Medical Bits – Vol. 3.6: Your Health and Medical News

Osteoarthritis

Most of you know the features of osteoarthritis (OA), (also known as degenerative joint disease, degenerative arthritis, arthrosis or “wear and tear”) through that non-transferable and unique experience we call “Pain”. And if you are fortunate to have been spared, you certainly have friends and family members who suffer from the most common ailment afflicting Humans.

Osteoarthritis (Osteo: “bone” – arthro: “joint” – Itis: “inflammation”) is the most common form of arthritis and it is caused by the thinning and wearing of the cartilage that cushions and protects the joint spaces (but inflammation is not always present). Due to the durability of bones, OA is one of the conditions that has the best pathology record, studied among others, by the modern “Fathers of Paleopathology” (Drs. Enrique Gerszten and Marvin Allison from VCU).

One of the characteristics of Homo Sapiens (although the “sapiens” part has always been in question and more so in our times) is the ability to walk erect on two feet: bipedalism, shared by some monkeys and all hominids). Evolution led to skeletal adaptations that made walking possible, freeing our upper limbs to explore and modify our environment, undoubtingly promoting further brain growth. A less fortunate consequence has been the “overload” of the joints of the lower limbs, bearing the weight of the full body when ambulating or standing, in itself a mechanical risk factor for osteoarthritis.

Curiously, arthritis of the hips has been described in other great bipedal creatures that preceded our arrival by more than 200 million-years: Dinosaurs. Ancient civilizations, recognized and described OA and Egyptian and pre-Columbian mummies in the Atacama Desert have provided perfectly preserved skeletons to study the condition. Most commonly affecting the spine of peasants but also the hips of scribes (who sat cross-legged predisposing them to hip OA).

Greeks did not make much reference to the condition, but likely because poor longevity and prevalence of slavery made it a less common condition among the very small – educated class.

Dioscorides, in early Imperial Rome, promoted the virtues of ivy extract for treatment, likely achieving the 30% response observed when treating a subjective experience like pain, and called “the placebo effect”.

In China, pain control is described in the “Neiching”, written as a dialogue between the emperor “Huang Ti” and the doctor “Chi Po” (“The Yellow Emperor’s Classic of Internal Medicine”). This is a compilation written by many authors between 2700-1000 BC and the first reference book on Acupuncture (the techniques have remained virtually unchanged since those initial descriptions).

References to OA became less common in the Middle Ages, but certainly existed. Anthropology teaches us that longevity in the 13th century was only about 25 years. Over the next few centuries, references to OA are limited, but certainly depicted by artists through Western Europe and other continents. In the late XVIII century and more frequently in the XIX century, as more physicians use their observations to describe pathologic conditions, several publications appear, including those by Sandiford of Leiden, William Heberden, John Haygarth, AE Garrod (who coined the term “osteoarthritis”) and others, leading to discrimination between OA and other specific rheumatologic conditions.

The causes include previous joint injury, abnormal joint or limb development. There is a strong genetic predisposition, but the risk rises in those who are overweight.

Osteoarthritis is the most common “arthritis”, afflicting 250 million humans and almost 4% of the world’s population with 10% of men and 18% of women suffering from the condition in those over age 60. In the US, it is responsible for more than $20 billion in healthcare expenditures and it is the second most expensive condition in terms of disability and direct/indirect social costs. More than 50 million people globally suffer from OA-related moderate to severe disability.

Manifestations:

• Pain: usage related and relieved by rest, worse upon awakening and early evenings.
  • Initially sharp and brought on by mechanical insult
  • May become more constant +/- stiffness over time
  • Constant dull/aching pain with increasing intensity.
• Limitation of motion
• Bony swelling, reflecting bone remodeling
• Joint deformity, indicating advanced joint damage
• Instability, of some joints (knee).
• Predilection for knees, hips, fingers, thumbs, first toes and facet joints of the lower cervical and lumbar spine.

Treatment

Treatment strategies include exercise, weight loss, analgesics, anti- inflammatories, local injection within the synovial space with anesthetics and steroids, and if limiting motion and quality of life, joint replacements.

Chondroitin sulfate and glucosamine are as effective as placebo.

Before you decide to go for invasive procedures, discuss the situation with your doctor as more is not best and multiple studies over the past two decades have indicated that frequently (as usual) less is more.

