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Forty years after can zithromax cause constipation the first AIDS cases were reported, the harsh reality is that deep inequalities continue to exist in the global response to HIV and AIDS, with gaps in rights and services preventing real progress.And while it is painful to admit, one of the most overlooked segments of the population has been children.As the âEnd Inequalities, End AIDSâ strategy proposed by the Joint United Nations Program on HIV and AIDS (UNAIDS) makes clear, âOne of the most glaring disparities in the HIV response is the failure to meet the needs of children living with or at risk of HIV.âadvertisement The final progress report on the âStart Free, Stay Free, AIDS Freeâ initiative just released by our organizations, UNAIDS (B.W.), and how can i buy zithromax the Elizabeth Glaser Pediatric AIDS Foundation (C.L.), and partners, offers a grim look at HIV and children. Approximately 1.7 million children are currently living with HIV. Every week nearly 2,000 how can i buy zithromax of them die and 5,900 children and adolescents are newly infected with the zithromax. Only 54% of children living with HIV have access to the treatment that will save their lives. Although children accounted for just 5% of people living with HIV in 2020, they represented 15% of all AIDS-related deaths.

Almost 90% of all children living how can i buy zithromax with HIV globally are located in Africa. Without a voice in the response, children have an unequal opportunity to call for solutions to their needs. buy antibiotics has further intensified existing inequities, diverting funds and other resources away from critical health services.advertisement Yet even before buy antibiotics took hold, the picture was troubling. New pediatric HIV s were on the rise in a handful of African countries, pediatric treatment coverage had stalled, and the global community had failed to identify and reach almost how can i buy zithromax half of the children living with HIV. None of the âStart Free, Stay Free, AIDS Freeâ targets set for 2020 were achieved and were, in fact, missed by a wide margin.World leaders gathered in June for the UN High-Level Meeting on HIV and AIDS to chart the future course of the global AIDS response.

As leaders of organizations committed to ending HIV and AIDS, we were encouraged by the inclusion of a new global pledge in the resulting political declaration to eliminate transmission of HIV from mother to child and how can i buy zithromax to end pediatric AIDS by 2025.Commitments are meaningless without action. As global, national, and community leaders move to develop an action framework, we call upon them to intensify efforts for children in real and meaningful ways, catalyzing momentum to achieve the first AIDS-free generation, with specific focus in four key areas:Find the children. Improving efforts to âfindâ and diagnose children of all ages living with HIV is an essential gateway to increasing the number of children accessing medicine and ensuring viral load suppression. The effectiveness of point-of-care early infant diagnosis is a well-documented game changer, yet adoption and scale-up of this strategy is stalled and must be how can i buy zithromax scaled up in countries around the world. Help children access lifesaving treatment.

Without treatment, one of every two babies with HIV will die before their second birthday. Children living with HIV require how can i buy zithromax age-appropriate, effective, and accessible formulations. Yet children in low- and middle-income countries often wait years to access the same medications as adults, eroding their health, or even resulting in preventable deaths. The development and uptake of optimal, child-friendly HIV treatment lag far behind such work in adults, leading to poorer how can i buy zithromax health outcomes for the youngest patients. Recent UNAIDS data indicate that 800,000 children living with HIV went without medication in 2020, a deeply concerning reversal of recent progress.

Rapid transition to better pediatric formulations, in combination with improved HIV diagnosis for children is desperately needed.Focus on prevention. Mother-to-child transmission how can i buy zithromax rates of HIV have been cut in half over the past decade. But that success has plateaued in troubling ways. Ending mother-to-child transmission requires HIV testing and support for adolescent girls and young women that includes prevention of unintended pregnancies and intensified primary prevention efforts for both pregnant and breastfeeding women â including pre-exposure prophylaxis (PrEP) â as the global community seeks to advance President Bidenâs call to ârestore a government-wide focus on lifting up women and girls around the world.âAddress structural barriers for women at the community level. A range of socioeconomic and structural factors that include unequal power dynamics and gender norms, gender-based violence, poverty, stigma, and discrimination undermine the ability of many women to access and remain engaged clinical services how can i buy zithromax and psychosocial support.

Womenâs needs must be at the center of every effort. Stakeholders must recognize the obstacles to drug adherence or consistent clinic visits and respond with improved options and community-level support.To end AIDS in children, governments, civil society, and other stakeholders must act with urgency, following up the political declaration with concrete action to match its aspiration. That means providing resources and services to protect the unique rights, needs, and perspectives of children and young women â and doing so with a clear focus on human rights and equity.Ending pediatric AIDS is both ambitious how can i buy zithromax and achievable. Let us make 2021 another turning point in the history of ending AIDS â and in the process, create the first AIDS-free generation.Winnie Byanyima is the executive director of UNAIDS and under-secretary-general of the United Nations. Chip Lyons is the CEO of how can i buy zithromax the Elizabeth Glaser Pediatric AIDS Foundation.Hired someone new and exciting?.

Promoted a rising star?. Finally solved that hard-to-fill spot?. Share the news with how can i buy zithromax us, and weâll share it with others. Thatâs right. Send us your changes, and weâll find a home for them.

Donât be shy how can i buy zithromax. Everyone wants to know who is coming and going.And here is our regular feature in which we highlight a different person each week. This time around, how can i buy zithromax we note that Gilead Sciences (GILD) hired Bill Grossman as senior vice president, oncology clinical research. Previously, he worked at Arcus Biosciences (RCUS), where he was chief medical officer. Unlock this article by subscribing to STAT+ and enjoy your first 30 days free!.

GET STARTED how can i buy zithromax Log In | Learn More What is it?. STAT+ is STAT's premium subscription service for in-depth biotech, pharma, policy, and life science coverage and analysis. Our award-winning team covers news on Wall Street, policy developments in Washington, early science breakthroughs and clinical trial results, and health care disruption in Silicon Valley and beyond. What's included? how can i buy zithromax. Daily reporting and analysis The most comprehensive industry coverage from a powerhouse team of reporters Subscriber-only newsletters Daily newsletters to brief you on the most important industry news of the day STAT+ Conversations Weekly opportunities to engage with our reporters and leading industry experts in live video conversations Exclusive industry events Premium access to subscriber-only networking events around the country The best reporters in the industry The most trusted and well-connected newsroom in the health care industry And much more Exclusive interviews with industry leaders, profiles, and premium tools, like our CRISPR Trackr.Good morning.

Elizabeth Cooney sitting in for Ed Silverman on what from here looks like a perfect summer day. Before you leave your laptop for the weekend, here are some news how can i buy zithromax items to ponder. As Ed would say, fire up some stimulation and keep us in mind should you have spicy tips to share.Even when all responses are âneverâ to six questions on a website co-sponsored by Biogen (BIIB), maker of the controversial new Alzheimerâs drug Aduhelm â such as, do you lose your train of thought or feel a bit more anxious â the quiz still issues a âtalk to your doctorâ recommendation about the potential need for additional cognitive testing, Kaiser Health News says. The campaign â which also includes a detailed advertisement on The New how can i buy zithromax York Timesâ website, a Facebook page, and partnerships aimed at increasing the number of places where consumers can get cognitive testing â is drawing fire from critics. Unlock this article by subscribing to STAT+ and enjoy your first 30 days free!.

GET STARTED Log In | Learn More What is it?. STAT+ is STAT's premium subscription service for in-depth biotech, pharma, policy, and how can i buy zithromax life science coverage and analysis. Our award-winning team covers news on Wall Street, policy developments in Washington, early science breakthroughs and clinical trial results, and health care disruption in Silicon Valley and beyond. What's included?. Daily reporting and analysis The most comprehensive industry coverage from a powerhouse team of reporters Subscriber-only newsletters Daily newsletters to brief you on the most important industry news of the day STAT+ Conversations Weekly opportunities to engage with our reporters and leading industry experts in live video conversations Exclusive industry events Premium access how can i buy zithromax to subscriber-only networking events around the country The best reporters in the industry The most trusted and well-connected newsroom in the health care industry And much more Exclusive interviews with industry leaders, profiles, and premium tools, like our CRISPR Trackr.In the past week, you may have heard about Olympic athletes who are fully vaccinated getting positive buy antibiotics tests or people in Provincetown, Mass., or Texas Democrats or the New York Yankees.

These are called breakthrough s, and theyâre causing a lot of anxiety about whether the treatments hold up against the hyper-transmissible Delta variant.But how concerning are they?. And as cases are surging across the country, how much do they matter as a metric of the zithromax when we have a treatment to protect against how can i buy zithromax severe disease?. STAT spoke with CÃ©line Gounder, a clinical assistant professor of medicine and infectious disease at NYUâs Grossman School of Medicine, host of the âEPIDEMICâ podcast, member of the Biden-Harris Transition buy antibiotics Advisory Board, and a member of the class of people we are calling zithromax celebrities.advertisement This interview has been condensed and edited for clarity.Dr. Gounder, how concerned are you about these instances of breakthrough s in people who are fully vaccinated?. Advertisement I think we really need to better define what we mean how can i buy zithromax by breakthrough s.

Thatâs really a catch-all for people who might have an with no, or very mild, symptoms, all the way to somebody who might end up in the ICU, or even dead. What concerns me is breakthrough disease â people who have significant symptoms, who are struggling to breathe, who are ending up in the hospital, and we really havenât seen breakthrough disease with the treatments.Weâve seen a lot of criticism in recent weeks about the way the CDC is handling the release of data and tracking of these breakthrough s. Do you think their actions have been sufficient or is there more information that how can i buy zithromax you think we need to have from from federal regulators?. I really think we should be tracking breakthrough s. And hereâs why.

Those people who are still getting infected despite being how can i buy zithromax vaccinated, they may not get sick, but it is possible that they could transmit the on to others. And so thatâs something we still donât really have a handle on. There is some evidence from the sports leagues, where they do a how can i buy zithromax lot of testing, that some of these people may, in fact, be contagious. And so that is concerning. The second reason that we really want to be tracking breakthrough s is for what we call genomic surveillance, which is where we look at new variants that are starting to emerge and what do those look like?.

Youâre more likely to find new emerging variants among people who have breakthrough s how can i buy zithromax. Weâre sort of flying blind with respect to that, because weâre not assessing those breakthrough s.All this talk about breakthrough s or breakthrough disease has also raised the issue of boosters, whether Americans will be required to go back and get reinjected with buy antibiotics treatment. What are your thoughts on that?. First of all, booster is really not the how can i buy zithromax right terminology here. I think the problem with boosters is when people hear that word, theyâre like, oh, well, itâs going to be like a flu shot.

Iâm going to need to get a shot every how can i buy zithromax year. The way I would frame this is much more like, say, a blood pressure medicine that your doctor prescribes you â where you start at one dose and they might adjust the dose over time. Just because we are still figuring out the best dosage regimen for the buy antibiotics treatment does not mean that the treatments donât work, and does not mean youâre going to need a yearly buy antibiotics shot.Thatâs really interesting. Where do you fall how can i buy zithromax on the J&J treatment and the current information we have about it?. Thereâs so much anxiety because itâs just one dose.

