Thanksgiving Small Bits & Pieces

I’m going to kick off this Doc Gumshoe missive with a little bit of undoubtedly excellent news, albeit information that isn’t more likely to have an effect on many voters of Gumshoe Nation. In a nutshell, it’s this: on September twenty sixth, the FDA authorised the primary new drug to deal with schizophrenia in additional than 30 years. The drug is Cobenfy (xanomeline/trospium chloride, a fixed-dose mixture treatment. It was initially developed by Lilly (LLY), which bought the license to Karuna Therapeutics. Karuna has since been acquired by Bristol Myers Squibb (BMY).

Dr Tiffany Farchione, director of the FDA’s Division of Psychiatry, mentioned “This drug takes the primary new method to schizophrenia remedy in many years. This approval gives a brand new different to the antipsychotic medicines individuals with schizophrenia have beforehand been prescribed. Schizophrenia is a number one explanation for incapacity worldwide. It’s a extreme, continual psychological sickness that’s usually damaging to an individual’s high quality of life.”

For a lot of many years, remedy of schizophrenia relied on blocking dopamine receptors. Widespread dopamine receptor blockers embrace Thorazine (chlorpromazine), Prolixin (fluphenazine), and Haldol (haloperidol). These have been round a very long time. For instance, Thorazine acquired its FDA approval in 1954.

Blocking dopamine receptors has advantages in addition to drawbacks. It reduces signs like hallucinations and paranoia to a stage that sufferers discover livable. However dopamine receptor blockers continuously lead to vital weight acquire, such that sufferers taking these medication are inclined to have greater charges of cardiac ailments, leading to diminished life expectancy. And lots of sufferers have discontinued taking these just because these medication made them really feel sluggish and unmotivated.

Cobenfy has an impact on dopamine ranges, however its principal goal is one other neurotransmitter, acetylcholine.

About 25 years in the past, the muscarinic acetylcholine receptor agonist xanomeline (which is likely one of the two compounds in Cobenfy) was reported to scale back psychotic signs and enhance cognition in sufferers with Alzheimer’s illness. The antipsychotic and procognitive properties of xanomeline have been subsequently confirmed in a small examine of acutely psychotic sufferers with continual schizophrenia.

The origins of the phrase “schizophrenia” counsel that the important dysfunction is a mind whose completely different features are basically disjointed – basically a “break up thoughts.”

In accordance with the Nationwide Institute of Psychological Well being, schizophrenia is a psychological dysfunction characterised by disruptions in thought processes, perceptions, emotional responsiveness, and social interactions. Though the course of schizophrenia varies amongst people, schizophrenia is often persistent and might be each extreme and disabling.

Schizophrenia is comparatively unusual. Within the US, it impacts between 0.25 and 0.75% of the inhabitants. Nevertheless, it’s a disproportionately costly situation. The monetary burden of schizophrenia consists of the direct value of healthcare, which frequently entails life-long institutionalization, but additionally prices resembling misplaced productiveness, involvement with the prison justice system, and social providers.

Signs of schizophrenia embrace psychotic signs resembling hallucinations, delusions, and thought dysfunction (uncommon methods of pondering), in addition to diminished expression of feelings, diminished motivation to perform objectives, problem in social relationships, motor impairment, and cognitive impairment.

The proof supporting Cobenfy as a remedy for schizophrenia is, thus far, slightly sparse. There have been solely three managed trials of the drug, and every trial lasted solely 5 weeks. In these trials, Cobenfy diminished the signs of schizophrenia to a manageable stage, with out producing the unwanted side effects linked with dopamine receptor blockers resembling cardiac illness or weight acquire. BMY launched outcomes of long-term observational research of Cobenfy, during which sufferers didn’t expertise metabolic modifications or motion issues resembling affected sufferers taking different medication to regulate schizophrenia.

Pharmaceutical firms are enthusiastic in regards to the Cobenfy outcomes, and are engaged on comparable medicines which could possibly be efficient in treating such situations as bipolar dysfunction, autism, and Alzheimer’s illness.

BMY has set the wholesale value of Cobenfy at about $22,500 per 12 months. It’s anticipated to generate revenues between $3 billion and $5 billion per 12 months.

