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Little known (and generally worthless) fact: I sold beer at Super Bowl VIII. However, it is with increasing guilt pangs that I plan to tune in to tonight's Super Bowl LVII game almost half a century later. The National Football League's highly discriminatory business practices and the medical risks to players color my appreciation of the game itself. From the medical perspective, of course it's the numerous instances of trauma more commonly involving the musculoskeletal system and brain that stand out; this year we've seen what was likely a rare instance of commotio cordis as well. Not to be overlooked, infectious diseases also have played a small role in the NFL, including an outbreak of MRSA on the then St. Louis Rams team. More on that later.

I'm happy to report nothing noteworthy in the past week's epidemiology of winter respiratory viruses, so I'll forego the usual graphs this week.

Promising New Therapy for Covid-19

Pegylated interferon lambda given as a single subcutaneous injection appears to be an effective new treatment for early covid 19 illness, according to results of a phase 3 trial published last week. About 1000 subjects received the treatment drug with an equal number receiving placebo. Subjects were at least 18 years of age, outpatients, and within 7 days of symptom onset. Most had at least 1 high risk criterion for disease progression. Eighty-three percent of the subjects were vaccinated, and the study spanned multiple variants including omicron. The active drug recipients had a 2.7% rate of hospitalization or emergency department visit compared to 5.6% of placebo recipients, which was highly statistically significant. The benefit was evident regardless of the infecting variant and the vaccination status. Treatment appeared very safe, although of course the study lacked enough participants to look for rarer side effects.

A couple of caveats as usual. This study was part of the ongoing TOGETHER trial, which has an adaptive trial design. This is a more efficient trial design method to test multiple treatments for a given condition; FDA provided guidance for this a little over a year before the pandemic began. Secondly, I was very confused by a NY Times article commenting on statements by the drug's maker referring to conversations with the FDA that could delay drug approval. What was stated in the article doesn't sound anything like what FDA regulations require, so I suspect there is more to this story than what we hear from big pharma. Still, it could signal a delay in drug availability. In general, this approach to covid treatment could be a game-changer for other infectious diseases, so I'm looking forward to more studies of interferon therapies.

New Immunization Schedules from CDC

As always at this time of year, CDC's Advisory Committee on Immunization Practices released updated immunization schedules for children and adults. It has the seal of approval from multiple organizations including the American Academy of Pediatrics. I don't see anything particularly controversial, but it does have recommendations for routine incorporation of covid-19 vaccination for all ages 6 months and above. It should be required reading not only for primary care providers but also for sub-specialists, since they need to be aware of recommendations for people with immunocompromising or other high risk conditions. Individual jurisdictions will decide how this is implemented for circumstances such as public school attendance.

More Good News on Vaccination and Pregnancy

A few new studies add more evidence for the benefits of vaccines for pregnant individuals. First, investigators from multiple countries reported that covid-19 vaccination during a time when omicron was the predominant variant significantly reduces severe symptoms, complications, and death in that population. In another study, maternal covid vaccination also was beneficial for their newborn infants, with lower rates of infection and hospitalization during the first 6 months of life.

We also have additional new data that pertussis vaccination of pregnant individuals offers significant benefit to their newborn infants. Since maternal immunization was recommended in the US in 2012, rates of pertussis particularly in the age group less than 2 months have decreased considerably. Note that this is the age group where the most severe disease and deaths have been seen in the past.

I hope those providing care to pregnant individuals will stress the benefits of these vaccines both for these individuals as well as their newborns.

Allergy Labels: Garbage In, Garbage Out

Please excuse my bias, but a study just published touched on one of my all-time pet peeves: labelling someone with a drug allergy without documenting the clinical circumstances. Often it isn't even a true allergy. This particular report looked at a sampling of children labelled as allergic to penicillin and enrolled in primary care practices affiliated with Texas Children's Hospital and Children's Hospital of Philadelphia. Not surprising (to me), the description of details of the reactions were dismally incomplete, and very few children had this label removed. However, of the children delabelled by either the primary care provider or an allergist, over 90% tolerated subsequent penicillin doses just fine. I issue a plea to all healthcare providers to not just label someone as allergic to a drug without providing a detailed description of the reaction. It makes it so much easier to assess risk of drug therapies in the future. Failure to do so sometimes results in children (and adults) being prescribed suboptimal treatments for future illnesses.

A Picture is Worth a Thousand Words

I told you I would get back to today's NFL activities, just bear with me a moment.

I have long been interested in the graphical display of information. In another part of my life, I led workshops on how to use PowerPoint and other slide presentations more effectively (short synopsis - PowerPoint was designed as a tool for advertisement, presenting a biased view, rather than to encourage critical thinking by the audience). Florence Nightingale published a terrific graph in 1858 detailing causes of death in the British military during the Crimean War. Offshoots of this graphing type are used to represent excess causes of death even today in the covid pandemic. A print of Charles Joseph Minard's map of Napolean's Russian campaign hung in my office for many years and now stares at me just beside my home work desk.

How does this relate to football? Another pretty good pictorial representation appeared in the 2005 report of an MRSA outbreak among St. Louis Rams players. Although it involved just a few players, you can see in Figure 1 how things played out. Of course, MRSA is a real problem in sports as well as in the general population. We still don't have effective preventive measures, though common sense, soap, and water go a long way in keeping everyone healthy.

