We’ll start out with the COVID-19 news. Yes, we’re all sick and tired of all COVID-related matters, but it doesn’t much lift our spirits to ignore COVID and pretend that it’s well and truly gone. We know better. It still lurks, and even though case rates and hospitalization rates are way down, people we know keep catching it, and some of them feel pretty lousy. It’s not that they caught COVID – COVID caught them.

COVID news – some good, some not so good

Let’s lead off with the good news. The bivalent vaccine that was introduced just a couple of months ago gives recipients antibody levels against the Omicron variants dominant at that time (BA.4 and BA.5) that are about four times higher than the antibody levels produced by the original vaccine. That particular bit of data comes from the results of a small clinical trial run by Pfizer and BioNTech.

In that trial, 36 participants over the age of 55 received the new bivalent booster, and 40 age-matched participants received the original booster. The trial results were limited to measuring the antibody levels one month after dosage; infection rates and significant illness rates were not part of the study.

What was measured in this study was the level of neutralizing antibodies targeting Omicron BA.4 and BA.5 viruses. In adults older than 55 years, these neutralizing antibodies increased 13.2 times over pre-booster levels. In another group of participants, younger than 55 years, they increased 9.5 times over pre-booster levels. In comparison, in adults over than 55 who received a booster dose of the original, monovalent vaccine, antibody levels against those Omicron variants increased by a factor of 2.9.

The results of that study were released to the public on Friday, November 4th.
As of that date, only about 8% eligible persons in the US had received the bivalent booster. And as of mid-November, only about 12% of adults had received the bivalent shot. Even in the highest-risk group, persons over 65 years of age, only 23% have gotten the bivalent booster, despite urging from the health authorities.

In the meantime, the lay of the land has changed. The BA.4 variant has greatly receded, and the BA.5 variant is responsible for about 20% of new cases in the US. However, there are (and will continue to be) new variants. BQ.1 and BQ.1.1 are now the cause of about 57% of the new cases. BQ.1.1 has been reported to be 7 times more resistant to the natural immune system than BA.5, and 175 times more resistant than the original coronavirus strain.

Another variant has surfaced, dubbed XXB. It has been reported in a very few cases in the US thus far, but travelers at international airports have tested positive for XXB, and it has become established in India and Singapore. Dr Fauci commented on the new variants, observing that they were agile at evading the antibodies that are created by vaccination or prior infection. Those antibodies form the first line of defense against infection, but other parts of the immune response can step up to provide protection against severe disease if antibodies fail to protect against the virus.

This obviously calls for the development of yet another round of boosters with a broader range of effectiveness in generating antibodies against the seemingly never-ending succession of coronavirus variants. However, there are non-medical obstacles. Funding for next-generation vaccines has been requested – about $5 billion – but Congress is thus far showing no signs of coming up with the cash. The US is behind foreign rivals in producing and making available spray vaccines, even the ones that were invented in the US. Some observers are predicting that Americans may need to travel to Europe to have access to the most recently-developed vaccines.

Another look at the polypill

A polypill, as the name suggests, is a single pill (tablet, capsule, etc) that contains several different medications. More than twenty years ago, the World Health Organization and The Wellcome Trust convened a high level meeting to discuss interventions for non-communicable diseases. They noted that “the use of a single pill could well encourage patients to adhere to treatment as well as seriously reduce the cost of the drugs.” The particular focus was cardiovascular disease. Based on the assumption that a single pill could have components that would reduce blood pressure, cholesterol, and clot formation due to platelet aggregation, in 2002 the WHO emphasized the substantial potential public health impact and cost effectiveness of increasing access to combination cardiovascular treatment. An editorial in The Lancet in 2002 projected that a four-component combination pill could reduce cardiovascular risk by about 75% in persons with vascular disease.