Eisai and Eli Lilly conceal instances of mind accidents linked to their Alzheimer’s medication

Clearly, these are genuinely dreadful information objects. The medication in query are Eisai’s Leqembi (lecanemab) and Eli Lilly’s Kisunia (donanemab). The NY Instances lately devoted greater than a full web page to this example, describing a number of instances during which sufferers taking these medication skilled mind accidents, which might have been anticipated primarily based on their genetic profiles.

In 2021, Eisai put out a name for volunteers to take part in a scientific trial of their experimental drug lecanemab (then known as BAN2401) for the remedy of Alzheimer’s illness. Almost 2,000 individuals answered the decision. Eisai sought particularly to incorporate people whose genetic profiles made them particularly prone to develop Alzheimer’s. However these similar people have been extra prone to mind bleeding or swelling in the event that they obtained the drug.

Eisai made a public assertion that every one volunteers can be given a genetic check to establish the precise people who have been at specific threat for mind accidents. Nevertheless, Eisai didn’t inform these trial volunteers that they have been at particularly excessive threat of experiencing these mind accidents. It has been revealed {that a} whole of 274 volunteers joined the trial unaware that they have been at elevated threat. Two of those volunteers died of their mind accidents, and greater than 100 others skilled mind bleeding or swelling.

On July 6, 2023, the FDA granted accelerated approval to Leqembi/lecanemab for the remedy of Alzheimer’s, noting that its modest profit outweighed its dangers. The advantages of Leqembi/lecanemab for the remedy of Alzheimer’s are certainly modest. Remedy with the drug slows cognitive decline for a number of months solely.

An analogous scenario has emerged with regard to Eli Lilly’s anti-Alzheimer’s drug Kisunia (donanemab). Lilly selected to not inform 289 volunteers in a scientific trial of donanemab that their genetic profiles made them particularly susceptible to mind accidents. A couple of quarter of volunteers within the Kisunia trials skilled mind swelling or bleeding.

The FDA granted approval to Kisunia virtually precisely a 12 months after Leqembi’s FDA blessing – July 2, 2024.

In each the Leqembi and Kisunia trials, volunteers first needed to signal consent types that mentioned that individuals with sure genetic traits confronted greater dangers of mind accidents from receiving the medication, and that contributors within the trial can be given genetic checks for these traits. However they have been instructed that they’d not be told as to the outcomes.

Primarily, the volunteers in these trials have been anticipated to go forward and take part within the trials with out understanding whether or not they have been at elevated threat for mind injury. The individuals conducting the trial would know, however the trial topics wouldn’t know.

Each Leqembi/lecanemab and Kisunia/donanemab are BACE inhibitors (beta-site amyloid precursor protein cleaving enzyme inhibitors), that means that they aim amyloid beta, a type of plaque that clogs mind connections. The unlucky Aduhelm/aducanumab (from Biogen), which was taken off the market on account of its poor efficiency in addition to the tendency to lead to mind bleeds, can be a BACE inhibitor.

Mind bleeding and mind swelling is particularly prevalent in individuals with the APOE4 gene. About 40% of people with two copies of the gene skilled mind bleeding, and about 35% skilled mind swelling. This gene is very correlated with Alzheimer’s illness. Folks with one copy of APOE4 have double or triple the danger of creating Alzheimer’s illness, whereas individuals with two copies have an eight- to twelvefold improve in threat.

It ought to be identified that the profit these BACE inhibitors ship is minimal. It slows the onset of dementia in sure Alzheimer’s sufferers for lower than a 12 months earlier than the illness resumes its harmful course.

The annual value of Leqembi/lecanemab is $26,500. For Kisunia/donanemab it’s $32,000. Evidently, neither Eisai nor Lilly wish to allow unlucky particulars, such because the frequency of mind bleeds, to intervene with their gross sales prospects.

A drug-free nasal spray could defend in opposition to respiratory infections

The nasal spray we’re discussing is a gel-like spray formulated with out lively pharmaceutical substances. It has but to be examined in people, however the researchers say it created a protecting coating that lasted for as much as eight hours within the nasal cavities of mice. If the spray’s security and efficacy are confirmed in people, the analysis group mentioned the method might play an necessary position in lowering respiratory ailments and safeguarding public well being in opposition to new threats.

The nostril is a standard passage into the physique for a lot of viruses and micro organism. Most respiratory infections, resembling flu and COVID, are transmitted when an individual inhales tiny droplets of fluid that carry the pathogen. As soon as they get contained in the nostril, the viral or bacterial particles contained in the droplets infect the cells that line the nasal cavity. These pathogens replicate and journey additional down the respiratory tract of the contaminated particular person, generally reaching the lungs, the place they’ll trigger bronchitis and pneumonia. Pathogens will also be launched again into the air when an contaminated particular person sneezes, coughs, laughs, sings, talks, and even simply breathes out and in.

