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One-Minute Telegram Archive

Last updated: April 26, 2021

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This article contains a collection of content written during 2021 for the One-Minute Telegram, a biweekly newsletter that presents the newest medical research condensed into just one minute of reading. This newsletter is designed for all of our colleagues who want to stay current on the latest medical literature without having to comb through and dissect medical studies themselves. It is peer-reviewed by our team of physician editors and integrated into the Amboss library. Even after a long night shift or a busy day on the wards, it should go down easy. Subscribe by clicking on the image or via the link in “Tips and Links” below.

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See also our One-Minute Telegram Archive 2020

Budesonide shows promise in reducing symptoms and preventing progression of mild COVID-19

One-Minute Telegram 24-2021-1/3 - It is known already that oral and IV dexamethasone can improve the outcomes of patients with COVID-19 who require respiratory support. [1] However, this is not applicable to patients with mild COVID-19, and effective treatment options for this group are still lacking. [2] Researchers set out to determine if the use of inhaled glucocorticoids could be beneficial in mild COVID-19.

This phase II open label randomized control trial included 146 patients ≥ 18 years who had been diagnosed with mild symptomatic COVID-19 within the preceding 7 days. Patients were randomly assigned in a 1:1 ratio to a usual care group (i.e., antipyretics and honey for cough) or a usual care plus inhaled budesonide group (800 mcg twice daily). Both groups were monitored at home for 14 days. Participants already on budesonide were excluded. Patients’ age, baseline symptoms, and comorbidities were similar between the groups.

  • Compared to the usual care group, the budesonide group had the following outcomes:
    • Main composite outcome: reduced number of COVID-19 related visits to the ER and/or admissions (3 vs 15%; P =0.009); number needed to treat of 8
    • Secondary outcomes:
      • Earlier recovery (median 7 vs. 8 days, P = 0.007)
      • Fewer patients with persistent symptoms at day 14 (10 vs. 30% P = 0.003)
      • Lower proportion of days with fever (2 vs. 8%, P = 0.051) and use of antipyretics (27 vs. 50%, P = 0.025)
      • No significant difference in oxygen saturation and SARS-CoV-2 viral load
  • Safety profile: Five participants reported mild adverse events.

Limitations of this study include the lack of placebo group and a relatively small sample size.

The take‑home message?

Results from this study suggest that the addition of inhaled budesonide to the usual outpatient treatment can reduce the likelihood of clinical deterioration and need for hospitalization in adults with mild COVID-19. Since budesonide is an easily accessible medication, this could become a widely applicable measure to treat mild COVID-19 worldwide and ease the burden on hospitals.

  • Title of study: Inhaled budesonide in the treatment of early COVID-19 (STOIC): a phase 2, open-label, randomised controlled trial [3]
  • Authors: Ramakrishnan S et al.
  • Journal: Lancet Respiratory Medicine
  • AMBOSS links: COVID-19

Hard work pays off: High vs. low intensity walking interventions in patients with peripheral artery disease

One-Minute Telegram 24-2021-2/3 - Interventions to curb the progression of peripheral artery disease (PAD) are limited and often require challenging lifestyle changes, which may be difficult to adhere to (e.g., supervised exercise). [4]

This multicenter randomized clinical trial aimed to determine the effect of two different home-based exercise interventions on walking capacity (defined as maximal distance walked in 6 minutes) and self-reported limitations (measured by the Walking Impairment Questionnaire) in individuals with PAD. [5] Participants were randomized to a low-intensity walking group (not inducing ischemic symptoms; n = 116), a high-intensity walking group (inducing ischemic symptoms; n =124), and a non-exercise control group (n= 65). Patients in the intervention groups were instructed to complete five 50-minute sessions per week for 1 year.

Changes in 6-minute walking distance after 12 months:

  • Non-exercise control group: 15-meter mean reduction
  • Low-intensity walking group: 6.4-meter mean reduction (mean difference compared to no exercise, + 8.7 meters; P =0.44)
  • High-intensity walking group: 34.5-meter mean increase (mean difference compared to low-intensity + 40.9 meters; P < 0.001)
  • While low-intensity walking was not found to significantly improve objective walking capacity compared with no exercise, patients in the low-intensity walking group did show significant improvement in self-reported limitations of both walking distance and speed.

Limitations of this study include a lack of data on 18% of participants who did not return for testing after 12 months. Some follow-ups could not be completed due to the onset of the COVID-19 pandemic.

The take‑home message?

A home-based high-intensity walking exercise intervention was effective in significantly improving the 6-minute walk distance of patients with PAD, while low-intensity walking improved self-reported limitations but did not improve the 6-minute walk distance compared to no exercise.

  • Title of study: Effect of low-intensity vs high-intensity home-based walking exercise on walk distance in patients with peripheral artery disease: The LITE randomized clinical trial [6]
  • Authors: McDermott MM et al.
  • Journal: JAMA

Long COVID after mild COVID?

One-Minute Telegram 24-2021-3/3 - Patients hospitalized with COVID-19 report symptoms like dyspnea and fatigue many months after overcoming the disease. [7] However, information regarding the persistence of symptoms after mild COVID-19 is scarce.

Participants in this study were 1395 health care professionals recruited between April and May 2020, who were followed for a period of 8 months. Blood samples were collected at baseline and every four months thereafter. Seropositive participants with severe symptoms and seronegative participants who subsequently seroconverted were excluded. Information regarding the presence, duration, and severity of long-term symptoms (e.g., anosmia, fatigue, dyspnea) was collected via a smartphone questionnaire.

Participants who were SARS-CoV-2 seropositive at baseline (n = 323) were compared to those who were SARS-CoV-2 seronegative at baseline (n = 1072) with the following results:

  • 26% of seropositives vs. 9% of seronegatives reported ≥ 1 moderate or severe symptom, lasting ≥ 2 months (RR, 2.9; 95% CI, 2.2-3.8)
  • 15% of seropositives vs. 3% of seronegatives reported ≥ 1 moderate or severe symptom lasting ≥ 8 months (RR, 4.4; 2.9-6.7)
  • The most commonly reported symptom persisting ≥ 2 months was anosmia.

Using the Sheehan disability scale it was determined that symptoms lasting ≥ 2 months caused long-term functional impairment. [8] Compared to seronegative participants, seropositive participants reported higher rates of disruption in their work, social, and home life.

Limitations of this study include case-definition by serology rather than PCR and the potential for recall bias.

The take‑home message?

Results from this study suggest that long-term symptoms potentially disruptive to work, social, and home life are frequent even after mild COVID-19.

  • Title of study: Symptoms and functional impairment assessed 8 months after mild COVID-19 among health care workers [9]
  • Authors: Havervall S et al.
  • Journal: JAMA
  • AMBOSS links: COVID-19

Prevention of HIV infection using neutralizing antibodies?

One-Minute Telegram 23-2021-1/3 - It is estimated that there are about 30 million people worldwide currently living with HIV/AIDS. Even though global efforts since 2010 have led to a decline in new HIV infections by almost a quarter, there were still over 1.5 million new infections in 2019. [10][11]

Two parallel phase 2 randomized controlled trials aimed to determine the efficacy of the novel HIV-1 neutralizing antibody VRC01 in preventing infection among persons at risk (e.g., high-incidence populations). Trial one was conducted in North America, South America, and Europe (n = 2699), trial two in sub-Saharan Africa (n = 1924). Participants were randomly assigned 1:1:1 to receive intravenous low-dose VRC01, intravenous high-dose VRC01, or placebo every 8 weeks for 20 months. Median age was 28 years in trial one and 26 years in trial two. 98 and 76 infections were registered during follow-up in trial one and trial two, respectively.