Now, twenty years later, the polypill aimed at the reduction of cardiovascular disease – even if such a pill exists in some form – has not come into use. A comment in Lancet on November 12th re-introduced the subject, noting that 80% of CVD events occur in persons with no previous CVD history. The comment points out that although the control of elevated risk factors is widely advocated, it has had at best a modest overall effect. On a global basis, control of blood pressure is achieved in at most 15% of persons with hypertension, and statins are used in fewer than 5% of persons who do not have active cardiovascular disease, but may have elevated serum cholesterol. Use of what they refer to as “proven therapies” for secondary prevention of CVD, such as statins, aspirin, ACE inhibitors, and beta blockers, is minimal. The authors, Salim Yusuf of the World Heart Foundation, and Fausto J. Pinto of the Lisbon Heart Center, point out that the traditional approach to risk factor control is complex and expensive, requiring screening and risk stratification.

They cite data from three large long-term trials in primary prevention, demonstrating that a combination of blood-pressure lowering agents and statins at low doses, without aspirin, lowers the risk of CVD by about 38%. When the polypill includes aspirin as well as the other agents, the risk reduction increases to 50%.

Let me point out the essential difference between primary and secondary prevention. Primary prevention aims at preventing the onset of a disease before there is any suggestion of a threat from that disease. Secondary prevention is preventing the threat of a disease after there is an indication that the disease may affect the patient. Thus, primary prevention would include giving a person antihypertensives, a statin, and aspirin, to prevent high blood pressure, elevated cholesterol, and the occurrence of blood clots, before there is any indication that the person is actually experiencing any of those threats.

The authors estimate that widespread use of the polypill could reduce the global burden of cardiovascular disease by more than 50%, and also that even if the adoption of the polypill was only 50%, it could avoid more than two million CVD deaths and four million CVD events each year.

In theory, I suppose it’s possible. In practice, I’m pretty sure it’s impossible. I could see the polypill being adopted in some Scandinavian country. But India (for example), with its billion-and-a-half humans, is not going to add the polypill to the government’s obligations, and very, very few of those billion-and-a-half are going to pay for it out of their own pockets. Simply manufacturing the pill and making it available on the market will go nowhere. And there would be fierce, widespread opposition to the very notion of a polypill for everybody.

I would venture a guess that practicing physicians would not favor a polypill for every person, whether or not they had been examined by a health professional. Yes, people should be screened for risk factors, and individuals with risk factors should receive appropriate treatment for the control of the risk factors, but recommending treatment for everyone without specific examination seems to fly in the face of careful medical practice.

Would Doc Gumshoe himself take a polypill? On balance, I would say no. Sorry, Drs Yusuf and Pinto, your intentions are worthy, but reality points in the opposite direction.

A drug that delays the onset of type 1 diabetes

The drug is teplizumab, made by Provention Bio (PRVB), which will partner with Sanofi to market the drug in the US. It was approved by the FDA on November 8th and will be sold under the name Tzield.

Teplizumab, as the name indicates, is a monoclonal antibody that prevents T cells from attacking the insulin-producing cells of the pancreas.

Type 1 diabetes mellitus (T1DM) is essentially different from the much more common type 2 diabetes (T2DM) in that it is caused by a total lack of insulin. Persons with T2DM produce insulin, but their insulin receptors do not respond to the insulin – they are essentially exhausted from having had to deal with excessive blood sugar levels. Most people with T2DM can manage their disease with oral medications, which tend to increase the uptake of blood sugar and also increase the effectiveness of insulin.

Type 1 diabetes usually occurs earlier in life, mostly in adolescence, but sometimes much earlier. In T1DM, the blood sugar level needs to be monitored several times per day, and based on those levels, patients must be injected with insulin, also several times per day. Getting the right dose of insulin is crucial. An insulin overdose may cause loss of consciousness or seizure. Insufficient insulin results in elevated levels of blood sugar, which, if not corrected over time, can lead to such dire outcomes as blindness or limb amputations.

