written by reader Tidings, Mostly Glad

Stocking stuffers and some brief comments from Doc Gumshoe

By Michael Jorrin, "Doc Gumshoe", December 18, 2013

[ed note: We feature the musings of our favorite health and medicine writer, Michael Jorrin, a couple times a month, and we’ve taken the liberty of calling him “Doc Gumshoe” (he’s not a doctor). You’ll find no stock picks in his pieces, but hopefully will get plenty of insight into the medical matters he explains so well. Michael’s words and opinions are his own, and they always spur plenty of discussion. Enjoy!]

We’ll start off with some stocking stuffers and work up to a couple of major items. But don’t be surprised if there are a few lumps of coal along the way!

A few of these are not quite new, but I think they bear repeating:

Dark Chocolate May Lower Blood Pressure

You have probably already heard that dark chocolate is “good for you,” but here are some data to back it up. This comes from a small but well-conducted study, in Italy, naturally. Subjects, 20 in all, had untreated hypertension at least greater than 140/90 mm Hg. They had either 3.5 ounces of dark or while chocolate per day, every day for a week. Then they were off chocolate altogether for another week, and finally they switched to the other kind of chocolate for a third week – the people who had been taking dark chocolate switched to white, and vice-versa. The dark chocolate lowered systolic blood pressure by 12 mm Hg and diastolic blood pressure by 8.5 mm Hg. And dark chocolate also improved insulin sensitivity and lowered LDL cholesterol. White chocolate didn’t do a thing. The difference was attributed to the high level of flavonoids in dark chocolate; these are absent in white chocolate and nearly absent in milk chocolate.

Coffee May Protect Against Diabetes

Lots of studies have confirmed this, including a huge meta-analysis from the Harvard School of Public Health. The most persuasive was a trial in 910 adults with impaired glucose tolerance, which is a stage leading to definite type 2 diabetes. The study reported that both past and present drinkers of coffee with caffeine had about a 60% reduction in diabetes risk, compared with coffee teetotalers. There weren’t enough decaf drinkers in the study to come to any conclusions, but caffeine by itself doesn’t seem to be the answer. Is there something else in the coffee? Or are the coffee teetotalers doing something else to increase their risk of diabetes, such as knocking back a sugary soft drink? As we go through this “mostly glad tidings” piece, the question of what people do instead comes up again and again, as you’ll see. In fact, here’s one …

Diet Soda Is Associated with Higher Risk of Stroke?

There was a presentation at a meeting of the American Stroke Association with a highly counter-intuitive finding: that consumption of diet soda was associated with a markedly higher risk of stroke. Diet soda increases stroke risk? What next?

This was based on the ongoing Northern Manhattan Study (Columbia University, Division of Stroke and Critical Care), in which 2,564 subjects were categorized into seven cohorts based on soda consumption, ranging from no soda at all (meaning less than one soda per month), regular soda, cohorts consuming various combinations of regular and diet soda, and the cohort of daily diet soda drinkers. Subjects were followed for 9.3 years, during which 559 cerebrovascular events – i.e., either strokes or transient ischemic events (TIAs) – were recorded. After compensating for age, sex, race, and “lifestyle,” diet soda drinkers had a 61% higher risk of stroke than those who drank no diet soda. Adjusting for previous heart disease, peripheral vascular disease, and metabolic syndrome lowered this difference, but it was still 48% higher in subjects who drank diet soda than in those who drank no diet soda.

The study authors did not suggest that they had any basis for believing that the artificial sweeteners themselves contributed to stroke risk. The senior author, Ralph Sacco (president of the American Heart Association), theorized that some people might wash down a high-fat meal with a diet drink, or that they ease their guilt about eating a sweet dessert by drinking diet soda. Others have commented that, while diet soda may taste sweet, it does not provide a sense of satiety, leading users to seek other means of satisfying their cravings.

Another puzzling finding from the ASA meetings was that the incidence of stroke is rising alarmingly in a most unlikely population: young males, aged 15 to 34, in whom stroke incidence increased by 51% from 1994 to 2005. Stroke incidence also increased in young women, but only by about 17%. During the same period, stroke incidence actually decreased in older people – in whites over age 65, and in blacks over age 85.

I wonder if those two findings – that both diet soda drinkers and young males are at a higher risk of stroke – could be linked. Both could point to dietary choices that are the real culprits. Is diet soda a marker for an overall preference for junk food? No doubt explanatory theories will soon emerge.

Breast Cancer Survival Improves!

