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Thursday, April 2, 2020

Ranitidine (Zantac) recall expanded, many questions remain

Update: On April 1, 2020, the FDA requested manufacturers to withdraw all prescription and over-the-counter (OTC) ranitidine drugs (Zantac, others) from the market immediately, due to the presence of a contaminant known as N-Nitrosodimethylamine (NDMA). Although the FDA did not observe unacceptable levels of NDMA in many of the samples they tested, they have determined that the impurity in some ranitidine products increases over time and when stored at higher than room temperatures. As a result of this recall, ranitidine products will no longer be available for prescription or OTC use in the US.

The FDA is also advising consumers taking OTC ranitidine to stop taking this medication, including any unused ranitidine medication they may still have at home. Other FDA-approved OTC medications are available to treat heartburn. Patients taking prescription ranitidine should speak with their doctor about other treatment options before stopping the medicine.


As anticipated, recall of the popular heartburn medicine ranitidine (Zantac) has expanded. But we still have more questions than answers.

As I mentioned in my original blog post on this topic, the online pharmacy Valisure, which originally alerted the FDA to the issue, found what they called “extremely high levels” of the probable cancer-causing substance N-nitrosodimethylamine (NDMA) in ranitidine products.

The FDA has indicated that its own preliminary testing has detected low levels of NDMA in ranitidine.

Testing methods may have influenced NMDA results

The FDA has clarified that the testing method that found the “extremely high levels” of NDMA applied high heat, at a level much higher than normal body temperature. In other words, the testing did not reflect typical conditions under which the medication would be stored or taken.

The FDA is asking all companies that manufacture ranitidine, as well as other similar medications (both H2 blockers, the class of drugs to which ranitidine belongs, and proton-pump inhibitors, or PPIs, a different class of drugs used for similar conditions), to test their products using lower heat closer to normal body temperature. So far, there is no indication that these other products are affected; the FDA is likely asking for these tests only as a precaution.

As of now, the FDA has allowed ranitidine to remain on the market. Still, some manufacturers have issued voluntary recalls and some pharmacies have pulled it off the shelves.

FDA estimates ranitidine NMDA risk with other medications

The FDA has not yet released the results of its own tests of ranitidine. But they previously estimated the likely impact of NDMA found in another class of medications, called angiotensin receptor blockers, on the risk of cancer. That estimate provides some context for the current circumstances.

Angiotensin receptor blockers, including the drug valsartan (Diovan), are used to treat high blood pressure and other heart conditions. They were recalled beginning last year due to the presence of NDMA and other related impurities. The FDA estimated that, if 8,000 people took the highest dose of valsartan containing NDMA every day for four years, there would be one additional case of cancer over the lifetimes of these 8,000 people.

Currently, we do not know how the amount of NDMA found in ranitidine compares to the amount found in valsartan.

Until we know more, the best course of action if you are taking ranitidine is to talk to your doctor about whether treatment is still needed. For some conditions, the benefits likely outweigh the risks. Although some ranitidine products remain available, consider alternative medications such as cimetidine (Tagamet) or famotidine (Pepcid) if you need long-term treatment.

Follow me on Twitter @JoshuaJGagne

The post Ranitidine (Zantac) recall expanded, many questions remain appeared first on Harvard Health Blog.

Wednesday, April 1, 2020

Covid-19 Update: Lifestyle changes caused by covid-19 result in more healthy behaviors; patient says she's happy with new telehealth visit