There are people who got J&J who are feeling not fully vaccinated with one shot. What do you think? how can i buy zithromax. So first of all, the CDC is looking at this. In fact, the CDCâs ACIP, which is a group of people who advise the CDC on their vaccination guidelines, is meeting today as we speak to evaluate whether additional doses of treatment should be given, specifically in this case for people who have immunosuppression. But I anticipate they will be looking at other categories how can i buy zithromax of patients as well.

With respect to the J&J treatment, I think itâs really important for people to understand that this is a very good treatment. This is why we thought that one dose would be how can i buy zithromax sufficient. Now, what weâre learning is that, particularly against some of these new variants, that one dose of J&J may not be enough. And I think what you will see over the next month or two are recommendations, at least for some subsets of people who got J&J, that they do get an additional dose of treatment. The other thing that weâre seeing is when you mix and match different how can i buy zithromax types of treatment, so say J&J, which is very similar to the AstraZeneca treatment.

If you mix and match that with one of the many treatments like Pfizer or Moderna, you actually get an even better immune response. So I do think youâre going to see more mixing and matching in the future as well.So sort of a separate matter. Weâve seen cases on how can i buy zithromax the rise across the United States. And as you mentioned, thereâs this important differentiation between what might be a positive test versus what might be symptomatic disease or something more serious. And we know that treatments are effective at how can i buy zithromax limiting severe disease.

But at the same time, cases are going up. How should we look at this when we have a relatively high vaccination rate and a lot of available treatment for anyone who might want it?. How should we perceive these rising case how can i buy zithromax counts?. How worried should we be, you know, vis-a-vis last year when there were no treatments?. We are seeing this decoupling between cases and hospitalizations and deaths.

So what we mean by decoupling is weâre seeing the cases shoot up more steeply than we are seeing how can i buy zithromax hospitalizations and deaths shoot up. That said, it remains to be seen whether that decoupling holds because weâre still early in our own surge with Delta. And unfortunately, there are parts of the country that how can i buy zithromax really have very low vaccination rates. And we donât know how much some of these breakthrough s among vaccinated people might then be contributing to onward transmission and circulation of the zithromax among unvaccinated people. So thatâs really a black box at this time.

It seems like the rise in case counts has also resurrected the whole mask debate and whether we need how can i buy zithromax to be wearing masks. Do we need to think about going back to wearing them?. So this is a really good question. Many local municipalities are looking at this question how can i buy zithromax right now. I was on a call with several New York City public officials yesterday where they were asking for my advice on this question.

I think, unfortunately, with the rise of Delta, which is about a thousand times more infectious than the original strains of the zithromax, we really do need to think about layering protections. And so what how can i buy zithromax are those layers?. Vaccination. But some of the other layers that we should consider would be masking indoors when youâre outside of your household how can i buy zithromax bubble, optimizing ventilation in the home â just opening your window works really well. It works even better than many of those units that you can buy to filter the air.

I think people really underestimate the power of opening windows. And finally, socializing outdoors as much how can i buy zithromax as possible to minimize your risk. Those would be the things that I think we do need to be thinking about. At the beginning of the zithromax, the CDC said that a close contact was somebody that youâre indoors with unmasked for 15 minutes or more. The equivalent of how can i buy zithromax that with the Delta variant is not 15 minutes, itâs one second.

Does the indoor/outdoor difference in protection still hold?. Letâs say, somebody is worried about their unvaccinated child playing in the playground how can i buy zithromax. Is it OK if theyâre not wearing a mask?. The way to think about your exposure is dose times time. So your how can i buy zithromax dose is a reflection of how much zithromax the person is carrying, but itâs also diluted in the air around them.

So if youâre indoors, thereâs not a lot of air dilution unless youâre opening up windows and doing that sort of thing. When youâre outdoors, itâs almost infinitely diluted. And so outdoors, how can i buy zithromax your risk is really low. I think the only places that would concern me outdoors is if youâre packed in together with people, say, at an outdoor concert or in an outdoor sports sporting event. But in general, outdoors is really pretty safe.That is reassuring.

How are you looking at where how can i buy zithromax the zithromax goes from here?. There were a lot of stories a couple of months ago thinking about how does this zithromax end. But weâre in how can i buy zithromax a fourth surge now. And of course, many countries donât have access to the treatment yet. How much longer is this going to go on?.

Well, remember, zithromax means around the world, so across how can i buy zithromax multiple continents. So if youâre asking, you know, when is the zithromax going to be over?. Itâs going to be years before this is over. I think what really worries me as somebody who, for the better part of my career, worked in HIV and tuberculosis, those are zithromaxs how can i buy zithromax. Youâre looking at about 3 million or so people dying from TB a year.

A similar number of how can i buy zithromax people dying from HIV per year. And thatâs something thatâs been going on for decades. And so I think this is going to become another disease of the poor and marginalized as the zithromax continues to evolve.To listen to the full interview, check out the latest episode of âThe Readout LOUDâ podcast.In the wake of last monthâs controversial Food and Drug Administration approval of Biogenâs Aduhelm, Alzheimerâs Association CEO Harry Johns condemned the ânegative voicesâ concentrating on the flaws in the FDAâs approval as ânot pro-patient.âThe Alzheimerâs Association wasnât the only patient advocacy organization applauding the FDAâs questionable decision, which was based on changes in a surrogate endpoint for Alzheimerâs disease â reduction of amyloid in the brain, an outcome the FDA had previously rejected and that dozens of previous studies had failed to associate with better dementia outcomes.âWe are heartened by the FDAâs decision to speed new treatments to people with Alzheimerâs and we need them to do the same for people with ALS [amyotrophic lateral sclerosis] immediately,â Neil Thakur, chief mission officer of the ALS Association, told NPR. The ALS Association has long been pushing for approval of new treatments and for more how can i buy zithromax lax FDA approval standards. Apparently, more lax approval standards count as being âpro-patientâ.

The organizationâs president and CEO, Calaneet Balas, recently remarked that ALS patients should âdetermine the risks theyâre willing to take and the value they see in the benefits, not anyone else.âadvertisement Before its Aduhelm decision, we believe the FDAâs worst approval in recent memory belonged to Exondys 51, a drug to treat Duchenne muscular dystrophy. Patient advocacy organizations (PAOs) vociferously supported its approval at a how can i buy zithromax heated FDA advisory committee meeting. Following a controversial approval, in which Janet Woodcock, who was then director of the FDAâs Center for Drug Evaluation and Research, called for âthe greatest flexibility possibleâ in determining Exondys 51âs effectiveness, patient advocates lamented the $300,000 per year price tag Sarepta put on the drug. It is understandable that patients and families hope for â and will push for â new therapies, and that patient advocacy organizations will represent those priorities. But no-holds-barred advocacy for approval of therapies, based on insufficient data and without regard to price, has its own history of failing to be how can i buy zithromax âpro-patient.âadvertisement Revamped role for patient advocacy organizationsPAOs are crucial to the process of drug development.

The FDA has cemented their role in creating the CDER Patient-Focused Drug Development Program. Drug products developed how can i buy zithromax without meaningful input from patients or caregivers may be effective by standard metrics yet may ignore the way those products will be used, tolerated, or paid for. In some areas, including Alzheimerâs disease and Parkinsonâs disease, patient advocacy organizations are paying for an ever-growing share of research as pharmaceutical companies pull back.Given these realities, we believe that patient advocacy is at a crossroads. To that end, we propose three best practices for PAO involvement in drug discovery.Advocate for drugs that identify meaningful clinical endpoints. The last few decades have ushered in how can i buy zithromax an era of biomarker-centered drug development.

There are potential advantages to this approach, especially for diseases with outcomes that may take years to measure. Biomarkers allow for earlier entry to the market based on indicators that are reasonably likely to correlate with meaningful clinical outcomes. The issue is that few biomarkers are truly validated for this purpose and some â including progression-free survival in oncology and the reduction in amyloid plaques in Alzheimerâs disease â may not correlate with more meaningful clinical outcomes.Drugs approved based on surrogate endpoints via the accelerated approval pathway are given long periods of time in which to how can i buy zithromax validate their effectiveness, with companies rarely meeting extended deadlines to complete post-market studies. For Exondys 51, the deadline was May 2021, but the company is reportedly years behind on such studies. For Aduhelm, Biogen has been given how can i buy zithromax nine years to complete follow-up studies.

Patient advocacy groups should focus on getting drugs approved for their effects on meaningful clinical endpoints, even though demonstrating improvement in a surrogate endpoint is far easier than demonstrating benefit to patients. When biomarkers must be used, they should be validated (such as HbA1c for diabetes), and follow-up studies should be both mandatory and completed on a shorter timeline. PAOs should prioritize funding for such follow-ups, both to ensure that their constituents are receiving cost-effective treatment and to minimize how can i buy zithromax improvidently-targeted follow-on research.Insist on clear inclusion/exclusion criteria. PAOs should demand that clinical trial populations are representative of the patients with the disease. Exondys 51, for instance, was only studied in patients with Duchenne muscular dystrophy due to a specific mutation in exon 51 (hence the drugâs brand name), but the drug was approved for use in all patients with the disease.

Similarly, Aduhelm was tested only in people with mild-to-moderate symptoms of Alzheimerâs disease but the FDA awarded a broad indication for use in Alzheimerâs disease until public protest â not PAO protest â caused it to modify its recommendation.Patient advocacy how can i buy zithromax groups should also be aware of the diversity of clinical trials. Alzheimerâs disease is estimated to be more prevalent in Black and Hispanic people than in white individuals, yet there were only 11 Black and 67 Hispanic participants enrolled in the âsuccessfulâ trial for Aduhelm, compared with 1,285 white participants. In fact, Biogen listed only white and Asian categories in its investor presentations despite a 2020 Centers for Disease Control and Prevention report projecting that by 2060 2.2 million Black Americans and 3.2 million Hispanic Americans will be affected by Alzheimerâs or other forms of dementia.Press for cost-effectiveness. PAOs should how can i buy zithromax be the leading players in arguing for more reasonable drug prices. Hardly anyone else is suited for the role.

Individual patients are how can i buy zithromax powerless. The FDA historically has not considered cost as part of the approval process, though interim FDA Commissioner Woodcock and others at the agency have taken the financial stability of companies like Sarepta into consideration when making approval determinations. With the FDA seemingly concerned about corporate revenue streams, patient advocacy organizations must use their power as funders of research and patient representatives to insist upon the affordability of medications.Practically speaking, cost is often less important to patient groups when theyâll be borne mostly by federal programs or by private insurance. In the case of Aduhelm, however, how can i buy zithromax there are likely to be substantial out-of-pocket costs, even to those covered by Medicare. Even though the FDA walked back its inappropriately broad approval for the drug, off-label prescribing will likely generate excess spending for patients with more advanced dementia.

Cost will also be a consideration for diseases that hit more people who are younger than 65, the age at which Medicare coverage kicks in. Itâs also important to consider the fact that drug companies are allowed to how can i buy zithromax discuss health care economic information on off-label uses with insurers, pursuant to the 21st Century Cures Act. In fact, the FDA has organized a meeting later this month to discuss coverage of Aduhelm and similar Alzheimerâs disease therapies with insurance companies and other stakeholders.If patients were paying out of pocket for a drug with proven outcomes, they would at least be paying for value. For now, patients are paying how can i buy zithromax an increasing share of costs for expensive drugs that lack effectiveness data. Paying a high cost for unknown effectiveness is, by definition, not cost-effective.