As my educated patients know (or suspect), knowledge impacts healthcare utilization and the way the information is presented may have major consequences. The prevalence of OA in older Americans is similar across races and yet several studies have confirmed significant differences in treatment. Medicare Black Americans are 40-50% less likely than their white fellow citizens to undergo joint replacement.

Joint replacements are among the most successful surgical procedures in history and are projected to grow exponentially in the next decades as our population ages and the obesity epidemic of the last century takes its toll. Shared decision making between physicians, surgeons and patients improves outcomes and leads to better long-term satisfaction for doctors and patients alike, it appears to decrease “physician burnout”! More on this on the next Bits!

Anti-inflammatories are not without risks. Avoid oral meloxicam, diclofenac or indomethacin if possible and limit the doses of ibuprofen, naproxen and celecoxib. Topical anti-inflammatories are safe. Hyaluronic acid (“lubricant”) injections have questionable benefits and the same applies to “PRP” (Platelet- rich plasma).

Arthroscopy to “clean up debris” was shown to be equal to a placebo procedure almost 20 years ago and since, fallen out of favor. And before you “embrace” the “needle”, consider physical therapy (PT), shown to be safer and more effective. A randomized controlled trial favored PT versus glucocorticoid injection, with less pain and functional disability and thicker cartilage at 1 year.

PREVENTION IS ALWAYS THE BEST DEFENSE

Fortunately, Covid-19 infections continue to decline nationwide but the US is underperforming other wealthy nations with a much higher mortality rate. This is squarely due to the low vaccination rate, which is a consequence of polarized politics and our high socioeconomic and by extension educational inequality.

Only 67% of adults without a college degree received the jab but 82% of college graduates as reported by the Kaiser Family Foundation. And only 58% of Republicans are vaccinated, compared to 90% of Democrats. Many mistakenly take their chances, hoping they will not become deadly ill. Or believe the misinformation promoted by “self-proclaimed” experts (exponentially disseminated by social platforms) that some medications such as ivermectin, the “Trump monoclonal antibodies” (effective only when used early and before severe pneumonitis) will prevent disease or abort progression immediately.

The reality is that when these unfortunate individuals who refused vaccination become deadly ill, they all expect life-saving treatment, sometimes demanding ineffective therapies, (immune plasma, plasma exchange, immunomodulators). Other times, extremely costly and risky treatments such as Extra-Corporeal Membrane Oxygenator (ECMO) or even Lung Transplantation.

Let’s remember that at the peak of the “Delta Wave” this past August, 25 out of 10,000 unvaccinated adults were hospitalized and many of them died while only 1.5 out of 10,000 vaccinated adults required hospitalization and fatalities were exceptional. An investment of $10 per vaccine works miracles! Here you can find amazing data collected by our scientists and epidemiologists at the CDC.

As a society, we should have an open discussion about all of these measures and come to terms with what is reasonable to do, as we all bear the cost of these interventions. Some patients and family members become aggressive while in the ICU, when asked about vaccination status, with comments such as “I am an adult and I know what to do with my body” or “If I drive a motorcycle without a helmet or a car without a seat-belt and I have an accident, it is your duty to care for me without asking questions and the same applies if I don’t accept a vaccine”. But these are not equivalent risks. One is an accident with low chances. Becoming infected during a pandemic will happen. It’s just a matter of time, unless you are properly immunized.

Hence, should we support all members of society without attention to sweat, blood and treasure?

In my opinion. NO. We should assess each and every case and evaluate risk/benefits in an individualized manner and the medical teams should be given more latitude to decide what is rational care with good chances of success and when we enter the realms of futility.

COVID-19 VACCINE: TO BOOST OR NOT TO BOOST?

 As more data has become available over the past few months, it has become clear that another dose of antigen to “boost” our immune system and maintain protection is necessary.

This is not surprising. Our “Immunization schedule” is constantly monitored and updated. This applies to other infectious diseases as well. The amount of antigen in influenza vaccine has been increased. MMR booster is required for those born between 1958-1983. Hepatitis B is now recommended for all, etc.

You can imagine that for a new entity, such as SARS-CoV2 it was impossible to ascertain the right amount of antigen and the best immunization schedule from the outset.