Both high- and low-dose VRC01 were highly effective compared to placebo in preventing infection with HIV-1 strains susceptible to VRC01 in vitro (75.4%; 95 CI 45.5 to 88.9). However, such strains represented only a third of the strains identified in the trial regions, so that efficacy as a whole turned out to be low compared to placebo (P values for efficacy 0.15 and 0.70).

Limitations include that the use of the antibody may have applied selective pressure at early stages of the study, consequently inducing infections by HIV-1 strains resistant to VRC01.

The take‑home message?

In these two trials conducted in 4 different continents, the neutralizing antibody VRC01 was generally not effective in preventing new HIV-1 infection. However, for HIV-1 strains with in vitro susceptibility to the antibody, prevention efficacy was high. These results suggest a potential benefit of neutralizing antibodies in preventing HIV infection, possibly using combination regimens in order to cover HIV-1 strains with different susceptibilities, but further trials are needed to confirm these hypotheses.

  • Title of study: Two randomized trials of neutralizing antibodies to prevent HIV-1 acquisition [12]
  • Authors: Corey L et al.
  • Journal: NEJM

The age of innocence: Younger patients less likely to develop symptoms after SARS-CoV-2 infection

One-Minute Telegram 23-2021-2/3 - Since the beginning of the pandemic, there have been numerous questions regarding the proportion of infected patients that remain asymptomatic and the role these individuals play in the transmission of the virus. Especially, whether certain groups are more prone to being asymptomatic than others remains a matter of debate. [13]

Researchers conducted a cohort study to determine if the development of COVID-19 symptoms is associated with age.

5,484 participants who had had close contact with patients with confirmed COVID-19 were included and monitored for 2 weeks for the development of infection and symptoms. Median age was 50 years (IQR 30–61), 56.3% were female. 51.5% tested positive for SARS-CoV-2 infection (n = 2824), either via RT-PCR or serological assay; 69% of the infected contacts did not develop respiratory symptoms or fever (n = 1948), and 2.7% developed severe disease (n = 75). The development of symptoms was associated with increasing age, with the highest rates of symptomatic disease and critical illness seen in patients ≥ 80 years (64.56% and 18.35%, respectively) and the lowest rates occurring in patients ≤ 19 years (18.1% and 0%, respectively).

Limitations of this study include that the infection rate seen was not representative of the general population, as only close contacts were included, and that different laboratory methods were used to define infection.

The take‑home message?

In this study, younger age was associated with a lower rate of symptomatic SARS-CoV-2 infection, while higher age was associated with both symptomatic infection and a higher risk of progression to critical illness, with the group of patients ≥ 80 years being the most severely affected. The high rate of asymptomatic infection among young patients warrants further discussion regarding the best prevention strategy to stop viral transmission in these age groups.

  • Title of study: Association of age with likelihood of developing symptoms and critical disease among close contacts exposed to patients with confirmed SARS-CoV-2 infection in Italy [14]
  • Authors: Poletti P et al.
  • Journal: JAMA Network Open
  • AMBOSS links: COVID-19

COVID-19: Helmet noninvasive ventilation associated with lower rates of endotracheal intubation compared to high-flow oxygen

One-Minute Telegram 23-2021-3/3 - The best strategy for ventilation in patients with hypoxemic respiratory failure due to SARS-CoV-2 infection remains a pressing area of research. Helmet-based ventilation, a noninvasive form of ventilation that delivers oxygen to the patient via a helmet secured to the shoulders, is one option. [15]

This multicenter randomized clinical trial conducted between October and December 2020 in 4 ICUs evaluated the effect of at least 48 hours of continuous treatment with helmet ventilation (initial PEEP 10–12 cm H2O; initial pressure support 10–12 cm H2O), followed by continuous Venturi mask or high-flow nasal oxygen (intervention group; n = 54), compared to high-flow nasal oxygen 60 L/min alone (control group; n =55).

Patients had a PCR-confirmed COVID-19 infection and moderate to severe hypoxemic respiratory failure (PaO2/FIO2 < 200).

Results in the intervention group compared to the control group:

  • Primary outcome: no difference in median days free of respiratory support [20 (IQR 0–25) vs. 18 days (0–22), P = 0.26]
  • Secondary outcomes:
    • Lower rate of endotracheal intubation within 28 days of hospitalization in intervention group of 30% vs. 51% (OR, 0.41; 95% CI, 0.18 to 0.89)
    • No difference in mortality rates at 28 and 60 days and mean duration of stay
  • Safety endpoints: no difference in the median hours to intubation and no need for emergency intubation in either group.

Limitations include that, due to the relatively small sample size, the study may have been underpowered to detect differences in the primary outcome. These results cannot be generalized to patients with respiratory failure from causes other than COVID-19.

The take‑home message?

Results from this study show that in patients with moderate/severe hypoxemia, helmet ventilation compared to high flow nasal oxygen alone was not associated with a reduced number of respiratory support days. However, results suggest that helmet ventilation may prevent the necessity of endotracheal intubation within 28 days of hospitalization, but this result requires confirmation by future trials.

  • Title of study: Effect of helmet noninvasive ventilation vs high-flow nasal oxygen on days free of respiratory support in patients with COVID-19 and moderate to severe hypoxemic respiratory failure [16]
  • Authors: Grieco DL et al.
  • Journal: JAMA
  • AMBOSS links: COVID-19

Your Easter edition: Rabbit fever, baskets and eggs!

One-Minute Telegram 22-2021-1/3

Rabbit fever – If the Killer Rabbit of Caerbannog has taught us anything [17], it’s that a cottontail’s adorable appearance can be deceptive, but it isn’t just its bite that’s potentially deadly. Rabbit fever, or tularemia, is a vector-borne disease predominantly transmitted by ticks and caused by the bacteria Francisella tularensis, for whom rabbits are a common reservoir host. A recent case report by Lukas Antonitsch and colleagues narrates the case of a 53-year-old man who presented with a 3-week history of fever, diarrhea, vomiting, cough, and significant weight loss unresponsive to supportive measures. [18] While the patient did not report attacks by ferocious rabbits or ravenous ticks, a more detailed investigation of his history revealed that he had been working in the woods over the past 6 weeks. Accordingly, a diagnosis was suspected and serological testing with ELISA confirmed the presence of IgG and IgM antibodies against F. tularensis. This case report highlights the importance of proper history taking when it comes to patients with fever of unknown origin – and of keeping rabbit fever in mind as a differential diagnosis, considering its very variable manifestations (e.g., ulceroglandular, glandular, oculoglandular, pharyngeal, pulmonary, typhoid).

Are your baskets ready? – Word around town is the Easter Bunny is already busy decorating eggs and we’re all itching to go hunt them! But what if the Easter Bunny gets COVID-19?! There is plenty of evidence that animals (e.g., minks) are susceptible to SARS-CoV-2 infection and that some may even develop symptoms. [19][20] But what about bunnies? Anna Z. Mykytyn and colleagues recently conducted an experimental study to determine the response of rabbits to inoculation with SARS-CoV-2 and found that, while no rabbits developed symptoms, they were indeed susceptible to infection. [21] However, transmission between themselves and to other species is yet to be determined. In conclusion, we probably shouldn’t be all too concerned about the Easter Bunny developing COVID-19, nor do we believe the Easter Bunny poses much of a risk to humans, considering his shy and sneaky nature. However, we would greatly appreciate Dr. Fauci’s opinion just to be sure!

The take‑home message?