This is an unquestionably glad tiding. The Journal of Clinical Oncology published a study reporting that breast cancer survival in women aged from 20 – 49 has improved dramatically, at the rate of 2.4% per year. The smallest improvement was in women aged 75 and older – 1.1% per year. This was attributed in large part to a big difference in the rate of screening mammograms – 80% to 90% in women under 65, compared to only 50% in women over 75. This despite the recommendation by the US Preventive Services Task Force that women below the age of 50 do not need mammograms. To the USPSTF I say, here’s mud in your eye!

Saturated Fat May Not Be Quite as Evil as It’s Made Out to Be!

How much harm does saturated fat in our diet actually do? A huge meta-analysis of prospective epidemiological studies concluded that evidence for increased cardiovascular risk due to dietary saturated fat is exceedingly weak. The study analyzed 21 studies with 347,747 subjects, who were followed for 5 to 23 years. The risk for total coronary heart disease, fatal CHD events, or stroke was assessed for subjects consuming the highest versus the lowest amounts of dietary saturated fat. And the results were that for all CHD, subjects that consumed the most saturated fat had a 7% higher risk than those who consumed the least saturated fat. The hazard ratio was 1.07, but the 95% confidence interval was 0.96 to 1.19, meaning that there was a statistical chance that the risk could be anywhere between 4% lower to 19% higher. For stroke, the hazard ratio was 0.81 – or about 19% lower for subjects consuming the highest versus lowest amounts of saturated fat. The overall hazard ratio for all heart disease and stroke combined was 1.00 on the nose, suggesting that saturated fat consumption – in these studies, at any rate – made no difference at all.

The question not asked by that study is, what do people eat instead of saturated fat? And does that make any difference? A group of Danish scientists tried to answer that question. They found that substituting polyunsaturated fat (as in olive oil) for saturated fat does (slightly) reduce cardiovascular risk, but substituting mono-unsaturated fat has no benefit, and substituting transfats, as in margarine, is definitely worse. The big surprise is that substituting carbohydrates for the saturated fats in our diets is not beneficial, and may actually be harmful, particularly if the carbs are refined or have a high glycemic index (think high-fructose corn syrup). Possible consequences are thought to be mixed dyslipidemia (i.e., higher triglycerides and lower HDL-cholesterol), obesity, insulin resistance, and diabetes.

Do NSAIDs Increase Cardiovascular Risk or Not?

Considering that most of us take an NSAID from time to time, it would be nice to know whether they do or do not increase cardiovascular risk. We know that aspirin (a selective cox-1 inhibitor), tends to reduce the risk of stroke, and also probably the risk of heart attacks, because of its activity in reducing the tendency of blood to form clots. And we remember the bad news about increased CV risk with Vioxx (rofecoxib), a selective cox-2 inhibitor. But there has also been news trickling out over the past several years that the non-selective cox inhibitors, i.e., all the other NSAIDs, might also increase CV risk. So where are we?

Now, along comes a really huge study, conducted in Denmark, and based on the entire Danish population greater than 10 years of age – about 4.6 million. They found that more than half of these, about 2.7 million, had had at least one NSAID prescription in the past 8 years, and they weeded this population down to a little over a million, excluding individuals with established cardiovascular disease and other confounding comorbidities . What they found was that the ones who had taken either diclofenac (Voltaren) or rofecoxib (Vioxx) had a higher risk of cardiovascular death – nearly double for Voltaren and about 1.6 times higher for Vioxx – than individuals who had never taken an NSAID. These adverse events, by the way, were highly dose-related. On the other hand, the risk of CV events with ibuprofen (i.e., Advil, Motrin, etc.) was just a bit higher, and with naproxen (Naprosyn) it was actually lower.

How useful is this information, really? My guess is, not much. For one thing, Voltaren and Vioxx (for sure, Vioxx!) are not the drugs we take when our knees are aching. However, the crucial factor is; why were these individuals taking high doses of those drugs? Answer: because they were in pretty severe pain. You’re thinking, “well, that’s obvious.” But one of the adverse health consequences of musculoskeletal conditions like osteoarthritis is that it tends to limit patients’ capacity for exercise or even normal activity, which contributes significantly to cardiovascular risk. So maybe those Danes were more affected by their lack of exercise than by NSAIDs.

Will we ever know for sure? For now anyway, when I have aches and pains, I’ll reach for an NSAID.

