Alzheimer’s Sex Differences May Not Be What They Appear
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Alzheimer’s Sex Differences May Not Be What They Appear
Women get Alzheimer’s at nearly twice the rate than men do, and deteriorate more rapidly after onset, too.
So… Why?
There are many potential things to look at, but four stand out for quick analysis:
- Chromosomes: women usually have XX chromosomes, to men’s usual XY. There are outliers to both groups, people with non-standard combinations of chromosomes, but not commonly enough to throw out the stats.
- Hormones: women usually have high estrogen and low testosterone, compared to men. Again there are outliers and this is a huge oversimplification that doesn’t even look at other sex hormones, but broadly speaking (which sounds vague, but is actually what is represented in epidemiological studies), it will be so.
- Anatomy: humans have some obvious sexual dimorphism (again, there are outliers, but again, not enough to throw out the stats); this seems least likely to be relevant (Alzheimer’s is probably not stored in the breasts, for examples), though average body composition (per muscle:fat ratio) could admittedly be a factor.
- Social/lifestyle: once again, #NotAllWomen etc, but broadly speaking, women and men often tend towards different social roles in some ways, and as we know, of course lifestyle can play a part in disease pathogenesis.
As a quick aside before we continue, if you’re curious about those outliers, then a wiki-walk into the fascinating world of intersex conditions, for example, could start here. But by and large, this won’t affect most people.
So… Which parts matter?
Back in 2018, Dr. Maria Teresa Ferretti et al. kicked up some rocks in this regard, looking not just at genes (as much research has focussed on) or amyloid-β (again, well-studied) but also at phenotypes and metabolic and social factors—bearing in mind that all three of those are heavily influenced by hormones. Noting, for example, that (we’ll quote directly here):
- Men and women with Alzheimer disease (AD) exhibit different cognitive and psychiatric symptoms, and women show faster cognitive decline after diagnosis of mild cognitive impairment (MCI) or AD dementia.
- Brain atrophy rates and patterns differ along the AD continuum between the sexes; in MCI, brain atrophy is faster in women than in men.
- The prevalence and effects of cerebrovascular, metabolic and socio-economic risk factors for AD are different between men and women.
See: Sex differences in Alzheimer disease—the gateway to precision medicine
So, have scientists controlled for each of those factors?
Mostly not! But they have found clues, anyway, while noting the limitations of the previous way of conducting studies. For example:
❝Women are more likely to develop Alzheimer’s disease and experience faster cognitive decline compared to their male counterparts. These sex differences should be accounted for when designing medications and conducting clinical trials❞
~ Dr. Feixiong Cheng
Read: Research finds sex differences in immune response and metabolism drive Alzheimer’s disease
Did you spot the clue?
It was “differences in immune response and metabolism”. These things are both influenced by (not outright regulated by, but strongly influenced by) sex hormones.
❝As [hormonal] sex influences both the immune system and metabolic process, our study aimed to identify how all of these individual factors influence one another to contribute to Alzheimer’s disease❞
~ Dr. Justin Lathia
Ignoring for a moment progesterone’s role in metabolism, estrogen is an immunostimulant and testosterone is an immunosuppressant. These thus both also have an effect in inflammation, which yes, includes neuroinflammation.
But wait a minute, shouldn’t that mean that women are more protected, not less?
It should! Except… Alzheimer’s is an age-related disease, and in the age-bracket that generally gets Alzheimer’s (again, there are outliers), menopause has been done and dusted for quite a while.
Which means, and this is critical: post-menopausal women not on HRT are essentially left without the immune boost usually directed by estrogen, while men of the same age will be ticking over with their physiology that (unlike that of the aforementioned women) was already adapted to function with negligible estrogen.
Specifically:
❝The metabolic consequences of estrogen decline during menopause accelerate neuropathology in women❞
~ Dr. Rasha Saleh
Critical idea to take away from all this:
Alzheimer’s research is going to be misleading if it doesn’t take into account sex differences, and not just that, but also specifically age-relevant sex differences—because that can flip the narrative. If we don’t take age into account, we could be left thinking estrogen is to blame, when in fact, it appears to be the opposite.
