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Month: July 2023

Published on Leave a comment on Time for a Deep Dive

Seems like Shark Week has been everywhere the past few days. I can't recall ever watching anything on the Discovery Channel's Shark Week offerings, but I was very aware of it because I live a 20-minute walk from their (now former) corporate headquarters in Silver Spring, MD. Every year around Shark Week they transformed their several story building into a shark.

Perhaps this all influenced me to provide you with an in-depth look at how I approach evaluating an article that might change medical practice. It's a routine I've refined over several years and taught in my prior EBM classes as well as in other settings.

A Deep (Nose)dive

In early June I saw the advance publication of a randomized controlled trial of antibiotic versus placebo for acute bacterial sinusitis. I made the conscious decision at that time not to mention it in this blog because I decided it did not have direct applicability to clinical practice. I might also have been swayed by the fact that I wanted to mention my new washing machine in that blog, and, well, some things just gotta make room for the important stuff.

However, the article appeared in last week's JAMA and was accompanied by an editorial in JAMA as well as an editorial in JAMA Otolaryngology, plus appeared in several medical feeds. Given all the hoopla, I acknowledge I made a mistake in early June and should revisit the article, this time in depth. I'll lead you through the process and my conclusions.

Step 1 - Is it worth my time to evaluate an article in depth?

This step only takes a minute, usually from reading the title and the abstract. If it sounds intriguing and has a study design likely to yield accurate results (e.g. a double-blinded randomized controlled trial for therapeutic interventions) I keep going.

This report is a randomized controlled trial aiming to determine "if antibiotic therapy [for acute bacterial sinusitis] could be appropriately withheld in prespecified subgroups." The abstract sounded interesting with a good study design, so on to the next step.

Step 2 - Immediately go to the Methods section; do not read the Introduction, Results, or Discussion sections.

Whenever I think about this step I'm reminded of the sea (intentional shark pun) of horrified faces in my student/trainee audiences when they first hear this. There's nothing more mundane than the Methods section of a scientific article, but if the methods aren't sound I don't waste my time reading the rest of the paper.

This was a study taking place over 6 years, extended due to pandemic interference with enrollment, at 6 different study sites. In a multi-center study, especially one interrupted by a pandemic, there is a risk that lower-enrolling centers will make mistakes in following the protocol that could cause loss of subjects or missing data. Looking at the enrollment and follow-up diagram, fortunately this did not appear to be a big problem for this study. Also, looking at their Table 1, most of the subjects were enrolled at just 2 centers: Children's Hospital of Pittsburgh (about 3/4 of enrollees) and Kentucky Pediatric and Adult Research (about 15%). The latter organization is a for-profit company, a feature that always raises my eyebrows with medical research, but they've been in business in rural Kentucky since the 1980s, and I don't have any particular concerns about them.

Eligible subjects were children ages 2-11 years who fulfilled criteria for persistent or worsening acute sinusitis in the AAP's 2013 clinical practice guideline. They also needed to have an initial score of at least 9 on the validated Pediatric Rhinosinusitis Symptom Scale (PRSS) which was used as the primary means of evaluating treatment results. Here's a quick look at the scale from the article's online supplemental information.

Points are assigned as 0 for No, then 1-5 from Almost None to An Extreme Amount. As you can see, the minimum score of 9 to be eligible for the study can be achieved with fairly mild symptoms. More on that later.

I won't mention this in depth, but I felt the exclusion criteria were reasonable. In particular, those with more severe symptoms such as temperature > 39 C for 3 or more consecutive days were excluded.

The enrolled children were stratified according to whether parents reported presence or absence of colored nasal discharge and then randomized randomly to receive amoxillin/clavulanate 90 mg/kg/day/6.4 mg/kg/day or placebo divided in 2 doses for 10 days, in a double-blinded fashion. Anticipating later problems with side effects that did occur, the authors mention that they chose amoxicillin/clavulanate over amoxicillin alone to provide broader coverage for all pathogens, presumably those producing beta-lactamase. So, I did note this wasn't quite a real-world situation where amoxicillin might be a better choice based on less GI side effects. Children had nasopharyngeal swabs for Streptoocccus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis obtained at enrollment, and outcomes were compared based on these results.