As news develops in Kentucky about the coronavirus and its covid-19 disease, this item will be updated. Official state guidance is at https://kycovid19.ky.gov.
  • "Among those lucky enough to have access to food and safe housing, and not be sickened by covid-19, there are indicators that the pandemic itself, and the massive shutdown it has triggered, is forcing the adoption of more-healthful behaviors,"Dr. Daphne Miller, a family physician and author, writes for The Washington Post. To support this claim she writes that  many are exercising more, spending more time nature, eating out less and cooking from scratch at home, mental health apps are showing a dramatic increase in downloads, and a slowing of manufacturing and vehicles off the roads and airplanes out of the sky have resulted in air pollutants and gas emissions plummeting. 
  • Blood donation centers across the nation are ramping up their efforts to collect plasma from people who have recovered from covid-19 in hopes it can be used to save the lives of others infected with the virus, JoNel Aleccia reports for Kaiser Health News. "The treatment is not a sure thing," she writes, adding that studies show injecting the plasma from those who have recovered into those who are still suffering has had some success in reducing symptoms and death in past outbreaks, but has not been proven to be effective in clinical trials.
  • Betty Nunn, a patient at Norton HealthCare in Louisville, tells Deborah Yetter with the Louisville Courier Journal that she was very happy with her decision to do a  telehealth visit, which she did through an app on her phone. "I was really happy with it," she said. "I would do it again." This sentiment comes as Kentucky primary care providers and behavioral health providers transition to caring for their patients through telehealth during the covid-19 outbreak. 

COVID-19: If you’re older and have chronic health problems, read this

By now, you’ve probably heard this warning about the new coronavirus pandemic: those who are older and have a chronic medical condition are at increased risk for severe disease and death. If you fall into this category, here’s important information about the coronavirus outbreak tailored to you.

If you look at the data, older adults and those with chronic health problems who get COVID-19 are more likely to require hospitalization and admission to an intensive care unit. And so far in the US, 80% of the deaths from the new coronavirus virus have occurred in people who were older.

But this raises a number of questions:

  • What do they mean by “older”?
  • Which chronic diseases are most important?
  • Why does older age and chronic disease increase your risk?
  • What are you (or your loved ones) supposed to do if you’re at increased risk?

“Older” is more than a number

When it comes to coronavirus, the CDC’s magic number is now set at 65. That’s the age at which risk of severe disease, complications, and death from COVID-19 appears to rise. But while risk does rise with age, infants, children and adults under age 65 have become infected in significant numbers, and some have severe disease, so everyone needs to take precautions.

Which chronic diseases put people at higher risk from COVID-19?

What do health experts mean when they talk about chronic diseases that put some people at increased risk of severe disease with COVID-19? It varies, but generally includes people who have

  • heart disease
  • high blood pressure
  • diabetes
  • asthma or other chronic lung diseases
  • HIV
  • a suppressed immune system due to a disease or a treatment

Within these groups, there is much uncertainty. For example, if you had cancer years ago but are now in remission, are you at increased risk? What if your diabetes is mild and well controlled?

Why do older age and chronic disease increase risk for severe illness if a person gets COVID-19?

It’s not entirely clear, but here are some possibilities:

  • An immune system weakened by age or illness is unable to fight off the virus, which could lead to an overwhelming infection.
  • The immune system “misfires” or has an exaggerated response in some people, triggering so much inflammation and tissue damage that the immune reaction itself causes complications.
  • Organ damage due to existing or past illness might make additional damage caused by the virus more than a person can handle; one example is smoking-related lung disease complicated by respiratory infection from the new coronavirus.
  • The stress of a viral infection can increase demand on already damaged or aging organs (such as the heart).
  • Medications taken to treat chronic conditions could increase the severity of infection. One suggestion (unproven so far) is that a family of medicines called ACE inhibitors allows more viral organisms to enter cells. ACE inhibitors are commonly taken by people with diabetes and hypertension, perhaps explaining why these conditions are linked to more severe disease.

We need more research to understand whether one or more of these is most important, or whether there are other factors at play.

What are you or your loved ones supposed to do to lower your risk?