In the meantime, if you’re a woman of a certain age, you might talk with a doctor about whether HRT could be beneficial for you, if you haven’t already:
❝Women at genetic risk for AD (carrying at least one APOE e4 allele) seem to be particularly benefiting from MHT❞
(MHT = Menopausal Hormone Therapy; also commonly called HRT, which is the umbrella term for Hormone Replacement Therapies in general)
~ Dr. Herman Depypere
Source study: Menopause hormone therapy significantly alters pathophysiological biomarkers of Alzheimer’s disease
Pop-sci press release version: HRT could ward off Alzheimer’s among at-risk women
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Why do I need to take some medicines with food?
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Have you ever been instructed to take your medicine with food and wondered why? Perhaps you’ve wondered if you really need to?
There are varied reasons, and sometimes complex science and chemistry, behind why you may be advised to take a medicine with food.
To complicate matters, some similar medicines need to be taken differently. The antibiotic amoxicillin with clavulanic acid (sold as Amoxil Duo Forte), for example, is recommended to be taken with food, while amoxicillin alone (sold as Amoxil), can be taken with or without food.
Different brands of the same medicine may also have different recommendations when it comes to taking it with food.
Ron Lach/Pexels Food impacts drug absorption
Food can affect how fast and how much a drug is absorbed into the body in up to 40% of medicines taken orally.
When you have food in your stomach, the makeup of the digestive juices change. This includes things like the fluid volume, thickness, pH (which becomes less acidic with food), surface tension, movement and how much salt is in your bile. These changes can impair or enhance drug absorption.
Eating a meal also delays how fast the contents of the stomach move into the small intestine – this is known as gastric emptying. The small intestine has a large surface area and rich blood supply – and this is the primary site of drug absorption.
Eating a meal with medicine will delay its onset. Farhad/Pexels Eating a larger meal, or one with lots of fibre, delays gastric emptying more than a smaller meal. Sometimes, health professionals will advise you to take a medicine with food, to help your body absorb the drug more slowly.
But if a drug can be taken with or without food – such as paracetamol – and you want it to work faster, take it on an empty stomach.
Food can make medicines more tolerable
Have you ever taken a medicine on an empty stomach and felt nauseated soon after? Some medicines can cause stomach upsets.
Metformin, for example, is a drug that reduces blood glucose and treats type 2 diabetes and polycystic ovary syndrome. It commonly causes gastrointestinal symptoms, with one in four users affected. To combat these side effects, it is generally recommended to be taken with food.
The same advice is given for corticosteroids (such as prednisolone/prednisone) and certain antibiotics (such as doxycycline).
Taking some medicines with food makes them more tolerable and improves the chance you’ll take it for the duration it’s prescribed.
Can food make medicines safer?
Ibuprofen is one of the most widely used over-the-counter medicines, with around one in five Australians reporting use within a two-week period.
While effective for pain and inflammation, ibuprofen can impact the stomach by inhibiting protective prostaglandins, increasing the risk of bleeding, ulceration and perforation with long-term use.
But there isn’t enough research to show taking ibuprofen with food reduces this risk.
Prolonged use may also affect kidney function, particularly in those with pre-existing conditions or dehydration.
The Australian Medicines Handbook, which guides prescribers about medicine usage and dosage, advises taking ibuprofen (sold as Nurofen and Advil) with a glass of water – or with a meal if it upsets your stomach.
If it doesn’t upset your stomach, ibuprofen can be taken with water. Tbel Abuseridze/Unsplash A systematic review published in 2015 found food delays the transit of ibuprofen to the small intestine and absorption, which delays therapeutic effect and the time before pain relief. It also found taking short courses of ibuprofen without food reduced the need for additional doses.
To reduce the risk of ibuprofen causing damage to your stomach or kidneys, use the lowest effective dose for the shortest duration, stay hydrated and avoid taking other non-steroidal anti-inflammatory medicines at the same time.
For people who use ibuprofen for prolonged periods and are at higher risk of gastrointestinal side effects (such as people with a history of ulcers or older adults), your prescriber may start you on a proton pump inhibitor, a medicine that reduces stomach acid and protects the stomach lining.
How much food do you need?
When you need to take a medicine with food, how much is enough?
Sometimes a full glass of milk or a couple of crackers may be enough, for medicines such as prednisone/prednisolone.