Yet the Alzheimerâs Associationâs gentle pushback against Biogenâs pricing of Aduhelm has been derided as a âbox-checking exerciseâ rather than a critique backed by sustained public pressure. Such pressure can how can i buy zithromax be politically difficult for patient advocacy groups which, like the Alzheimerâs Association, receive significant funding from drug manufacturers, but it ought to be a vital part of their mission.As researchers who study clinical trials and drug approvals, we want nothing more than to see the development and approval of transformative drugs that are made accessible to patients at reasonable cost. We believe that patient advocacy organizations are best situated to make the case for higher approval standards that produce better-quality therapies, ones that stand the best chance of delaying or reversing disease progression.As the FDA expands its consideration of the patient perspective in drug development, refocused objectives are needed. The paradigm must be shifted from âany drug at any costâ to âthe best drug at the right cost.â Patient advocacy organizations must demand more, both from the pharmaceutical industry and from the FDA.Michael S. Sinha is a physician, lawyer, adjunct how can i buy zithromax faculty member at Northeastern University School of Law in Boston, and visiting scholar at the schoolâs Center for Health Policy and Law.

Stephen R. Latham is the director of the Interdisciplinary Center for Bioethics at Yale University..

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Patients of MidMichigan Medical Center â Clare will benefit from the support of the Medical Centerâs volunteers with zithromax for otitis media the recent purchase can you get zithromax over the counter of a new Stryker wheelchair. Left. Caylyn Boadway, executive assistant, volunteer zithromax for otitis media coordinator.

Sandy Wolfe, volunteer, and Shirley Conn, volunteer.Patients of MidMichigan Medical Center â Clare will benefit from the support of the Medical Centerâs volunteers with the recent purchase of a new Stryker wheelchair.Caylyn Boadway, volunteer coordinator, says she is grateful for the work done by all the volunteers, especially during these extraordinary times. ÂThe volunteer is normally the first zithromax for otitis media person our patients meet at the front door and they know wheelchairs are needed 90 percent of the time for the safety of our patients,â said Boadway. ÂThe volunteers took the opportunity to help us fill a need and we are very appreciative.âThe Clare volunteer groups has nearly 35 volunteers that serve across the Medical Center.

ÂNo matter where you go in our Medical Center, the volunteers are there, giving their time, expertise, and devotion to all they zithromax for otitis media encounter,â continued Boadway. ÂOur volunteers have many unique experiences, but one thing is the same no matter where you go, they share a common interest in helping others.âOn behalf of the MidMichigan Health Foundation, Becky Church, development director, thanked the volunteers at their October meeting. ÂWe are extremely grateful to our zithromax for otitis media volunteers and the impact they have on our patients and visitors.

We are thankful for their generous donation and their desire to give to others,â said Church.The volunteers of MidMichigan Medical Center â Clare give time to the organization and participate in many notable projects, including organizing book sales, employee logo sales, and staffing the reception area for outpatient surgeries. In addition, volunteers raise funds through the Medical Centerâs Gift Shop, jewelry sales, and other special projects to purchase non-budgeted items requested by departments as funds allow.Those interested in learning more about zithromax for otitis media the volunteer service program at the Medical Center in Clare may contact Boadway at (989) 802 -5102.Pictured. Karen Morey, fundraising chair, in front of this yearâs Koeze Nut sale at MidMichigan Medical Center â Alpena.

Orders are now being accepted by calling (989) 356-8045 or (313) 378-1879 for curbside delivery service.Area residents have access to state-of-the-art technology and patient care services at MidMichigan Medical Center â Alpena thanks in large part to the ongoing fundraising of the Medical Centerâs volunteers.The annual Koeze Nut Sale has been one of the groups most popular and long-standing events as well as the top earner with all dollars raised used to support ongoing projects zithromax for otitis media. The sale has appealed to donors and shoppers throughout the holiday season for many years and features a variety of specialty candy and nuts.Amanda Timm, volunteer services manager, is pleased that the volunteers have redesigned a sale fitting for the times that she hopes will garner some of the usual community excitement. ÂIn these difficult times, our volunteers felt it was more important than ever zithromax for otitis media to continue the tradition of our Annual Koeze Nut Sale,â said Timm.

ÂThey were up for the challenge of offering creative options to our supporters. This year, zithromax for otitis media we will be taking phone and email orders and offer curbside pick-up service. Our fundraiser chair, Karen Morey, has been very open-minded and does an excellent job rallying the troops.âCurbside pick up orders can be placed by calling Morey at (313) 378-1829 or the volunteer office at (989) 356-8045.

An order zithromax for otitis media form is available at www.midmichigan.org/nutsale. Both Morey and Timm are encouraging shoppers to place orders as early as possible.âSo many supply chains have been disrupted this year,â said Morey. ÂItâs a little hard to predict what will happen zithromax for otitis media.

Right now, though, we have an excellent selection of items that any business or family would love to have to celebrate the holidays.âThe Nut Sale runs Monday, Nov. 16 through zithromax for otitis media Friday, Dec. 18 (pending inventory availability).

All proceeds from the sale will be used to support facility upgrades, advanced technology and patient care at the zithromax for otitis media Medical Center in Alpena. ÂThe passion and commitment our volunteers exhibit is always impressive,â Timm added. ÂThey do so much for our patients and staff and their efforts to ensure this tradition continues for our community is a great testament to their dedication.â.

Patients of MidMichigan Medical Center â Clare will benefit from how can i buy zithromax the support of the Medical Centerâs volunteers with the recent purchase of a new Stryker wheelchair. Left. Caylyn Boadway, how can i buy zithromax executive assistant, volunteer coordinator. Sandy Wolfe, volunteer, and Shirley Conn, volunteer.Patients of MidMichigan Medical Center â Clare will benefit from the support of the Medical Centerâs volunteers with the recent purchase of a new Stryker wheelchair.Caylyn Boadway, volunteer coordinator, says she is grateful for the work done by all the volunteers, especially during these extraordinary times.

ÂThe volunteer is normally the first person our patients meet at the front door and they know wheelchairs are needed 90 percent of the time for how can i buy zithromax the safety of our patients,â said Boadway. ÂThe volunteers took the opportunity to help us fill a need and we are very appreciative.âThe Clare volunteer groups has nearly 35 volunteers that serve across the Medical Center. ÂNo matter how can i buy zithromax where you go in our Medical Center, the volunteers are there, giving their time, expertise, and devotion to all they encounter,â continued Boadway. ÂOur volunteers have many unique experiences, but one thing is the same no matter where you go, they share a common interest in helping others.âOn behalf of the MidMichigan Health Foundation, Becky Church, development director, thanked the volunteers at their October meeting.

ÂWe are extremely grateful to our volunteers and the impact how can i buy zithromax they have on our patients and visitors. We are thankful for their generous donation and their desire to give to others,â said Church.The volunteers of MidMichigan Medical Center â Clare give time to the organization and participate in many notable projects, including organizing book sales, employee logo sales, and staffing the reception area for outpatient surgeries. In addition, volunteers raise funds through the Medical how can i buy zithromax Centerâs Gift Shop, jewelry sales, and other special projects to purchase non-budgeted items requested by departments as funds allow.Those interested in learning more about the volunteer service program at the Medical Center in Clare may contact Boadway at (989) 802 -5102.Pictured. Karen Morey, fundraising chair, in front of this yearâs Koeze Nut sale at MidMichigan Medical Center â Alpena.

Orders are now being accepted by calling (989) 356-8045 or (313) 378-1879 for curbside delivery service.Area residents have access to state-of-the-art technology and patient care services at how can i buy zithromax MidMichigan Medical Center â Alpena thanks in large part to the ongoing fundraising of the Medical Centerâs volunteers.The annual Koeze Nut Sale has been one of the groups most popular and long-standing events as well as the top earner with all dollars raised used to support ongoing projects. The sale has appealed to donors and shoppers throughout the holiday season for many years and features a variety of specialty candy and nuts.Amanda Timm, volunteer services manager, is pleased that the volunteers have redesigned a sale fitting for the times that she hopes will garner some of the usual community excitement. ÂIn these difficult times, our volunteers felt it was more important than ever to continue the how can i buy zithromax tradition of our Annual Koeze Nut Sale,â said Timm. ÂThey were up for the challenge of offering creative options to our supporters.

This year, we will how can i buy zithromax be taking phone and email orders and offer curbside pick-up service. Our fundraiser chair, Karen Morey, has been very open-minded and does an excellent job rallying the troops.âCurbside pick up orders can be placed by calling Morey at (313) 378-1829 or the volunteer office at (989) 356-8045. An order form is how can i buy zithromax available at www.midmichigan.org/nutsale. Both Morey and Timm are encouraging shoppers to place orders as early as possible.âSo many supply chains have been disrupted this year,â said Morey.

ÂItâs a little hard to predict what how can i buy zithromax will happen. Right now, though, we have an excellent selection of items that any business or family would love to have to celebrate the holidays.âThe Nut Sale runs Monday, Nov. 16 through how can i buy zithromax Friday, Dec. 18 (pending inventory availability).

All proceeds from how can i buy zithromax the sale will be used to support facility upgrades, advanced technology and patient care at the Medical Center in Alpena. ÂThe passion and commitment our volunteers exhibit is always impressive,â Timm added. ÂThey do so much for our patients and staff and their efforts to ensure this tradition continues for our community is a great testament to their dedication.â.

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Credit. IStock Share Fast Facts New @HopkinsMedicine study finds African-American women with common form of hair loss at increased risk of uterine fibroids - Click to Tweet New study in @JAMADerm shows most common form of alopecia (hair loss) in African-American women associated with higher risks of uterine fibroids - Click to Tweet In a study of medical records gathered on hundreds of thousands of African-American women, Johns Hopkins researchers say they have evidence that women with a common form of hair loss have an increased chance of developing uterine leiomyomas, or fibroids.In a report on the research, published in the December 27 issue of JAMA Dermatology, the researchers call on physicians who treat women with central centrifugal cicatricial alopecia (CCCA) to make patients aware that they may be at increased risk for fibroids and should be screened for the condition, particularly if they have symptoms such as heavy bleeding and pain. CCCA predominantly affects black women and is the most common form of permanent alopecia in this population.

The excess scar tissue that forms as a result of this type of hair loss may also explain the higher risk for uterine fibroids, which are characterized by fibrous growths in the lining of the womb. Crystal Aguh, M.D., assistant professor of dermatology at the Johns Hopkins University School of Medicine, says the scarring associated with CCCA is similar to the scarring associated with excess fibrous tissue elsewhere in the body, a situation that may explain why women with this type of hair loss are at a higher risk for fibroids.People of African descent, she notes, are more prone to develop other disorders of abnormal scarring, termed fibroproliferative disorders, such as keloids (a type of raised scar after trauma), scleroderma (an autoimmune disorder marked by thickening of the skin as well as internal organs), some types of lupus and clogged arteries. During a four-year period from 2013-2017, the researchers analyzed patient data from the Johns Hopkins electronic medical record system (Epic) of 487,104 black women ages 18 and over.

The prevalence of those with fibroids was compared in patients with and without CCCA. Overall, the researchers found that 13.9 percent of women with CCCA also had a history of uterine fibroids compared to only 3.3 percent of black women without the condition. In absolute numbers, out of the 486,000 women who were reviewed, 16,212 had fibroids.Within that population, 447 had CCCA, of which 62 had fibroids.