While there is no way to completely eliminate risk, it makes sense to:

  • Carefully follow the recommendations of health experts that apply to everyone, regardless of age or other risk factors, including:
    • Frequent handwashing (reminding others around you, also) and avoiding touching your face as much as possible
    • Social distancing (six feet of distance between you and anyone you don’t live with daily)
    • Avoid “emotional distancing” by using phones and apps to stay connected (some grandchildren or children can provide tech support by phone)
    • Wipe down “high-touch” areas of your home with approved household disinfectants
    • Stay home as much as possible
    • Avoid anyone who you know is sick
  • Be especially attentive to managing your medical conditions
    • Take your medications exactly as prescribed
    • If possible, keep a 90-day supply of your medications on hand
    • Monitor your condition frequently (for example, talk to your doctor about home blood pressure monitoring, home blood sugar checks, or tests of lung function you can do at home)
    • Don’t smoke!
  • Make sure your routine medical and nutritional needs are met by keeping adequate health supplies (such as a thermometer, acetaminophen, and a first-aid kit) and several weeks’ supply of nonperishable foods on hand.
  • Maintain connections to family, friends, and your doctors so you don’t feel isolated.
    • Talk early and often about your medical or other needs with friends and family by phone or online.
    • Socialize! Whether by phone or online, connect with friends and family to commiserate, discuss current events, or play games.
    • Arrange to have someone check in on you regularly by phone, online, or in person.
    • Keep a “who-to-call” list on your refrigerator with phone number of close family members, caretakers, doctors, pharmacy, and the local board of health.
    • Give a set of keys to your home to a neighbor that you or your family members can call in case of emergency.

The bottom line

Much of what is recommended for older adults with chronic medical conditions is the same as what would be recommended even without the pandemic.

Yet there are still lots of things you can do to keep busy, maintain morale, and keep from going stir crazy. Get outside and go for walks. Call friends and family you’ve been meaning to call before this outbreak. Write that novel or haiku or letter to the editor you’ve been thinking about.

These are unusual times. Hearing that you’re at increased risk of severe illness from a rapidly spreading and potentially serious virus is frightening to say the least. One way to manage the fear and uncertainty is to take action: be prepared, take the advice of experts, and keep a positive attitude. That’s about the best you can do.

Follow me on Twitter @RobShmerling

For more information, listen to our podcasts and see our Coronavirus Resource Center.

The post COVID-19: If you’re older and have chronic health problems, read this appeared first on Harvard Health Blog.

Older adults and medical marijuana: Reduced stigma and increased use

As a primary care doctor who has incorporated medical cannabis into his practice, it is notable how many silver-haired patients are coming in to discuss the pros and cons of a trial of medical cannabis. These patients range from people in their 60s with kidney failure who can no longer take certain pain medications but still need to manage chronic pain, to patients in their 90s, who are looking for a good night’s sleep and are leery of the side effects of traditional sleep medications. Some of them — typically “children of the 60s” — are quite comfortable with the idea of using medical marijuana; others bring it up quietly, as if they are asking permission to break the law.

According to a recent study in the Journal of the American Medical Association, cannabis use among older adults (defined as 65 and older) in the US has been steadily increasing. In this study, the prevalence of past-year use increased from 2.4% to 4.2% from 2015 to 2018. This study is consistent with other research, as well as with reports from physicians who recommend cannabis in their daily practices.

What might be behind this trend?

A confluence of factors seems to be responsible, including the decrease in stigma associated with cannabis use and the increased interest in the use of medical marijuana by older patients. Stigma is a complicated issue, but most would agree that the stigma associated with cannabis use is lessening, especially for medical cannabis. In a recent poll, 94% of Americans voiced support for legal access to medical marijuana, and most states have approved some form of legal access.

One marker for the decrease in stigma is the recent statement by the 38 million-member AARP, in which they declared their support for the medical use of marijuana for older adults in states that have legalized it, in close consultation with their medical providers, where they can discuss the most up-to-date clinical evidence, weighing the balance of benefits and harms.

What conditions are older adults using cannabis for?

Studies show that older adults commonly use medical cannabis for the same conditions younger patients do: pain, insomnia, neuropathy, and anxiety.

What are the risks for older people using medical cannabis?

This is new territory, as either there haven’t been large numbers of older adults who report using medical cannabis, or if they have been using it they have kept it quiet, due to its illegality and due to the stigma. Medical cannabis is typically well tolerated among older adults; however, as with all medications, there is no such thing as a free lunch, meaning that there are always side effects and downsides to consider.