However, most head-to-head studies that compare the effects of a medicine “with food” and without, usually use a heavy meal to define “with food”. So, a cracker may not be enough, particularly for those with a sensitive stomach. A more substantial meal that includes a mix of fat, protein and carbohydrates is generally advised.
Your health professional can advise you on which of your medicines need to be taken with food and how they interact with your digestive system.
Mary Bushell, Clinical Associate Professor in Pharmacy, University of Canberra
This article is republished from The Conversation under a Creative Commons license. Read the original article.
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Could ADHD drugs reduce the risk of early death? Unpacking the findings from a new Swedish study
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Attention-deficit hyperactivity disorder (ADHD) can have a considerable impact on the day-to-day functioning and overall wellbeing of people affected. It causes a variety of symptoms including difficulty focusing, impulsivity and hyperactivity.
For many, a diagnosis of ADHD, whether in childhood or adulthood, is life changing. It means finally having an explanation for these challenges, and opens up the opportunity for treatment, including medication.
Although ADHD medications can cause side effects, they generally improve symptoms for people with the disorder, and thereby can significantly boost quality of life.
Now a new study has found being treated for ADHD with medication reduces the risk of early death for people with the disorder. But what can we make of these findings?
A large study from Sweden
The study, published this week in JAMA (the prestigious journal of the American Medical Association), was a large cohort study of 148,578 people diagnosed with ADHD in Sweden. It included both adults and children.
In a cohort study, a group of people who share a common characteristic (in this case a diagnosis of ADHD) are followed over time to see how many develop a particular health outcome of interest (in this case the outcome was death).
For this study the researchers calculated the mortality rate over a two-year follow up period for those whose ADHD was treated with medication (a group of around 84,000 people) alongside those whose ADHD was not treated with medication (around 64,000 people). The team then determined if there were any differences between the two groups.
What did the results show?
The study found people who were diagnosed and treated for ADHD had a 19% reduced risk of death from any cause over the two years they were tracked, compared with those who were diagnosed but not treated.
In understanding this result, it’s important – and interesting – to look at the causes of death. The authors separately analysed deaths due to natural causes (physical medical conditions) and deaths due to unnatural causes (for example, unintentional injuries, suicide, or accidental poisonings).
The key result is that while no significant difference was seen between the two groups when examining natural causes of death, the authors found a significant difference for deaths due to unnatural causes.
So what’s going on?
Previous studies have suggested ADHD is associated with an increased risk of premature death from unnatural causes, such as injury and poisoning.
On a related note, earlier studies have also suggested taking ADHD medicines may reduce premature deaths. So while this is not the first study to suggest this association, the authors note previous studies addressing this link have generated mixed results and have had significant limitations.
In this new study, the authors suggest the reduction in deaths from unnatural causes could be because taking medication alleviates some of the ADHD symptoms responsible for poor outcomes – for example, improving impulse control and decision-making. They note this could reduce fatal accidents.
The authors cite a number of studies that support this hypothesis, including research showing ADHD medications may prevent the onset of mood, anxiety and substance use disorders, and lower the risk of accidents and criminality. All this could reasonably be expected to lower the rate of unnatural deaths.
Strengths and limitations
Scandinavian countries have well-maintained national registries that collect information on various aspects of citizens’ lives, including their health. This allows researchers to conduct excellent population-based studies.
Along with its robust study design and high-quality data, another strength of this study is its size. The large number of participants – almost 150,000 – gives us confidence the findings were not due to chance.
The fact this study examined both children and adults is another strength. Previous research relating to ADHD has often focused primarily on children.
One of the important limitations of this study acknowledged by the authors is that it was observational. Observational studies are where the researchers observe and analyse naturally occurring phenomena without intervening in the lives of the study participants (unlike randomised controlled trials).
The limitation in all observational research is the issue of confounding. This means we cannot be completely sure the differences between the two groups observed were not either partially or entirely due to some other factor apart from taking medication.
Specifically, it’s possible lifestyle factors or other ADHD treatments such as psychological counselling or social support may have influenced the mortality rates in the groups studied.
Another possible limitation is the relatively short follow-up period. What the results would show if participants were followed up for longer is an interesting question, and could be addressed in future research.
What are the implications?