Pfizer decided to go with 30 ucg of antigen. Moderna used 100 ucg per dose. We have now learned that the vaccines remain highly effective to prevent severe disease and hospitalization, but waning of protection allows for transmission and also mild to moderate disease, which accelerates after 6-8 months Therefore, boosters will likely be required by all. Do not delay or skip yours!

Our regulatory agencies endorsed booster doses for more COVID-19 vaccine recipients on October 21st, now including the Pfizer-BioNTech or Moderna-NIAID COVID-19 and Johnson & Johnson vaccines and also mixing and matching was authorized (the links have supporting data for each vaccine if you want to read more) with similar statements from both, FDA and CDC:

“For individuals who received a Pfizer-BioNTech or Moderna-NIAID COVID-19 vaccine, the following groups are eligible for a booster shot at 6 months or more after their initial series:

• 65 years and older
• Age 18+ who live in long-term care settings
• Age 18+ who have underlying medical conditions
• Age 18+ who work or live in high-risk settings

For the nearly 15 million people who got the Johnson & Johnson COVID-19 vaccine, booster shots are also recommended for those who are 18 and older and who were vaccinated two or more months ago.

There are now booster recommendations for all three available COVID-19 vaccines in the United States. Eligible individuals may choose which vaccine they receive as a booster dose. Some people may have a preference for the vaccine type that they originally received, and others may prefer to get a different booster. CDC’s recommendations now allow for this type of mix and match dosing for booster shots.

Millions of people are newly eligible to receive a booster shot and will benefit from additional protection. However, today’s action should not distract from the critical work of ensuring that unvaccinated people take the first step and get an initial COVID-19 vaccine. More than 65 million Americans remain unvaccinated, leaving themselves – and their children, families, loved ones, and communities– vulnerable.

Available data right now show that all three of the COVID-19 vaccines approved or authorized in the United States continue to be highly effective in reducing risk of severe disease, hospitalization, and death, even against the widely circulating Delta variant. Vaccination remains the best way to protect yourself and reduce the spread of the virus and help prevent new variants from emerging”.

Fortunately, most of you have already been vaccinated and many have now received a “booster”. Our region enjoys one of the highest vaccination rates of the nation and in fact, Montgomery County of MD has the highest vaccination rate at the top of the 3,243 counties in the US. Over the past 7 days, county wide we had 455 + cases with a positive rate of 1.43% and 11 deaths

I don’t need to repeat to my educated patients that vaccines are safe and effective. They work! In my personal ICU experience working at several hospitals, finding a vaccinated patient with severe COVID-19 associated pneumonitis and respiratory failure is rare.

Almost 7 billion vaccines and 3.83 billion (49.8%) people have now been inoculated worldwide and several new studies are able to put into context some of the few adverse effects from vaccination for physicians and their patients to make better informed decisions for those few “hold-outs” and may also help parents trying to decide if their adolescent children should be vaccinated or children older > 5-yo should be immunized.

In late August 2021, a study involving the largest Israeli healthcare system published their observations, demonstrating that the excess risk for each one of the reported significant adverse events in this population of 1.7 million individuals, was many folds higher from infection with SARS-CoV2 than from vaccination.

The only exception was a minimal increased risk of Herpes Zoster (shingles) (those older than 50, should all be vaccinated with the two-shots of recombinant Shingrix Vaccine) and development of lymphadenopathy. This is not unexpected, as we want vaccination to trigger an immunologic response and activation of lymph nodes and their lymphocytic foci to foster adequate immunologic protection.

Some of you remain concerned about rare complications such as  vaccine- induced immune thrombotic thrombocytopenia (VITT) reported to European and US agencies. Fortunately, VITT is very rare (approximately 1 case per ½ million doses) more common in young women and we know how to recognize it and treat it promptly without consequences.

Several new studies report on the efficacy of vaccines and the minimal decline in efficacy with the new Delta variant.

In a case-control study of almost 11,500 fully vaccinated Israeli health care workers (Pfizer-BioNTech), 1500 of them, were exposed to infected individuals or became symptomatic. There were 39 breakthrough cases and in this mostly young (mean age 45) group, all were mild or asymptomatic but the delta variant accounted for only 15% of cases in the study period.

Another study published on August 12th demonstrated a modest decline in efficacy against the Delta Variant of 5-6%

but remained highly effective to prevent hospitalization and severe disease.