Cardiac health and cannabis use

Cannabis is known to increase heart rate and can increase blood pressure, though there doesn’t seem to be much if any quality evidence directly linking cannabis use with coronary events, according to a recent review by the Journal of the American College of Cardiology. Still, the authors of this review do recommend screening people with coronary disease for cannabis use. The scenario that I would be most concerned about is an older patient, with underlying coronary disease, taking a very high dosage of cannabis (perhaps by mistake via edibles) and then having an anxiety attack, which could trigger a coronary syndrome or an arrhythmia.

Medication interactions

Older people tend to have comorbid health conditions and may be taking multiple medications. Cannabis has about 600 chemicals in it, and in theory, the two main active ingredients in cannabis, THC and CBD, could either increase or decrease the blood levels of other drugs you are taking, by affecting the enzymes in your liver that help metabolize your medications. CBD, in particular, is at risk for increasing the other drugs in your system by “competitively inhibiting” (or, in plain English, using at the same time) the molecules that you need to break down and clear these medications from your body.

People should be particularly cautious using cannabis with anti-seizure medications and with blood thinners, as these medications tend to have serious side effects and not as much room for error, and it is important that you always communicate with your medical providers about your cannabis use. Disclosing marijuana use is particularly important if you plan to have surgery, as the drugs used for anesthesia and post-surgical pain management may need to be adjusted.

Changes in thinking, both pro and con

The psychoactivity, or the high that cannabis causes, is another potential concern for older adults, especially those at risk for confusion and dementia. These days, with the ability to buy cannabis in medical dispensaries, there is more control over the types or strains of cannabis that one can buy and consume, and it is easier to avoid the high by controlling the dose and by keeping the THC content low. Strains that are low in THC (the chemical that causes the high) and higher in CBD, which is non-intoxicating, may be preferable to avoid the psychoactive experience of marijuana. Still, if an older person has experienced delirium, or any psychiatric conditions, they and their doctors should proceed with caution.

Interestingly, there is some research that cognitive functioning can actually improve when patients use medical cannabis, due to, among other things, improved sleep and pain control. It seems plausible that older patients might be using lower doses of pain and sleep medications, which can affect thinking, and they are combatting the negative effects of chronic pain and insomnia, which also have an effect on cognitive functioning. However, as with most things cannabis-related, this too needs further study to confirm and clarify.

What’s the bottom line?

Cannabis use among the elderly is growing as there is more public acceptance and reduced stigma. Medical cannabis is increasingly viewed as an effective option for managing insomnia and chronic pain. It’s key to have an informed discussion with your doctor to weigh the safety risks, especially if you have cardiac issues, are taking multiple medications, or have cognitive changes due to aging. Educate yourself (and your doctor) as much as possible about cannabis before starting to use it. Most of the adverse effects associated with cannabis usage are dose-related, so it is important to know the strength of the marijuana you are taking and to “start low and go slow”: start with the lowest effective dose and take your time working your way up to a dose that alleviates your symptoms with a minimum of side effects.

The post Older adults and medical marijuana: Reduced stigma and increased use appeared first on Harvard Health Blog.

Strong caveats are lacking as news stories trumpet preliminary COVID-19 research

For years medical researchers held off while scientists in other fields embraced online platforms for posting rough drafts of manuscripts, known as preprints.

Those websites accelerate basic science by allowing researchers to disseminate findings and get feedback on their work before submitting them to a traditional journal.

Some argue that such rapid data sharing is ideally suited for infectious disease outbreaks like the one we’re experiencing now.

However, the prospect of public access to unvetted work sparked worry about potential health scares and patients demanding unproven treatments. A BMJ editorial put it this way: “Can the need for speed be balanced with suitable safeguards to protect the public?”

We’re now finding out.

A medical preprint server called medRxiv (pronounced “med-archive”) went live last summer. It’s a partnership of BMJ (publisher of The BMJ), Yale University, and Cold Spring Harbor Laboratory.

