Welcome to the January 2024 Newsletter for

Santa Monica Primary Care

We start the New Year with a recap of the biggest medical stories of 2023. The
top story will come as no surprise – Ozempic. We will cover its development,
mechanism of action and evidence for use both in diabetes and obesity. We
will also review the new Pneumonia vaccine, Prevnar-20, and try to
understand why it costs nearly $300 a dose. Did we see an expected COVID
surge in December? Oh yes we did – we will cover this as well with at least
one colorful graph.

The Biggest Medical Story of 2023 - Ozempic and Its Cousins

2023 was definitely the year of Ozempic (Semaglutide) and its counterparts – Wegovy, Rybelsus and Mounjaro (Tirzepatide). Obesity has become a global epidemic with its worldwide prevalence tripling since 1975. It has a strong association with cardiovascular disease, diabetes, several cancers and kidney disease. A body mass index exceeding 30 kg/m2 has been associated with an increase in annual healthcare costs of over 35%. Given the difficulty that patients have in regaining weight after achieving weight-loss goals, these newer medications have shown promise in both weight loss and maintenance.

COVID-19: A Seasonally Expected Rise in December

Unsurprisingly, December saw a significant uptick in COVID cases in the practice with a total of 19 new cases reported; two of these led to hospitalization. It was the highest monthly total we had experienced in all of 2023, exceeding the 13 of August seen during our late summer surge (Figure 1 below).

Initially, Ozempic / Semaglutide treatment was associated with significant weight loss in clinical trials involving patients with Type 2 diabetes with a nearly 10% weight loss after a bit over a year of treatment as compared to 3.4% among a placebo group. In a class of medications called glucagon-like peptide-1 (GLP-1) receptor agonists, it works in three separate ways:

1. Decreases inappropriate glucagon secretion – or, in English, – glucagon is a hormone
that prevents the blood sugar from dropping too low. But inappropriate secretion of such, which can occur in Type 2 diabetes, triggers the liver to release stored glucose into the bloodstream and prevents it from being reabsorbed. Ozempic inhibits this process.

2. Slows gastric emptying which makes one feel full after a smaller meal and less hungry afterwards. This is also why nausea can be an observed side effect and why patients report feeling more ‘full’ after smaller portions.

3. Stimulates areas of the brain involved in the regulation of appetite and caloric intake. Many patients relate that they just don’t ‘feel hungry’ when taking the medication.

One of the most compelling studies comes from Jastreboff et al. which evaluated the efficacy of Mounjaro in weight loss alone, exclusive of diabetes (the average HgA1c was 5.6% which is below the ‘prediabetes’ threshold of 5.7%; link:

https://www.nejm.org/doi/full/10.1056/NEJMoa2206038). A total of 2539 patients were randomized in a 1:1:1:1 ratio to receive once weekly Mounjaro in escalating doses (5mg, 10mg or 15mg) or placebo for 72 weeks. All of the active treatment groups lost a significant amount of weight trending higher with higher doses. At 5mg, there was a decrease of 15% in weight, at 10mg: 19.5% and at 15mg: 20.9% with placebo at a loss of 3.1%.

In addition to ongoing diet and exercise, consideration for pharmacotherapy seems to be a reasonable option (see Mediterranean diet in Topic #4 below). Both Tirezpatide (Mounjaro) and Semaglutide (Ozempic, Wegovy, Rybelsus) have FDA approval for weight loss. However, we have had significant difficulties this past year not only in obtaining insurance coverage (less of an issue for patients with diabetes) but also simply in availability of the medication. The high cost of the medications themselves can be an additional barrier for patients. Lastly, the duration of treatment is as yet unknown but it may indeed need to be lifelong to prevent weight regain.

COVID-19: A Seasonally Expected Rise in December

Unsurprisingly, December saw a significant uptick in COVID cases in our practice with a total of19 new cases reported; two of these led to hospitalization. It was the highest monthly total we had experienced in all of 2023, more than the 13 cases in August seen during our late summer surge (Figure 1 below). Many of these were repeat (second or third) infections.

Total COVID-19 Cases (Blue) and Repeat infections (Red) by Month in 2023: Santa Monica Primary Care.

A rise in COVID infection rates was also seen at the County level although was less pronounced than the increase we saw in our practice. Incidence rates doubled from 3.8 new daily cases per 100,000 population in the last week of November to 7.4 new daily cases per 100,000 the last week of December (Figure 2 below). This increase remained below the August peak however of 8.3 new daily cases per 100,000.

Smoothed Daily incident Case Rate (Per 100, 000 population) of SARS-CoV2: Los Angeles Country, California

Historically a post-Thanksgiving increase in COVID cases has been the norm, most particularly in 2020 (blue) and 2021 (red) when rates skyrocketed. This phenomenon was seen to a lesser degree in 2022 (yellow) where an uptick in cases occurred but peaked the week of December 8th before dropping down; prior years continued to spike upwards into January. Rates in 2023 are quite low in comparison to earlier years (green) to such a degree that the doubling in cases from November to December barely registers on the Year over Year graph (Figure 3 below).

Smoothed Daily incident Case Rate (Per 100, 000 population) of SARS-CoV2: Los Angeles Country, California for 2020 (blue), 2021 (Red), 2022 (Yellow) and 2023(Green)

Pneumonia and the New Prevnar-20 Vaccine

As we covered in previous newsletters, 2023 has been a boggling array of vaccines including (but not limited to) the new COVID booster, RSV, seasonal influenza, and a new Pneumonia vaccine. The landscape has become so crowded that upon logging onto the CDC website, there is a highlighted section at the very top that asks “Recommendations too complex? We agree!” That doesn’t exactly strike a tone of confidence. But, in truth, the Pneumonia vaccination process can be greatly simplified for most adults to Prevnar-20, and is to be given only once at the age of 65 or older.