I immediately wondered about the placebo which was said to be "matching." Most pediatric healthcare providers, as well as parents of young children, know that it is pretty easy to determine if a child is receiving an antibiotic containing amoxicillin due to the odor of the medication and also sometimes urine odor. I wanted to find out if the placebo was truly a good match for the study drug, but the article itself had no further details. Fortunately, the online supplemental materials included the 73-page study protocol. On page 31 beginning on line 790, the placebo is well-described and included reassurance that it was identical in appearance, odor, and texture to the amox/clav.

I'll spare you the statistical details; although I'm not a statistician, I didn't notice anything nonstandard in the analytic methods.

Step 3 - Results

Finally we get to some of the meat of the article! In total, 254 children were evaluable in the treatment group and 256 in the placebo group. Almost 2/3 of enrollees were 2-5 years of age, so a bit skewed towards the younger part of the age range. I was interested in the PRSS scores of those evaluated. In general there was good distribution along the PRSS range, and the 2 treatment groups were similar:

Now, what about the outcomes. The investigators predetermined that a difference in PRSS scores of 1.0 was clinically meaningful. I would question this, given that it doesn't take much to drop a point from a PRSS score - just rating stuffy nose as dropping from "a little" to "almost none" would do it. Here is what was seen for the group as a whole:

Here's what was found when broken down by culture results:

I did notice in all the analyses that children experienced the biggest 1-day drop in PRSS scores in that first day, regardless of treatment group. This represents either natural history or perhaps a placebo effect of just being enrolled in the study and parents being required to pay close attention to their child's symptoms.

With further analysis, it turned out that children with cultures showing pneumococcus or Hi showed statistically significant improvement with antibiotic compared to placebo. Presence of Moraxella, absence of any pathogens in culture, and snot color had no predictive value of response. So, the implication is that culture showing pneumococcus or Hi in culture, along with the clinical AAP guidelines, could be used to further narrow the number of children receiving antibiotic treatment unnecessarily.

In terms of the down side, the main problem was clinically significant diarrhea seen in 11% of the antibiotic group and 5% of the placebo group. If amoxicillin had been used the rate in the antibiotic group likely would have been much lower.

Step 4 - Now read the rest of the article

I look particularly at the Discussion section to see how the authors propose using the results and also how they describe limitations of their study. They describe their study findings as being used in 1 of 4 ways:

  1. Treat everyone fulfilling AAP guidelines, no testing for pathogens
  2. Start presumptive treatment for everyone fulfilling AAP guidelines, test for pathogens, and stop treatment if no pneumococcus or Hi found
  3. Test for pathogens, wait for results, and treat those who have positive pathogen test
  4. Watchful waiting for everyone

All of those options seem possible to me, given that diagnosis is so difficult and the vast majority of these children do fine as long as they are followed closely. Multiple practical problems arise with options 2 and 3 because they require sending a culture and presumably making a special request to the lab to look for and report presence of any pneumococcus or Hi. Depending on the office practice, this takes time and has additional problems/delays if a weekend or holiday is involved, plus making sure the patient isn't lost to follow up. If your practice is situated in a hospital like Children's Hospital of Pittsburgh this might be more feasible than if this is a practice site that sends cultures to a commercial lab.

The authors listed 5 study limitations, some of which seemed trivial to me. First, their original target sample size wasn't reached due to the pandemic. However, their results still reached statistical significance, so this isn't a real limitation. Second, changes in gut microbiome weren't examined. As we find out more about how the microbiome interacts with other aspects of health, it becomes even more important to limit unnecessary antibiotic use. Third, as stated previously children with certain severe symptoms were excluded use of cultures in that setting can't be assessed. Similarly, the fourth limitation was that children not meeting study entry criteria, or even those with parent characteristics less likely to enroll in research studies, might have introduced bias. This is true of all prospective clinical trials so hardly needs to be mentioned here. The fifth and final limitation mentioned was that the gold standard for diagnosis of bacterial sinusitis, quantitative culture of a sinus aspirate, wasn't used. This would have been ideal, but it would be extremely difficult to enroll a child with a relatively minor illness if they would be required to undergo an invasive procedure with little direct benefit to the child.

The main study limitation I appreciated is that the differences in PRSS scores between antibiotic and placebo groups weren't terribly large, an average of 1.69 points. I wonder whether parents would find this an important difference, particularly since after a couple days we are talking about the milder end of the scoring system. There isn't enough detail provided, even in the supplemental data, to know how many individual patients experienced a decrease in symptoms that might be important to parents.

