.9Schunk SJ, Kleber ME, März W, Pang S, Zewinger S, Triem S, Ege P, Reichert MC, Krawczyk M, Weber SN, Jaumann I, Schmit D, Sarakpi T, Wagenpfeil S, Kramann R, Boerwinkle E, Ballantyne CM, Grove ML, Tragante V, Pilbrow AP, Richards AM, Cameron VA, Doughty RN, Dubé MP, Tardif JC, Feroz-Zada Y, Sun M, Liu C, Ko YA, Quyyumi AA, Hartiala JA, Tang WHW, Hazen SL, Allayee H, McDonough CW, Gong Y, Cooper-DeHoff RM, Johnson JA, Scholz M, Teren A, Burkhardt R, Martinsson A, Smith JG, Wallentin L, James SK, Eriksson N, White H, Held C, Waterworth D, Trompet S, Jukema JW, Ford I, Stott DJ, Sattar N, Cresci S, Spertus JA, Campbell H, Tierling S, Walter J, Ampofo E, Niemeyer BA, Lipp P, Schunkert H, Böhm M, Koenig W, Fliser D, Laufs U, Speer T. Genetically determined NLRP3 inflammasome activation associates with systemic inflammation and cardiovascular mortality.

Eur Heart J 2021;42:1742–1756.10Papac-Milicevic N, Binder CJ. Can a single genetic variant explain residual cardiovascular risk by modifying NLRP3 expression?. Eur Heart J 2021;42:1757–1759.11Giacoppo D, Alfonso F, Xu B, Claessen B, Adriaenssens T, Jensen C, Pérez-Vizcayno MJ, Kang DY, Degenhardt R, Pleva L, Baan J, Cuesta J, Park DW, Schunkert H, Colleran R, Kukla P, Jiménez-Quevedo P, Unverdorben M, Gao R, Naber CK, Park SJ, Henriques JPS, Kastrati A, Byrne RA. Paclitaxel-coated balloon angioplasty vs. Drug-eluting stenting for the treatment of coronary in-stent restenosis.

A comprehensive, collaborative, individual patient data meta-analysis of 10 randomized clinical trials (DAEDALUS study). Eur Heart J 2020;41:3715–3728.12Byrne RA, Joner M, Kastrati A. Stent thrombosis and restenosis. What have we learned and where are we going?. The Andreas Grüntzig Lecture ESC 2014.

Eur Heart J 2015;36:3320–3331.13Diaz-Rodriguez S, Rasser C, Mesnier J, Chevallier P, Gallet R, Choqueux C, Even G, Sayah N, Chaubet F, Nicoletti A, Ghaleh B, Feldman LJ, Mantovani D, Caligiuri G. Coronary stent CD31-mimetic coating favours endothelialization and reduces local inflammation and neointimal development in vivo. Eur Heart J 2021;42:1760–1769.14Lansky A, Chun H, Pietras C, Hussain Y. Refining drug-eluting stent technologies. From engineering to basic science.

Eur Heart J 2021;42:1770–1772.15Wierer M, Werner J, Wobst J, Kastrati A, Cepele G, Aherrahrou, Sager HB, Erdmann J, Dichgans M, Flockerzi V, Civelek M, Dietrich A, Mann M, Schunkert H, Kessler T. A proteomic atlas of the neointima identifies novel druggable targets for preventive therapy. Eur Heart J 2021;42:1733–1785.16Caligiuri G, Frack G. Hitting the right channels to spread a ‘no-restenosis’ message to vascular wall cells. Eur Heart J 2021;42:1786–1788.17Ntaios G, Wintermark M, Michel P.

Supracardiac atherosclerosis in embolic stroke of undetermined source. The underestimated source. Eur Heart J 2021;42:1789–1796.18Borén J, Chapman MJ, Krauss RM, Packard CJ, Bentzon JF, Binder CJ, Daemen MJ, Demer LL, Hegele RA, Nicholls SJ, Nordestgaard BG, Watts GF, Bruckert E, Fazio S, Ference BA, Graham I, Horton JD, Landmesser U, Laufs U, Masana L, Pasterkamp G, Raal FJ, Ray KK, Schunkert H, Taskinen MR, van de Sluis B, Wiklund O, Tokgozoglu L, Catapano AL, Ginsberg HN. Low-density lipoproteins cause atherosclerotic cardiovascular disease. Pathophysiological, genetic, and therapeutic insights.