Present nasal sprays supply restricted safety in opposition to respiratory pathogens as a result of they’ve a single mechanism of safety. They both neutralize pathogens or block their entry into the cells lining the nostril, they usually carry out each duties with restricted efficacy.

The projected new drug-free nasal spray was developed to dam germs in 3 ways — the spray types a gel-like matrix that enhances the seize of respiratory droplets, immobilizes the germs, blocking their transport into the nasal lining, and successfully neutralizes the germs, stopping an infection. The nasal spray, known as Pathogen Seize and Neutralizing Spray (PCANS), was developed with nonpharmaceutical substances already utilized in authorised nasal sprays or listed within the FDA’s Typically Acknowledged as Secure (GRAS) listing.

The researchers designed the formulation and studied its means to seize respiratory droplets in a 3D-printed reproduction of the human nasal passages. The experiments confirmed that when administered into the nasal cavity mannequin, the spray captured twice as many droplets as naturally occurring mucus produced as a part of the physique’s innate protection system.

The researchers examined the spray’s protecting results in opposition to a pressure of influenza in mice. The spray was quickly activated following administration into the nostril and lasted as much as eight hours. A single dose might successfully block an infection from an influenza virus at 25 occasions the deadly dose of the virus. Which means that the spray was able to averting an infection even when animals have been uncovered to a heavy load of the virus. In accordance with the investigators, virus ranges within the lungs of pretreated animals have been diminished by almost 100% p.c, in contrast with virus ranges within the lungs of nontreated animals.

The nasal spray was developed by Harvard Medical College researchers working with Brigham and Girls’s Hospital. The data above got here from a Harvard Medical College launch.

It might be anticipated that the builders of the nasal spray can be extremely passionate about its advantages. Doc Gumshoe’s skeptical flip of thoughts poses a query: even when this superb drug-free nasal spray completed in human topics outcomes similar to these in mice, would extraordinary people be more likely to routinely spray a gel coating into their nasal passages to guard themselves in opposition to pathogens? People who had continuously skilled higher respiratory ailments, or who had been warned that they have been at elevated threat for higher respiratory ailments may use this machine. Such individuals may take up the behavior of a every day dose of this nostril spray, kind of as a routine follow, like brushing their tooth. I emphasize the phrase “may” in that sentence. It might rely, to a substantial diploma, on what the nostril spray felt like whenever you press the button or squeeze the tube. Extra considerably, it will rely on whether or not these people perceived precise enchancment: did spraying gel of their noses truly lead to fewer instances of colds or the flu?

At this second, the protecting nasal spray is a great distance from the scientific trials that might be essential to fulfill the FDA and get the nasal spray authorised as a medical machine. Designing scientific trials themselves can be a problem. The trial would want to enlist voluntary topics, a few of whom can be spraying a placebo of their noses. Then, to be able to confirm the efficacy of the nasal spray in stopping an infection, the themes – together with these within the placebo arm – must be uncovered to pathogens, to be able to confirm that the nasal spray diminished an infection. Due to this fact, some trial topics would undoubtedly expertise precise infections. Primarily based on the experimental proof that the gel captured twice as many respiratory droplets as naturally occurring mucus, those that acquired the true nasal spray would presumably expertise infections at half the speed, however they’d be uncovered to infectious viruses and micro organism, and if the an infection fee matched that within the mice, maybe half of the themes would truly get sick. And the an infection fee within the placebo group can be twice as excessive.

There could also be methods round this, however it strikes this observer as an extended, lengthy shot.

Attempting to make sense of lengthy COVID

Sure, COVID 19 continues to be with us, though a lot much less of a risk. The newest figures for deaths, hospitalizations, emergency division visits, and constructive checks are manner, manner down. There have been 444 deaths within the US on account of COVID throughout the week ending November 3. This was about 1.0% of all of the deaths within the US at that time. And solely 0.5% of the emergency division visits have been on account of COVID. Listed here are some mortality figures going again to the beginning of the epidemic to supply some perspective in regards to the present state.