Despite some limitations, this study adds to the evidence that diagnosis and treatment for ADHD can make a profound difference to people’s lives. As well as alleviating symptoms of the disorder, this study supports the idea ADHD medication reduces the risk of premature death.
Ultimately, this highlights the importance of diagnosing ADHD early so the appropriate treatment can be given. It also contributes to the body of evidence indicating the need to improve access to mental health care and support more broadly.
Hassan Vally, Associate Professor, Epidemiology, Deakin University
This article is republished from The Conversation under a Creative Commons license. Read the original article.
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Functional Exercise For Seniors – by James Atkinson
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A lot of exercises books are tailored to 20-year-old athletes training for their first Tough Mudder. Others, that the only thing standing between us and a perfect Retroflex Countersupine Divine Pretzel position is a professionally-lit Instagrammable photo.
This one’s not like that.
But! Nor does it think being over a certain age is a reason to not have genuinely robust health, of the kind that may make some younger people envious. So, it lays out, in progressive format, guidelines for exercises targeted at everything we need to build and maintain as we get older.
The writing style is clear, and the illustrations too (the cover art is the same style as the illustrations inside).
Bottom line: if you’re looking for a workout guide that understands you are nearer 80 than 18, and/but also doesn’t assume your age limits your exercise potential to “wrist exercises in chair”, then this book is a fine pick.
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Asparagus vs Eggplant – Which is Healthier?
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Our Verdict
When comparing asparagus to eggplant, we picked the asparagus.
Why?
In terms of macros, they’re very similar. Technically asparagus has twice the protein, but it’s at 2.2g/100g compared to eggplant’s 0.98g/100g, so it’s not too meaningful. They’re both mostly water, low in carbs, with a little fiber, and negligible fat (though eggplant technically has more fat, but again, these numbers are miniscule). For practical purposes, the two vegetables are even in this category, or if you really want decisive answers, a tiny margin of a win for asparagus.
In the category of vitamins, asparagus is much higher in vitamins A, B1, B2, B3, B5, B6, B9, E, & K, as well as choline. Eggplant is not higher in any vitamins. A clear win for asparagus.
When it comes to minerals, asparagus is much higher in calcium, copper, iron, phosphorus, selenium, and zinc, while eggplant is a little higher in manganese. Another easy win for asparagus.
Lastly, asparagus wins on polyphenols too, with its high quercetin content. Eggplant does contain some polyphenols, but in such tiny amounts that even added up they’re less than 7% of what asparagus has to offer in quercetin alone.
Obviously, enjoy both, though! Diversity is healthy.
Want to learn more?
You might like to read:
Fight Inflammation & Protect Your Brain, With Quercetin
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How Much Can Hypnotherapy Really Do?
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Sit Back, Relax, And…
In Tuesday’s newsletter, we asked you for your opinions of hypnotherapy, and got the above-depicted, below-described, set of responses:
- About 58% said “It is a good, evidenced-based practice that can help alleviate many conditions”
- Exactly 25% said “It is a scam and sham and/or wishful thinking at best, and should be avoided by all”
- About 13% said “It works only for those who are particularly suggestible—but it does work for them”
- One (1) person said “It is useful only for brain-centric conditions e.g. addictions, anxiety, phobias, etc”
So what does the science say?
Hypnotherapy is all in the patient’s head: True or False?
True! But guess which part of your body controls much of the rest of it.
So while hypnotherapy may be “all in the head”, its effects are not.
Since placebo effect, nocebo effect, and psychosomatic effect in general are well-documented, it’s quite safe to say at the very least that hypnotherapy thus “may be useful”.
Which prompts the question…
Hypnotherapy is just placebo: True or False?
False, probably. At the very least, if it’s placebo, it’s an unusually effective placebo.
And yes, even though testing against placebo is considered a good method of doing randomized controlled trials, some placebos are definitely better than others. If a placebo starts giving results much better than other placebos, is it still a placebo? Possibly a philosophical question whose answer may be rooted in semantics, but happily we do have a more useful answer…
Here’s an interesting paper which: a) begins its abstract with the strong, unequivocal statement “Hypnosis has proven clinical utility”, and b) goes on to examine the changes in neural activity during hypnosis:
Brain Activity and Functional Connectivity Associated with Hypnosis
It works only for the very suggestible: True or False?