If you are getting ready to hunt for eggs this Easter, try not to get bitten by ticks (or killer rabbits) and, as always, take a look at the CDC holiday tips to protect yourself and your loved ones against SARS-CoV-2 infection. [22]

Combination of remdesivir and baricitinib in fighting COVID-19

One-Minute Telegram 22-2021-2/3: So far, dexamethasone is the only drug that has clearly been shown to reduce mortality in severe COVID-19, most likely due to its antiinflammatory effects. [1][23] This has inspired research into the effects of other immunosuppressants as well. One such candidate is baricitinib, a selective inhibitor of Janus kinase (JAK) 1 and 2 that inhibits the intracellular signaling pathway of cytokines, which are known to be elevated in patients with severe COVID-19.

In this multicenter study, 1033 hospitalized patients with moderate or severe COVID-19 were randomized to receive either a combination treatment with remdesivir and baricitinib (n = 515) or remdesivir and placebo (n = 518). The primary outcome measure was the time to recovery.

Patients who received the combination treatment with remdesivir and baricitinib showed the following results in comparison to those receiving remdesivir alone:

  • Shorter median time to recovery: 7 days versus 8 days (rate ratio, 1.16; 95% CI, 1.01 to 1.32) and 10 days versus 18 days in patients who were receiving high-flow oxygen or noninvasive ventilation at enrollment (rate ratio, 1.51; 1.10 to 2.08). This beneficial effect was not seen in patients receiving low-flow oxygen or no oxygen at baseline.
  • Higher odds of improved clinical status at day 15 (OR, 1.3; 1.0 to 1.6)
  • Lower frequency of serious adverse events (16.0% vs. 21.0%; P = 0.03)
  • Lower incidence of new use of oxygen (difference, -17.4%; -31.6 to -2.1) and new use of mechanical ventilation or ECMO (difference, -5.2%; -9.5 to -0.9)
  • Lower 28-day mortality 5.1% vs. 7.8%, though this did not reach statistical significance (HR for death, 0.65; 0.39 to 1.09)

Limitations of this study include the fact that it was not powered to detect differences in mortality between the two groups and the lack of follow-up on potential longer-term drug effects beyond 28 days.

The take‑home message?

This study showed that a combination of remdesivir and baricitinib compared to remdesivir monotherapy reduced the median time to recovery in hospitalized patients with COVID-19, with the highest efficacy seen in patients receiving high-flow oxygen or noninvasive ventilation at baseline. Combination therapy was also associated with a reduced need for respiratory support and lower incidence of serious short-term adverse events. Further studies are needed to assess the effect of baricitinib PLUS remdesivir on mortality and to compare the efficacy, safety, and cost-effectiveness of baricitinib with that of dexamethasone.

Recolonizing the colon: New treatment for recurrent Clostridioides difficile infection

One-Minute Telegram 22-2021-3/3: Fecal microbiota transplantation (FMT) is a highly effective therapy for recurrent C. difficile infection, but carries a certain risk of infection transmission (e.g., pathogenic E. coli), besides being potentially unpleasant. [25] Now, a safer and possibly more appealing way to reconstitute the gut microbiome has been developed. The Microbial Ecosystem Therapeutic 2 (MET-2) is an encapsulated formulation of 40 bacterial species that were extracted from the stool of a healthy donor and subsequently highly purified and cultured independently of donor stool.

In this phase 1, open-label, single-group study, 19 patients with mild or moderate recurrent C. difficile infection received an oral course of treatment with MET-2 after completing initial treatment with oral vancomycin. Of these, 15 participants (79%) showed absence of recurrent C. difficile infection at day 40. The four patients who did not respond to initial treatment were retreated with a higher dose of MET-2. Three of these did not experience recurrence of C. difficile at 30 days following retreatment. By day 130 of the initial treatment 16 of 19 patients (84%) did not experience C. difficile recurrence.

No serious adverse events, MET-2-associated infections, or deaths were observed.

Limitations include the absence of a control group, the small sample size, and lack of longer-term follow-up.

The take‑home message?

In this small, industry sponsored phase-1 trial, MET-2, a highly purified orally administered mix of gut bacteria was shown to be well-tolerated and effective in treating recurrent C. difficile infection. Randomized-controlled studies are required to confirm these results and to compare the efficacy of MET-2 against that of FMT.

  • Title of study: The effect of a microbial ecosystem therapeutic (MET-2) on recurrent Clostridioides difficile infection: a phase 1, open-label, single-group trial [26]
  • Authors: Kao D et al.
  • Journal: Lancet Gastroenteroly & Hepatology

Do antibodies against SARS-CoV-2 protect against reinfection?

One-Minute Telegram 21-2021-1/3 - Case reports on COVID-19 reinfection raise the question of whether or not SARS-CoV-2 antibodies from a previous infection provide long-term immunity. [27]

Using laboratory data from 3,257,478 US patients, this retrospective cohort study attempted to determine if previous exposure to SARS-CoV-2 (defined as an initial positive antibody test) resulted in protection against future infection as confirmed by nucleic acid amplification test (NAAT). At baseline, 88.3% of patients had negative and 11.6% had positive antibody test results. From day 0 to 30, initially seropositive patients were more likely to have positive NAAT results, probably due to continued viral shedding (ratio 2.85; 95% CI, 2.73–2.97). After 30 days of follow-up, however, patients who were initially seropositive became much less likely than initially seronegative patients to have positive NAAT for SARS-CoV-2:

  • Day 31–60: ratio 0.67; 95% CI, 0.6–0.74
  • Day 61–90: ratio 0.29; 95% CI, 0.24–0.35
  • After day 90: ratio 0.10; 95% CI, 0.05–0.19

Limitations include a lack of data regarding possible differences in viral exposure between the groups. In addition, patients’ awareness of their initial serological test result may have influenced their behavior, including their engagement in social activities and motivation to seek further tests. Furthermore, the study did not provide information on whether positive NAAT results in either group were associated with the development of symptoms.

The take‑home message?

Results from this large study with over 3 million participants suggest that patients who are seropositive for SARS-CoV-2 have a decreased risk of future SARS-CoV-2 infection. However, the duration of immunity from infection remains to be determined.

  • Title of study: Association of SARS-CoV-2 seropositive antibody test with risk of future infection [28]
  • Authors: Harvey RA et al.
  • Journal: JAMA Internal Medicine
  • AMBOSS links: COVID-19

Amoxicillin-clavulanate: An alternative to fluoroquinolones in treating diverticulitis?

One-Minute Telegram 21-2021-2/3 - Concerns over the adverse effects of fluoroquinolones have led the FDA to advise restricting their use to conditions for which there is no equivalent treatment. However, data regarding the comparative effectiveness of fluoroquinolones and other antibiotics in various infections is scarce. [29]

This retrospective study compared the outpatient treatment of diverticulitis with a combination of metronidazole and fluoroquinolone (n = 124,000) vs. amoxicillin-clavulanate (n = 15,869) in immunocompetent patients, measuring the risks for admission, urgent surgery, and Clostridium difficile infection over the following year and the need for elective surgery over the following 3 years.

There was no difference between the groups in 1-year admission risk, 1-year urgent surgery risk, or 3-year elective surgery risk. In the subgroup of patients aged over 65 years, the 1-year risk of infection with C. difficile was slightly higher for patients treated with metronidazole and fluoroquinolone (risk difference 0.6%; 95% CI, 0.2–1.0).

Limitations include the retrospective study design based on insurance claims, which may have led to residual confounding as a result of missing data on potentially relevant patient characteristics. In addition, the study did not report on adverse effects associated with these antibiotics (e.g., drug-induced liver injury from amoxicillin-clavulanate).

The take‑home message?