At this time, there are twelve vaccines against COVID-19 approved in different nations and 41 vaccines making progress at the final Phase III clinical trials. In the US, the Pfizer – BioNTech, Moderna – NIH-NIAID and Johnson & Johnson modified adenovirus vaccine have been approved.

Moderna – NIAID has completed studies in adolescents 12-17 using a 50 ucg- dose and trials continue in younger children. The Novavax vaccine announced results of phase III clinical trial of its NVX-CoV2373 Vaccine in late June 2021, with 90.4% overall efficacy and 93% efficacy against the five most prevalent SARS-CoV2 variants of concern, but problems with manufacturing have hampered deployment. The Gaithersburg company is contracted to supply up to 1.1 billion doses to the international Vaccine Alliance – GAVI, supported by the WHO, the Bill and Melinda Gates Foundation, UNICEF and The Worldbank Group, and unfortunately their delays have also impaired vaccination progress in many low-income Nations.

The US has pledged to donate another 500 million doses to poorer nations bringing the total up to more than 1 billion. Of course, you remember that good deeds will be punished as that seems to be human nature. Autocrats and populists in many nations enjoy decrying the US in public, scapegoating “Capitalism and Imperialism” while privately envying and admiring its achievements. And you remember local autocrats who enjoy misinformation as the daily mantra.

COVID-19 VACCINE FOR CHILDREN 5 – 11 YEARS

On September 20th, Pfizer-Bio-N-Tech announced results of their Phase 2/3 clinical trial that enrolled close to 4,500 children from 6 months to 11 years of age in the US, Finland, Poland and Spain. Two doses of 10 ucg (instead of 30 ucg for older children and adults) generated an equivalent immunogenic response and it was safe and effective. Those 6 months-5 years received two doses of 3 ucg of antigen with results on this subgroup anticipated before December.

More than 40% of children were found to have antibodies against coronavirus. The FDA Immunization Advisory panel voted earlier today, unanimously to approve the vaccine for children and it could be ready to be deployed at your children pediatrician’s office by next week. The CDC has coordinated with states, public and private healthcare systems to distribute the vaccines and make it more accessible.

Unfortunately, a recent survey from the Kaiser Family Foundation disclosed that only 1/3 of parents plan to vaccinate their children promptly. There is no sense urgency in getting them vaccinated as most children do not develop serious complications. But many suffer significant health and academic disruptions and more than 150,000 have lost a caregiver. The benefits outweigh the risks by many-folds and we should encourage our fellow citizens big and small and all family members to go forward with the JABS!

COVID-19 Variants and Mutants

There are several open-source databases tracking SARS-CoV-2 genomic sequences, but the largest and most popular is GISAID.

It was originally conceived in 2006 as a “bank” of genomic data from flu viruses, but the Pandemic has expanded its mission to promote the rapid sharing of data from all influenza and coronaviruses to help researchers understand how viruses evolve and spread during epidemics and pandemics. Scientists are able to upload the genomic sequence of the viral strain present in their communities. Their hard work has led to the sharing of more than 2.3 million coronavirus genome sequences from 179 nations, allowing researchers to track the development and movement of new variants across the planet.

Nextstrain, is another open-source consortium that follows numerous infectious diseases and updated several times weekly, tracking the global spread and flow of variants. You can read and explore more here.

The frequently updated Coronavirus Vaccine Tracker from the NYT is an excellent resource. Another excellent Covid-19 Research update from Nature.

National and International Vaccine Rollout information.

This NYT link has National and International Vaccine Rollout information.

COVID-19 Vaccines: Q & A

1. Do we need vaccine mandates?
In my opinion, YES. We have vaccines that are highly effective, safe and fully authorized. For humans who want to continue to participate in social functions, such as public venues, concerts, sporting events, restaurants, schools or work- places, vaccination should be required. Even if we are immunocompetent and do not fear poor outcomes, it is our personal and social responsibility to assist with the creation of an immunologic wall to prevent disease transmission and the rise of new variants. We should remember that many of our fellow travelers in this interesting Journey we call Life, are not as fortunate and may suffer from refractory immunologic deficits. Think of the friends you may have who dealt with autoimmune conditions, or require long-term corticosteroids, or who had an organ transplant, or require active treatment for cancer, or have a history of lymphoma, or leukemia, or myeloma, or hypogammaglobulinemia. The list is long.