MedRxiv has been flooded with COVID-19 research. As of Tuesday, the server hosted 799 preprints about the virus. A related site for biosciences, bioRxiv, had 237.

Predictably, those draft manuscripts have become fodder for news stories as journalists race to report any and all information about the virus.

“Until COVID-19 there was no reason for the press to pay attention (to preprints) because they could count on the journals to curate what they felt was most important, most impactful,” said one of medRxiv’s founders, Joseph Ross, MD, a professor of medicine and public health at the Yale School of Medicine. “But now it’s chaotic. Science is moving really quickly and we’re all trying our best to understand things.”

Unfortunately, some news stories have cited preprints with little or no explanation of what they are and with no strong cautions about their uncertain quality. Unlike published journal articles, preprints haven’t been peer-reviewed by independent experts who might point out errors or weaknesses.

For example, Wired and Vice covered a preprint of a lab study that examined how long the virus lasts on different types of surfaces and in the air. The stories ran after a researcher Tweeted a link:

Both news stories said the data came from a preprint but did not define what a preprint is. Both of these publications target mainstream audiences that can’t be expected to be know what preprints are and how they fit into the research process. (Wired did caution that this was lab data that might not pan out in the real world, but Vice provided no such caveat.)

The medRxiv website was not much help, either. Days later the site stated that the preprint had been “published in The New England Journal of Medicine,” which might suggest that it had been peer-reviewed and published as an article. In fact, it ran as a letter to the editor.

More problematic were numerous sensational news stories based on a preprint claiming people with blood type A have “significantly higher risk for acquiring Covid-19”. Here are a few:

New York Post: People with blood type A might be more susceptible to coronavirus, study finds

Daily Mail: People with Type A blood are MORE likely to catch coronavirus than those with Type O, study claims

WVLT Knoxville: Study says your blood type could make you more susceptible to coronavirus

The coverage wasn’t void of cautions. The Post story called the study “preliminary” in the lead, and the Daily Mail story mentioned in the fifth paragraph that the research “has yet to be scrutinized by other academics in peer review.” The WVLT story stated at the end: “The study has not yet been peer-reviewed.”

But even if those caveats registered with readers, was this story — based on a single unvetted study — worth reporting at all? Even if proven true — which is far from certain — what difference would it make in testing and treatment?

In days that followed, other news organizations ran stories highlighting the study’s flaws. Some of WVLT’s fellow affiliates in the Cox Media Group ran “fact check” stories that offered more caveats, like one from WPXI Pittsburgh. Medical News Today quoted a researcher who said the results “might be purely coincidental. Importantly, people should not panic about these results, as, clearly, further scientific research is required to substantiate these claims.”

A ‘big red flag’

Steven Woloshin, MD, co-director of the Center for Medicine and Media at The Dartmouth Institute, said journalists should view preprints as “a big red flag” about the quality of evidence, similar to an animal study that doesn’t apply to humans or a clinical trial that lacks a control group.

“I’m not saying the public doesn’t have the right to know this stuff,” Woloshin said. “But these things are by definition preliminary. The bar should be really high” for reporting them.

In some cases, preprints have shown to be completely bogus. As FactCheck.org reported, a preprint suggesting that the new coronavirus might have been created in a lab was shared widely on Twitter and posted on conspiracy websites before it was taken down by bioRxiv.

Readers might not heed caveats about “early” or preliminary” evidence, Woloshin said. “The problem is, once it gets out into the public it’s dangerous because people will assume it’s true or reliable, and I don’t think that’s true.”

Woloshin suggested news organizations refrain from saying a preprint was “published,” which wrongly signals that a manuscript “must have gone through some sort of editorial review.”

Both the Wired story and a New York Times piece about potential drug treatments used the word “published.” By contrast, a STAT story assessing evidence on how long the virus can remain airborne reported that a preprint was “posted to” a preprint site. (The STAT story also took care to explain that the preprint had not been peer-reviewed.)