Step 5 - Is there evidence of bias in the study?

The study was funded by NIAID, probably the cleanest funding source there is in terms of bias. I did note that a couple of the authors disclosed financial arrangements with a company called Kaizen Bioscience. I had to research the company a little, it is a small for-profit pharmaceutical company. One of the arrangements involved a proprietary formulation of amoxicillin/clavulanate, so this is a very real potential conflict of interest with the study. On the other hand, I am acquainted with a few of the study's authors, and I don't for a minute suspect they would purposely alter their report based on this connection. The problem, however, is really with implicit bias, the bias we all have but aren't aware of. Did the authors subconsciously "spin" their report to appear more favorable? I don't view this article any differently based on the potential for implicit bias, it's just something to keep in mind particularly if future studies show different results.

After all of this, how do I put everything together?

I wish I had been keeping track of time, but I estimate it took me at least 3 hours of working through the article, not counting time thinking about it while in the shower or writing this post. Ultimately I came back to my original thought - this study isn't ready for adoption into clinical practice.

But, after picking through this with a very fine-(shark)tooth comb, this study's design and reporting are almost impeccable, really a model for others who are beginning clinical treatment research careers.

In the interests of not boring you completely, I left out a lot of other details in the study (see metatranscriptomics for example). Read the article if you have more interest in pediatric sinusitis.

'Demic Doldrums

We continue to see some uptrending in SARS-CoV-2 in wastewater, but still at low levels, according to Biobot.

Similarly, CDC reports slight upticks in covid hospitalizations and ED visits.

Dr. Rivers at Force of Infection notes that the current upticks resemble what we saw in the summer of 2021, just before the delta wave. I think it's a little early to be saying that, plus so far nothing as virulent as the delta variant is prominent. I wouldn't be surprised by at least a mini-wave this fall.

Shark Week

I decided to explore more about Shark Week; one of my (surfer) brothers-in-law did survive a shark attack many years ago, requiring several surgical procedures. I was sorry to learn that the Shark Week shows have become a form of docufiction, whereby true documentary filming is overlaid with fictional information or staged events to increase viewers or readers. In our current age of fake news and artificial intelligence doctoring of reality, we don't need this.

Published on Leave a comment on More Dogs

Last week's post dove into the dog days of summer, and another article this week kept my canine focus centered; I learned about a new breed to me, the Pyrenean Mountain Dog.

New Hope for Group B Strep Vaccine?

I don't usually hype phase I or phase II trials, but this past week's article in the New England Journal offers a glimmer of hope for maternal GBS vaccination to prevent neonatal disease. Maybe it's just wishful thinking, but we might have a breakthrough after decades of failures. We'll need to wait for a definitive phase III trial before we know. I refer you to the accompanying editorial by Carol Baker, the investigator most responsible for "discovering" the emergence of neonatal GBS disease in the 1970s. As in aside, I was a subject in her phase I trial of a GBS vaccine in the early 1980s. The fact that she was my fellowship director at the time wouldn't pass ethical muster today, but I had no side effects and I recall that I did have a good antibody response. Still, that vaccine didn't make it past further testing.

Bacterial Vaginosis

Other than neonatologists, most pediatric providers don't think about BV that often. However, it is very likely a factor contributing to preterm delivery. It's a confusing infection, or perhaps better termed a dysbiosis, consisting of vaginal colonization with various anaerobic bacteria and absence of lactobacilli. A few diagnostic criteria have been in use, but lately molecular screening tools have improved. A new study suggests that molecular screening of pregnant people could be cost effective in preventing pre-term births by identifying individuals with BV and treating them early. Investigators randomized 6671 pregnant people before 20 weeks gestation to have self-administered screening swabs versus regular care. Molecular testing was with a research (not commercially available) tool looking for high levels of Atopobium vaginae and/or Gardnerella vaginalis, and those testing positive were treated with azithromycin or amoxicillin. The differences in the rates of pre-term births in the treatment (3.8%) versus control (4.6%) groups were not statistically significant. However, results in the 3000+ nulliparous (could have had previous miscarriage or abortion) subjects did reach significant difference: 3.6% versus 5.9%. In my current telemedicine practice I see many pregnant individuals who have undergone some type of BV screening. I'm hoping more studies like this will shed light on this somewhat confusing dysbiosis.