Week ending 09/14/2024 – 563 deaths on account of COVIDWeek ending 08/31/2024 – 663 deaths on account of COVIDWeek ending 05/18/2024 – 336 deaths on account of COVIDWeek ending 01/27/2024 – 2,131 deaths on account of COVIDWeek ending 01/17/2023 – 3,870 deaths on account of COVIDWeek ending 01/15/2022 – 19,078 deaths on account of COVIDWeek ending 01/19/2021 – 25,974 deaths on account of COVID

The parade of variants continues. At the moment, the dominant variant nationwide is KP.3.1.1, which accounts for 52% of instances, adopted by XEC, with 28% of instances, and MC.1, with 6% of instances. The unique Omicron variant has been changed by subvariants, together with LB.1, KP.2, and KP.3. As I’ve tediously famous, because the virus mutates, essentially the most “profitable” variants – profitable when it comes to their very own survival as a viral species – are the variants that allow the human illness sufferer to outlive and cross the virus on to different. A virus that kills its victims rapidly is doomed to extinction.

All in all, COVID as an acute an infection is receding. However what continues to have an effect on plenty of individuals, and trigger quite a lot of concern to the healthcare neighborhood, is lengthy COVID, which continues to be a puzzle. Lengthy COVID signs are just like the signs of an acute COVID an infection. Generally reported lengthy COVID signs included fatigue, mind fog, muscle ache, joint ache, again ache, headache, sleep disturbance, lack of odor or style, and gastrointestinal signs.

The CDC’s criterion for lengthy COVID is that the virus that causes COVID-19 is “current for no less than three months as a steady, relapsing and remitting, or progressive illness state that impacts a number of organ techniques.”

In accordance with the CDC, estimates of the prevalence of lengthy COVID differ on account of completely different examine standards, signs investigated, affected person populations, and timing of when signs are assessed. In 2022, 6.9% of adults and 1.3% of youngsters (roughly 17 million and 1 million, respectively) in america reported ever experiencing lengthy COVID. The newest figures I might discover, dated February fifteenth of this 12 months, ranged from 1.9% within the US Virgin Islands to 10.6% in West Virginia. These are clearly outliers; general, the prevalence remained on the similar stage because it had been in 2022.

I ought to add right here that an AI-enabled method, developed by Mass Normal Brigham, means that lengthy COVID prevalence is way greater – about 22%. The algorithm used was developed by drawing nameless affected person information from the scientific information of almost 300,000 sufferers throughout 14 hospitals and 20 neighborhood well being facilities within the Mass Normal Brigham system. That algorithm might establish extra individuals who ought to be receiving look after this debilitating situation.

Whereas lengthy COVID can happen in anybody who will get the coronavirus an infection, some individuals or teams of individuals are at greater threat of creating lengthy COVID. These embrace ladies, individuals with underlying situations, individuals who skilled extra extreme outcomes of COVID-19, and other people of Hispanic ethnicity.  Roughly 1 in 4 adults with lengthy COVID reported experiencing vital limitations of their every day exercise.

A examine carried out by a group of researchers at Brigham and Girls’s Hospital targeted particularly on lengthy COVID. Researchers discovered individuals with wide-ranging lengthy COVID signs have been twice as more likely to have SARS-CoV-2 proteins of their blood, in comparison with these with out lengthy COVID signs.

The group discovered that 43% of these with lengthy COVID signs affecting three main techniques within the physique – the cardiovascular, digestive, and respiratory techniques – examined constructive for COVID viral proteins inside 1 to 14 months of their preliminary constructive COVID check. However solely 21% of those that didn’t report any lengthy COVID signs examined constructive for the COVID virus on this similar interval.The hope expressed by the researchers is that by figuring out a subset of people that have a reservoir of the coronavirus of their our bodies, it might be attainable to deal with these individuals with efficient antivirals to alleviate their signs.

The examine analyzed 1,569 blood samples collected from 706 people, together with 392 contributors from the Nationwide Institutes of Well being-supported Researching COVID to Improve Restoration (RECOVER) Initiative, who had beforehand examined constructive for a COVID an infection. Utilizing SIMOA, an ultrasensitive check for detecting single molecules, researchers seemed for complete and partial proteins from the SARS-CoV-2 virus. Additionally they analyzed information from the contributors’ lengthy COVID signs, utilizing digital medical chart data or surveys that have been gathered concurrently the blood samples have been taken.

Researchers identified that it’s attainable {that a} persistent an infection explains some however not the entire lengthy COVID signs. If so, testing and remedy might support in figuring out sufferers who could profit from different therapies.