Teplizumab will delay the onset of type 1 diabetes by at least two years, and in many cases, longer than two years. So far, the longest onset delay has been 11 years. It is given by infusion over a period of 14 days. The estimated cost of the 14 day treatment is $193,000.

Actually prescribing teplizumab to individuals who are at risk for developing T1DM will be complex and also expensive. Type 1 diabetes is relatively rare, affecting about 0.4% of persons in the US. Identifying that slim percentage would entail screening a much larger share of the population, at a considerable expense.

There are several risk factors that increase the likelihood that an individual will develop T1DM, in particular a human leukocyte antigen complex on chromosome 6; also family history and having been infected with some viruses such as German measles, mumps, and coxsackie virus.

I can see that for a person who is likely to develop type 1 diabetes, a drug that will delay the onset for at least a couple of years is “Manna from Heaven”. No sticking yourself with needles for blood tests and insulin several times a day, and no need to be on the lookout for insulin reactions or the consequences of elevated blood sugar. As to who pays for the manna, that question is up in the air.

Pulse oximeters are not totally reliable…

…and they can lead to health risks. Pulse oximeters became a good deal more commonplace during the pandemic, when the need arose to monitor the blood-oxygen levels of COVID patients to determine whether they needed to be hospitalized and receive oxygen supplementation. These devices are small, inexpensive, little things that fit over the tip of the finger. They basically estimate the percentage of a person’s blood-oxygen saturation.

But it has been known for some time that they don’t work as well on darker-skin individuals, since the way these devices estimate the blood-oxygen saturation is based on the color of the blood. Pulse oximeters mistakenly register that darker-skin persons have higher percentages of blood-oxygen saturation, and the result is that such persons are less likely to get oxygen supplementation, even when they really need it – or even to be admitted to hospitals.

An FDA meeting in mid-November discussed this topic. It was agreed that the current rules for patient care decisions should not be principally based on those devices.

Another issue concerning pulse oximeters, which to my knowledge was not discussed at that FDA meeting, is that they are inaccurate when it comes to detecting the effect of carbon monoxide poisoning. For example, my wife was exposed to carbon monoxide, and was admitted to a hospital where they used a pulse oximeter to estimate her blood-oxygen saturation. The device registered the saturation in the high 90s percentage range, meaning that she was supposedly not affected by the carbon monoxide. But what the technicians at the hospital did not happen to know is that carbon monoxide keeps the blood bright red, the same as if the blood-oxygen saturation was normal. Who was aware of that fact, by the way, was a certain friend of Travis’s. And my wife, thankfully, came out of it just fine.

Making these pulse oximeters more accurate is apt to be difficult, and chances are that if the manufacturers ever do figure out how to accomplish that, the devices themselves will become substantially more expensive, meaning that most people won’t be able to use them routinely whenever they suspect that their oxygen levels are low. In the meantime, the cheap ones continue to have their uses. Doc Gumshoe would not recommend tossing them in the trash.

The CDC updates and revises its guidelines for opioid prescription

The first opioid guidelines issued by the CDC in 2016 were primarily focused on reducing opioid misuse. Physicians, health care systems, insurance companies, even state legislatures seized on the guidelines to reduce dosages, shorten prescriptions, or totally cut off patients from the drugs. And, also as a result, many patients who had not misused opioids, but simply used them as a way of managing their pain, were deprived of the most effective pain treatment options and were driven to seek alternatives, which in many cases were less effective and in some cases were actually risky.

Many individuals and many health-care organizations interpreted the 2016 guidelines as saying that patients should never be on opioids for long-term pain management in the first place. Many doctors stopped prescribing opioids altogether, out of fear lest they be labeled as facilitators of drug abuse. Many health-care facilities either prevented their chronic pain clinics from prescribing opioids, or closed them down altogether. Some insurers stopped covering long-term opioid prescriptions. The sudden reduction in the number of opioids prescribed nationally probably contributed to more people using heroin and fentanyl, which almost certainly drove up our national overdose rates. As a result, many patients experienced worsened pain, leading to adverse mental health and, in some cases, suicide.