All data should be ‘scrutinized beyond belief’

Ivan Oransky, MD, vice president of editorial at Medscape and a Distinguished Writer in Residence at New York University’s Arthur Carter Journalism Institute, agreed that the public should be alerted about what preprints are. However, he said journalists should vet all COVID-19 research with equal vigor, whether it’s a preprint or a peer-reviewed journal article.

Oransky is a co-founder of the science blog Retraction Watch, which spotlights problematic journal articles. 

“To me the rules for reporting on preprints shouldn’t be any different from reporting on journal articles,” Oransky said. “I think everything needs to be scrutinized beyond belief.”

Arguably the most damaging COVID-19 hype so far sprung from a study that ran in a journal. The malaria medicine hydroxychloroquine, touted by President Trump as a potential “cure,” gained traction based in part on an shaky study of just 42 patients in France. 

The study’s authors concluded that the drug, when used in combination with an antibiotic, decreased patients’ levels of the virus. However, the findings were deemed unreliable due to numerous methodological flaws. Patients were not randomized, and six who received the treatment were inappropriately dropped from the study.

The findings made a news splash and led to drug hoarding and deaths as people self-medicated.

The paper appeared to have escaped editorial scrutiny, and it’s been noted that one of the co-authors is the editor-in-chief of the journal that published it.  One researcher complained on Twitter:

A call for extra diligence

Despite uneven editorial rigor, Woloshin said journal publication is “still an extra layer of scrutiny that just isn’t there with a preprint.” In sound peer review, analyses are questioned, assertions toned down, and hypotheses challenged, he said. “If they are good reviewers and editors, they make sure the researchers are up front about the limitations and caveats.”

Ross agreed journalists should use extra caution with preprints. 

“Preprints themselves are not directed toward the public and the media,” Ross said. “I think a journalist could argue we’re in the middle of a pandemic — that’s a good reason to write about preliminary work. But then they should do extra due diligence.”

That said, medRxiv has “tried to be careful and not just let anything go live,” said Ross.

According to its guidelines, submissions “undergo a basic screening process for offensive and/or non-scientific content and for material that might pose a health risk.” Editorials and case studies are not allowed. Submissions must be registered on a public database of clinical trials and comply with established transparency guidelines.

In addition, warnings on medRxiv and bioRxiv state that preprints “should not be reported in news media as established information.”

While we’ve criticized the promotion of unvetted study abstracts at scientific meetings, Ross believes preprints offer more transparency than those preliminary summaries because they are complete manuscripts. “You can really scrutinize the work in the way you can’t when it presented as an abstract at a conference,” he said.

But it’s still up to journalists to do that scrutiny, including reaching out to independent experts and checking to see whether other research concurs. Those steps aren’t always taken.

Institutions are touting their preprints

Editors and producers also might consider whether the public would truly benefit from knowing about a preprint now, before the scientific community has had a chance to kick the tires. One preprint that falls short of the mark is a preprint covered in Wired about the possible future use of gene-editing technology to fight viruses.

Strong editorial filters are needed as researchers and their institutions tout unvetted work.

Among those that have issued news releases about COVID-19 preprints are the University of Michigan and MIT. Both included prominent caveats about the preliminary nature of the findings.

In an email, Rick Fitzgerald, Michigan’s Assistant Vice President for Public Affairs, provided a rationale for publicizing a preprint about an analysis of containment measures: 

In this rapidly changing environment, we can be of greater service to society by getting the word out now, rather than always waiting for traditional peer review. We considered what potential harm could come if the results turned out to be erroneous and we believe the benefits of publicizing were enough to merit an earlier news release in this instance. The paper provides evidence that containment measures work, and if we were to wait six months for it to be peer-reviewed, we could lose opportunities for it to inform how we handle this current pandemic.

It’s anybody’s guess whether news organizations will continue to cover preprints after the current crisis abates. But for now, even the experts can’t make sense of them all.

“You can’t ignore them,” Anthony Fauci, MD, head of the U.S. National Institute of Allergy and Infectious Diseases, told Science magazine. But sometimes he said, “It gets a little confusing what you can really believe.”