False, broadly. As with any medical and/or therapeutic procedure, a patient’s expectations can affect the treatment outcome.
And, especially worthy of note, a patient’s level of engagement will vastly affect it treatment that has patient involvement. So for example, if a doctor prescribes a patient pills, which the patient does not think will work, so the patient takes them intermittently, because they’re slow to get the prescription refilled, etc, then surprise, the pills won’t get as good results (since they’re often not being taken).
How this plays out in hypnotherapy: because hypnotherapy is a guided process, part of its efficacy relies on the patient following instructions. If the hypnotherapist guides the patient’s mind, and internally the patient is just going “nope nope nope, what a lot of rubbish” then of course it will not work, just like if you ask for directions in the street and then ignore them, you won’t get to where you want to be.
For those who didn’t click on the above link by the way, you might want to go back and have a look at it, because it included groups of individuals with “high/low hypnotizability” per several ways of scoring such.
It works only for brain-centric things, e.g. addictions, anxieties, phobias, etc: True or False?
False—but it is better at those. Here for example is the UK’s Royal College of Psychiatrists’ information page, and if you go to “What conditions can hypnotherapy help to treat”, you’ll see two broad categories; the first is almost entirely brain-stuff; the second is more varied, and includes pain relief of various kinds, burn care, cancer treatment side effects, and even menopause symptoms. Finally, warts and other various skin conditions get their own (positive) mention, per “this is possible through the positive effects hypnosis has on the immune system”:
RCPsych | Hypnosis And Hypnotherapy
Wondering how much psychosomatic effect can do?
You might like this previous article; it’s not about hypnotherapy, but it is about the difference the mind can make on physical markers of aging:
Aging, Counterclockwise: When Age Is A Flexible Number
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What Would a Second Trump Presidency Look Like for Health Care?
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On the presidential campaign trail, former President Donald Trump is, once again, promising to repeal and replace the Affordable Care Act — a nebulous goal that became one of his administration’s splashiest policy failures.
“We’re going to fight for much better health care than Obamacare. Obamacare is a catastrophe,” Trump said at a campaign stop in Iowa on Jan. 6.
The perplexing revival of one of Trump’s most politically damaging crusades comes at a time when the Obama-era health law is even more popular and widely used than it was in 2017, when Trump and congressional Republicans proved unable to pass their own plan to replace it. That failed effort was a big part of why Republicans lost control of the House of Representatives in the 2018 midterms.
Despite repeated promises, Trump never presented his own Obamacare replacement. And much of what Trump’s administration actually accomplished in health care has been reversed by the Biden administration.
Still, Trump secured some significant policy changes that remain in place today, including efforts to bring more transparency to prices charged by hospitals and paid by health insurers.
Trying to predict Trump’s priorities in a second term is even more difficult given that he frequently changes his positions on issues, sometimes multiple times.
The Trump campaign did not respond to a request for comment.
Perhaps Trump’s biggest achievement is something he rarely talks about on the campaign trail. His administration’s “Operation Warp Speed” managed to create, test, and bring to market a covid-19 vaccine in less than a year, far faster than even the most optimistic predictions.
Many of Trump’s supporters, though, don’t support — and some even vehemently oppose — covid vaccines.
Here is a recap of Trump’s health care record:
Public Health
Trump’s pandemic response dominates his overall record on health care.
More than 400,000 Americans died from covid over Trump’s last year in office. His travel bans and other efforts to prevent the global spread of the virus were ineffective, his administration was slower than other countries’ governments to develop a diagnostic test, and he publicly clashed with his own government’s health officials over the response.
Ahead of the 2020 election, Trump resumed large rallies and other public campaign events that many public health experts regarded as reckless in the face of a highly contagious, deadly virus. He personally flouted public health guidance after contracting covid himself and ending up hospitalized.
At the same time, despite what many saw as a politicization of public health by the White House, Trump signed a massive covid relief bill (after first threatening to veto it). He also presided over some of the largest boosts for the National Institutes of Health’s budget since the turn of the century. And the mRNA-based vaccines Operation Warp Speed helped develop were an astounding scientific breakthrough credited with helping save millions of lives while laying the groundwork for future shots to fight other diseases including cancer.
Abortion
Trump’s biggest contribution to abortion policy was indirect: He appointed three Supreme Court justices, who were instrumental in overturning the constitutional right to an abortion.