But to backtrack, pneumonia or pneumococcal infections are a significant cause of morbidity and mortality among adults, particularly those over the age of 65. It is for this reason that pneumococcal vaccination is recommended for all adults 65 and older. But which vaccine do you give and when? Currently there are 5 difference pneumococcal vaccines available: PCV10 (Sunflorix), PCV13 (Prevnar 13), PCV15 (Vaxneuvance which is a great name), PCV 20 (Prevnar 20, lacks originality) and PPSV23 (Pneumovax 23 or Pnu-Immune).

Fortunately, and to greatly simplify the process, the CDC’s Prevention Advisory Committee of Immunization Practices (ACIP) now just recommends a single administration of PCV20 for all patients with an indication for pneumococcal vaccination. Patients can also have PVC15 followed by PPSV23 one year later, but that seems overly complex when one vaccination will do.

But what about revaccination? This is where topic experts and the CDC part ways. Whereas the CDC ACIP does not recommend revaccination at all, topic experts recommend revaccination for those receiving the PPSV23 (Pneumovax) every 5 to 10 years. There are no data as yet to support revaccination with PVC20 or PVC15 so the only revaccination recommendation is for PPSV23.

So this, then, leads us to the nearly $300 cost for PVC20 which is a ‘one and done’ vaccination protocol. This compares somewhat favorably to the other option wherein PVC15 costs $95 and is followed in one year by PPSV23 ($140) and the PPSV23 is repeated again every 5 to 10 years ($140 each time). Suddenly, $300 doesn’t seem like such a bad deal.

Another Big Medical Story of 2023: The Mediterranean Diet

Although Ozempic dominated the headlines of 2023, a study by Delgado-Lista et al. conducted a large, randomized controlled clinical trial to assess the efficacy of a Mediterranean diet in the secondary prevention of cardiovascular events. Secondary prevention is not a concept we have covered in previous newsletters but is one commonly employed among patients who have already had a health event, such as heart attack, stroke, or cancer. It is distinct from primary prevention which seeks to avoid an outcome entirely. But with secondary prevention, we are asking, “is there anything that can be done to prevent such from happening again?”

The Mediterranean diet – characterized by an emphasis on fruits, vegetables, legumes and nuts with white meat and fish as the primary sources of protein and olive oil as a primary source of fat – has been shown to be more effective in primary prevention of cardiovascular disease. But until the Delgado-Lista study, there was no evidence that the Mediterranean diet could work in prevention of a subsequent event.

A total of 1,002 patients with established heart disease were studied for 7 years randomized to a low fat diet or a Mediterranean-diet. One perk of the study is that participants received a Liter of extra-virgin olive oil at no charge, and the low fat group received a bag of healthy complex carbohydrate rich food also at no charge. By the end of 7 years, a total of 87 events occurred in the Mediterranean-diet group (17.3% of the group) and 111 in the low-fat-diet group (22.2%) which represented at 25% risk reduction. This is a resource for more detailed on a
Mediterranean diet: https://www.health.harvard.edu/blog/a-practical-guide-to-the-mediterranean-diet-201903211619

Paxlovid: Questions Abound and Rebound

We have covered Paxlovid for the treatment of acute COVID infection in prior newsletters. It has been well established that among high risk and unvaccinated individuals that Paxlovid reduces viral load and progression to severe disease. As yet, there are not randomized clinical trial data to support its use amongst vaccinated individuals although a September 2022 CDC study showed a 51% lower hospitalization rate within 30 days of infection amongst those who had received a primary mRNA vaccine series and at least one booster.

An additional reason I have been a proponent of Paxlovid was a 30% reduction in risk of Long COVID – which are symptoms that persist after the acute phase of infection – suggested by a VA study. Vaccination reduces but does not eliminate the risk of Long COVID. Higher viral load and/or prolonged viral shedding appear to act as risk factors for increased Long COVID risk.

However, an early January 2024 paper from UCSF suggests that Paxlovid administration did not modify the risk of Long COVID symptoms among vaccinated individuals experiencing their first infection (link: https://onlinelibrary.wiley.com/doi/full/10.1002/jmv.29333). An online cohort study of over 100,000 individuals identified 4684 eligible individuals of whom 21% were treated with Paxlovid and 79% went untreated. About 35% of eligible individuals responded to symptom survey requests and there was no difference in reported Long COVID symptoms between
treated and untreated. About 15% of all those surveyed did report Long COVID symptoms extending past 90 days of infection with the most common symptoms being fatigue, shortness of breath, confusion, headache and alterations in sense of taste and smell. Rates were 16.1% among those treated and 14.0% among those untreated.

Although there are limitations to this study (e.g. 35% response rate, online assessment of symptoms, those treated more often older, male, and with chronic conditions), one interesting aspect of the study was the 15% Long COVID rate among vaccinated patients. The UK Ofice for National Statistics has estimated that 22.1% of patients continue to experience post-acute COVID symptoms 5 weeks after infection and 9.9% at 12 weeks which are worrying numbers for patients and medical professionals alike. The UCSF group also reported a 19.7% Paxlovid rebound positivity rate (i.e. return of both symptoms and a positive test). This rate is remarkably close to the rebound frequency we have seen here at Santa Monica Primary Care; of 134 patients we have treated with Paxlovid, 24 (17.9%) reported a clinical rebound, typically about two weeks after treatment.

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