This month, the CDC issued a new guideline that emphasize non-opioid alternatives when available, but also flexibility. The guideline, entitled “CDC Clinical Practice Guideline for Prescribing Opioids for Pain,” was released on November 4th, 2022, and goes to considerable lengths to stress the flexibility that clinicians and health systems have with this guideline, and to make it clear that the intention of the revised guideline is not to prevent patients with pain from receiving opioids, but that physicians should be exercising caution in prescribing opioids. Physicians are urged to maximize the use of other non-opioid pain therapies before resorting to opioids. However, opioids should still be available when their benefits outweigh their potential risks. Without question, there are instances where opioids are totally appropriate for treating pain, and many patients do very well while being treated with opioids, managing their pain effectively without becoming addicted.

During the heights of the COVID pandemic, when medical attention to matters such as routine pain were greatly diminished, there was a sharp uptick in overdose deaths, in many cases due to high-potency fentanyl, which was the cause of about three-quarters of overdose deaths in teens. However, poor access to addiction treatment and health-care in general made significant contributions to overdosing. The role of prescription opioids in overdosing has been steadily diminishing over time, and the new CDC guideline acknowledges this fact.

The revised CDC guideline does not go so far as to admit that the 2016 guideline was deeply flawed and overly focused on preventing opioid misuse and addiction, while ignoring the underlying reality that many, many persons relied on opioids to manage their pain and make their lives livable. I am reminded of the effects of prohibition, which was in effect in the US from 1920 to 1933. Did prohibition have any positive effects in terms of reducing drunken driving? Possibly. But the negative effects were many – it was an enormous boon to organized crime, and it eroded respect for the law. And it deprived millions of people of innocent pleasures, such as a glass of wine with a meal. The CDC’s 2016 guideline was perhaps not as stupid as prohibition, but it tended in the same direction.

An update on monkeypox

This is based on a release by the CDC on October 26th of this year. At approximately that date, a total of 27,884 monkeypox cases had been reported in the US. The great majority of these cases were in men who have sex with men, and persons with HIV infections as well as individuals from racial and ethnic minorities have been disproportionately affected. Globally, monkeypox has spread to over 100 countries, with over 80,000 confirmed cases.

The CDC report focuses particularly on 57 patients greater than 18 years of age who were hospitalized with severe manifestations of monkeypox during the two months from August 10 to October 10 of 2022. Overall, before monkeypox diagnosis, 82% of these patients (47) had HIV infection and 9% (four patients) were receiving antiretroviral therapy. Most patients were male (95%) and about two-thirds (68%) were non-Hispanic black. In this group, about one-third of the patients received ICU care. A total of 12 patients in this group died. Monkeypox was determined to be the cause of death in five of these deaths, and six deaths are under investigation. In one death, monkeypox was not a contributing factor.

All the patients in this group of 57 had skin rashes, and most also had severe skin lesions in the mouth, urethra, rectum, or vagina. About one patient in five had symptoms in their lungs and eyes, and in four patients the brain and spinal cord were also affected. Only four of the patients with HIV were taking any medication to suppress the virus prior to their being infected with monkeypox.

The CDC emphasized the link between monkeypox and the immunocompromised as follows:

“Health care providers and public health professionals should be aware that severe morbidity and mortality associated with monkeypox have been observed during the current outbreak in the United States, particularly among highly immunocompromised persons. Providers should test all sexually active patients with suspected monkeypox for HIV at the time of monkeypox testing unless a patient is already known to have HIV infection. Providers should consider early commencement and extended duration of monkeypox-directed therapy in highly immunocompromised patients with suspected or laboratory-diagnosed monkeypox. Engaging all persons with HIV in sustained care remains a critical public health priority.”