2. Could vaccination make conception more difficult or increase the risk of miscarriage?
No. This case-control study from the Norwegian registry following their population comparing vaccinated and unvaccinated outcomes confirmed that the risk of miscarriage were similar and conception rates were also similar.

3. Is Pregnancy a contraindication to Covid-19 vaccination?
No. In fact, a recent study confirmed no safety concerns with the mRNA vaccines and adequate protection.

The safest or most rational timing of vaccination during pregnancy has not been established, but as indicated in our prior “Bits”, best to inoculate in the second trimester, to ascertain protection to the mother in the third trimester (when infectious complications are more common) and to facilitate the placental transfer of antibodies and protection to the newborn.

4. Do we need to continue to decontaminate surfaces?
No. We know more about transmission. This is an airborne disease and it is unlikely that we can pick up an “infectious dose” on our fingertips.

5. How long patients continue to shed live viruses?

The median time from symptom onset to viral clearance in culture was 7 days (+/- 5 days) but the median time to clearance of PCR was 34 days. The latest positive viral culture was 12 days after symptom onset. Thus, we may continue to shed the viral particles for a while, but they may be inactive and not likely to cause disease. This period may be significantly longer in immunocompromised patients and shorter in fully immunized individuals.

6. Do I need to have oxygen available in case of need?
No. There is no evidence that more oxygen is better. In fact, multiple studies have shown that only patients with persistent oxygen saturation below 89% benefit from Oxygen. This applies to all humans, including patients with COPD, emphysema, heart failure and the rest. Most people discharged home on oxygen, do not need supplemental oxygen upon re-testing 2-3 weeks later. If you are “hoarding” an oxygen concentrator, have your physician return it and use those precious healthcare funds for other beneficial treatments.

7. What is the duration of the protection elicited by vaccines?
Protection appears to last 6-10 months, but likely longer to prevent serious disease, as the cellular immunity is stimulated as well and it is a long-lasting defense. Evidence of declining neutralizing antibodies and some breakthrough cases with mild and moderate disease, prompted decisions on boosters.

8. Can vaccines possibly aggravate pre-existing conditions?
Yes. There are few reports of flares of autoimmune and inflammatory conditions such as inflammatory bowel disease, Crohn’s ulcerative colitis, multiple sclerosis, and polymyalgia rheumatica reported. But the benefits of vaccination outweigh the risks by many folds.

9. Could the messenger RNA vaccines get integrated into my DNA and cause mutations or long-lasting ill-effects?
NO. This is biologically impossible. The small messenger RNA is quickly broken down and does not interact with humans’ DNA. Both vaccines have a tiny segment of mRNA encased in lipids that encode the cellular machinery of cells to produce the Spike-protein antigen to promote the immunogenic response we need.

10. Asymptomatic individuals do not transmit COVID-19.

They do. Multiple studies indicate that nearly ½ of transmissions are from people not feeling ill and about a third of all infected patients remain asymptomatic.

11. Is the virus mutating such that the efficacy of vaccines is in peril?
Of course, the virus is mutating, just like any other virus multiplying in the trillions and infecting millions of hosts. As discussed, some of the mutations may lead to increased infectivity and severity of disease. SARS-CoV2 is a stable, non- segmented RNA virus. The infectivity of the virus increased early, as a result of a specific mutation carrying the spike protein D614G substitution, augmenting the virus infectivity and becoming the dominant strain causing disease in Northern Italy and the most prevalent variant throughout the world for most of 2020. New variants with heightened infectivity such as B.1.1.7 and now B.1.617 (so called, Delta variant) displaced other less “efficient” strains. But vaccines remain effective and you are now ready for a booster vaccine “update” soon.

12. Should those who recovered from COVID-19 be vaccinated?
YES. It is not certain how long the immunity will last, and although long term humoral and cellular immunities are anticipated, the recommendation is to be vaccinated 90 days after the acute infection (mine: do it earlier!)

13. Do Vaccinations decrease the risk of transmission?

YES. Vaccines decrease the risk of transmission by at least 80% as demonstrated by this study.