The findings translate to a fivefold increased risk of uterine fibroids in women with CCCA, compared to age, sex and race matched controls. Aguh cautions that their study does not suggest any cause and effect relationship, or prove a common cause for both conditions. ÂThe cause of the link between the two conditions remains unclear,â she says.

However, the association was strong enough, she adds, to recommend that physicians and patients be made aware of it. Women with this type of scarring alopecia should be screened not only for fibroids, but also for other disorders associated with excess fibrous tissue, Aguh says. An estimated 70 percent of white women and between 80 and 90 percent of African-American women will develop fibroids by age 50, according to the NIH, and while CCCA is likely underdiagnosed, some estimates report a prevalence of rates as high as 17 percent of black women having this condition.

The other authors on this paper were Ginette A. Okoye, M.D. Of Johns Hopkins and Yemisi Dina of Meharry Medical College.Credit.

The New England Journal of Medicine Share Fast Facts This study clears up how big an effect the mutational burden has on outcomes to immune checkpoint inhibitors across many different cancer types. - Click to Tweet The number of mutations in a tumorâs DNA is a good predictor of whether it will respond to a class of cancer immunotherapy drugs known as checkpoint inhibitors. - Click to Tweet The âmutational burden,â or the number of mutations present in a tumorâs DNA, is a good predictor of whether that cancer type will respond to a class of cancer immunotherapy drugs known as checkpoint inhibitors, a new study led by Johns Hopkins Kimmel Cancer Center researchers shows.

The finding, published in the Dec. 21 New England Journal of Medicine, could be used to guide future clinical trials for these drugs. Checkpoint inhibitors are a relatively new class of drug that helps the immune system recognize cancer by interfering with mechanisms cancer cells use to hide from immune cells.

As a result, the drugs cause the immune system to fight cancer in the same way that it would fight an . These medicines have had remarkable success in treating some types of cancers that historically have had poor prognoses, such as advanced melanoma and lung cancer. However, these therapies have had little effect on other deadly cancer types, such as pancreatic cancer and glioblastoma.

The mutational burden of certain tumor types has previously been proposed as an explanation for why certain cancers respond better than others to immune checkpoint inhibitors says study leader Mark Yarchoan, M.D., chief medical oncology fellow. Work by Dung Le, M.D., associate professor of oncology, and other researchers at the Johns Hopkins Kimmel Cancer Center and its Bloomberg~Kimmel Cancer Institute for Cancer Immunotherapy showed that colon cancers that carry a high number of mutations are more likely to respond to checkpoint inhibitors than those that have fewer mutations. However, exactly how big an effect the mutational burden has on outcomes to immune checkpoint inhibitors across many different cancer types was unclear.

To investigate this question, Yarchoan and colleagues Alexander Hopkins, Ph.D., research fellow, and Elizabeth Jaffee, M.D., co-director of the Skip Viragh Center for Pancreas Cancer Clinical Research and Patient Care and associate director of the Bloomberg~Kimmel Institute, combed the medical literature for the results of clinical trials using checkpoint inhibitors on various different types of cancer. They combined these findings with data on the mutational burden of thousands of tumor samples from patients with different tumor types. Analyzing 27 different cancer types for which both pieces of information were available, the researchers found a strong correlation.

The higher a cancer typeâs mutational burden tends to be, the more likely it is to respond to checkpoint inhibitors. More than half of the differences in how well cancers responded to immune checkpoint inhibitors could be explained by the mutational burden of that cancer. ÂThe idea that a tumor type with more mutations might be easier to treat than one with fewer sounds a little counterintuitive.

Itâs one of those things that doesnât sound right when you hear it,â says Hopkins. ÂBut with immunotherapy, the more mutations you have, the more chances the immune system has to recognize the tumor.â Although this finding held true for the vast majority of cancer types they studied, there were some outliers in their analysis, says Yarchoan. For example, Merkel cell cancer, a rare and highly aggressive skin cancer, tends to have a moderate number of mutations yet responds extremely well to checkpoint inhibitors.

However, he explains, this cancer type is often caused by a zithromax, which seems to encourage a strong immune response despite the cancerâs lower mutational burden. In contrast, the most common type of colorectal cancer has moderate mutational burden, yet responds poorly to checkpoint inhibitors for reasons that are still unclear. Yarchoan notes that these findings could help guide clinical trials to test checkpoint inhibitors on cancer types for which these drugs havenât yet been tried.

Future studies might also focus on finding ways to prompt cancers with low mutational burdens to behave like those with higher mutational burdens so that they will respond better to these therapies. He and his colleagues plan to extend this line of research by investigating whether mutational burden might be a good predictor of whether cancers in individual patients might respond well to this class of immunotherapy drugs. ÂThe end goal is precision medicineâmoving beyond whatâs true for big groups of patients to see whether we can use this information to help any given patient,â he says.

Yarchoan receives funding from the Norman &. Ruth Rales Foundation and the Conquer Cancer Foundation. Through a licensing agreement with Aduro Biotech, Jaffee has the potential to receive royalties in the future..

The other authors on this paper were Ginette A. Okoye, M.D. Of Johns Hopkins and Yemisi Dina of Meharry Medical College.Credit.

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Our aim is to see every miner go home safe and healthy after every zithromax and advil shift. Keeping all miners safe means continued production of the indispensable products we use every day. Every time you drink from a glass, zithromax and advil thank a miner. Every time you ride a bike or take a drive in your car, thank a miner.

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Having worked in the mining industry for the majority of my life, I fully recognize the hazards that confined spaces, mobile equipment and complex electrical equipment, just to name a few, can present to working miners. This is how can i buy zithromax why my agency, the U.S. Department of Laborâs Mine Safety and Health Administration (MSHA), exists. MSHA enforces safety and health standards and regulations â at all American coal mines, quarries, copper and other metal mines, and many other facilities â to protect miners from the hazards they face each day.

Our aim how can i buy zithromax is to see every miner go home safe and healthy after every shift. Keeping all miners safe means continued production of the indispensable products we use every day. Every time you drink how can i buy zithromax from a glass, thank a miner. Every time you ride a bike or take a drive in your car, thank a miner.

Miners are the true backbone of not just our nationâs mining industry but also the many industries that could not operate without the raw materials that miners produce. So, on this National Miners Day, please join me in recognizing, honoring and thanking miners for their steady and courageous role in providing the products that make so much how can i buy zithromax of our daily life possible. David Zatezalo is the Assistant Secretary for Mine Safety and Health at the Mine Safety and Health Administration. Follow MSHA on Twitter at @MSHA_DOL..

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Shortlisted candidates will be interviewed by relevant institute.ZJU-UoE Institute (Biomedical Sciences). Ms. Xinyi YANG at Xinyi_yang@zju.edu.cn, +86 571 87572816For more information, please visit:ZJE. Http://zje.intl.zju.edu.cn/zje/home/indexInternational Campusï¼Zhejiang University (ZJU) invites applications for Postdoctoral ResearchersZJU International Campus is a strategic initiative of Zhejiang University. ÂGlobalâ and âinterdisciplinaryâ are our distinctions.

To date, two leading joint institutes in China have been successfully launched with the University of Edinburgh (the ZJU-UoE Institute) and the University of Illinois at Urbana-Champaign (the ZJU-UIUC Institute), as well as the Zhejiang University International Business School (ZIBS). In addition, a number of international innovation centers, including the Joint International Research Center for Advanced Photonics (Ministry of Education), the China-Portugal Joint Innovation Center for Advanced Materials (Ministry of Science and Technology) among others, have built labs on the Campus. Furthermore, the mission of Haining International Center of Zhejiang Intellectual Property Exchange Center, which is situated on campus, is to promote integration between university research and industry.In line with the accepted practice and working procedures of our partner universities, the Campus applies a comprehensive tenure system, which has successfully attracted an internationally leading faculty represented by winners of the National Science Fund for Distinguished Young Scholars.Eligibility:Having obtained a PhD degree in related areas from renowned universities.Good research potential and capability. High standard of ethics and academic integrity.At least one paper in internationally leading academic journal as first author.Ideally under 35 years of age.Work and Living Conditions:ZJU International Campus upholds the Universityâs tradition of valuing our faculty and are committed to promoting their career development. We continue to optimize the campus academic environment, implement support policies, and offer internationally competitive work and living facilities.1.

Academic environment. International and multidisciplinary research environment. Leading supervisor team from home and abroad.2. Remuneration:No less than RMB 150,000 or 200,000 yuan of annual salary provided by the institute or the international research center respectively,Plus RMB 150,000 or 200,000 yuan per year of subsidy by Haining municipal government according to credentials,Plus additional RMB 100,000 yuan per year for each successful applicant of âBoXinâ (a national support program for outstanding postdoctoral researchers)3. Research conditions:Research program fund provided by supervisors,Plus a one-time start-up fund of RMB 100,000 or 200,000 yuan by Haining municipal government according to credentials,Plus recommendation to and matching fund for national/provincial scientific research projects.4.

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A broadly neutralising antibody to prevent HIV transmissionTwo HIV prevention zithromax antibiotic medicine trials read (HVTN 704/HPTN 085. HVTN 703/HPTN 081) enrolled 2699 at-risk cisgender men and transgender persons in the Americas and Europe and 1924 at-risk women in sub-Saharan Africa who were randomly assigned to receive the broadly neutralising antibody (bnAb) VRC01 or placebo (10 infusions at an interval of 8 weeks). Moderate-to-severe adverse zithromax antibiotic medicine events related to VRC01 were uncommon. In a prespecified pooled analysis, over 20 months, VRC01 offered an estimated prevention efficacy of ~75% against VRC01-sensitive isolates (30% of zithromaxes circulating in the trial regions).

However, VRC01 did not prevent zithromax antibiotic medicine with other HIV isolates and overall HIV acquisition compared with placebo. The data provide proof of concept that bnAb can prevent HIV acquisition, although the approach is limited by viral diversity and potential selection of resistant isolates.Corey L, Gilbert PB, Juraska M, et al. Two randomized trials of neutralizing antibodies to zithromax antibiotic medicine prevent HIV-1 acquisition. N Engl J Med.

2021;384:1003â1014.Seminal cytokine profiles are associated with the risk of HIV transmissionInvestigators analysed a panel of 34 cytokines/chemokines in blood and semen of men (predominantly men who have sex with men) with HIV, comparing 21 who transmitted HIV zithromax antibiotic medicine to their partners and 22 who did not. Overall, 47% of men had a recent HIV , 19% were on antiretroviral therapy and 84% were viraemic. The cytokine profile in seminal fluid, but not in blood, differed significantly between transmitters and non-transmitters, with transmitters showing higher seminal concentrations of interleukin 13 (IL-13), IL-15 and IL-33, and lower concentrations of interferonâgamma, IL-15, macrophage colony-stimulating factor (M-CSF), IL-17, granulocyte-macrophage CSF (GM-CSF), IL-4, IL-16 and zithromax antibiotic medicine eotaxin. Although limited, the findings suggest that the seminal milieu modulates the risk of HIV transmission, providing a potential development opportunity for HIV prevention strategies.Vanpouille C, Frick A, Rawlings SA, et al.