Being A Bit Overweight Is Not So Terrible

Unless you want to be a fashion model, it might be that being overweight (i.e., BMI > 25 to 30) is not always and without exception a Bad Thing. The old familiar Goldilocks principle applies there as well. In a study in more than 9,000 patients aged 70 to 75, the lowest death rates for cardiovascular disease, cancer, and COPD, were in individuals with a BMI of about 27.5, which precisely in the middle of the “overweight” classification. Overall, the death rates in “overweight” subjects were about 13% lower than in those with “normal” BMIs. The highest risks were in underweight subjects of both sexes, and normal weight persons had approximately the same all-cause mortality hazard ratios as those who were over the “obese” marker – BMI greater than 30.0.
This certainly doesn’t mean that we should stuff ourselves with gigantic quantities of roast goose and flaming puddings over the holidays. And we should take note that the population in which that study was conducted was somewhat elderly, and sometimes underweight oldsters are a bit frail and don’t have much resistance when they get sick. But it does tell us that we should look at those vaunted BMI numbers with a skeptical eye.

Staying Alive

In baseball, “staying alive” means prolonging your time at bat by fouling off pitch after pitch, in the hope that you’ll eventually get a pitch you can wallop.

In treating a disease, it can mean something else. I know of no better example than the recently reported case of a man with refractory advanced chronic lymphocytic leukemia (CLL). He was not a candidate for a bone marrow transplant and was totally out of options. He was one of three patients who enrolled in a highly experimental clinical trial using genetically-modified T-cells to attack the malignant B-cells that cause CLL.

This was not a “last chance” trial; remission was not even an endpoint. The objective was to establish a safe dose; assessment of benefit was a secondary endpoint. However, two of the three patients in this trial have experienced complete remission; no evidence of leukemic cells was found in their blood, bone marrow, or lymph nodes one year after treatment. The third patient had a dramatic but partial response; his disease is now considered stable.

One of the patients who is now in total remission was so sick prior to treatment that on many days he was considered to be so close to death that his family was called to his bedside for final goodbyes. This man is now fully healthy; he gardens, plays golf, and has gained 40 pounds since his treatment.

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The treatment process, however, was exceedingly complex. First, about a billion T-cells were harvested from his blood. These were modified by exposure to an inactivated HIV-1 virus. DNA from humans, mice, cows, and viruses were used to modify the HIV-1 virus, which was used as a vector to engineer the T-cells to attack the leukemic B-cells. The modified T-cells were re-infused, and they then multiplied by a 1000-fold, expanding to a population of one trillion. These T-cells attacked and eradicated the patient’s entire B-cell population, eliminating all traces of leukemia. Because B-cells are active in combating infection, these patients may be susceptible to some infections and require periodic infusions of IVIg.

The study authors note that this therapy may also be useful for non-Hodgkin’s lymphoma and other leukemias, and that T-cells may be able to be modified with other vector types to treat other malignancies: in other words, a highly important breakthrough with the potential to change cancer care.

Whether this form of treatment can be more widely used in CLL and other cancer patients who have reached the end of the road will depend on whether the process of modifying the T-cells can be carried out more efficiently and economically. This will require the participation of the pharmaceutical industry, which is good at getting things done efficiently and economically. Personally, I can’t think of anything more important than pursuing life-saving medical treatment strategies; our experience shows that as treatment options are developed and employed, costs do eventually come down.

A Possible Cure for Hepatitis C

The rate of new hepatitis C infections in the US has plummeted in the past 30 years, from about 200,000 new cases per year in the 1980s to a bit more than 15,000 cases per year in 2010. But the death rate from hep C is at least 15,000 per year, and it’s not expected to diminish any time soon, because of the huge backlog of people who have been living with the disease for the past decades. Transmission of hep C is primarily through shared needles, and presumably the drug-addicted have gotten wise to the danger, to some degree at least. Another route of transmission was tattoo parlors, and maybe those have also cleaned up their acts. And it can also be transmitted during sex.

In patients who develop symptoms from hep C infections, it is typically treated with interferon, with or without ribaravin, by injection, for as long as a year, and this treatment produces dire side effects, which affect most patients – fatigue, nausea, headache, depression.

However, new drugs appear to be coming along that will change treatment radically. The front-runner is sofosbuvir, from Gilead (GILD), which just won FDA approval on December 7th. Gilead also has another hep C agent, ledipasvir, which they plan to market in combination with sofosbubir so as to provide an oral treatment for the hep C subtype known as genotype 1, which accounts for about 70% of hep C infections. Other pharma outfits – AbbVie (ABBV), Merck (MRK), Bristol-Myers Squibb (BMY), and Johnson & Johnson (JNJ) – are also in the race to bring hep C drugs to market.