14. Are people who cough or sneeze more infectious than others?

No. Transmission appears to be driven by the viral load of index cases. A higher viral load also increases the risk of developing symptomatic disease shortens the incubation period in a “dose-dependent” manner, as reported by The Lancet.

15. When will vaccines become available for Children?
As indicated above, children 5-11 years may start receiving the vaccine by early November. The logistics of distribution and education of clinics and staff have been under way for several months.
Younger children 6 months-5 years will have to wait till late December or early January as the studies are concluded.

COVID-19 Treatments

You have all heard of multiple new treatments or re-purposed treatments against Covid-19 related disease.

It is important to emphasize what is effective and what has been proven to be worthless.

While working in ICU, I have witnessed expensive and potentially deleterious and invasive treatments being imposed sometimes by physicians and more frequently demanded by family members, despite the lack of evidence for benefit or other times possible harm. The Hippocratic oath reminds us: “Primum non Nocere”!

The National Institutes of Health has a wonderful resource available to all which summarizes the evidence in their NIH Covid-Treatment Guidelines, which grows steadily and now stands at over 350 pages. In summary:

1- Use Dexamethasone at 6 mg daily for 10 days after diagnosis of COVID- related pneumonitis.

2- In hospitalized patients, use IV Tocilizumab.

3- If Tocilizumab not available use Sarilumab IV

4- Use Casirivimab plus imdevimab SQ or IV for post-exposure prophylaxis in patients at high risk for progression to severe Covid-19 and unvaccinated.

5. May use Sotrovimab in similar

6. Azithromycin and Ceftriaxone have not

7- Immune convalescent plasma from previously infected patients: marginal benefit.

8- Plasma exchange – plasmapheresis. No benefit, costly and invasive.

9.- Colchicine. Insufficient evidence. Do not use

10.-  Interleukin 1 – 6 inhibitors. Insufficient Do not use.

11.- Ivermectin. Insufficient evidence and potentially toxic. Do not use.

12. – Janus Kinase Inhibitor Baricitinib. Promising. Use in the right setting.

13. – Anticoagulants. Only in prophylactic doses.

If you have 7 minutes daily, you can start to improve your fitness right now with the Scientific 7 Minute Workout. Get the app on your phone! And 11 more minutes will get you in shape!

For core strength, try this 9-minute routine!

Let’s all remember that the only certainty in life, is death and the only fountain of youth proven by science and experience are exercise, laughter, humor and a positive attitude!

OFFICE UPDATES:

• I will be absent the first week of November in Argentina, but always available on email and mobile
• Simran Singh, Samantha Morales, Sarah Molinari and Fiona MacNair are our current Medical Assistants and will continue to assist all of you with your healthcare need and the best disposition as always!
• Simran Singh at simrans@chevychasepulmonary.com is my personal assistant and always happy to help!

Wishing you a happy and healthy fall!

Carlos E. Picone, MD
5215 Loughboro Rd NW, Suite 400
Washington, DC 20016
301-656-7374

cpicone@chevychasepulmonary.com

References:

https://www.nejm.org/coronavirus

https://www.cdc.gov/coronavirus/2019-nCoV/index.html

https://www.who.int

https://clinicaltrials.gov/

https://www.nature.com/articles/d41586-020-00154-w]

https://science.sciencemag.org/content/early/2020/05/12/science.abc5312

https://www.nejm.org/doi/full/10.1056/NEJMp2005630?query=featured_corona virus

https://www.youtube.com/watch?v=-Gn8oJY1VHY&feature=youtu.be

https://www.cfr.org/backgrounder/what-world-doing-create-covid-19-vaccine

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3805090/

https://www.nejm.org/doi/full/10.1056/NEJMcibr2009737?query=featured_coro navirus

https://jamanetwork.com/journals/jama/fullarticle/2767840

https://www.nature.com/articles/d41586-020-00502-w

https://www.nap.edu/catalog/25914/discussion-draft-of-the-preliminary- framework-for-equitable-allocation-of-covid-19-vaccine https://www.economist.com/briefing/2020/11/14/an-effective-covid-19-vaccine- is-a-turning-point-in-the-pandemic https://www.economist.com/briefing/2021/02/13/vaccine-hesitancy-is-putting- progress-against-covid-19-at-risk

https://www.nature.com/articles/d41586-020-00502