Double Post- Sorry...beware of IUDs

I know I just posted but I just recalled another extremely interesting thing I learned.

I worked as a clinical researcher for the CU School of Medicine in the Division of Rheumatology. As many people know, women get Rheumatoid Arthritis (and autoimmune diseases) more than men, so one of the research studies in the division was looking at women specifically. The studies generally college self-reported information on diet, health history, family history, and other general data points. On top of the paperwork, we'd collect blood (to test for antibodies), sputum (also to check for antibodies...long story, but ~50% of RA patients also have lung disease so it's almost standard to always consider the lungs as a factor), vaginal + cervical fluids, and sometimes stool (to also test for antibodies and the bacteria).

Some of you may already know, but most of the people who develop RA (and other autoimmunity) are usually pretty young. Most of the people in our studies who had RA were often young women. The PI of this study essentially came to the conclusion that IUDs played a significant role in the development of RA!

Netflix Documentary, "The Bleeding Edge"

I recently watched this documentary called, "The Bleeding Edge". It was about faulty medical devices and how these devices were able to land on the market. One interesting example it showed was hip replacements.

Currently, one of the options for hip replacements is to use cobalt. It was advertised to be the most effective and longest-lasting material to use. The person who has advocating to educate surgeons to NOT use cobalt was a surgeon himself; he got a cobalt hip replacement and suffered neurological consequences. He was starting to have Alzheimer's/Dementia-like symptoms and had a severe mental relapse.

He later discovered that the cobalt used for his hip replacement was seeping into his blood and he had 100x the normal amount of cobalt in his blood. His health improved after removing the cobalt hip.

He did studies on his own patients (he was an orthopedic surgeon) and did scans of the brains of his patients and saw that patients with cobalt hips had scans that are similar to Alzheimer's patients.

It was interesting to learn that the FDA regulates both drugs and medical devices but the latter has been much more profitable and often times much more dangerous.

Possible Hangover Cure?

I am sure that most of us have, at one point, experienced a hangover. If you are lucky enough to have never experienced one, congratulations. However, if you have, you might have tried countless different ways that are supposedly “hangover cures.” With the search to find the “miracle pill” to cure all symptoms of a hangover, there have been some research that has tested multiple ideas. One, specifically, was done in 2016 by Chinese researchers who studied 57 different herbal and carbonated drinks and the impact they had on the enzymes that break down acetaldehyde and acetate.

If you are unaware, when you drink alcohol, an enzyme called alcohol dehydrogenase metabolizes the ethanol (alcohol) into acetaldehyde, which is then metabolized into acetate by aldehyde dehydrogenase (ALDH) in the liver. The more acetaldehyde in the system from too much drinking causes the terrible symptoms of “the hangover” such as nausea, dry mouth, headaches and dizziness.

The study observed how Sprite/7-up, which contains taurine (helps metabolize fats), showed the greatest increased ALDH activity, causing less acetaldehyde in the system. However, tea products such as green tea ended up prohibiting the metabolism of alcohol. So if you plan on going out, try drinking some Sprite to see if the research holds up to you.

Diclofenac, a common anti-inflammatory, may raise cardiovascular risk

Vioxx, a COX-2 inhibitor used as an anti-inflammatory and a painkiller was withdrawn from US markets in 2004 because of known cardiovascular risks—those who took it suffered blood clots and strokes, even though it was effective for pain reduction. This week, a study published in the British Medical Journal indicates that another common anti-inflammatory, diclofenac (also known by the brand name Voltaren) may cause similar problems. Diclofenac is also a selective COX-2 inhibitor, and is the most commonly used NSAID around the world, as it is commonly available over-the-counter in most countries. The authors of the study used the data of 6 million Danish adults over two decades (1996-2016) to create virtual trials in which they compared the 12-month health outcomes of patients who started taking diclofenac for pain as compared to those who took acetaminophen (Tylenol), naproxen (Aleve), and those who took nothing at all. The adults taking diclofenac were 50 percent more likely to have a cardiac event within a month than those who took no pain medication. They were also at a higher risk than those who took the other pain medications.