More Tick Reminders

Folks at the CDC remind us about tickborne relapsing fever, aka soft tick relapsing fever (STRF). As the name implies it is a relapsing/remitting type of fever and can be pretty tough to diagnose, especially since it isn't seen equally in all parts of the US and is reportable only in 12 states (Arizona, California, Colorado, Idaho, Montana, Nevada, New Mexico, Oregon, Texas, Utah, Washington, and Wyoming) as of 2021. Think of it in campers or others who are active in the outdoors who have had recurrent fevers. CDC investigators reported on 251 cases over a 10-year period, 61 < 18 years of age. Here are some key geographic and clinical points to keep in mind for diagnosis:

'Demic Doldrums

Things remain calm, with a few things to report. Pediatrics published a supplement on covid and school management a couple weeks ago, took me a little while to go through everything. Hindsight usually is 20/20, but I'd say with the pandemic it's more like 20/60, largely due to incomplete data and a moving target with viral variants. However, I would draw your attention to one of the article about lessons learned. The authors include 8 lessons learned; I would put most of this still in the realm of opinion but it is well-reasoned:

  • School closures were necessary initially but should have been shorter
  • Masking works in schools (covered in 2 of the lessons)
  • In-person teaching with masking is better than school closure or hybrid education
  • Covid exposure is not a good reason to exclude school attendance
  • Efficacy of school ventilation improvement is not well-substantiated
  • Asymptomatic screening is ineffective
  • Vaccine trials should be carried out in adults and children in parallel, rather than delaying pediatric trials until adult data are available

Also in both covid and canine realms, the Pyrenean mountain dogs pictured below are actually sniffing out covid.

A new article reviewed evidence to date of dogs trained to sniff out the infection through various methods. A variety of dogs were trained, including mutts. However, the numbers are very low; it's hard for me to imagine a practical use of covid-sniffing dogs, but maybe this will lead to an effective breath test.

You also may have heard nirsevimab, the long-acting monoclonal antibody to prevent RSV in young children, was officially approved by the FDA. Next up is a CDC/ACIP meeting on August 3 to discuss nirsevimab and maternal RSV vaccination, with votes scheduled on recommendations for use.

Playing Games

No, I didn't forget that challenge in last week's post. Blame one of my sons for this. He told me that the New York Times games and puzzles are major revenue sources for the publisher. I receive bupkis for this blog, but I'm not above trying something that might keep readers interested. I couldn't find a credible study for his claim, but there is some evidence.

So, the answer to last week's challenge of the correct number of weather- and temperature-related references and puns in the Dog Days post is 16, including 1 in the Title (summer), 1 in the intro (steaming), 4 in the Bugs section (heating up, hot off the presses, febrile illness, tip of the iceberg), 2 in hep C (cool, clouded), 4 in 'Demic (hot air, cooled, boiling point, hot spots), and 4 in the Astrology section (summer, heat, cool, thunderbolt). Decision of the judges (me) is final.

And by the way, my house is back in the cool as of Friday, unfortunately following purchase and installation of a new air conditioner.

Published on Leave a comment on Dog Days of Summer

I've just returned from a wonderful family week at the beach to a steaming suburban DC and an annoying surprise at home. I'll just bask in my vacation afterglow and belatedly compose this post.

Bugs cont'd

I didn't think it was possible, but there are more mosquitos around my house now than before I left for vacation. Right on schedule, West Nile Virus infections are starting to heat up.

Hot off the presses, you can also add Texas to the list. Remember that although West Nile Virus is feared for its neurologic manifestations, most infections are either asymptomatic or result in a nonspecific febrile illness. The neurologic cases are the tip of the iceberg.

Hepatitis C - We're Missing the Mark in Public Awareness

A recent publication noted a big gap in delivery of care for hepatitis C, summarized below. I really like their cool poster-type depiction, check out the bottom line (at the bottom, of course).

Once again, our wonderful technologic advances in medicine are clouded by a failure to have them reach those who need them most.

More on Neonatal ECHOvirus Infections

The World Health Organization reported more cases of neonatal ECHO-11 infections in newborns, originally in France as discussed in these pages on June 4. Now WHO reports new cases from Croatia, Italy, Spain, Sweden, and the UK. No evidence so far that these events in different countries are connected; this might just reflect enhanced surveillance given the initial alert from France. The link above has a nice discussion of various aspects of the cases. Again, keep severe enteroviral disease in mind with any sick newborn in whom bacterial etiologies are not revealing.