A consensus statement from the European Atherosclerosis Society Consensus Panel. Eur Heart J 2020;41:2313–2330.19Lüscher TF. Understanding and preventing atherosclerosis. From bench to bedside. Eur Heart J 2019;40:323–327.20Akhmedov A, Sawamura T, Chen CH, Kraler S, Vdovenko D, Lüscher TF.

Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1). A crucial driver of atherosclerotic cardiovascular disease. Eur Heart J 2021;42:1797–1807.21Koh KK. Which biomarker to use, when to start, and how to improve adherence for reducing atherosclerotic cardiovascular disease risk?. Eur Heart J 2021;42:1808.22Mortensen MB, Nordestgaard BG.

2019 vs. 2016 ESC/EAS statin guidelines for primary prevention of atherosclerotic cardiovascular disease. Eur Heart J 2020;41:3005–3015.23Mortensen MB, Nordestgaard BG. Examine low-density lipoprotein, remnants, and lipoprotein(a) in parallel in high risk patients. Eur Heart J 2021;42:1809–1810.

Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email. Journals.permissions@oup.com.Comment on ‘Statin treatment and muscle symptoms.

Series of randomised, placebo controlled n-of-1 trials’ published in the British Medical Journal (DOI. Http://dx.doi.org/10.1136/bmj.n135).Key pointsStatinWISE (Statin Web-based Investigation of Side Effects)1 was a series of institutionally funded, randomized, double-blind, placebo-controlled n-of-1 trials, recruiting 200 participants from general practices across 50 sites in the UK to establish the effect of statins on muscle symptoms. Participants, who were taking any type of statin at any dose before trial enrolment, had recently stopped or were considering stopping treatment with statins because of muscle symptoms. Exclusion criteria were previously raised levels of serum alanine aminotransferase (≥3 times the upper limit of normal). Persistent, generalized, unexplained muscle pain.

Levels of creatine kinase ≥5 times the upper limit of normal. Any contraindication to atorvastatin treatment.The overall length of the trial was 1 year for each participant and comprised six 2-month treatment periods (three of placebo, three of atorvastatin 20 mg daily) in a randomly allocated order. At the end of each treatment period, participants rated their muscle symptoms on a visual analogue scale. The primary outcome compared symptom scores (score 0 = no symptoms, 5 = moderate symptoms, and 10 = worst possible symptoms) in the statin and placebo periods. Three months after the end of the final treatment period, participants were asked whether they had, or intended to restart treatment with statins.Of the 200 participants, 151 (76%) provided one or more visual analogue scale measurements in both a statin and a placebo period and were included in the primary analysis.

No statistically significant difference in muscle symptom scores was found between the statin and placebo periods [mean ± SD. 1.7 ± 2.6 vs. 1.8 ± 2.7. Mean difference statin minus placebo −0.1. 95% confidence interval (CI) −0.4 to 0.1.

P = 0.40]. Atorvastatin showed no significant effect on development of muscle symptoms overall with an odds ratio (OR) of 1.11 (99% CI, 0.62–1.99). Nor was there any effect on muscle symptoms that could not be attributed to another cause (OR, 1.22. 95% CI, 0.77–1.94).Of the 80 withdrawals during the study for any reason, 42% occurred when the patient was on the statin, 49% when the patient was on placebo, and 9% after randomization but before either statin or placebo had been initiated. Withdrawals because of intolerable muscle symptoms were 9% during a statin period and 7% during a placebo period.