This retrospective study showed that outpatient treatment of diverticulitis with amoxicillin-clavulanate was as effective as treatment with metronidazole and fluoroquinolone, providing a safe alternative to fluoroquinolones. However, randomized-controlled studies are needed to verify these results.

Effects of a diet with a high glycemic index and glycemic load on cardiovascular events and death

One-Minute Telegram 21-2021-3/3 - The glycemic index (GI) reflects the glucose-raising effect of any carbohydrate relative to the glucose-raising effect of glucose, while the glycemic load (GL) accounts for both the GI and the quantity of carbohydrates consumed. High-GI and high-GL diets have been linked to diabetes and cardiovascular disease (CVD) in high-income countries; however, this association has not been studied as extensively in other regions of the world. [31]

The present study included 137,851 individuals living in high-, middle-, and low-income countries across five continents. The GI and GL of their diets were estimated using questionnaires, and participants were followed for a median of 9.5 years. During this period, the investigators recorded 8,780 deaths and 8,252 major cardiovascular events.

A high-GI diet was associated with an increased risk of a major cardiovascular event or death. This association was seen in participants with preexisting CVD (HR 1.51; 95% CI, 1.25–1.82) as well as in those without preexisting CVD (HR 1.21; 1.11–1.34). In participants with preexisiting CVD, a high-GL diet was likewise associated with major cardiovascular events and death (HR 1.34; 1.08-1.67).

Limitations of this study include the reliance on self-reported dietary intake data and the questionnaire’s limited scope. In addition, the number of participants per country was too low to permit regional analyses.

The take‑home message?

This international study shows that a high-GI and high-GL diet is associated with an increased risk of major cardiovascular events and death. It furthermore provides evidence that this association is not limited to high-income countries.

  • Title of study: Glycemic index, glycemic load, and cardiovascular disease and mortality [32]
  • Authors: Jenkins DJA et al.
  • Journal: NEJM

Better outcomes after implementation of critical care management protocols?

One-Minute Telegram 20-2021-1/3 - An effective pharmacological therapy for COVID-19 remains elusive, but clinical experience in the critical care of other respiratory conditions may lead the way in establishing management protocols for SARS-CoV-2 infection.

This multi-center retrospective cohort US study determined the 28-day outcomes of 147 critically ill patients with COVID-19 to evaluate the impact of an evidence-based management protocol for respiratory failure and ARDS (n=54) compared to standard ICU care (n=93). The primary outcome was ventilator-free days. [33]

The study found the following benefits in patients treated according to the evidence-based management protocol:

Limitations include potential differences not accounted for between the groups, given that patients came from hospitals serving different populations and with different standards for ICU care. In addition, the retrospective design of this study makes it susceptible to bias and residual confounding and limits the ability to attribute superior outcomes to protocol implementation.

The take‑home message?

In this study, ICU patients with COVID-19 who were treated with an evidence-based respiratory management protocol had lower mortality, more ventilator-free days, and less need for renal replacement therapy compared to those treated with standard ICU care during a 28-day observation. While it remains to be seen which parts of the protocol benefited the patients most, it is good news that the experience of intensive care medicine translates into measurable benefits in the treatment of COVID-19.

Hepatitis C vaccine: The search continues

One-Minute Telegram 20-2021-2/3 - Chronic hepatitis C virus (HCV) infection is a leading cause of death worldwide, and incidence has sharply increased in the United States, in part due to the opioid crisis. Although there are drugs that can cure HCV infection, treatment regimens last for 8–12 weeks and require strict adherence, which is frequently lacking in high-risk groups. The advent of a vaccine would be a game-changer in the fight against HCV, especially in at-risk patient groups. [35][36][37]

This double-blinded study used a heterologous prime-boost immunization strategy, based on a recombinant chimpanzee adenovirus and an attenuated poxvirus vaccine. 548 HCV-uninfected adults who had injected drugs within 90 days before study participation were randomly assigned in a 1:1 ratio to the vaccine or placebo group. Both groups received an intramuscular injection on days 0 and 56 of the study, containing either the vaccine or placebo.

At 9 months follow-up, 14 participants in each group had developed chronic HCV infection defined as persistent viremia for 6 months (HR [vaccine vs. placebo] 1.53; 95% CI, 0.66-3.55). However, T-cell responses to HCV were present in 78% of participants in the vaccine group but only in 3% of participants in the placebo group. There were no reports of vaccine-related serious adverse events.

Limitations of this study include the fact that, while groups were stratified by sex, men were significantly overrepresented (78%).

The take‑home message?

The HCV vaccine candidate evaluated in this study elicited HCV-specific T-cell responses but failed to prevent chronic HCV infection. The search for an HCV-vaccine, therefore, remains ongoing.

Semaglutide helps reduce weight – in patients without diabetes

One-Minute Telegram 20-2021-3/3 - Semaglutide is a modified human glucagon-like peptide-1 (GLP-1) analogue that has been approved and successfully used to reduce weight, improve glycemic control, and reduce adverse cardiovascular events in patients with type 2 diabetes. Whether the positive effects of the drug extend to patients without type 2 diabetes has been a matter of ongoing research. [39][40]

In this double-blinded international trial, 1961 adults without diabetes and a body-mass index of 30 or greater (or ≥ 27 in persons with ≥ 1 weight-related coexisting condition) were randomized in a 2:1 ratio for 68 weeks of treatment with a once-weekly dose of 2.4 mg subcutaneous semaglutide or placebo. All participants additionally received counseling sessions targeting lifestyle interventions.

At week 68, patients in the semaglutide group had lost 14.9% of their body weight compared to 2.4% in the placebo group (treatment difference of -12.4% [95% CI, -13.4 to -11.5; P < 0.001]). Compared to patients in the placebo group, patients in the semaglutide group were more likely to achieve body weight reductions of ≥ 5% (86.4% vs. 31.5%), ≥ 10% (69.1% vs. 12.0%), and ≥ 15% (50.5% vs. 4.9%) during the study period (P < 0.001 for all three comparisons of odds). In addition, physical functioning scores (SF-36) improved significantly in the semaglutide group (P < 0.001).

Adverse events were mild to moderate, with gastrointestinal side-effects (i.e., nausea, diarrhea) sometimes leading to termination of participation in the semaglutide group.

Limitations include the lack of long-term follow-up and the high percentage of female (74.1%) and white participants (75.1%) included in the study.

The take‑home message?

In this randomized double-blinded trial the use of once weekly semaglutide in obese and overweight patients without diabetes led to clinically significant weight loss. However, longer-term follow-up is necessary to determine whether the treatment effect lasts and whether semaglutide also improves cardiovascular outcomes in this population.

  • Title of study: Once-weekly semaglutide in adults with overweight or obesity [41]
  • Authors: Wilding JPH et al.
  • Journal: NEJM

Anticoagulation in COVID-19 – does it affect mortality?

One-Minute Telegram 19-2021-1/3 - Early in the pandemic, reports of high rates of venous and arterial thromboembolism gave rise to recommendations for empiric therapeutic anticoagulation in critically ill patients with COVID-19. However, comprehensive data regarding the effects of therapeutic anticoagulation on mortality has remained scarce. [42][43]

This multicenter US cohort study analyzed the incidence of venous thromboembolism (VTE) and major bleeding in patients with COVID-19 within 14 days of admission to an intensive care unit (ICU). Of 3239 critically ill patients with COVID-19 who were included, 43.6% received therapeutic anticoagulation, 6.3% developed VTE, and 2.8% developed major bleeding.