One of many questions raised by the examine is why greater than half of sufferers with wide-ranging lengthy COVID signs examined detrimental for persistent viral proteins.

Dr David Walt, principal investigator on the examine noticed that the discovering famous above suggests there may be seemingly multiple explanation for lengthy COVID. For instance, one other attainable explanation for lengthy COVID signs could possibly be that the virus harms the immune system, such that immune dysfunction continues after the virus is cleared.

Dr Walt and his group are at present conducting follow-up research to higher perceive whether or not an ongoing an infection is behind some individuals’s lengthy COVID signs. They’re analyzing blood samples and symptom information in bigger teams of sufferers, together with individuals of huge age ranges and people with compromised immune signs. It might be necessary to establish people who usually tend to have persistent virus of their our bodies, resulting in lengthy COVID.

The coronavirus inflicting COVID isn’t distinctive in staying within the physique and inflicting ongoing signs months after the preliminary acute an infection. Animal research have discovered Ebola and Zika proteins in tissues post-infection and these viruses have additionally been related to post-infection sickness.

My tackle this matter is that, whereas acute COVID infections are a lot much less frequent and rarely trigger severe sickness or loss of life, they’ll and do result in lengthy COVID, which is an consequence to be assiduously averted. Due to this fact, cautious people (my spouse and myself) proceed to put on masks in some public locations, together with the road on the pharmacy to choose up our medicines and medical amenities.

Who is aware of when – if ever! – it’ll actually and really be over.

A Division of Power regulation might drastically change our mild bulbs

That regulation might have a big opposed impact on the well being of many individuals within the US, particularly epileptics and migraineurs.

The regulation is scheduled to take impact in July 2028, and it’s targeted fully on power effectivity, as one would count on of a regulation coming from the Division of Power. The related assertion is as follows:

“The adopted requirements, that are expressed in minimal lumens (“lm”) output per watt (“W”) of a lamp or lamp efficacy (“lm/W”). These requirements apply to all merchandise manufactured in, or imported into, america beginning on July 25, 2028.”

At current, the one mild bulbs (“lamps,” within the official DOE parlance) that might meet these requirements are the LEDs that emit mild within the 460 – 495 nm (nanometer) vary. A nanometer, by the way in which, is a billionth of a meter. Gentle in that vary is emphatically on the blue finish of the spectrum, ranging into the ultraviolet.

However mild at that frequency has clear and distinct points. Within the night, it messes up our circadian rhythms. Our mind thinks it’s nonetheless broad daylight, undoubtedly not time to fall asleep. Blue mild suppresses the manufacturing of melatonin, which helps us fall asleep and keep asleep. We’ve got all been instructed that staring into our laptop screens or watching tv within the half-hour or so earlier than bedtime is a really dangerous concept, as a result of the blue mild will make it tougher to get a great evening’s sleep.

Past the circadian rhythm concern that impacts us all, blue LED mild is a significant public well being concern for epileptics and migraineurs, lots of whom are extraordinarily delicate to the standard of sunshine and easily can’t tolerate blue LED mild. Yellow and white LEDs, though problematic, are extra acceptable, however the LEDs on the blue finish of the spectrum are past what these individuals can tolerate.

For these people, even transient publicity to unnatural mild, significantly on the blue finish of the spectrum, can set off epileptic seizures and migraine complications. And a migraine is rather more and far worse than a nasty headache. Along with the pounding ache, a migraine can convey on different signs, resembling extreme nausea and vomiting, in addition to excessive sensitivity to any mild, such that the migraineur must shelter in a darkish room.

The prevalence of migraines within the US inhabitants is surprisingly excessive – virtually 10% of males and about 21% of girls report migraines or exceptionally extreme complications throughout a three-month interval.

What we want is mild whose frequencies are extra evenly distributed over the seen spectrum, not concentrated on the blue finish. Sure, broader spectrum mild bulbs are much less power environment friendly, however they’re more healthy and far, rather more nice.

It’s price stating that we people, together with all different creatures whether or not animal or vegetable, developed with incandescent mild, and I don’t imply Edison mild bulbs. The solar and all the celebs in our cosmos emit incandescent mild, as do candles and torches and cooking fires. Incandescence is mild produced by any sizzling or burning matter.