Cytokine network and sexual HIV transmission zithromax antibiotic medicine in men who have sex with men. Clin Infect Dis. 2020;71:2655â2662.The challenge of estimating global treatment eligibility for chronic hepatitis B from incomplete datasetsWorldwide, over 250 million people are estimated to live with chronic hepatitis B (CHB), although only ~11% is diagnosed and a minority receives zithromax antibiotic medicine antiviral therapy. An estimate of the global proportion eligible for treatment was not previously available.

A systematic zithromax antibiotic medicine review analysed studies of CHB populations done between 2007 and 2018 to estimate the prevalence of cirrhosis, abnormal alanine aminotransferase, hepatitis B zithromax DNA >2000âor >20â000âIU/mL, hepatitis B e-antigen, and overall eligibility for treatment as per WHO and other guidelines. The pooled treatment eligibility estimate was 19% (95% CI 18% to 20%), with about 10% requiring urgent treatment due to cirrhosis. However, the estimate should zithromax antibiotic medicine be interpreted with caution due to incomplete data acquisition and reporting in available studies. Standardised reporting is needed to improve global and regional estimates of CHB treatment eligibility and guide effective policy formulation.Tan M, Bhadoria AS, Cui F, et al.

Estimating the proportion of people with chronic hepatitis B zithromax zithromax antibiotic medicine eligible for hepatitis B antiviral treatment worldwide. A systematic review and meta-analysis. Lancet Gastroenterol Hepatol, zithromax antibiotic medicine 2021. 6:106â119.Broad geographical disparity in the contribution of HIV to the burden of cervical cancerThis systematic review and meta-analysis estimated the contribution of HIV to the global and regional burden of cervical cancer using data from 24 studies which included 236â127 women with HIV.

HIV markedly increased zithromax antibiotic medicine the risk of cervical cancer (pooled relative risk 6.07. 95%âCI 4.40 to 8.37). In 2018, 4.9% (95% CI 3.6% to 6.4%) of cervical cancers were attributable to HIV globally, although the population-attributable fraction for HIV varied geographically, reaching 21% (95% CI 15.6% to 26.8%) in zithromax antibiotic medicine the African region. Cervical cancer is preventable and treatable.

Efforts are needed to expand access to HPV zithromax antibiotic medicine vaccination in sub-Saharan Africa. More immediately, there is an urgent need to integrate cervical cancer screening within HIV services.Stelzle D, Tanaka LF, Lee KK, et al. Estimates of the global burden of cervical cancer associated with HIV zithromax antibiotic medicine. Lancet Glob Health.

2020. 9:e161â69.The complex relationship between serum vitamin D and persistence of high-risk human papilloma zithromax Most cervical high-risk human papilloma zithromax (hrHPV) s are transient and those that persist are more likely to progress to cancer. Based on the proposed immunomodulatory properties of vitamin D, a longitudinal study examined the association between serum concentrations of five vitamin D biomarkers and short-term persistent (vs transient or sporadic) detection of hrHPV in 72 women who collected monthly cervicovaginal swabs over 6 months. No significant associations were detected in the primary analysis.

In sensitivity analyses, after multiple adjustments, serum concentrations of multiple vitamin D biomarkers were positively associated with the short-term persistence of 14 selected hrHPV types. The relationship between vitamin D and hrHPV warrants closer examination. Studies should have longer follow-up, include populations with more diverse vitamin D concentrations and account for vitamin D supplementation.Troja C, Hoofnagle AN, Szpiro A, et al. Understanding the role of emerging vitamin D biomarkers on short-term persistence of high-risk HPV among mid-adult women.

J Infect Dis 2020. Online ahead of printPublished in STIâthe editorâs choice. One in five cases of with Neisseria gonorrhoeae clear spontaneouslyStudies have indicated that Neisseria gonorrhoeae (NG) s can resolve spontaneously without antibiotic therapy. A substudy of a randomised trial investigated 405 untreated subjects (71% men) who underwent both pretrial and enrolment NG testing at the same anatomical site (genital, pharyngeal and rectal).

Based on nuclear acid amplification tests, 83 subjects (20.5%) showed clearance of the anatomical site within a median of 10 days (IQR 7â15) between tests. Those with spontaneous clearance were less likely to have concurrent chlamydia (p=0.029) and dysuria (p=0.035), but there were no differences in age, gender, sexual orientation, HIV status, number of previous NG episodes, and symptoms other than dysuria between those with and without clearance. Given the high rate of spontaneous resolution, point-of-care NG testing should be considered to reduce unnecessary antibiotic treatment.Mensforth S, Ayinde OC, Ross J. Spontaneous clearance of genital and extragenital Neisseria gonorrhoeae.

Data from GToG. STI 2020. 96:556â561.BackgroundReproductive aged women are at risk of both pregnancy and sexually transmitted s (STI). The modern contraceptive prevalence among married and unmarried women in South Africa is 54% and 64%, respectively, with injectable progestins being most widely used.1 Moreover, current global efforts aim towards all women having access to a range of reliable contraceptives options.2 The prevalences of chlamydia and gonorrhoea are high among women in Africa, particularly among younger women.

A recent meta-analysis of over 37â000 women estimated prevalences for chlamydia and gonorrhoea by region and population type (South Africa clinic/community-based, Eastern Africa higher-risk and Southern/Eastern Africa clinic community-based). High chlamydia and gonorrhoea prevalences were found among 15â24âyear-old South African women and high risk populations in East Africa.3 Both chlamydia and gonorrhoea are associated with numerous comorbidities including pelvic inflammatory disease (PID), ectopic pregnancy, infertility, increased risk of HIV and other STIs, as well as significant social harm.4While STIs are a significant global health burden, data on STI prevalence by gender and drivers of are limited, hindering an effective public health response.5 Moreover, data on the association between contraceptive use and risk of non-HIV STIs are limited. The WHO recently reported stagnation in efforts to decrease global STI incidence.5 Understanding drivers of STI acquisition, including any possible associations with widely used contraceptive methods, is necessary to effectively target public health responses that reduce STI incidence and associated comorbidities.The ECHO Trial (ClinicalTrials.gov Identifier. NCT02550067) was a multicentre, open-label randomised trial of 7829 HIV-seronegative women seeking effective contraception in Eswatini, Kenya, South Africa and Zambia.

Detailed trial methods and results have been published.6 7 We conducted a secondary analysis of ECHO trial data to evaluate absolute and relative chlamydia and gonorrhoea final visit prevalences among women randomised to intramuscular depot medroxyprogesterone acetate (DMPA-IM), a copper intrauterine device (IUD) and a levonorgestrel (LNG) implant.MethodsStudy design, participants and ethicsWomen were enrolled in the ECHO trial from December 2015 through September 2017. Institutional review boards at each site approved the study protocol and women provided written informed consent before any study procedures. In brief, women who were not pregnant, HIV-seronegative, aged 16â35 years, seeking effective contraception, without medical contraindications, willing to use the assigned method for 18 months, reported not using injectable, intrauterine or implantable contraception for the previous 6 months and reported being sexually active, were enrolled. At every visit, participants received HIV risk reduction counselling, HIV testing and STI management, condoms and, as it became a part of national standard of care, HIV pre-exposure prophylaxis.

Counselling messages related to HIV risk were implemented consistently across the three groups throughout the trial.6The trial was implemented in accordance with the Declaration of Helsinki and Good Clinical Practice. Informed consent was obtained from participants or their parents/guardians and human experimentation guidelines of the United States Department of Health and Human Services and those of the authors' institution(s) were followed.Contraceptive exposureAt enrolment, women were randomly assigned (1:1:1) to DMPA-IM, copper IUD or LNG implant.6 Participants received an injection of 150âmg/mL DMPA-IM (Depo Provera. Pfizer, Puurs, Belgium) at enrolment and every 3 months until the final visit at 18 months after enrolment, a copper IUD (Optima TCu380A. Injeflex, Sao Paolo, Brazil) or a LNG implant (Jadelle.

Bayer, Turku, Finland) at enrolment. Women returned for follow-up visits at 1âmonth after enrolment to address initial contraceptive side-effects and every 3 months thereafter, for up to 18 months with later enrolling participants contributing 12 to 18 months of follow-up. Visits included HIV serological testing, contraceptive counselling, syndromic STI management and safety monitoring.STI outcomesThe primary outcomes of this secondary analysis were prevalent chlamydia and gonorrhoea at the final visit. Syndromic STI management was provided at screening and all follow-up visits.

Nucleic acid amplification testing (NAAT) for Chlamydia trachomatis and Neisseria gonorrhoeae was conducted at screening and final visits, at the visit of HIV detection for participants who became HIV infected and at clinical discretion. Any untreated participants with positive NAAT results were contacted to return to the study clinic for treatment.CovariatesAt baseline (inclusive of screening and enrolment visits), we collected demographic, sexual and reproductive risk behaviour and reproductive and contraceptive history data. Baseline risk factors evaluated as covariates included age, whether the participant earned her own income, chlamydia and gonorrhoea status, herpes simplex zithromax type 2 (HSV-2) sero-status and suspected PID. Final visit factors evaluated as covariates included number of sex partners in the past 3 months, number of new sex partners in the past 3 months, HIV serostatus, HSV-2 serostatus, condom use in the past 3 months, sex exchanged for money/gifts, sex during vaginal bleeding, follow-up time and number of pelvic examinations during follow-up.

Age and HSV-2 serostatus were evaluated for effect measure modification.Statistical analysisWe conducted analyses using R V.3.5.3 (Vienna, Austria), and log-binomial regression to estimate chlamydia and gonorrhoea prevalences within each contraceptive group and pairwise prevalence ratios (PR) between each arm in as-randomised and consistent use analyses.In the as-randomised analysis, we analysed participants by the contraceptive method assigned at randomisation independent of method adherence. We estimated crude point prevalences by arm and study site and pairwise adjusted PRs.In the consistent use analysis, we only included women who initiated use of their randomised contraceptive method and maintained randomised method adherence throughout follow-up. We estimated crude point prevalences by arm and pairwise adjusted PRs, with evaluation of age and HSV-2 status first as potential effect measure modifiers, and all covariates above as potential confounders. Study site and age http://luxurypropertiesofmarcoisland.com/2011/06/marco_island_luxury/ were retained in the final model.

Other covariates were retained if their inclusion in the base model led to a 10% change in the effect estimate through backwards selection.Supplementary analysesAdditional supporting analyses to assess postrandomisation potential sources of bias were conducted to inform interpretation of results. These include evaluation of recent sexual behaviour at enrolment, month 9 and the final visit. Cohort participation (ie, follow-up time, early discontinuation and timing of randomised method discontinuation) and health outcomes (ie, final visit HIV and HSV-2 status) and frequency and results of pelvic examinations by STI status, site and visit month by randomised arm.ResultsA total of 7829 women were randomly assigned as follows. 2609 to the DMPA-IM group, 2607 to the copper IUD group and 2613 to the LNG implant group (figure 1).

Participants were excluded if they were HIV positive at enrolment, did not have at least one HIV test or did not have chlamydia and gonorrhoea test results at the final visit. Overall, 90%, 94% and 93% from the DMPA-IM, copper IUD and LNG implant groups, respectively, were included in analyses.Study profile. DMPA-IM, depot medroxy progesterone acetate. IUD, intrauterine device.