'Demic Doldrums

Remember wastewater monitoring? It's not the greatest tool in the US due to the fact that monitoring is voluntary and leaves much of the US with no data. However, an epidemiologist at Johns Hopkins has been blogging on this and is predicting we are about to see an uptick in southern states. She admits the data are iffy, we'll know eventually if she is full of hot air or not.

Some interesting data appeared regarding maternal covid vaccination and newborn antibody levels. This was a small but well-studied group of 76 mothers who received an mRNA vaccine during pregnancy. Higher maternal antibody levels were seen in mothers who had systemic symptoms following the second vaccine dose, though all had good responses. Maternal transfer of IgG to infants was highest in those vaccinated in the second trimester. Breast milk IgG and IgA antibody to SARS-CoV-2 persisted about 5-6 months, just in time for the infants to start their own vaccine series! There were no significant adverse events in mothers or infants. Bottom line: since we don't know what covid will do in the future, pregnant persons would be well advised to get that new vaccine dose during their second trimester.

The US Government Accounting Office published some further recommendations for pandemic preparedness. I'm very glad these are appearing, but public interest and funding have cooled dramatically.

Also, I was pleased to see an analysis of journalistic coverage of preprint publication before and during the pandemic appearing (where else) but on the well-known preprint site BioRxiv. This coverage hit the boiling point during the pandemic but applied only to covid preprints, not to other scientific reports. Next up I hope we see some analysis of how many of those preprints never appeared in a peer-reviewed publication; some have attempted chart this already, but we probably need to wait another 2-3 years before passing judgement. I continue to worry that too much attention was focused on preprint postings during the pandemic; the blame for this is shared by journalists, scientists, and the universities and other organizations where the work was performed.

Lest we forget about flu, things aren't too bad worldwide but WHO did report some close-to-home hot spots in Costa Rica, Honduras, Nicaragua, and Panama.

My Astrologic Education

I always assumed the saying "dog days of summer" had something to do with a panting dog in the heat. I was barking up the wrong tree; now I've found out it originated with Hellinistic astrology. Officially, the dog days run from July 3 to August 11, according to the Farmer's Almanac.

I had a great time with my 3 sons and families at the beach, enough to keep me somewhat cool and calm after the thunderbolt of finding my air conditioner on the fritz when I returned home. Fortunately for my dog days, my house has 2 air conditioners. Until now, this was a complete mistake - our house could be handled by just one unit if only the ducts were all linked together. So, for now half the house is tolerable and I won't complain too much, at least until I get the bill from the air conditioning service.

Oh, and in case you haven't noticed, I've sprinkled weather- and temperature-related references and puns throughout this week's post. To keep your mind from sweating, see if you can find all of them. Answers in next week's post.

Published on Leave a comment on Hotter Than a Pepper Sprout

I'm a longtime Johnny Cash fan, and the weather reminds me of his cover of the song Jackson with his wife June Carter Cash. Things are heating up in the country and world-wide now. We'll certainly see all kinds of health effects from this, including but not limited to infectious diseases. For now, try to keep cool, hydrated, and apply plenty of sun screen.

Also Remember Mosquito Protection

Speaking of climate change, the Florida Department of Health reported 2 more cases of autochthonous malaria in Sarasota County (see below), bringing the total to 6 cases in that region. Now is the time to take extra precautions for mosquitoes for residents of and travelers to that area.

By David Benbennick - The maps use data from nationalatlas.gov, specifically countyp020.tar.gz on the Raw Data Download page. The maps also use state outline data from statesp020.tar.gz. The Florida maps use hydrogm020.tar.gz to display Lake Okeechobee., Public Domain, https://commons.wikimedia.org/w/index.php?curid=570156.

CDC Budget Cuts

I can't find any official announcement on the CDC website, but Kaiser Family Foundation and various media entities have reported seeing emails from CDC to state health departments detailing some of the effects of the recent Biden administration budget cuts. Specifically, funding for sexually transmitted infection and pediatric vaccine support are being cut significantly. This couldn't come at a worse time. The impact will be most severe on those populations already at high risk such as rural populations and others lacking medical insurance coverage and access to healthcare. Here's hoping the feds find a workaround for these cuts.