Two-thirds of those completing the six treatment periods (74/113 participants) reported restarting long-term statin treatment. CommentThe European Atherosclerosis Society Consensus Panel and other groups established that there is evidence for causality for only three statin-related adverse effects. Muscle side effects, new-onset diabetes, and transient elevations of liver enzymes, with muscle symptoms being the most common complaint during statin treatment.2 Systematic reviews and meta-analyses of randomized controlled trials (RCTs) have confirmed the safety of statins, showing that the risk of myopathy and its progression to severe rhabdomyolysis are rare, and suggesting that symptomatic adverse events may be misattributed to statins.3–5 Indeed, the association between muscle symptoms and statins has suffered the bias of observational studies, reinforced by media reports. Patients taking statins expect to experience adverse effects, and therefore reporting of symptoms in statin users may be higher than in a comparable population not on statins. This phenomenon, known as the ‘nocebo’ effect, often leads to patients discontinuing treatment, exposing them to an increased risk of cardiovascular events.6In the present study, patients who had previously faced severe muscle symptoms on a statin reported similar muscle symptom prevalence or severity during blinded statin or placebo periods.

Also, there were no differences for the effect of muscle symptoms on several aspects of daily life between statin and placebo periods. Thus, the study adds to the evidence from SAMSON,7 a recent trial with similar design, and from RCTs like ODYSSEY ALTERNATIVE8 and GAUSS-39 showing that a significant number of people who have problems with muscle pain associated with statins are experiencing a ‘nocebo’ effect, and that re-challenge with statins can be tolerated by most patients.StatinWISE, however, has several limitations. (i) the lack of creatine kinase measurement did not allow establishing what proportion of participants had symptoms associated with biochemical signs of muscle damage. (ii) the trial results may not apply to higher doses of atorvastatin or other statins, as only the effects of atorvastatin 20 mg were assessed. (iii) most importantly, 86 of the original 200 participants did not complete the whole trial, 49 of whom did not provide sufficient data to contribute to the primary analysis.

Furthermore, withdrawals due to intolerable muscle symptoms were not significantly different between statin (9%) and placebo (7%) periods, but StatinWISE was not powered to detect a difference in such withdrawals. (iv) the study participants may not be representative of all those who believe they experience side effects with statins. On one hand, the study may have selected people who were less susceptible to the ‘nocebo’ effect. On the other hand, the majority (70%) of study participants had a history of cardiovascular disease, and they may have had a higher commitment to statin therapy than those in primary prevention. And (v) the 2-month treatment period should be long enough to allow washout between different treatments and avoid the carry-over of symptoms between statin and placebo periods.

However, while muscle pain/weakness typically occurs within 4–6 weeks after starting statin treatment, the onset may be delayed months or years.10Despite these limitations, these findings underscore the need for clinicians to acknowledge their patients’ muscle symptoms on statin therapy and, using a StatinWISE-like approach, ensure that as many as possible continue on a statin to reduce their cardiovascular risk.Conflict of interest. G.L. Received grant support (to the Institution) for investigator-initiated research from American Heart Association, Italian National Health Service and Italian Minister of Education, University and Research. She is currently involved in the Research Programmes of the Italian Cardiovascular Network. C.P.

Received consultant and speaker fees from Acticor Biotech, Amgen, Bayer, Eli Lilly, GlaxoSmithKline, Tremeau, Zambon, and grant support (to the Institution) for investigator-initiated research from AIFA (Italian Drug Agency), Bayer, Cancer Research UK, and European Commission. He chairs the Scientific Advisory Board of the International Aspirin Foundation. References1Herrett E, Williamson E, Brack K, Beaumont D, Perkins A, Thayne A, Shakur-Still H, Roberts I, Prowse D, Goldacre B, van Staa T, MacDonald TM, Armitage J, Wimborne J, Melrose P, Singh J, Brooks L, Moore M, Hoffman M, Smeeth L, on behalf of the StatinWISE Trial Group. Statin treatment and muscle symptoms. Series of randomised, placebo controlled n-of-1 trials.