LNG, levonorgestrel." data-icon-position data-hide-link-title="0">Figure 1 Study profile. DMPA-IM, depot medroxy progesterone acetate. IUD, intrauterine device. LNG, levonorgestrel.Participant characteristicsBaseline characteristics were similar across groups (table 1).

Nearly two-third of enrolled women (63%) were aged 24 and younger and 5768 (74%) of the study population resided in South Africa.View this table:Table 1 Participant baseline and final visit characteristicsThe duration of participation averaged 16 months with no differences between randomised groups (table 1). A total of 1468 (19%) women either did not receive their randomised method or discontinued use during follow-up. Overall method continuation rates were high with minimal differences between randomised groups when measured by person-years.6 The proportion, however, of method non-adherence as defined in this analysis (ie, did not receive randomised method at baseline or discontinued randomised method at any point during follow-up), was greater in the DMPA-IM group (26%), followed by the copper IUD (18%) and LNG implant (12%) groups. Timing of discontinuation also differed across methods.

During the first 6âmonths, method discontinuation was highest in the copper IUD group (7%) followed closely by DMPA-IM (6%) and LNG implant (4%) groups. Between 7 and 12 months of follow-up, it was highest in DMPA-IM group (15%), with equivalent proportions in the LNG implant (5%) and copper IUD (5%) groups.Point prevalences of chlamydia and gonorrhoea at baseline and final visitsIn total, 18% of women had chlamydia at baseline (figure 2A) and 15% at the final visit. Among women 24 years and younger, 22% and 20% had chlamydia at baseline and final visits, respectively. Women aged 25â35 at baseline were less likely to have chlamydia at both baseline (12%) and final visits (8%) compared with younger women.

Baseline chlamydia prevalence ranged from 5% in Zambia to 28% in the Western Cape, South Africa (figure 2B).Point prevalence (per 100 persons) of chlamydia and gonorrhoea at baseline and final visit by age category and study site region. Y-axis scale differs for chlamydia and gonorrhoea figures." data-icon-position data-hide-link-title="0">Figure 2 Point prevalence (per 100 persons) of chlamydia and gonorrhoea at baseline and final visit by age category and study site region. Y-axis scale differs for chlamydia and gonorrhoea figures.Among all women, 5% had gonorrhoea at baseline and the final visit (figure 2C). Women aged 24 and younger were more likely to have gonorrhoea compared with women aged 25 and older at both baseline (5% vs 4%, respectively) and the final visit (6% vs 3%, respectively).

Baseline gonorrhoea prevalence ranged from 3% in Zambia and Kenya to 9% in the Western Cape, South Africa (figure 2D). Similar prevalences were observed at the final visit.Point prevalences of chlamydia and gonorrhoea at final visit by randomised contraceptive methodFourteen per cent of women randomised to DMPA-IM, 15% to copper IUD and 17% to LNG implant had chlamydia at the final visit (table 2).View this table:Table 2 Chlamydia trachomatis and Neisseria gonorrhoeae prevalence at final visitThe prevalence of chlamydia did not significantly differ between DMPA-IM and copper IUD groups (PR 0.90, 95%âCI (0.79 to 1.04)) or between copper IUD and LNG implant groups (PR 0.92, 95%âCI (0.81 to 1.04)). Women in the DMPA-IM group, however, had a significantly lower risk of chlamydia compared with the LNG implant group (PR. 0.83, 95%âCI (0.72 to 0.95)).

Findings from the consistent use analysis were similar, and neither age nor HSV-2 status modified the observed associations.Four per cent of women randomised to DMPA-IM, 6% to copper IUD and 5% to LNG implant had gonorrhoea at the final visit (table 2). Gonorrhoea prevalence did not significantly differ between DMPA-IM and LNG implant groups (PR. 0.79, 95%âCI (0.61 to 1.03)) or between copper IUD and LNG implant groups (PR. 1.18, 95%âCI (0.93 to 1.49)).

Women in the DMPA-IM group had a significantly lower risk of gonorrhoea compared with women in the copper IUD group (PR. 0.67, 95%âCI (0.52 to 0.87)). Results from as randomised and continuous use analyses did not differ. And again, neither age nor HSV-2 status modified the observed associations.Clinical assessment by randomised contraceptive methodTo assess the potential for outcome ascertainment bias, we evaluated the frequency of pelvic examinations and abdominal/pelvic pain and discharge by study arm.

Women in the copper IUD group were generally more likely to receive a pelvic examination during follow-up as compared with women in the DMPA-IM and LNG implant groups (online supplemental appendix 1). Similarly, abdominal/pelvic pain on examination or abnormal discharge was observed most frequently in the copper IUD group. The number of pelvic examinations met the prespecified criteria for retention in the adjusted gonorrhoea model but not in the chlamydia model.Supplemental materialFrequency of syndromic symptoms and potential reAmong women who had chlamydia at baseline, 23% were also positive at the final visit (online supplemental appendix 2, figure 3A). Nine per cent of gonorrhoea-positive women at baseline were also positive at the final visit (online supplemental appendix 2, figure 3B).

Across both baseline and final visits, a minority of women with chlamydia or gonorrhoea presented with signs and/or symptoms. Among chlamydia-positive women, only 12% presented with either abnormal vaginal discharge and/or abdominal/pelvic pain at their test-positive visit (online supplemental appendix 2, figure 3C). Similarly, only 15% of gonorrhoea-positive women presented with abnormal vaginal discharge and/or abdominal/pelvic pain at their test-positive visit (online supplemental appendix 2, figure 3D).Potential re and symptoms among women with chlamydia or gonorrhoea. Data are pooled across the screening and final visits in figures (C) and (D).

Final visit is described as potential re because test of cure was not conducted following baseline diagnosis and treatment.DiscussionWe observed differences in final prevalences of chlamydia and gonorrhoea by contraceptive group in both as-randomised and consistent-use analyses. The DMPA-IM group had lower final visit chlamydia and gonorrhoea prevalences as compared with copper IUD and LNG implant groups, though only the DMPA-IM versus the copper IUD comparison of gonorrhoea and DMPA-IM versus LNG implant comparison of chlamydia reached statistical significance. These are novel findings that have not previously been reported to our knowledge and were determined in a randomised trial setting with high participant retention, robust biomarker testing and high randomised method adherence. Interestingly, the copper IUD group had higher gonorrhoea and lower chlamydia prevalence compared with the LNG implant group, though neither finding was statistically significant.Two recent systematic reviews of the association between contraceptives and STIs found inconsistent and insufficient evidence on the association between the contraceptive methods under study in ECHO and chlamydia and gonorrhoea.8 9 Neither systematic review identified any randomised studies or any direct comparative evidence for DMPA-IM, copper IUD and LNG implant, thus enabling a unique scientific contribution from this secondary trial analysis.

Nonetheless, these findings should be interpreted in light of biological plausibility, as well as the design strengths and limitations of this analysis.The emerging science on the biological mechanisms underlying HIV susceptibility demonstrates the complex relationship between the infectious pathogen, the host innate and adaptive immune response and the interaction of both with the vaginal microbiome and other -omes. Data on these factors in relationship to chlamydia and gonorrhoea acquisition are much more limited but can be assumed to be equally complex. Vaginal microbiome composition, including microbial metabolic by-products, have been shown to significantly modify risk of HIV acquisition and to vary with exogenous hormone exposure, menstrual cycle phase, ethnicity and geography.10â12 These same biological principles likely apply to chlamydia and gonorrhoea susceptibility. While DMPA-IM has been associated with decreased bacterial vaginosis (BV), initiation of the copper IUD has been associated with increased BV prevalence, and BV is associated with chlamydia and gonorrhoea acquisition.13 14 Moreover, Lactobacillus crispatus, which is less abundant in BV, has been shown to inhibit HeLa cell by Chlamydia trachomatis and inhibits growth of Neisseria gonorrhoeae in animal models.15 16 In addition, microbial community state types that are deficient in Lactobacillus crispatus and/or dominated by dysbiotic species are associated with inflammation, which is a driver of both STI and HIV susceptibility.

Thus, while the exact mechanisms of chlamydia and gonorrhoea in the presence of exogenous hormones and varying host microbiomes are unknown, it is biologically plausible that these complex factors may result in differential susceptibility to chlamydia and gonorrhoea among DMPA-IM, copper IUD and LNG implant users.An alternative explanation for these findings may be postrandomisation differences in clinical care and/or sexual behaviour. Participants in the copper IUD arm were more likely to have pelvic examinations and more likely to have discharge compared with women in the DMPA-IM and LNG implant groups. While interim STI testing and/or treatment were not documented, women in the copper IUD arm may have been more likely to receive syndromic STI treatment during follow-up due to more examination and observed discharge. More frequent STI treatment in the copper IUD group would theoretically lower the final visit point prevalence relative to women in the DMPA-IM and LNG implant arms, suggesting that the observed lower risk of STI in the DMPA-IM arm is not due to differential examination, testing and treatment.

Differential sexual risk behaviour may also have influenced the results. As reported previously, women in the DMPA-IM group less frequently reported condomless sex and multiple partners than women in the other groups, and both DMPA-IM and LNG implant users less frequently reported new partners and sex during menses than copper IUD users.6 Statistical control of self-reported sexual risk behaviour in the consistent-use analysis may have been inadequate if self-reported sexual behaviour was inaccurately or insufficiently reported.A second alternative explanation may be differences in randomised method non-adherence, which was greater in the DMPA-IM group, compared with copper IUD and LNG implant groups. Yet, the consistency of findings in the as-randomised and continuous use analyses suggests that method non-adherence had minimal effect on study outcomes. Taken as a whole, these findings indicate that there may be real differences in chlamydia and gonorrhoea risk associated with use of DMPA-IM, the copper IUD and LNG implant.

However, any true differential risk by method must be evaluated in light of the holistic benefits and risks of each method.The high observed chlamydia and gonorrhoea prevalences, despite intensive counselling and condom provision, warrants attention, particularly among women ages 24 years and younger and among women in South Africa and Eswatini. While the ECHO study was conducted in settings of high HIV/STI incidence, enrolment criteria did not purposefully target women at highest risk of HIV/STI in the trial communities, suggesting that the observed prevalences may be broadly applicable to women seeking effective contraception in those settings. Improved approaches are needed to prevent STIs, including options for expedited partner treatment, to prevent re.As expected, few women testing positive for chlamydia or gonorrhoea presented with symptoms (12% and 15%, respectively), and a substantial proportion of women who were positive and treated at baseline were infected at the final visit despite syndromic management during the follow-up. Given that syndromic management is the standard of care within primary health facilities in most trial settings, these data suggest that a large proportion of among reproductive aged women is missed, exacerbating the burden of curable STIs and associated morbidities.

Routine access to more reliable diagnostics, like NAAT and novel point-of-care diagnostic tests, will be key to managing asymptomatic STIs and reducing STI prevalence and related morbidities in these settings.17This secondary analysis of the ECHO trial has strengths and limitations. Strengths include the randomised design with comparator groups of equal STI baseline risk. Participants had high adherence to their randomised contraceptive method.6 While all participants received standardised clinical care and counselling, the unblinded randomisation may have allowed postrandomisation differences in STI risk over time by method. It is possible that participants modified their risk-taking behaviour based on study counselling messages regarding the potential association between DMPA-IM and HIV.In conclusion, our analyses suggest that DMPA-IM users may have lower risk of chlamydia and gonorrhoea compared with LNG implant and copper IUD users, respectively.