The Glad Tidings about these drugs is that – so far at least! – the cure rates are much higher, near 100%, than for interferon-based treatments, and the side effects profiles are much, much more benign.

The Lump of Coal in connection with these tidings is that the drugs will cost lots and lots of money – perhaps as much as $100,000 for a course of treatment. And since the hep C demographic is probably neither prosperous nor equipped with Cadillac insurance plans, this will likely be a problem – for all of us, except for those pharma outfits which stand to profit, and their stockholders (full disclosure, Doc Gumshoe is a Gilead stockholder!)

And another Lump of Coal …

A Hoped-For Cure for HIV Fails

The hope was that a bone-marrow transplant would be an effective cure for HIV infections – that is, a definitive cure, not just a treatment that would keep the virus in check. We don’t want to go into it in detail, but the current accepted standard of treatment for HIV is what’s termed HAART – highly active antiretroviral therapy – which consists of a combination of agents that attack the virus on several fronts. At its best, HAART works quite well, reducing the viral load in HIV patients to levels so low that they cannot be detected by usual laboratory tests. But that doesn’t mean that the virus has been totally eliminated. Nor does it mean that the virus cannot be transmitted from one person to another – it greatly reduces the risk, but it does not totally eliminate it. Therefore, many persons with HIV continue taking drugs after viral loads have dropped to undetectable levels, enduring the many adverse effects that this entails.

For that reason, the hope was that giving HIV patients a bone-marrow transplant would result in a total cure. The rationale is that the process replaces all of a patient’s bone marrow with donor bone-marrow, and that the new blood cells generated by the new bone-marrow would entirely replace all of the old blood cells which were infected with HIV. The patients in this experimental treatment were two men who had been on antiretroviral therapy for years, and whose viral load was undetectable. They continued on HAART while preparing for the bone-marrow transplant. The preparation for the transplant includes a regimen that weakens the existing bone-marrow, so that the new marrow can more easily replace it.

The precedent for this attempt was that a man with HIV who received a bone-marrow transplant 5 years ago has been virus free since then. However, in that case the donor had a rare mutation that made his blood cells highly resistant to HIV. The donors in this present attempt did not have this mutation; the experiment (if we can call it that) was to see whether new bone-marrow, and therefore new blood cells, could wipe out the HIV-infected blood cells and thus cure the disease.

For a few months after the transplant, the treatment seemed to be working. No virus was detectable, and the men stopped taking the antiretroviral drugs. But, unfortunately, the virus came back in both men. So they have gone back on drug therapy, and presumably will stay on it indefinitely.

It had not been proposed that bone-marrow transplantation would be the answer for the many millions of HIV-infected people in the world. But if the experiment had worked, it might have led to treatment modalities that could be more widely adopted. This failure is at least a major stumbling block in that quest.

Some People May Think These Are Goodies, To Others …

More sleep appears to lower coronary artery calcification. This may be good news or bad news, depending on how much sleep you ordinarily get. A study in about 500 adults aged 35 to 47, followed for five years, found that for every extra hour of sleep they got beyond the mean of 6.1 hours, the odds of coronary artery calcification were lowered by 34%, which is equivalent to a 16.5 mm Hg drop in systolic blood pressure.

And, finally, eating too much tofu may lead to cognitive deficits. This comes from a really long-term study in 3700 Japanese in Hawaii which found that those who ate tofu twice a week doubled their risk of developing cognitive deficits in old age. The theory is that some chemicals in soy may interfere with the brain’s ability to maintain nerve connections. That’s only a theory, of course. Doc Gumshoe’s theory is that dedicated tofu-gobblers are avoiding some activity, as yet unidentified, that is good for brain health. Or maybe it’s a special characteristic found only in Japanese who have taken residence in Hawaii. I’m happy to have an excuse to avoid tofu, but as for my loyal readers, I would bet that tofu once a year, as a special penance, is entirely harmless.

* * * * * * *

Doc Gumshoe wishes all his readers – and indeed, all that vast population of non-readers – the best of the season and any other ensuing seasons. Do please keep the comments coming – I’ll do my best to respond before too much water flows under the bridge. A future topic I have in mind is how best to avoid migraines and how to manage them when they occur. And I’ve been reading a bit about the possible merits of deliberately employing placebos for some clinical treatments. I wiIl carefully consult with the spirit of Miss Charlotte Truesdell before launching on that one. Best to all, Michael Jorrin (aka Doc Gumshoe)



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