'Demic Doldrums

We continue in a covid lull worldwide, with only a few areas showing increasing activity according to WHO.

On the variant front, not a lot to report although a new omicron subvariant, XBB.1.5.26.1 abbreviated as EU.1, may be the latest to watch. It's still at very low numbers in the US but has a significant growth advantage over other circulating variants. Remember that XBB.1.5 is the variant included in the upcoming covid vaccine for this fall.

My Entomophobia

I don't strictly fulfill diagnostic criteria for entomophobia, but my long-suffering wife would disagree when it comes to my fear of mosquitoes. I believe it dates back to a camping trip to Big Bend National Park when I was maybe 7 or 8 years old. I woke up to about 100 bites on my body, while my best friend in the same tent had about 2. It was then that I realized I was very popular with mosquitoes; I'm a mosquito magnet.

I'm particularly reminded of this with the current malaria transmission in Florida and Texas. One of my earliest childhood memories is of my father intermittently taking to his bed with high fevers and shaking chills, a vigorous man reduced almost to an invalid for a few days. He knew this was his malaria relapsing, related to his World War II service in North Africa. He had either Plasmodium ovale or Plasmodian vivax, the 2 types of malaria that have an exoerythocytic phase that requires primaquine treatment to eradicate, after initial treatment with choroquine or other agent. Apparently he didn't have access to primaquine, although it was discovered in 1946 and approved for use in the US in 1952, before I was born. Either he ultimately did get treatment or the episodes just burned out by themselves, but he didn't suffer from relapses in later life. Even though these forms of malaria aren't as deadly as P. falciparum, morbidity is still significant.

So, make my summer cocktail sunscreen, plenty of water, and DEET. (Not to be confused with prior advice of some extremists for covid treatment, the sunscreen and DEET are topical agents, only the water is to be ingested!)

Published on Leave a comment on Try to See It From Grendel’s Perspective

Ever read Beowulf? Me neither. Nor do I plan to ever read this epic poem consisting of 3182 lines of alliterative verse. Recently I did read Grendel by John Gardner. Grendel is the monster who was killed by Beowulf in the famous poem. Gardner's book is told entirely from Grendel's perspective, very different from how Beowulf and the other humans saw things of course.

Malaria Season

Practicing in the Washington, DC, area for almost 40 years meant that I had a steady diet of malaria. Our "malaria season" was towards the end of summer when vacationing families returned home after visiting relatives in malaria-endemic countries. This seasonality abated a bit during the pandemic when international travel was scarce, then came back with a vengeance. Now, however, autochthonous malaria has been reported in Florida and Texas.

Autochthonous, from the Greek autokhthon meaning "sprung from the land itself," in this instance refers to malaria acquired without visiting a malaria-endemic country. I didn't mention the initial CDC report a couple weeks ago, but now that a second state is involved and CDC issued a health alert advisory, I'll attempt to summarize what's happening.

We still have virtually no clinical details about any of the 5 cases, but CDC implied they are all due to Plasmodium vivax which is not as severe/deadly as P. falciparum. Autochthonous malaria in the US was common in the old days, but since effective mosquito control programs in the 1950s it has been scarce. Prior to the current reports, we hadn't seen autochthonous malaria since 2003. High risk areas in the US are those that have high population density, plenty of Anopheles mosquitoes (including favorable conditions for their reproduction), and a source of people who have recently traveled from malaria-endemic areas. So, it's not surprising that Florida and Texas are points of origin now.

Speaking of mosquitoes, climate change has greatly increased the range of various insect vectors of disease; for example, Lyme disease risk has expanded geographically in recent years as deer ticks broaden their range. Anopheles mosquitoes are present in virtually the entire US.

For frontline providers, malaria shouldn't be the first thing to suspect in a child with fever in the US, but recognize that in cases of prolonged fever it is a consideration even without a history of international travel. Look at the CDC's malaria website for more details, and read this article if you want to see a longer discussion of (prepandemic) autochthonous malaria.

Foodborne Disease is Back

Another sign that the pandemic is lifting is this CDC report of 2022 data. Certain foodborne illnesses such as Shiga toxin-producing Escherichia coli, Yersinia, Vibrio, and Cyclospora infections increased compared to 2016–2018 data; Campylobacter, Salmonella, Shigella, and Listeria incidences didn't change much. Although they didn't show the data in this report, foodborne diseases decreased in the 2020-2021 time period.