During his 2024 campaign, Trump has been all over the place on the red-hot issue. Since the Supreme Court overturned Roe v. Wade in 2022, Trump has bemoaned the issue as politically bad for Republicans; criticized one of his rivals, Florida Gov. Ron DeSantis, for signing a six-week abortion ban; and vowed to broker a compromise with “both sides” on abortion, promising that “for the first time in 52 years, you’ll have an issue that we can put behind us.”
He has so far avoided spelling out how he’d do that, or whether he’d support a national abortion ban after any number of weeks.
More recently, however, Trump appears to have mended fences over his criticism of Florida’s six-week ban and more with key abortion opponents, whose support helped him get elected in 2016 — and whom he repaid with a long list of policy changes during his presidency.
Among the anti-abortion actions taken by the Trump administration were a reinstatement of the “Mexico City Policy” that bars giving federal funds to international organizations that support abortion rights; a regulation to bar Planned Parenthood and other organizations that provide abortions from the federal family planning program, Title X; regulatory changes designed to make it easier for health care providers and employers to decline to participate in activities that violate their religious and moral beliefs; and other changes that made it harder for NIH scientists to conduct research using fetal tissue from elective abortions.
All of those policies have since been overturned by the Biden administration.
Health Insurance
Unlike Trump’s policies on reproductive health, many of his administration’s moves related to health insurance still stand.
For example, in 2020, Trump signed into law the No Surprises Act, a bipartisan measure aimed at protecting patients from unexpected medical bills stemming from payment disputes between health care providers and insurers. The bill was included in the $900 billion covid relief package he opposed before signing, though Trump had expressed support for ending surprise medical bills.
His administration also pushed — over the vehement objections of health industry officials — price transparency regulations that require hospitals to post prices and insurers to provide estimated costs for procedures. Those requirements also remain in place, although hospitals in particular have been slow to comply.
Medicaid
While first-time candidate Trump vowed not to cut popular entitlement programs like Medicare, Medicaid, and Social Security, his administration did not stick to that promise. The Affordable Care Act repeal legislation Trump supported in 2017 would have imposed major cuts to Medicaid, and his Department of Health and Human Services later encouraged states to require Medicaid recipients to prove they work in order to receive health insurance.
Drug Prices
One of the issues the Trump administration was most active on was reducing the price of prescription drugs for consumers — a top priority for both Democratic and Republican voters. But many of those proposals were blocked by the courts.
One Trump-era plan that never took effect would have pegged the price of some expensive drugs covered by Medicare to prices in other countries. Another would have required drug companies to include prices in their television advertisements.
A regulation allowing states to import cheaper drugs from Canada did take effect, in November 2020. However, it took until January 2024 for the FDA, under Trump’s successor, to approve the first importation plan, from Florida. Canada has said it won’t allow exports that risk causing drug shortages in that country, leaving unclear whether the policy is workable.
Trump also signed into law measures allowing pharmacists to disclose to patients when the cash price of a drug is lower than the cost using their insurance. Previously pharmacists could be barred from doing so under their contracts with insurers and pharmacy benefit managers.
Veterans’ Health
Trump is credited by some advocates for overhauling Department of Veterans Affairs health care. However, while he did sign a major bill allowing veterans to obtain care outside VA facilities, White House officials also tried to scuttle passage of the spending needed to pay for the initiative.
Medical Freedom
Trump scored a big win for the libertarian wing of the Republican Party when he signed into law the “Right to Try Act,” intended to make it easier for patients with terminal diseases to access drugs or treatments not yet approved by the FDA.
But it is not clear how many patients have managed to obtain treatment using the law because it is aimed at the FDA, which has traditionally granted requests for “compassionate use” of not-yet-approved drugs anyway. The stumbling block, which the law does not address, is getting drug companies to release doses of medicines that are still being tested and may be in short supply.
Trump said in a Jan. 10 Fox News town hall that the law had “saved thousands and thousands” of lives. There’s no evidence for the claim.
KFF Health News is a national newsroom that produces in-depth journalism about health issues and is one of the core operating programs at KFF—an independent source of health policy research, polling, and journalism. Learn more about KFF.
Subscribe to KFF Health News’ free Morning Briefing.
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