The picture/1000 words title of this heading is a common aphorism that I think most of us agree is true. I had trouble pinning down the origins of this adage, variously attributed to Leonardo da Vinci, Ivan Turgenev, Henrik Ibsen, and even Napoleon Bonaparte - quite the collection of suspects. However, the credit for the verbatim aphorism I think belongs to the January 10, 1918, edition of a newspaper from my hometown. And, no, it's not a coincidence that you don't see any pictures or graphs in today's post. If you find yourself wishing I had thrown in a few, you've proved my point!

I co-opted the title above from last week's New England Journal of Medicine perspective article by Dr. Anthony Fauci. It's 3 pages, read it if you have a chance. Mostly by virtue of working in the same infectious diseases community as Fauci for the past few decades, I've been privileged to interact with him on a number of occasions both formal and informal. He is a true genius but also a warm and caring person.

His timeline of emerging infectious diseases, copied below, particularly spoke to me as it coincided with my entry into the pediatric infectious diseases subspecialty. Because my practice was located in an area of high international travel, I had to respond very quickly to possibilities of new infectious diseases. Each time I felt exhilaration with a tinge of fear.

DRC = Democratic Republic of Congo; MERS = Middle East respiratory syndrome; SARS = severe acute respiratory syndrome; XDR = extensively drug-resistant

I also note that, of the 21 infectious diseases listed, I've only directly cared for children who truly had 10 of them. However, I was prepared and did evaluate children for all of them. I suspect all infectious diseases clinicians are accustomed to working in hyperdrive at the slightest hint of something new appearing.

Overdiagnosis of Penicillin Allergy

Most healthcare providers know that penicillin and other drug allergies are over-diagnosed. Also, drug allergy is not a lifelong condition but rather is very dynamic. That amoxicillin "allergy" in an infant, even if a true type 1 hypersensitivity reaction, often resolves in later life. Penicillin allergy is a real problem in pediatric healthcare; I long ago lost track of the number of children I've seen who were hospitalized with a serious infection and treated with broad spectrum antibiotics chosen because of a penicillin allergy history. With further probing, it was readily clear that the original so-called allergic event was poorly documented, making it difficult to remove that label in real time. Virtually none of the children had ever been referred to an allergist to sort out the penicillin allergy label. The unnecessary use of broad spectrum therapy contributes to antimicrobial resistance.

This brings us to a recent systematic review and meta-analysis of studies of adult and pediatric patients referred to non-allergists for de-labelling of penicillin allergy. After an extensive systematic literature review of over 11,000 articles, the authors from the UK selected 69 that were of sufficient quality to include in the analysis based on pre-established quality criteria. [Note, this winnowing of articles from 11,000 down to 69 isn't unusual. It's another way of saying that most published articles add little to our understanding of medical management, probably a by-product of "publish or perish" pressure in academic medicine that sometimes rewards quantity over quality.]

Meta-analyses require some of the most sophisticated statistical evaluation in all of medicine; these authors did follow fairly standard methodology in their approach. What's interesting to me are the bottom line numbers. Looking at just the studies that had complete data listed for the proportion of patients tested who were de-labelled, 5072 were tested of which 4698 (92.6%) were de-labelled and 76 (1.5%) were harmed. None of those harmed had serious reactions. Digging a little deeper, 14% of 4350 patients assessed by history alone, 98% of 4207 patients assessed by drug provocation, and 41% of 2890 assessed by skin testing followed by drug provocation were de-labelled.

The take-home points I see from this study are: 1) most subjects labelled as penicillin-allergic aren't truly allergic; 2) front-line healthcare providers need to carefully document possible drug reactions, i.e. don't just record "rash" but rather a complete description of the event in the patient's medical record; 3) for those with possible type-1 hypersensitivity reactions, re-evaluate those patients at the next well visit and consider referral to a provider who can assess for true allergy if needed; and 4) don't let that patient languish for years with a penicillin (or other drug allergy) label. Reassess at every well-child visit and consider a de-labelling process before many years have passed.

COVID-19 Cutaneous Findings

Another group of primarily UK researchers reported findings of cutaneous symptoms from 348,691 participants in an ongoing self-reporting system for COVID-19 symptoms. This is essentially a retrospective case series study. The time period covers both delta and omicron variant waves. They found that skin findings were reported more commonly during the delta time period, 17% versus 11% during omicron, and that cutaneous findings rarely (<2%) were the initial or only findings of infection. The most prominent cutaneous features were unusual hair loss and rashes described as burning, acral, erythematopapular, or urticarial. Skin findings lasted slightly longer in the delta period compared to omicron, and both were shorter than what was reported from the onset of the pandemic with the ancestral strain. Vaccination status didn't seem to have a bearing on cutaneous findings with the exception that vaccinated individuals were less likely to report a burning rash.

Last year some of these same authors developed a nice website to view these cutaneous findings of COVID-19 illness. I look forward to seeing updates of this study as we see new variants and waves.

The Doctor's Dilemma

Fauci referred to an older article by Robert Petersdorf, an early infectious diseases giant, titled The Doctor's Dilemma. That in turn referred to the play by George Bernard Shaw which has been one of my favorites for many years. It is a satire and critique of the medical profession and expresses strong anti-vivisectionist viewpoints. I strongly disagree with some of the tenets presented while agreeing with others, but overall it is very entertaining. If you're looking for some high-quality escapist reading, try it!