Further investigation is warranted to better understand the mechanisms of chlamydia and gonorrhoea susceptibility in the context of contraceptive use. Moreover, the high chlamydia and gonorrhoea prevalences in this population, independent of contraceptive method, warrants urgent attention.Key messagesThe prevalence of chlamydia and gonorrhoea varied by contraceptive method in this randomised trial.High chlamydia and gonorrhoea prevalences, despite intensive counselling and condom provision, warrants attention, particularly among young women in South Africa and Eswatini.Most chlamydia and gonorrhoea s were asymptomatic. Therefore, routine access to reliable diagnostics are needed to effectively manage and prevent STIs in African women..

A broadly how can i buy zithromax neutralising antibody to prevent HIV transmissionTwo HIV prevention trials (HVTN 704/HPTN 085 this link. HVTN 703/HPTN 081) enrolled 2699 at-risk cisgender men and transgender persons in the Americas and Europe and 1924 at-risk women in sub-Saharan Africa who were randomly assigned to receive the broadly neutralising antibody (bnAb) VRC01 or placebo (10 infusions at an interval of 8 weeks). Moderate-to-severe adverse events related to VRC01 were uncommon how can i buy zithromax. In a prespecified pooled analysis, over 20 months, VRC01 offered an estimated prevention efficacy of ~75% against VRC01-sensitive isolates (30% of zithromaxes circulating in the trial regions). However, VRC01 did not prevent with other HIV isolates and overall how can i buy zithromax HIV acquisition compared with placebo.

The data provide proof of concept that bnAb can prevent HIV acquisition, although the approach is limited by viral diversity and potential selection of resistant isolates.Corey L, Gilbert PB, Juraska M, et al. Two randomized trials how can i buy zithromax of neutralizing antibodies to prevent HIV-1 acquisition. N Engl J Med. 2021;384:1003â1014.Seminal cytokine profiles are associated with the risk of HIV transmissionInvestigators analysed a panel of 34 cytokines/chemokines in blood and semen how can i buy zithromax of men (predominantly men who have sex with men) with HIV, comparing 21 who transmitted HIV to their partners and 22 who did not. Overall, 47% of men had a recent HIV , 19% were on antiretroviral therapy and 84% were viraemic.

The cytokine profile in seminal fluid, but not in blood, differed significantly between transmitters and non-transmitters, with transmitters showing higher seminal concentrations of interleukin 13 (IL-13), IL-15 and IL-33, and lower concentrations of interferonâgamma, IL-15, how can i buy zithromax macrophage colony-stimulating factor (M-CSF), IL-17, granulocyte-macrophage CSF (GM-CSF), IL-4, IL-16 and eotaxin. Although limited, the findings suggest that the seminal milieu modulates the risk of HIV transmission, providing a potential development opportunity for HIV prevention strategies.Vanpouille C, Frick A, Rawlings SA, et al. Cytokine network and sexual HIV transmission in men who have sex with men how can i buy zithromax. Clin Infect Dis. 2020;71:2655â2662.The challenge of estimating global treatment eligibility for chronic hepatitis B from incomplete datasetsWorldwide, over 250 million people are estimated to live with chronic hepatitis B (CHB), how can i buy zithromax although only ~11% is diagnosed and a minority receives antiviral therapy.

An estimate of the global proportion eligible for treatment was not previously available. A systematic review analysed studies of CHB populations done between 2007 and 2018 to estimate the prevalence of cirrhosis, abnormal alanine how can i buy zithromax aminotransferase, hepatitis B zithromax DNA >2000âor >20â000âIU/mL, hepatitis B e-antigen, and overall eligibility for treatment as per WHO and other guidelines. The pooled treatment eligibility estimate was 19% (95% CI 18% to 20%), with about 10% requiring urgent treatment due to cirrhosis. However, the estimate should be interpreted with caution due to incomplete data acquisition how can i buy zithromax and reporting in available studies. Standardised reporting is needed to improve global and regional estimates of CHB treatment eligibility and guide effective policy formulation.Tan M, Bhadoria AS, Cui F, et al.

Estimating the proportion of people how can i buy zithromax with chronic hepatitis B zithromax eligible for hepatitis B antiviral treatment worldwide. A systematic review and meta-analysis. Lancet Gastroenterol Hepatol, how can i buy zithromax 2021. 6:106â119.Broad geographical disparity in the contribution of HIV to the burden of cervical cancerThis systematic review and meta-analysis estimated the contribution of HIV to the global and regional burden of cervical cancer using data from 24 studies which included 236â127 women with HIV. HIV markedly increased the risk of cervical cancer (pooled relative risk how can i buy zithromax 6.07.

95%âCI 4.40 to 8.37). In 2018, 4.9% (95% CI 3.6% to 6.4%) of cervical cancers were how can i buy zithromax attributable to HIV globally, although the population-attributable fraction for HIV varied geographically, reaching 21% (95% CI 15.6% to 26.8%) in the African region. Cervical cancer is preventable and treatable. Efforts are needed to expand access how can i buy zithromax to HPV vaccination in sub-Saharan Africa. More immediately, there is an urgent need to integrate cervical cancer screening within HIV services.Stelzle D, Tanaka LF, Lee KK, et al.

Estimates of the global burden of cervical cancer associated with how can i buy zithromax HIV. Lancet Glob Health. 2020. 9:e161â69.The complex relationship between serum vitamin D and persistence of high-risk human papilloma zithromax Most cervical high-risk human papilloma zithromax (hrHPV) s are transient and those that persist are more likely to progress to cancer. Based on the proposed immunomodulatory properties of vitamin D, a longitudinal study examined the association between serum concentrations of five vitamin D biomarkers and short-term persistent (vs transient or sporadic) detection of hrHPV in 72 women who collected monthly cervicovaginal swabs over 6 months.

No significant associations were detected in the primary analysis. In sensitivity analyses, after multiple adjustments, serum concentrations of multiple vitamin D biomarkers were positively associated with the short-term persistence of 14 selected hrHPV types. The relationship between vitamin D and hrHPV warrants closer examination. Studies should have longer follow-up, include populations with more diverse vitamin D concentrations and account for vitamin D supplementation.Troja C, Hoofnagle AN, Szpiro A, et al. Understanding the role of emerging vitamin D biomarkers on short-term persistence of high-risk HPV among mid-adult women.

Those with spontaneous clearance were less likely to have concurrent chlamydia (p=0.029) and dysuria (p=0.035), but there were no differences in age, gender, sexual orientation, HIV status, number of previous NG episodes, and symptoms other than dysuria between those with and without clearance. Given the high rate of spontaneous resolution, point-of-care NG testing should be considered to reduce unnecessary antibiotic treatment.Mensforth S, Ayinde OC, Ross J. Spontaneous clearance of genital and extragenital Neisseria gonorrhoeae. Data from GToG. STI 2020.

96:556â561.BackgroundReproductive aged women are at risk of both pregnancy and sexually transmitted s (STI). The modern contraceptive prevalence among married and unmarried women in South Africa is 54% and 64%, respectively, with injectable progestins being most widely used.1 Moreover, current global efforts aim towards all women having access to a range of reliable contraceptives options.2 The prevalences of chlamydia and gonorrhoea are high among women in Africa, particularly among younger women. A recent meta-analysis of over 37â000 women estimated prevalences for chlamydia and gonorrhoea by region and population type (South Africa clinic/community-based, Eastern Africa higher-risk and Southern/Eastern Africa clinic community-based). High chlamydia and gonorrhoea prevalences were found among 15â24âyear-old South African women and high risk populations in East Africa.3 Both chlamydia and gonorrhoea are associated with numerous comorbidities including pelvic inflammatory disease (PID), ectopic pregnancy, infertility, increased risk of HIV and other STIs, as well as significant social harm.4While STIs are a significant global health burden, data on STI prevalence by gender and drivers of are limited, hindering an effective public health response.5 Moreover, data on the association between contraceptive use and risk of non-HIV STIs are limited. The WHO recently reported stagnation in efforts to decrease global STI incidence.5 Understanding drivers of STI acquisition, including any possible associations with widely used contraceptive methods, is necessary to effectively target public health responses that reduce STI incidence and associated comorbidities.The ECHO Trial (ClinicalTrials.gov Identifier.

NCT02550067) was a multicentre, open-label randomised trial of 7829 HIV-seronegative women seeking effective contraception in Eswatini, Kenya, South Africa and Zambia. Detailed trial methods and results have been published.6 7 We conducted a secondary analysis of ECHO trial data to evaluate absolute and relative chlamydia and gonorrhoea final visit prevalences among women randomised to intramuscular depot medroxyprogesterone acetate (DMPA-IM), a copper intrauterine device (IUD) and a levonorgestrel (LNG) implant.MethodsStudy design, participants and ethicsWomen were enrolled in the ECHO trial from December 2015 through September 2017. Institutional review boards at each site approved the study protocol and women provided written informed consent before any study procedures. In brief, women who were not pregnant, HIV-seronegative, aged 16â35 years, seeking effective contraception, without medical contraindications, willing to use the assigned method for 18 months, reported not using injectable, intrauterine or implantable contraception for the previous 6 months and reported being sexually active, were enrolled. At every visit, participants received HIV risk reduction counselling, HIV testing and STI management, condoms and, as it became a part of national standard of care, HIV pre-exposure prophylaxis.

Women returned for follow-up visits at 1âmonth after enrolment to address initial contraceptive side-effects and every 3 months thereafter, for up to 18 months with later enrolling participants contributing 12 to 18 months of follow-up. Visits included HIV serological testing, contraceptive counselling, syndromic STI management and safety monitoring.STI outcomesThe primary outcomes of this secondary analysis were prevalent chlamydia and gonorrhoea at the final visit. Syndromic STI management was provided at screening and all follow-up visits. Nucleic acid amplification testing (NAAT) for Chlamydia trachomatis and Neisseria gonorrhoeae was conducted at screening and final visits, at the visit of HIV detection for participants who became HIV infected and at clinical discretion. Any untreated participants with positive NAAT results were contacted to return to the study clinic for treatment.CovariatesAt baseline (inclusive of screening and enrolment visits), we collected demographic, sexual and reproductive risk behaviour and reproductive and contraceptive history data.

Baseline risk factors evaluated as covariates included age, whether the participant earned her own income, chlamydia and gonorrhoea status, herpes simplex zithromax type 2 (HSV-2) sero-status and suspected PID. Final visit factors evaluated as covariates included number of sex partners in the past 3 months, number of new sex partners in the past 3 months, HIV serostatus, HSV-2 serostatus, condom use in the past 3 months, sex exchanged for money/gifts, sex during vaginal bleeding, follow-up time and number of pelvic examinations during follow-up. Age and HSV-2 serostatus were evaluated for effect measure modification.Statistical analysisWe conducted analyses using R V.3.5.3 (Vienna, Austria), and log-binomial regression to estimate chlamydia and gonorrhoea prevalences within each contraceptive group and pairwise prevalence ratios (PR) between each arm in as-randomised and consistent use analyses.In the as-randomised analysis, we analysed participants by the contraceptive method assigned at randomisation independent of method adherence. We estimated crude point prevalences by arm and study site and pairwise adjusted PRs.In the consistent use analysis, we only included women who initiated use of their randomised contraceptive method and maintained randomised method adherence throughout follow-up. We estimated crude point prevalences by arm and pairwise adjusted PRs, with evaluation of age and HSV-2 status first as potential effect measure modifiers, and all covariates above as potential confounders.