A last-minute news item on this subject: the World Health Organization made an announcement on Monday, November 28th, that monkeypox is renamed as “mpox.” There was talk of an impending renaming several months ago, but the WHO renaming department didn’t get around to it until just now. The reason for the renaming, as they re-stated, is that the original name of the disease – which indeed originates in simians – could be construed as discriminatory and racist. We’ll see whether this is widely taken up. WHO said that both names could be used for the next year or so, while the old name is phased out. The old name, WHO said, led to “racist and stigmatizing language.” WHO has naming authority for diseases in the International Classification of Diseases, which contains codes used for billing purposes and research data. The virus itself will continue to be called “monkeypox.”

Uncertainty about the causes of obesity

A rational person, reading that phrase, might say, “Well, of course!” It seems obvious to me that obesity has many causes, and that trying to pinpoint a single cause is a vain enterprise. Other than the obvious – the cause of obesity mostly goes in through the mouth somehow – we’re far from certainty.

The reason that topic makes it into this dispatch from Doc Gumshoe is that there was an elite gathering at the Royal Society in London to discuss the causes of obesity, and it attracted a great deal of attention, including a piece in the NY Times. The press coverage mostly followed the guidance of the meeting’s press release, with articles titled “Scientists Don’t Agree of What Causes Obesity, but They Know What Doesn’t.”

The subject of the meeting was obesity and what causes obesity, which supposedly affects about 40% of adults in the US and costs the health system about $175 billion per year.

The meeting included researchers in a number of specialties, including nutritional biologists, endocrinologists, evolutionary anthropologists, physiologists, ethologists, and biochemists. Some of the possible causes of obesity discussed were:

• It was generally agreed that a diet heavy in carbohydrates is uniquely fat promoting.
• The carbohydrates and fats in our food dilute the proteins that our bodies need, driving us to consume more total calories to make up for the discrepancy.
• But in many hunter-gatherer societies, the diet is heavy in carbohydrates with a strong preference for honey, but the hunter-gatherers are lean.
• Ultraprocessed food products somehow entice people to eat more and gain more weight than a whole-food diet with the same nutrient composition.
• These ultraprocessed foods contain thousands of toxins in the form of fertilizers, insecticides, plastics, and additives of one sort or another, which interfere with metabolism.
• It was pointed out that there is a link between food insecurity and obesity. When food becomes scarce, some animals eat fewer calories but gain more weight.

Scientists have identified more than a thousand genes that increase an individual’s obesity risk, and pointed out the link between obesity and its associated complications, which include cancer, type 1 diabetes, hypertension, heart attacks, and strokes. But at the conclusion of the meeting it was generally agreed that no consensus had emerged as to the causes of obesity.

One view was generally agreed on, however: obesity is not an individual choice problem, but a societal problem. As long as the general view is that individuals can manage obesity by making choices – for example, to eat more vegetables and do more exercise – the problem will not go away. Therefore, the statement that “scientists know what doesn’t cause obesity.”

Of course, one of the subjects discussed was “fat shaming.” It was asserted that fat shaming itself sometimes caused the targets to gain, rather than lose weight.

I am far from being an advocate of fat shaming, but it strikes me as a bit extreme to state that obesity is not an individual choice problem. I had a fat friend in sixth grade whose idea of a treat was to go over to the Rainbow Bread bakery, whose back door was across the street from school, and buy a loaf of bread just out of the oven, as yet unsliced and unwrapped. He would tear the loaf apart and devour the whole thing. Sometimes I got a little piece. It was delicious. Was this not his individual choice?

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This piece covers only a few of the recent bits of interesting health news, so I will have to continue with more bits in an upcoming epistle. In the meantime, I hope everyone had an excellent Thanksgiving. We have enough left-overs to feed, perhaps not a regiment, but several able-bodied troopers. Please keep your comments coming. Thanks and best to all, Michael Jorrin (aka Doc Gumshoe)