In addition, the investigators performed a target trial emulation that compared survival in patients who had received therapeutic anticoagulation within 2 days of ICU admission to survival in those who had not. [44] Of the 2809 patients included in the analysis, 11.9% received early therapeutic anticoagulation. During follow-up (median of 27 days), the risk of death did not differ significantly between patients who received early therapeutic anticoagulation and those who did not (HR 1.12; 95% CI, 0.92–1.35).

Limitations of this study include observational design, heterogeneous anticoagulation dosing across study centers, and lack of data regarding reasons for the timing of anticoagulation in individual patients. Moreover, lack of specific screening may have led to underestimation of VTE rates.

The take‑home message?

This observational multicenter study reported 6.3% VTE and 2.8% major bleeding incidence among ICU-admitted COVID-19 patients of whom 43.6% had received therapeutic anticoagulation. A target trial emulation showed that early therapeutic anticoagulation did not reduce the risk of death compared to late or no therapeutic anticoagulation. Although the results aid our understanding of the role and timing of therapeutic anticoagulation in COVID-19 patients, they still require confirmation by randomized clinical trials.

  • Title of study: Thrombosis, bleeding, and the observational effect of early therapeutic anticoagulation on survival in critically ill patients with COVID-19 [45]
  • Authors: Al-Samkari H, et al.
  • Journal: Annals of Internal Medicine
  • AMBOSS links: COVID-19

The long shadow of COVID-19: Respiratory and functional sequelae in survivors

One-Minute Telegram 19-2021-2/3 - Evidence is mounting that COVID-19 has long-term sequelae ranging from neurological symptoms to persistent fatigue and lung damage. [46] However, large case series on this new entity termed “long COVID” remain scarce. [47]

This Italian case series included 238 hospitalized patients with severe COVID-19 and assessed pulmonary function, functional impairment, and psychological sequelae 4 months after discharge.

After 4 months, diffusing lung capacity for carbon monoxide (DLCO) was measured in 219 patients. Results showed a DLCO < 80% of normal capacity in 51.6% of patients and a DLCO < 60% of normal capacity in 15.5% of patients.

53.8% of patients showed some degree of functional impairment as measured by a Short Physical Performance Battery (SPPB) and, in some cases, a 2-minute walk test. Moderate or severe posttraumatic stress symptoms were reported in 17.2% of patients. Ageusia was present in 5.0%, anosmia in 4.6%, and arthralgia and myalgia in 5.9% of patients.

Limitations of this study include a high risk of selection bias, as 64.4% of eligible patients wished not to participate. Also, since only hospitalized patients with severe COVID-19 were included, the results cannot be generalized to other populations. Lastly, neurological symptoms were not specifically tested even though they are common and may have contributed to functional impairment. [48]

The take‑home message?

In this case series of patients who had been hospitalized for COVID-19, more than half showed reduced lung function (tested with DLCO) and functional impairments at 4 months after discharge. Posttraumatic stress symptoms were reported in almost one-fifth of patients, while ageusia, anosmia, arthralgias, and myalgias were less frequent. This report contributes to specifying the emerging entity termed “long COVID,” but comprehensive analyses and definitions are still lacking.

  • Title of study: Respiratory and psychophysical sequelae among patients with COVID-19 four months after hospital discharge [7]
  • Authors: Bellan M, et al.
  • Journal: JAMA Network Open
  • AMBOSS links: COVID-19

Your Valentine’s Day edition: Of broken hearts, happy hearts, and STIs

One-Minute Telegram 19-2021-3/3

Don’t go breaking my heart – Severe physical and emotional stress can literally break your heart or, as a physician might say, cause Takutsubo syndrome (TTS) – a ballooning of the ventricles that eventually leads to acute systolic heart failure. [49] TTS is typically thought to occur secondary to stressors such as negative life events; and – as if evidence of an association between COVID-19 and increased risk of cardiomyopathy weren’t enough – it now appears that the burden of the pandemic may be another such stressor. A recent case series by Devika Kir and colleagues discussed two women who presented with TTS. Upon questioning the first patient reported extreme emotional distress caused by social isolation, while the second was distressed by her inability to access routine healthcare. [50] The association of pandemic stress and TTS was confirmed by a recent retrospective cohort study by Ahmad Jabri and colleagues, which found that the incidence of TTS among patients presenting with acute coronary syndrome increased from 1.5–1.8% pre-pandemic to 7.8% during the pandemic (rate ratio = 4.58; 95% CI, 4.11–5.11). This increase was not attributable to SARS-CoV-2 infection, since all patients in the study were PCR negative. [51] Turns out the owner of a lonely heart is also at risk of owning a broken heart.

Happy heart syndrome – Can a heart also break from happiness? The short answer is: yes. Jelena R. Ghadri and colleagues studied data from the International Takotsubo Registry to determine whether there was an association between positive emotional stress and TTS. Of the 1750 patients with TTS included in the study, 485 reported a definite emotional trigger prior to the diagnosis, with 20 (4.1%) reporting a positive emotional trigger such as winning a jackpot, attending celebrations like birthday parties and weddings, or reveling in one's favorite driver winning a race. [52] Sure, we’re all eager for the COVID-19 restrictions to end, but maybe we shouldn’t get too excited when they actually do?

Love bites – The consequences of love are many and, unfortunately, include sexually transmitted infections (STIs). But what effect has the advice to stay home, keep your distance, and cover up infectious orifices had on the incidence of STIs? A study by Matthew A. Crane and colleagues looked at CDC data from 2020 and found that the mean number of reported cases of chlamydia and gonorrhea declined after week 11, near the date when the COVID-19 outbreak was declared a national emergency. [53] You might think this was a cause for celebration, heightened only by the fact that almost every other notifiable disease showed a decrease in reported cases during this period as well. But – and we do hope this emotional roller coaster ride won't give anyone TTS – it turns out the news is not so good after all. Rather than reduced transmission, the authors concluded that reduced testing and reporting were more likely responsible for the decrease in numbers.

The take‑home message?

This Valentine's Day don't go breaking any hearts, try to fall madly in love (just don’t get too emotional about it), and barrier-protect the ones you fall in love with!

Online harassment – how are physicians affected?

One-Minute Telegram 18-2021-1/3 - With social media today spanning all walks of life, online harassment has become a problem that affects all of society. As a professional group faced with moral decisions on a daily basis, physicians have always been exposed to their fair share of controversy, but how has social media changed the discourse, and what are the issues stirring the most controversy today?

This report discusses an online survey of 464 participants who self-identified as physicians, 57.8% of which were women and 76.9% of which were white. Nearly one-quarter of participants (23.3%) reported personal harassment on social media over the topics of vaccines (n=10), race (n=4), religion (n=3), gun control (n=3), abortion (n=2), and smoking (n=2), with no significant difference between men and women. However, women were significantly more likely than men to report online sexual harassment (16.4% vs 1.5%, P < 0.001), i.e., explicit messages (n=12) and threats of assault (n=2).

Limitations of the study include the high risk of a reporting and selection bias, as participants were recruited from the study authors’ Twitter followers; the self-report design of the study, which makes it impossible to confirm the accounts of harassment; and the fact that the majority of participants was white, limiting the generalizability of the results.

The take‑home message?

This report strongly suggests that physicians are no exception with regard to the harassment people face in social media. While anti-vaccination stances are a common trigger, harassment over non-medical issues such as race, religion, and gun control are also prevalent. Moreover, female physicians experience sexual harassment more frequently than their male colleagues, reflecting a similar situation in other areas of social and professional life. A more representative examination is needed to assess the extent of the problem in detail and to determine what actions should be taken to address it.