BMJ 2021;372:n135.2Stroes ES, Thompson PD, Corsini A, Vladutiu GD, Raal FJ, Ray KK, Roden M, Stein E, Tokgözoğlu L, Nordestgaard BG, Bruckert E, De Backer G, Krauss RM, Laufs U, Santos RD, Hegele RA, Hovingh GK, Leiter LA, Mach F, März W, Newman CB, Wiklund O, Jacobson TA, Catapano AL, Chapman MJ, Ginsberg HN, European Atherosclerosis Society Consensus Panel. Statin-associated muscle symptoms. Impact on statin therapy-European Atherosclerosis Society Consensus Panel Statement on Assessment, Aetiology and Management. Eur Heart J 2015;36:1012–1022.3Collins R, Reith C, Emberson J, Armitage J, Baigent C, Blackwell L, Blumenthal R, Danesh J, Smith GD, DeMets D, Evans S, Law M, MacMahon S, Martin S, Neal B, Poulter N, Preiss D, Ridker P, Roberts I, Rodgers A, Sandercock P, Schulz K, Sever P, Simes J, Smeeth L, Wald N, Yusuf S, Peto R. Interpretation of the evidence for the efficacy and safety of statin therapy.

Lancet 2016;388:2532–2561.4Gupta A, Thompson D, Whitehouse A, Collier T, Dahlof B, Poulter N, Collins R, Sever P, ASCOT Investigators. Adverse events associated with unblinded, but not with blinded, statin therapy in the Anglo-Scandinavian Cardiac Outcomes Trial-Lipid-Lowering Arm (ASCOT-LLA). A randomised double-blind placebo-controlled trial and its non-randomised non-blind extension phase. Lancet 2017;389:2473–2481.5Newman CB, Preiss D, Tobert JA, Jacobson TA, Page RL2nd, Goldstein LB, Chin C, Tannock LR, Miller M, Raghuveer G, Duell PB, Brinton EA, Pollak A, Braun LT, Welty FK, American Heart Association Clinical Lipidology, Lipoprotein, Metabolism and Thrombosis Committee, a Joint Committee of the Council on Atherosclerosis, Thrombosis and Vascular Biology and Council on Lifestyle and Cardiometabolic Health. Council on Cardiovascular Disease in the Young.

Council on Clinical Cardiology. Stroke Council. Statin safety and associated adverse events. A scientific statement from the American Heart Association. Arterioscler Thromb Vasc Biol 2019;39:e38–e81.6Mach F, Baigent C, Catapano AL, Koskinas KC, Casula M, Badimon L, Chapman MJ, De Backer GG, Delgado V, Ference BA, Graham IM, Halliday A, Landmesser U, Mihaylova B, Pedersen TR, Riccardi G, Richter DJ, Sabatine MS, Taskinen MR, Tokgozoglu L, Wiklund O, ESC Scientific Document Group.

2019 ESC/EAS Guidelines for the management of dyslipidaemias. Lipid modification to reduce cardiovascular risk. Eur Heart J 2020;41:111–188.7Wood FA, Howard JP, Finegold JA, Nowbar AN, Thompson DM, Arnold AD, Rajkumar CA, Connolly S, Cegla J, Stride C, Sever P, Norton C, Thom SAM, Shun-Shin MJ, Francis DP. N-of-1 trial of a statin, placebo, or no treatment to assess side effects. N Engl J Med 2020;383:2182–2184.8Moriarty PM, Jacobson TA, Bruckert E, Thompson PD, Guyton JR, Baccara-Dinet MT, Gipe D.

Efficacy and safety of alirocumab, a monoclonal antibody to PCSK9, in statin-intolerant patients. Design and rationale of ODYSSEY ALTERNATIVE, a randomized phase 3 trial. J Clin Lipidol 2014;8:554–561.9Nissen SE, Stroes E, Dent-Acosta RE, Rosenson RS, Lehman SJ, Sattar N, Preiss D, Bruckert E, Ceška R, Lepor N, Ballantyne CM, Gouni-Berthold I, Elliott M, Brennan DM, Wasserman SM, Somaratne R, Scott R, Stein EA, for the GAUSS-3 Investigators. Efficacy and tolerability of evolocumab vs ezetimibe in patients with muscle-related statin intolerance. The GAUSS-3 randomized clinical trial.

JAMA 2016;315:1580–1590.10Parker BA, Capizzi JA, Grimaldi AS, Clarkson PM, Cole SM, Keadle J, Chipkin S, Pescatello LS, Simpson K, White CM, Thompson PD. Effect of statins on skeletal muscle function. Circulation 2013;127:96–103. Published on behalf of the European Society of Cardiology. All rights reserved.

© The Author(s) 2021. For permissions, please email. Journals.permissions@oup.com..