15:54 PM

499 - Long COVID, Spironolactone for Acne, Creating “Safer Spaces”

Take 3 – Practical Practice Pointers©

From the Literature

1)    Toward a Better Understanding of Long COVID


According to the WHO, as of May 30, 2023 there have been more than 750 million confirmed cases of SARS-CoV-2 infection worldwide, and the actual number of those who have had the infection is likely quite higher, including many who have had multiple infections. Postacute sequelae of SARS-CoV-2 infection (PASC), also known as long COVID, is defined as ongoing, relapsing, or new symptoms or conditions present 30 or more days after infection and has become a major clinical and public health concern.

Most existing PASC studies have focused on individual symptom frequency and have generated widely divergent estimates of prevalence due to their retrospective design and lack of an uninfected comparison group. Moreover, defining PASC precisely is difficult because it is heterogeneous, composed of conditions with variable and potentially overlapping etiologies (eg, organ injury, viral persistence, immune dysregulation, autoimmunity, and gut dysbiosis).

The ability to better research the underlying mechanisms of PASC and develop potential preventive and therapeutic interventions requires data collection on SARS- CoV-2–infected and –uninfected individuals in a large longitudinal prospective cohort study designed specifically to study PASC. To that end, the National Institutes of Health initiated the Researching COVID to Enhance Recovery (RECOVER) study (https://recovercovid.org/) in 2021 to better understand, treat, and prevent PASC.

This study was intended to establish criteria for identifying PASC based on self-reported symptoms from the RECOVER adult cohort. Specifically, the authors were trying to identify what symptoms are differentially present in SARS-CoV-2–infected individuals 6 months or more after infection compared with uninfected individuals based on standardized questionnaires that included 44 potential symptoms.

Data from 9764 participants (89% SARS-CoV-2 infected) met selection criteria and were analyzed. A rule for identifying PASC was derived by analyzing symptoms differentiating infected and uninfected participants using a data analysis method called LASSO (least absolute shrinkage and selection operator). Each symptom was assigned a score based on this methodology and participants were assigned a total score by summing the symptom scores for each reported symptom. An optimal score threshold for PASC was selected using a 10-fold cross-validation, a standard validation tool for data sets. Participants meeting the PASC score threshold were classified as PASC positive; others were classified as PASC unspecified.

Symptoms that contributed to PASC positive scores (in decreasing order of frequency) included postexertional malaise, fatigue, brain fog, dizziness, gastrointestinal symptoms, palpitations, changes in sexual desire or capacity, loss of or change in smell or taste, thirst, chronic cough, chest pain, and abnormal movements. Among 2231 participants first infected on or after December 1, 2021 and enrolled within 30 days of infection (“acute Omicron group), 10% were PASC positive. This compared with 37%


PASC positive at 6 months in the “postacute (enrolled more than 30 days after infection) pre-Omicron group”.(infected with alpha, beta, and/or delta variants).

The proportion of PASC positivity was lower among fully vaccinated than unvaccinated participants in all subgroups (acute Omicron: 9.7% vs 17%; postacute pre-Omicron: 31% vs 37%; postacute Omicron: 16% vs 22%). In the Omicron cohorts, the estimated proportion of PASC positivity was greater among reinfected participants compared with participants with 1 reported infection (acute Omicron: 20% vs 9.7%; postacute Omicron: 21% vs 16%)

Mark’s Comments:

What prompted me to highlight this study (beyond the LASSO data analysis method!) is that given the potential numbers of patients who have PASC, it is imperative that we who practice primary care medicine (and medicine period) better understand this syndrome and ultimately those who are afflicted with it.                                                Of course, better characterizing PASC and its many maifestations only puts us at the starting line, but this is a necessary and important first step toward gaining an understanding as to “why” it is happening and “what” we can do about it


·         Thaweethai T, et al. Development of a Definition of Postacute Sequelae of SARS- CoV-2 Infection. JAMA. Published online May 25, 2023. Link

·         Gross R and Lo Re V. Editorial: Disentangling the Postacute Sequelae of SARS- CoV-2E Unibus Pluram (From One, Many). JAMA. Published online May 25, 2023. Link




From the Literature

2)    Spironolactone for Acne in Adult Women


Acne is a common complaint extending from adolescence into adulthood, with both cosmetic and psychological effects. Much of second-line acne treatment involves oral antibiotics, but dermatologists have been using spironolactone off-label for many years to combat acne. The authors of a recent study noted a “dearth” of high-quality evidence in the literature supporting the use of spironolactone, so, because of the potential benefits at reducing antibiotic use, decided to perform a pragmatic randomized controlled trial of spironolactone vs. placebo for acne in young women.