  • Title of study: Prevalence of personal attacks and sexual harassment of physicians on social media [54]
  • Authors: Pendergrast TR et al.
  • Journal: JAMA Internal Medicine

Transfusion of plasma with high antibody levels could reduce mortality in COVID-19 – if the timing is right

One-Minute Telegram 18-2021-2/3 - The evidence on whether the transfusion of plasma with anti-SARS-CoV-2 IgG antibodies reduces mortality in COVID-19 has so far been inconclusive, and there are no established protocols regarding the timing of the transfusion and the levels of antibodies required. [55]

This retrospective cohort study assessed the 30-day mortality of 3082 patients with COVID-19 who had received one unit of convalescent plasma with either low, medium, or high anti-SARS-CoV-2 IgG antibody levels. Demographic characteristics, risk factors associated with severe COVID-19, and concomitant use of therapeutic agents were similar in all three groups.

Among patients who were not on mechanical ventilation, those who received plasma with high levels of antibodies had a significantly lower 30-day mortality than those who received plasma with low levels of antibodies (RR 0.66; 95% CI, 0.48 to 0.91). Unadjusted mortality rates were lower for patients who received the transfusion within the first three days of COVID-19 diagnosis, compared to patients who received the transfusion ≥ 4 days after diagnosis (22.2% vs. 29.5%, respectively).

No effect on mortality was observed in patients who were on mechanical ventilation at the time of plasma transfusion.

Limitations include the retrospective design and the lack of a control group for comparison.

The take‑home message?

Hospitalized patients with COVID-19 who are not on mechanical ventilation may benefit from receiving plasma transfusions with high levels of anti-SARS-CoV-2 IgG antibodies, especially if the treatment is provided within 3 days of diagnosis. However, further studies are needed to confirm this benefit.

New monoclonal antibody helps to reduce body fat in patients with type 2 diabetes

One-Minute Telegram 18-2021-3/3 - Acknowledging the association between obesity and increased insulin resistance, the FDA has approved a number of weight-loss drugs in recent years. [57][58]

The novel antibody bimagrumab was originally developed to treat pathological muscle loss and weakness in sporadic inclusion body myositis but failed to meet its primary endpoint in a phase IIb/III study. The present double-blinded, randomized phase II clinical trial has investigated the drug’s weight-loss effects in patients with type 2 diabetes who were not taking any weight-reducing drugs and who had HbA1c levels between 6.5% and 10% and a BMI between 28 and 40 kg/m2. [59]

75 patients were randomized 1:1 and received either bimagrumab (n = 37, 62.2% women) or a placebo (n = 38, 31.6% women) every 4 weeks for 48 weeks. Furthermore, patients in both groups were advised to follow a calorie-restricted diet and met with a registered dietitian in person at each monthly study visit.

At week 48, patients treated with bimagrumab showed a significant reduction in total body fat mass of -7.31 kg (80% CI: -8.48 to -6.14; P < 0 .001) more than the placebo group. In addition, body weight and HbA1c level were significantly reduced in the bimagrumab group compared to the placebo group (P < 0.001 and P = 0.005, respectively).

More patients experienced transient elevations of pancreatic and liver enzymes in the bimagrumab group, but the frequency of adverse and serious adverse events did not differ between groups.

Limitations of this study include the small sample size and a slight gender imbalance between the groups.

The take‑home message?

In this phase II trial, 48 weeks of treatment with the novel antibody bimagrumab combined with lifestyle interventions helped to significantly reduce total body fat mass, body weight, and HbA1c levels in overweight and obese patients with type 2 diabetes. If a phase III trial can replicate these positive results, bimagrumab could become a valuable addition to the arsenal of treatment for type 2 diabetes.

A CRISPR-Cas miracle? Report on two successful attempts at treatment

One-Minute Telegram 17-2021-1/3 - Hopes are high that selective gene-editing therapy with CRISPR-Cas9 can provide a curative and safe alternative to bone marrow transplant for patients with sickle cell disease (SCD) and transfusion-dependent β-thalassemia (TDT). These reports discuss the use of CRISPR-Cas9 on autologous hematopoietic stem and progenitor cells (HSPCs) to reduce the expression of BCL11A, a transcription factor that suppresses the production of fetal hemoglobin. Two patients, one with SCD and the other with TDT, received the autologous CRISPR-Cas9–edited CD34 + HSPCs in a single transfusion following myeloablation with busulfan.

Serious adverse events were mostly related to severe neutropenia following myeloablation.

The take‑home message?

These two case reports demonstrate that CRISPR-Cas9 has evolved from the laboratory to become a real-world alternative in the treatment of monogenic hematological diseases. While large-cohort trials with long-term follow-up are needed to confirm the effects of treatment and assess adverse events, these reports already bear positive news for patients living with genetic diseases such as sickle cell disease and thalassemias.

COVID-19: The Moderna vaccine

One-Minute Telegram 17-2021-2/3 - The mRNA-1273 vaccine, developed by Moderna, relies on mRNA technology and is the second COVID-19 vaccine to receive emergency use approval by the FDA. [62][63]

A total of 30,420 participants aged 18 years or older were randomized 1:1 to receive either 2 doses of the vaccine or a placebo, 28 days apart. The mean age of the participants was 51.4 years; enrollment was adjusted for equal representation of racial and ethnic minorities.

  • Vaccine efficacy to prevent symptomatic COVID-19 with onset ≥ 14 days after the second injection was 94.1% (95% CI, 89.3% to 96.8%; 11 cases vs. 185 cases, respectively).
    • Efficacy was similar across age, sex, race, and ethnicity as well as in patients with and without risk factors for severe disease (e.g., chronic lung disease, cardiac disease, severe obesity).
    • There were no severe courses of COVID-19 (e.g., ARDS or shock) in the vaccine group, in contrast to the placebo group, in which 30 patients developed a severe course.
  • The safety profile was favorable.
    • The most common local reaction was mild to moderate pain at the injection site (reported in ∼ 75%). The most common systemic symptoms were fatigue, myalgia, arthralgia, and headache (reported in ∼ 50%).
    • The overall incidence of serious adverse events did not differ significantly between groups. No deaths occurred in relation to the vaccine.
    • Limitations include that the study was not powered to detect rare adverse events and that the long-term effects remain unknown. The exclusion of children, pregnant women, and immunocompromised patients limits the generalizability of the results.

The take‑home message?

This industry-sponsored study showed that the mRNA-1273 vaccine has a high efficacy and favorable safety profile (with the added benefit that it can be stored at 2–8°C). While this vaccine is already being administered, further investigations are necessary to establish safety and efficacy profiles for populations not included in this study as well as to assess its long term effects. [64]

COVID-19: Variation in hospital mortality rates across the US

One-Minute Telegram 17-2021-3/3 - Mortality from COVID-19 can be influenced by many factors, but does in-hospital mortality vary between hospitals, and has in-hospital mortality changed since the start of the pandemic? [66]

This cohort study used data from 38,517 adult patients with COVID-19 admitted to different hospitals in the US to analyze the differences in the hospital’s risk-standardized event rate (RSER), a composite of inpatient mortality or referral to hospice within 30 days of initial admission.

The overall mean RSER was 11.8% (SD 2.5%) but varied considerably across hospitals (ranging from 5.70% to 24.65%). There was no association between a hospital’s RSER and the number of intensive care unit beds, academic status, profit status, or urban/nonurban setting.

Changes in the RSER over time were assessed for a subset of 27,801 patients in 398 hospitals (n = 27,801; 72.2%). The mean RSERs improved from 16.56% (SD 3.99%) to 9.29% (SD 2.08%) between two study periods from January 1 to April 30, 2020, and May 1 to June 30, 2020. Worsening RSER was associated with an increase in the prevalence of COVID-19 in the hospital’s surrounding communities.