Study site and age were retained in the final model. Other covariates were retained if their inclusion in the base model led to a 10% change in the effect estimate through backwards selection.Supplementary analysesAdditional supporting analyses to assess postrandomisation potential sources of bias were conducted to inform interpretation of results. These include evaluation of recent sexual behaviour at enrolment, month 9 and the final visit. Cohort participation (ie, follow-up time, early discontinuation and timing of randomised method discontinuation) and health outcomes (ie, final visit HIV and HSV-2 status) and frequency and results of pelvic examinations by STI status, site and visit month by randomised arm.ResultsA total of 7829 women were randomly assigned as follows. 2609 to the DMPA-IM group, 2607 to the copper IUD group and 2613 to the LNG implant group (figure 1).

DMPA-IM, depot medroxy progesterone acetate. IUD, intrauterine device. LNG, levonorgestrel.Participant characteristicsBaseline characteristics were similar across groups (table 1). Nearly two-third of enrolled women (63%) were aged 24 and younger and 5768 (74%) of the study population resided in South Africa.View this table:Table 1 Participant baseline and final visit characteristicsThe duration of participation averaged 16 months with no differences between randomised groups (table 1). A total of 1468 (19%) women either did not receive their randomised method or discontinued use during follow-up.

Overall method continuation rates were high with minimal differences between randomised groups when measured by person-years.6 The proportion, however, of method non-adherence as defined in this analysis (ie, did not receive randomised method at baseline or discontinued randomised method at any point during follow-up), was greater in the DMPA-IM group (26%), followed by the copper IUD (18%) and LNG implant (12%) groups. Timing of discontinuation also differed across methods. During the first 6âmonths, method discontinuation was highest in the copper IUD group (7%) followed closely by DMPA-IM (6%) and LNG implant (4%) groups. Between 7 and 12 months of follow-up, it was highest in DMPA-IM group (15%), with equivalent proportions in the LNG implant (5%) and copper IUD (5%) groups.Point prevalences of chlamydia and gonorrhoea at baseline and final visitsIn total, 18% of women had chlamydia at baseline (figure 2A) and 15% at the final visit. Among women 24 years and younger, 22% and 20% had chlamydia at baseline and final visits, respectively.

Women aged 25â35 at baseline were less likely to have chlamydia at both baseline (12%) and final visits (8%) compared with younger women. Baseline chlamydia prevalence ranged from 5% in Zambia to 28% in the Western Cape, South Africa (figure 2B).Point prevalence (per 100 persons) of chlamydia and gonorrhoea at baseline and final visit by age category and study site region. Y-axis scale differs for chlamydia and gonorrhoea figures." data-icon-position data-hide-link-title="0">Figure 2 Point prevalence (per 100 persons) of chlamydia and gonorrhoea at baseline and final visit by age category and study site region. Y-axis scale differs for chlamydia and gonorrhoea figures.Among all women, 5% had gonorrhoea at baseline and the final visit (figure 2C). Women aged 24 and younger were more likely to have gonorrhoea compared with women aged 25 and older at both baseline (5% vs 4%, respectively) and the final visit (6% vs 3%, respectively).

Gonorrhoea prevalence did not significantly differ between DMPA-IM and LNG implant groups (PR. 0.79, 95%âCI (0.61 to 1.03)) or between copper IUD and LNG implant groups (PR. 1.18, 95%âCI (0.93 to 1.49)). Women in the DMPA-IM group had a significantly lower risk of gonorrhoea compared with women in the copper IUD group (PR. 0.67, 95%âCI (0.52 to 0.87)).

Results from as randomised and continuous use analyses did not differ. And again, neither age nor HSV-2 status modified the observed associations.Clinical assessment by randomised contraceptive methodTo assess the potential for outcome ascertainment bias, we evaluated the frequency of pelvic examinations and abdominal/pelvic pain and discharge by study arm. Women in the copper IUD group were generally more likely to receive a pelvic examination during follow-up as compared with women in the DMPA-IM and LNG implant groups (online supplemental appendix 1). Similarly, abdominal/pelvic pain on examination or abnormal discharge was observed most frequently in the copper IUD group. The number of pelvic examinations met the prespecified criteria for retention in the adjusted gonorrhoea model but not in the chlamydia model.Supplemental materialFrequency of syndromic symptoms and potential reAmong women who had chlamydia at baseline, 23% were also positive at the final visit (online supplemental appendix 2, figure 3A).

Nine per cent of gonorrhoea-positive women at baseline were also positive at the final visit (online supplemental appendix 2, figure 3B). Across both baseline and final visits, a minority of women with chlamydia or gonorrhoea presented with signs and/or symptoms. Among chlamydia-positive women, only 12% presented with either abnormal vaginal discharge and/or abdominal/pelvic pain at their test-positive visit (online supplemental appendix 2, figure 3C). Similarly, only 15% of gonorrhoea-positive women presented with abnormal vaginal discharge and/or abdominal/pelvic pain at their test-positive visit (online supplemental appendix 2, figure 3D).Potential re and symptoms among women with chlamydia or gonorrhoea. Data are pooled across the screening and final visits in figures (C) and (D).

Symptomatic is defined as presenting with abnormal vaginal discharge and/or abdominal/pelvic pain. Final visit is described as potential re because test of cure was not conducted following baseline diagnosis and treatment." data-icon-position data-hide-link-title="0">Figure 3 Potential re and symptoms among women with chlamydia or gonorrhoea. Data are pooled across the screening and final visits in figures (C) and (D). Symptomatic is defined as presenting with abnormal vaginal discharge and/or abdominal/pelvic pain. Final visit is described as potential re because test of cure was not conducted following baseline diagnosis and treatment.DiscussionWe observed differences in final prevalences of chlamydia and gonorrhoea by contraceptive group in both as-randomised and consistent-use analyses.

The DMPA-IM group had lower final visit chlamydia and gonorrhoea prevalences as compared with copper IUD and LNG implant groups, though only the DMPA-IM versus the copper IUD comparison of gonorrhoea and DMPA-IM versus LNG implant comparison of chlamydia reached statistical significance. These are novel findings that have not previously been reported to our knowledge and were determined in a randomised trial setting with high participant retention, robust biomarker testing and high randomised method adherence. Interestingly, the copper IUD group had higher gonorrhoea and lower chlamydia prevalence compared with the LNG implant group, though neither finding was statistically significant.Two recent systematic reviews of the association between contraceptives and STIs found inconsistent and insufficient evidence on the association between the contraceptive methods under study in ECHO and chlamydia and gonorrhoea.8 9 Neither systematic review identified any randomised studies or any direct comparative evidence for DMPA-IM, copper IUD and LNG implant, thus enabling a unique scientific contribution from this secondary trial analysis. Nonetheless, these findings should be interpreted in light of biological plausibility, as well as the design strengths and limitations of this analysis.The emerging science on the biological mechanisms underlying HIV susceptibility demonstrates the complex relationship between the infectious pathogen, the host innate and adaptive immune response and the interaction of both with the vaginal microbiome and other -omes. Data on these factors in relationship to chlamydia and gonorrhoea acquisition are much more limited but can be assumed to be equally complex.

Vaginal microbiome composition, including microbial metabolic by-products, have been shown to significantly modify risk of HIV acquisition and to vary with exogenous hormone exposure, menstrual cycle phase, ethnicity and geography.10â12 These same biological principles likely apply to chlamydia and gonorrhoea susceptibility. While DMPA-IM has been associated with decreased bacterial vaginosis (BV), initiation of the copper IUD has been associated with increased BV prevalence, and BV is associated with chlamydia and gonorrhoea acquisition.13 14 Moreover, Lactobacillus crispatus, which is less abundant in BV, has been shown to inhibit HeLa cell by Chlamydia trachomatis and inhibits growth of Neisseria gonorrhoeae in animal models.15 16 In addition, microbial community state types that are deficient in Lactobacillus crispatus and/or dominated by dysbiotic species are associated with inflammation, which is a driver of both STI and HIV susceptibility. Thus, while the exact mechanisms of chlamydia and gonorrhoea in the presence of exogenous hormones and varying host microbiomes are unknown, it is biologically plausible that these complex factors may result in differential susceptibility to chlamydia and gonorrhoea among DMPA-IM, copper IUD and LNG implant users.An alternative explanation for these findings may be postrandomisation differences in clinical care and/or sexual behaviour. Participants in the copper IUD arm were more likely to have pelvic examinations and more likely to have discharge compared with women in the DMPA-IM and LNG implant groups. While interim STI testing and/or treatment were not documented, women in the copper IUD arm may have been more likely to receive syndromic STI treatment during follow-up due to more examination and observed discharge.

More frequent STI treatment in the copper IUD group would theoretically lower the final visit point prevalence relative to women in the DMPA-IM and LNG implant arms, suggesting that the observed lower risk of STI in the DMPA-IM arm is not due to differential examination, testing and treatment. Differential sexual risk behaviour may also have influenced the results. As reported previously, women in the DMPA-IM group less frequently reported condomless sex and multiple partners than women in the other groups, and both DMPA-IM and LNG implant users less frequently reported new partners and sex during menses than copper IUD users.6 Statistical control of self-reported sexual risk behaviour in the consistent-use analysis may have been inadequate if self-reported sexual behaviour was inaccurately or insufficiently reported.A second alternative explanation may be differences in randomised method non-adherence, which was greater in the DMPA-IM group, compared with copper IUD and LNG implant groups. Yet, the consistency of findings in the as-randomised and continuous use analyses suggests that method non-adherence had minimal effect on study outcomes. Taken as a whole, these findings indicate that there may be real differences in chlamydia and gonorrhoea risk associated with use of DMPA-IM, the copper IUD and LNG implant.

Strengths include the randomised design with comparator groups of equal STI baseline risk. Participants had high adherence to their randomised contraceptive method.6 While all participants received standardised clinical care and counselling, the unblinded randomisation may have allowed postrandomisation differences in STI risk over time by method. It is possible that participants modified their risk-taking behaviour based on study counselling messages regarding the potential association between DMPA-IM and HIV.In conclusion, our analyses suggest that DMPA-IM users may have lower risk of chlamydia and gonorrhoea compared with LNG implant and copper IUD users, respectively. Further investigation is warranted to better understand the mechanisms of chlamydia and gonorrhoea susceptibility in the context of contraceptive use. Moreover, the high chlamydia and gonorrhoea prevalences in this population, independent of contraceptive method, warrants urgent attention.Key messagesThe prevalence of chlamydia and gonorrhoea varied by contraceptive method in this randomised trial.High chlamydia and gonorrhoea prevalences, despite intensive counselling and condom provision, warrants attention, particularly among young women in South Africa and Eswatini.Most chlamydia and gonorrhoea s were asymptomatic.

Therefore, routine access to reliable diagnostics are needed to effectively manage and prevent STIs in African women..