The trial was labeled “pragmatic” because subjects could be on any topical agent in addition to the study medication, were judged primarily by their physicians as having an indication for oral antibiotics for their acne (confirmed by an investigator assessment of at least mild severity) and were asked about validated acne-specific quality of life (QOL) outcomes. The study compared spironolactone 50 mg/day for 6 weeks, followed by 100 mg/day for 24 weeks with matched placebo. Subjects were excluded for kidney disease, high potassium or having taken the spironolactone before.

Four hundred and ten people were randomized, and 357 completed the trial. Mean age was just over 29 years. Most subjects were white and rated themselves as having “moderate” acne, whereas the investigators rated most “mild.”

There was a small but clinically significant adjusted improvement in mean Acne-QOL scale score on the spironolactone at 12 weeks (mean difference of 1.27 in a 30 point scale, 95% confidence interval 0.07 to 2.46) and at 24 weeks (mean difference 3.45, 955CI 2.16 to 4.75). Also at 24 weeks, overall self-assessed acne improvement was more likely in the spironolactone group (number needed to treat (NNT) ~ 5, 95%CI 3 to 12). Side effects were mild (headache, dehydration) and slightly increased in frequency in the spironolactone users.

John’s Comments:

While I’ve seen spironolactone used frequently off-label for acne, it’s nice to see a well- done study support its use. Remember that hyperkalemia is a potential concern, so we should be ready to check labs if our dermatology colleagues are prescribing this medication. Dehydration is also something to watch for. I liked the pragmatic design elements here– relatively broad inclusion criteria and co-prescribing options and patient- oriented (and reported) outcomes.


·         Santer M, Lawrence M, Renz S, et al. Effectiveness of spironolactone for women with acne vulgaris (SAFA) in England and Wales: pragmatic, multicentre, phase 3, double blind, randomised controlled trial. BMJ. 2023;381:e074349. Link



From PeerRxMed ( www.PeerRxMed.org )

3)    Creating “Safer Spaces” for “Braver Conversations”

“Psychological safety and courage are simply two sides of the same immensely valuable coin. Both are – and will continue to be – needed in a complex and uncertain world.” Amy Edmondson, PhD

Over the past three years of the pandemic, I have often thought about the concept of “psychological safety”; what it is, why it is so often missing on teams and in organizations (or even friendships), and what can be done to address that void. During that time, colleagues from around the country have shared numerous stories about a lack of psychological safety in their organizations and the negative impact this has had on patient care quality, team effectiveness, and individual and group morale. And if my conversations at the recent AAFP Physician Well-being Conference are any indication, it’s getting worse.

Amy Edmondson, who has her PhD in organizational psychology, has written and spoken extensively on the subject of psychological safety in organizations. She defines psychological safety as “ … a belief that the context is safe for interpersonal risk-taking

– that speaking up with ideas, questions, concerns, or mistakes will be welcomed and valued even when I’m wrong.”   It is this sense of safety to engage in open, risk-free dialogue that many colleagues are yearning for but has been missing for them.

In recent years, the conversation regarding psychological safety has shifted from the goal of creating “safe space” to a desire to create “brave space.” Indeed, safe space can never be guaranteed because it depends upon the behavior of others. What can be done is to create the conditions for “safer spaces”, where the subjective experience of safety (which is quite real) helps to overcome fear, increasing the possibility for “braver spaces” to manifest. To do that, one must move from feeling secure (“safe”) to feeling vulnerable (“brave”), from simply unarmored to open, from comfortable to curious, from working “safely” in the same space with others to truly working courageously side-by- side.

But how can we both help create such cultures and feel free to express ourselves within them? The Center for Creative Leadership notes some practical steps that each of us can take to help create optimal conditions for psychological safety and as a result, “safer” spaces. They include making it an explicit priority within your group, facilitating everyone to speak up, establishing norms for how “failure” is addressed, and encouraging and creating space for new ideas (even wild ones). Perhaps most importantly, groups should strive to embrace productive conflict by explicitly discussing the following questions: How will we communicate our concerns about a process that isn’t working? How can reservations be shared with each other in a respectful manner? and, What are our norms for managing conflicting perspectives?

So this week, consider how you are contributing to the psychological safety of those around you by being vulnerable, open, and curious, and consider those circumstances where you are not doing those things because you yourself are not feeling psychologically safe. And then take some steps to address it, so you and your team can move through safer space into braver space.  For it is from that space that everyone’s “best” will emerge, individually and collectively, and it is only under those circumstances that we will be able to provide both exceptional patient care … and caring. And that, after all, is why we’re here ….




Mark and John

Carilion Clinic Department of Family and Community Medicine

Feel free to forward Take 3 to your colleagues. Glad to add them to the distribution list.

Email: mhgreenawald@carilionclinic.org