Limitations include that the data was based on a single insurer’s claims. Also, out-of-hospital mortality was not considered. Furthermore, the reasons for the decrease in mortality remain unclear.

The take‑home message?

Overall mortality or referral to hospice in COVID-19 patients decreased in US hospitals over the early course of the pandemic. Hospitals with higher mortality rates had a higher prevalence of COVID-19 in their area compared to hospitals with lower rates. However, further studies are needed to identify other underlying mechanisms for the improvement in mortality, as they may help to guide future hospital policies and treatment strategies.

COVID-19: The BioNTech-Pfizer vaccine is here. How safe and effective is it?

One-Minute Telegram 16-2021-1/2 - After much research and effort, a highly effective and specific treatment for COVID-19 has not been found, but in less than one year after starting development, vaccines are here and have been granted emergency use approval by the FDA. [68][69]

This blinded study presents the results of the mRNA-vaccine (BNT162b2) developed by BioNTech and Pfizer. A total of 43,548 participants were randomized to receive either 2 doses of the vaccine (n = 21,720) or a placebo (n =21,728) 21 days apart. Participant ages ranged from 16 to 91 years and 35.1% of participants were classified as having obesity. Comorbidities included HIV, malignancy, diabetes, and vascular diseases.

  • Vaccine efficacy was 95.0% (95% CI, 90.3–97.6), ≥ 7 days after the second vaccine dose (8 cases vs. 162 cases, respectively).
    • Efficacy was similar among different groups of age, sex, race, ethnicity, BMI, and comorbidities.
    • Severe COVID-19 occurred in one patient in the vaccine group, and nine patients in the placebo group.
  • The safety profile was favorable.
    • The most common local reaction was mild to moderate pain at the injection site. The most common systemic symptoms were fatigue and headache (reported in ≥ 50%).
    • The incidence of serious adverse events did not differ significantly between the vaccine and the placebo groups (0.6% and 0.5%, respectively) and no deaths occurred related to the vaccine.

Limitations include that the study was not powered to detect rare adverse events (like anaphylaxis) and that long-term effects are unknown. [70] Exclusion of children, pregnant women, and immunocompromised patients limits the generalizability of the results.

The take‑home message?

This industry-sponsored study showed that the mRNA-vaccine BNT162b2 is safe and effective in protecting against COVID-19. However, further investigations are needed to confirm if protection is similar between different groups within the studied population, if the vaccine could limit severe disease in people who do get infected, and to establish safety and efficacy for populations not included in this study.

Impact of race and ethnicity on COVID-19 outcomes: what is driving the death rate?

One-Minute Telegram 16-2021-2/2 - Black and Hispanic populations are more affected by COVID-19, but are race and ethnicity independently driving these disproportionately high death rates? [72]

The aim of this retrospective cohort study was to compare the outcome of patients with COVID-19 based on race and ethnicity. Data from 9,722 patients in an integrated health-care system in New York City was used to explore the effect of race and ethnicity on the likelihood of having PCR positive COVID-19 and subsequently worse health outcomes, after adjusting for age, sex, insurance, and comorbidity.

  • Race or ethnicity were independent risk factors for testing positive for COVID-19 for black (adjusted OR 1.3; 95% CI, 1.2-1.6) and Hispanic patients (adjusted OR 1.5; 1.3–1.7), compared to white patients.
  • Among positive patients, Asian patients had the highest likelihood of hospitalization (adjusted OR 1.6; 1.1–2.3). Hispanic, black, and white patients had a similar likelihood of being hospitalized.
  • Black patients were less likely to have critical illness (adjusted OR 0.6; 0.4–0.8) and also had a lower risk of death compared with white patients (HR, 0.7; 0.6–0.9); the likelihood among Hispanic, Asian, and white patients was similar.

Limitations include that data on the final outcome was not available for 4.5% of the patients at the end of the study period.


The take‑home message?

Black and Hispanic patients had a higher likelihood than white patients of testing positive for COVID-19. However, once hospitalized, their health outcomes were similar to or better than white patient outcomes. So why then is their non-adjusted, general risk of death due to COVID-19 higher? The authors' hypothesis: social determinants of health increase the probability of contracting the disease and barriers to seeking healthcare increase the number of deaths occurring at home. [73]