I was a bit disappointed that, although the report did mention increased use of culture-independent diagnostic testing rather than culture, it did not mention the fact that the highly sensitive CIDT methods can be more prone to false positives. This makes it difficult to compare trends across time periods.

Ideally one would perform a backup culture test for bacterial pathogens particularly to detect antimicrobial resistance; CIDT can not test for this.

Can We Shorten Treatment Duration for Pediatric Urinary Tract Infection?

The short answer is yes, but the more difficult question is how to decide which patients are appropriate for shortened therapy. Even this randomized controlled trial couldn't answer that question. The study compared 5 versus 10 days of therapy for UTI in children 2 months to 10 years of age. Children who showed clinical improvement at 5 days treatment were then randomized to another 5 days of antibiotic versus placebo. Failure rate in the 10-day treatment group was 0.6% versus 4.2% in the 5-day group.

Ultimately I think the details of study design doomed this trial to leave this question mostly unanswered. In particular the duration of followup after stopping antibiotic was too short for the 10-day group (which would have skewed results to a falsely low failure rate). Fundamentally the problem with UTI treatment in children is trying to determine which children have pyelonephritis versus just cystitis, much more difficult in children than in adults. Pyelonephritis likely requires more than 5 days of treatment.

This study definitely adds to our understanding of pediatric UTI but I don't think is immediately transferrable to clinical practice. The accompanying editorial offers some ideas in this regard.

'Demic Doldrums

We continue to enjoy relief from covid from the standpoint of no evidence of major surges around the world, just continued pockets of upswings in disease activity (tempered by the knowledge that we aren't tracking it very well now). Of course, the number of total cases in this WHO graph, as of June 28, is pretty depressing overall.

According to WHO, confirmed covid deaths now number 6,947,192.

Blood Group and Covid

I have blood group A positive. Should I be worried? It's been known for a while that individuals with type A blood have a slightly higher risk of SARS-CoV-2 infection, and this recent article lends some credence to these observations by supplying a biologic explanation. The A blood group antigen is very attractive to the receptor binding domain of the virus, including omicron variants. But no, I'm not concerned. The increase in infection risk attributable to blood group is very small, paling in comparison to other risk factors.

Whatever Happened to Wastewater Monitoring?

In the US, wastewater monitoring for viruses like SARS-CoV-2 has great potential but is ineffective because it involves voluntary reporting by states. Most people in the US live in areas that don't monitor wastewater. Our northern neighbors in Canada, specifically Peel, Ontario, provide evidence that wastewater monitoring truly can be an early warning for increased infections. Investigators reported that wastewater levels predicted very reliably 1 day before the rise in infections and 4 days before a rise in hospitalizations during the omicron period of November 2021 to June 2022. At this point I'm not sure if the US has the resources to implement wastewater virus monitoring on a larger scale.

Better Evidence for MIS-C Treatment

The multi-system inflammatory syndrome in children is still difficult to diagnose precisely. Thankfully MIS-C seems less common in today's covid era with omicron dominance and high levels of antibody in the population. Now we have some better guidance for immunomodulatory therapy for MIS-C. This meta-analysis suggests that the combination of intravenous immunoglobulin plus glucocorticoid therapy improved cardiovascular dysfunction better than either agent alone. The study was very well done but had to rely heavily on nonrandomized cohort studies which introduces a great degree of bias in the results. We missed a chance by not conducting large RCTs of MIS-C treatment early in the pandemic.

Understanding Grendel

I needed to consult Wikipedia and other Cliff Notes-like versions of Beowulf to understand Gardner's book. As with everything I read, I think about what, if anything, might apply to me. With Grendel and Beowulf it was relatively easy. When faced with dramatically different perspectives, say for example pandemic deniers or anti-vaxxers (Grendel) versus traditional science and medicine (Beowulf), it's a good idea to try to see things from the opposing perspective. If one can do this without resorting to raised voices or worse, it's possible to have a meaningful dialog and even occasionally change minds, even my own! Next time you see me, look for Grendel perched on my shoulder. For those less prone to wild fantasies I recognize this is quite a stretch, but regular readers are accustomed to my tangents.

Unless otherwise indicated, the content and opinions expressed on this web site are those of the author(s). They are not endorsed by and do not necessarily reflect the views of the George Washington University.
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