The actual high quality of incandescent mild sources, which can’t be matched by LEDs, is that it emits mild all through all the steady spectrum. LED producers could make mild bulbs that mimic all the spectrum, mixing diodes that emit radiation at a variety of factors, from the ultraviolet to the infrared. However irrespective of what number of diodes the LED accommodates, it won’t be a steady spectrum like incandescent mild. Components of the spectrum will likely be lacking, and what we’re in a position to see illuminated by LEDs won’t cowl all the seen spectrum.

In Rockland, Maine, there may be an artwork museum, the Farnsworth, which homes a superb assortment of the works of Andrew Wyeth. The Wyeth work are illuminated by LEDs – all aside from one portray which is adjoining to a big window that allows the portray to be lit by daylight. The distinction between the LED-lit work and the only portray close to the window is large. The LED-lit work look drab compared.

It may be attainable to make LEDs which can be superior to those within the Farnsworth, however absence of all the seen spectrum will likely be a deficit. I wish to assume that sooner or later the Authorities, whether or not the Division of Power or the Division of Well being and Human Providers, will come to understand that mild bulbs that span the seen spectrum are, no less than in some instances, a necessity.

Power-efficient mild bulbs that emit a pleasing mild that may be tolerated by epileptics and migraineurs and are sympathetic to the wants of our circadian rhythms ought to, I deeply hope, develop into out there nicely earlier than that dire date in 2028.

Transient remark: is Lesstranol the reply to elevated ldl cholesterol?

A daily reader and web buddy despatched a bit about this complement with the query “Is there something to this?”

My reply is a cautious “possibly.”

The commercial selling Lesstranol isn’t a wild overstatement. Right here is the principal assertion of Lesstranol’s worth:

“After many years of treating 1000’s of sufferers with unhealthy levels of cholesterol, I got here to the conclusion that there needed to be a better all-natural manner to assist my sufferers help their levels of cholesterol. After meticulous analysis, I recognized 1 all-natural key nutrient that helps preserve each regular ldl cholesterol and triglyceride ranges whereas selling optimum LDL/HDL stability and cardiovascular well being.

This key nutrient is Crimson Yeast Rice. Historic Chinese language healers believed purple yeast rice might promote good blood circulation. At present, fashionable scientists know that it accommodates monacolins, substances identified to advertise regular levels of cholesterol. These monacolins cease the motion of the HMG-CoA reductase, an enzyme that helps make ldl cholesterol.”

Certainly, purple yeast rice can have a useful impact on levels of cholesterol. Right here’s what the Mayo Clinic says about it:

“Analysis exhibits that purple yeast rice containing appreciable quantities of monacolin Okay can decrease your whole blood ldl cholesterol stage, your low-density lipoprotein (LDL, or “dangerous”) ldl cholesterol stage and your triglyceride stage.

Whereas the complement is usually thought-about secure, it’d carry the identical potential unwanted side effects as statin ldl cholesterol medication.

Crimson yeast rice may cost lower than a statin. Nevertheless, with a complement, there’s much less assurance concerning high quality and the way a lot lively ingredient is definitely within the product. Some purple yeast merchandise may include solely small quantities of monacolin Okay and probably have little impact on levels of cholesterol.”

And who is aware of how a lot of that monocolin Okay is within the Lesstranol complement. As has been continuously identified in these items, dietary supplements are fully unregulated. There isn’t a manner of understanding what is definitely within the Lesstranol tablets. Talking for myself, if I had elevated ldl cholesterol (which, fortunately, I don’t!), I’d comply with the recommendation of my doctor, which might seemingly level me to a statin.

* * * * * * * *

In previous Doc Gumshoe epistles, we’ve mentioned elevated ldl cholesterol and methods of managing that situation, and in addition famous the introduction of latest statins. Is it maybe time to muster up an outline of that image?  Please let me know!

I used to be solely in a position to cowl a number of of the latest developments on this installment, so within the subsequent one I’ll choose up the place I left off and produce you extra bits and items.

Within the meantime, thanks for all feedback and benefit from the holidays, in addition to the non-holidays. Michael Jorrin (aka Doc Gumshoe).

[ed note: Michael Jorrin, who I dubbed “Doc Gumshoe” many years ago, is a longtime medical writer (not a doctor) and shares his commentary with Gumshoe readers once or twice a month. He does not generally write about the investment prospects of topics he covers, but has agreed to our trading restrictions.  Past Doc Gumshoe columns are available here.]