The authors suggest that this may be because diclofenac is prescribed at relatively high doses to be effective for pain since it has such a short half-life. The concentration of diclofenac in the plasma after high doses therefore exceeds the amount needed to inhibit COX-2 and so ends up inhibiting COX-1 as well. After the concentration of diclofenac decreases, the COX-1 effect subsides while the COX-2 inhibition continues. This selective inhibition of COX-2 leads to blood clots by inhibiting prostacyclin (clotting inhibitor) production without affecting thromboxane (clotting promoter) production. The researchers recommend that diclofenac only be prescribed by physicians (rather than being available OTC) and that providers consider the danger of increased clotting on a patient-by-patient basis to avoid unnecessary risk.

Steroid-induced ischemic necrosis in the hip: a frequent problem in physiatry

Before I came to study at Regis, I worked for approximately two years at physiatry clinic in Boulder. Some of our most popular treatments were corticosteroid injections into joint spaces and bursae, which can be very effective in the short term for pain and inflammation—we usually expected the results to last between 3-6 months without other treatment (for this reason, a steroid injection was usually followed with a referral to physical therapy for maximum benefit). I saw this treatment used for everything from carpal tunnel to trigger finger to “frozen” shoulders, often with good effect.

However, one use of the steroid injections the doctors were reluctant to use too frequently was in the case of hip joint pain caused by osteoarthritis in the hip. Technically, intra-articular hip joint steroid injections can be effective for arthritic hip pain when a patient is trying to postpone a replacement, but a rare side effect of a steroid injection there is avascular necrosis of the femoral head: complete bone death and sometimes collapse of the femoral head (visible on x-ray). In the time I worked there, I saw this twice, and both patients were subsequently referred out for hip replacements.

Above: Stages of SI-IBN-caused collapse in the hip (source) 

The mechanism behind steroid-induced ischemic bone necrosis (SI-IBN) is not well-understood. A 2014 review by Xie et al hypothesizes that the administration of steroids reduces bloodflow directly, or that it causes an increase in fat deposition resulting in higher pressure on the joint and compression of blood vessels. Steroids are the second most common cause of ischemic bone necrosis after trauma, but it is difficult to predict which patients are at risk simply from their x-rays. A 2009 study in rabbits showed that a functional perfusion MRI (a type of imaging that shows the amount of blood a particular joint is getting) could detect ischemia in bones before necrosis sets in, potentially allowing providers to monitor patients after high-dose steroid administration and to intervene before collapse. 

Providers can minimize the risk of SI-IBN by administering steroids by a low-dose oral route and advising patients to avoid alcohol while taking the steroids and also to consider bedrest during medication but this does not completely remove the risk. Stage I and II SI-IBN hips can be treated with a core decompression or bone graft when the patient is trying to postpone a total hip arthroplasty. Joint replacements are also an option, especially if the patient is older and less active, but for younger, more active patients, the failure rate of a THA is much higher so it is generally advised that providers consider joint-preserving methods first.

Better Late Than Never: Study Demonstrates Starting Exercise in Middle Age Can Reverse the Cardiac Effects of Sedentary Aging

Sedentary aging is associated with numerous deleterious health consequences. For example, sedentary seniors demonstrate significant changes in cardiovascular function and are at increased risk for cardiovascular disease, particularly heart failure. However, a recent study published in the journal Circulation, demonstrates that middle aged individuals can reverse or reduce the risk of heart failure caused by decades of sedentary living by exercising. Researchers conducted a prospective, parallel group, randomized controlled trial, examining the effect of 2 years of supervised high-intensity exercise training on left ventricular (LV) stiffness (which is associated with heart failure). The study's participants were divided into two groups, with one following an aerobic exercise routine that progressed in intensity over the two years and another doing yoga, balance training and weight training three times a week, also for two years. The aerobic exercise group demonstrated an 18% improvement in their Vo₂ max (maximum oxygen intake) during exercise and a more than 25% improvement in "plasticity" in the left ventricular muscle of the heart while these benefits were not observed in the second group. These results indicate that the optimal dose of exercise (4-5x/week) at the right time (when the heart risk from a lifetime of sedentary behavior can be modified) can reverse decades of a sedentary lifestyle on the heart. This is good news for those who fear it might be too late in life to improve their fitness and reduce risk of disease.