  • Title of study: Assessment of racial/ethnic disparities in hospitalization and mortality in patients with COVID-19 in New York City [74]
  • Authors: Ogedegbe et al.
  • Journal: JAMA Network Open
  • AMBOSS links: COVID-19
  1. Health data - HIV AIDS. http://www.healthdata.org/hiv-aids. . Accessed: April 12, 2021.
  2. Global HIV & AIDS statistics — 2020 fact sheet. https://www.unaids.org/en/resources/fact-sheet#:~:text=AIDS%2Drelated%20deaths%20have%20been,1.6%20million%5D%20people%20in%202010.. . Accessed: April 12, 2021.
  3. Corey L, Gilbert PB, Juraska M, et al. Two Randomized Trials of Neutralizing Antibodies to Prevent HIV-1 Acquisition.. N Engl J Med. 2021; 384 (11): p.1003-1014. doi: 10.1056/NEJMoa2031738 . | Open in Read by QxMD
  4. Nogrady B. What the data say about asymptomatic COVID infections. Nature. 2020; 587 (7835): p.534-535. doi: 10.1038/d41586-020-03141-3 . | Open in Read by QxMD
  5. Poletti P, Tirani M, Cereda D, et al. Association of Age With Likelihood of Developing Symptoms and Critical Disease Among Close Contacts Exposed to Patients With Confirmed SARS-CoV-2 Infection in Italy. JAMA Network Open. 2021; 4 (3): p.e211085. doi: 10.1001/jamanetworkopen.2021.1085 . | Open in Read by QxMD
  6. Helmet-based ventilation eases respiratory distress. https://www.nih.gov/news-events/nih-research-matters/helmet-based-ventilation-eases-respiratory-distress. Updated: May 24, 2016. Accessed: April 12, 2021.
  7. Grieco DL, Menga LS, Cesarano M, et al. Effect of Helmet Noninvasive Ventilation vs High-Flow Nasal Oxygen on Days Free of Respiratory Support in Patients With COVID-19 and Moderate to Severe Hypoxemic Respiratory Failure: The HENIVOT Randomized Clinical Trial.. JAMA. 2021 . doi: 10.1001/jama.2021.4682 . | Open in Read by QxMD
  8. The RECOVERY Collaborative Group. Dexamethasone in Hospitalized Patients with Covid-19 — Preliminary Report. N Engl J Med. 2020 . doi: 10.1056/nejmoa2021436 . | Open in Read by QxMD
  9. Shuto H, Komiya K, Yamasue M, et al. A systematic review of corticosteroid treatment for noncritically ill patients with COVID-19. Sci Rep. 2020; 10 (1): p.20935. doi: 10.1038/s41598-020-78054-2 . | Open in Read by QxMD
  10. Ramakrishnan S, Nicolau DV Jr, Langford B, et al. Inhaled budesonide in the treatment of early COVID-19 (STOIC): a phase 2, open-label, randomised controlled trial. Lancet Respir Med. 2021 . doi: 10.1016/S2213-2600(21)00160-0 . | Open in Read by QxMD
  11. Campia U, Gerhard-Herman M, Piazza G, Goldhaber SZ. Peripheral Artery Disease: Past, Present, and Future.. Am J Med. 2019; 132 (10): p.1133-1141. doi: 10.1016/j.amjmed.2019.04.043 . | Open in Read by QxMD
  12. Nicolaï SP, Kruidenier LM, Rouwet EV, Graffius K, Prins MH, Teijink JA. The walking impairment questionnaire: an effective tool to assess the effect of treatment in patients with intermittent claudication.. J Vasc Surg. 2009; 50 (1): p.89-94. doi: 10.1016/j.jvs.2008.12.073 . | Open in Read by QxMD
  13. McDermott MM, Spring B, Tian L, et al. Effect of Low-Intensity vs High-Intensity Home-Based Walking Exercise on Walk Distance in Patients With Peripheral Artery Disease. JAMA. 2021; 325 (13): p.1266. doi: 10.1001/jama.2021.2536 . | Open in Read by QxMD
  14. Bellan M, Soddu D, Balbo PE, et al. Respiratory and Psychophysical Sequelae Among Patients With COVID-19 Four Months After Hospital Discharge. JAMA Network Open. 2021; 4 (1): p.e2036142. doi: 10.1001/jamanetworkopen.2020.36142 . | Open in Read by QxMD
  15. Sheehan Disability Scale. https://www.psychcongress.com/saundras-corner/scales-screeners/disability-scales/sheehan-disability-scale-sds. Updated: January 1, 2021. Accessed: April 26, 2021.
  16. Havervall S, Rosell A, Phillipson M, et al. Symptoms and Functional Impairment Assessed 8 Months After Mild COVID-19 Among Health Care Workers. JAMA. 2021 . doi: 10.1001/jama.2021.5612 . | Open in Read by QxMD
  17. Ledford H. Coronavirus reinfections: three questions scientists are asking. Nature. 2020; 585 (7824): p.168-169. doi: 10.1038/d41586-020-02506-y . | Open in Read by QxMD
  18. Harvey RA, Rassen JA, Kabelac CA, et al. Association of SARS-CoV-2 Seropositive Antibody Test With Risk of Future Infection. JAMA Internal Medicine. 2021 . doi: 10.1001/jamainternmed.2021.0366 . | Open in Read by QxMD
  19. FDA updates warnings for fluoroquinolone antibiotics. https://www.fda.gov/news-events/press-announcements/fda-updates-warnings-fluoroquinolone-antibiotics. Updated: July 26, 2016. Accessed: March 15, 2021.
  20. Gaber CE, Kinlaw AC, Edwards JK, et al. Comparative Effectiveness and Harms of Antibiotics for Outpatient Diverticulitis. Ann Intern Med. 2021 . doi: 10.7326/m20-6315 . | Open in Read by QxMD
  21. Augustin LSA, Kendall CWC, Jenkins DJA, et al. Glycemic index, glycemic load and glycemic response: An International Scientific Consensus Summit from the International Carbohydrate Quality Consortium (ICQC). Nutrition, Metabolism and Cardiovascular Diseases. 2015; 25 (9): p.795-815. doi: 10.1016/j.numecd.2015.05.005 . | Open in Read by QxMD
  22. Jenkins DJA, Dehghan M, Mente A, et al. Glycemic Index, Glycemic Load, and Cardiovascular Disease and Mortality. N Engl J Med. 2021 . doi: 10.1056/nejmoa2007123 . | Open in Read by QxMD
  23. Killer Rabbit of Caerbannog. https://www.youtube.com/watch?v=5tqoHIzbneY. Updated: May 12, 2012. Accessed: March 26, 2021.
  24. Antonitsch L, Weidinger G, Stanek G, Markowicz M. Francisella tularensis as the cause of protracted fever. BMC Infect Dis. 2020; 20 (1). doi: 10.1186/s12879-020-05051-1 . | Open in Read by QxMD
  25. Mallapaty S. COVID mink analysis shows mutations are not dangerous — yet. Nature. 2020; 587 (7834): p.340-341. doi: 10.1038/d41586-020-03218-z . | Open in Read by QxMD
  26. Shi J, Wen Z, Zhong G, et al. Susceptibility of ferrets, cats, dogs, and other domesticated animals to SARS–coronavirus 2. Science (80- ). 2020; 368 (6494): p.1016-1020. doi: 10.1126/science.abb7015 . | Open in Read by QxMD
  27. Mykytyn AZ, Lamers MM, Okba NMA, et al. Susceptibility of rabbits to SARS-CoV-2. Emerg Microbes Infect. 2021; 10 (1): p.1-7. doi: 10.1080/22221751.2020.1868951 . | Open in Read by QxMD
  28. Holiday tips. https://www.cdc.gov/coronavirus/2019-ncov/daily-life-coping/holidays/winter.html. . Accessed: March 26, 2021.
  29. Mehta P, McAuley DF, Brown M, et al. COVID-19: consider cytokine storm syndromes and immunosuppression.. Lancet. 2020; 395 (10229): p.1033-1034. doi: 10.1016/S0140-6736(20)30628-0 . | Open in Read by QxMD
  30. Kalil AC, Patterson TF, Mehta AK, et al. Baricitinib plus Remdesivir for Hospitalized Adults with Covid-19. N Engl J Med. 2021; 384 (9): p.795-807. doi: 10.1056/nejmoa2031994 . | Open in Read by QxMD
  31. Van Nood E, Vrieze A, Nieuwdorp M, et al. Duodenal Infusion of Donor Feces for RecurrentClostridium difficile. N Engl J Med. 2013; 368 (5): p.407-415. doi: 10.1056/nejmoa1205037 . | Open in Read by QxMD
  32. Kao D, Wong K, Franz R, et al. The effect of a microbial ecosystem therapeutic (MET-2) on recurrent Clostridioides difficile infection: a phase 1, open-label, single-group trial. Lancet Gastroenterol Hepatol. 2021; 6 (4): p.282-291. doi: 10.1016/s2468-1253(21)00007-8 . | Open in Read by QxMD
  33. Frangoul H, Altshuler D, Cappellini MD, et al. CRISPR-Cas9 Gene Editing for Sickle Cell Disease and β-Thalassemia. N Engl J Med. 2020 . doi: 10.1056/nejmoa2031054 . | Open in Read by QxMD
  34. Jackson LA, Anderson EJ, Rouphael NG, et al. An mRNA Vaccine against SARS-CoV-2 — Preliminary Report. N Engl J Med. 2020; 383 (20): p.1920-1931. doi: 10.1056/nejmoa2022483 . | Open in Read by QxMD
  35. FDA emergency authorization - Moderna COVID-19 Vaccine. https://www.fda.gov/emergency-preparedness-and-response/coronavirus-disease-2019-covid-19/moderna-covid-19-vaccine. . Accessed: January 18, 2021.
  36. A Study to Evaluate the Safety, Reactogenicity, and Effectiveness of mRNA-1273 Vaccine in Adolescents 12 to <18 Years Old to Prevent COVID-19 (TeenCove). https://www.clinicaltrials.gov/ct2/show/study/NCT04649151?term=NCT04470427&draw=2&rank=2. . Accessed: January 18, 2021.
  37. Baden LR, El Sahly HM, Essink B, et al. Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine. N Engl J Med. 2020 . doi: 10.1056/nejmoa2035389 . | Open in Read by QxMD
  38. Why do COVID death rates seem to be falling?. https://www.nature.com/articles/d41586-020-03132-4. . Accessed: January 18, 2021.
  39. Asch DA, Sheils NE, Islam MN, et al. Variation in US Hospital Mortality Rates for Patients Admitted With COVID-19 During the First 6 Months of the Pandemic. JAMA Intern. Med.. 2020 . doi: 10.1001/jamainternmed.2020.8193 . | Open in Read by QxMD
  40. Infectious Diseases Society of America Guidelines on the Treatment and Management of Patients with COVID-19. https://www.idsociety.org/practice-guideline/covid-19-guideline-treatment-and-management/#toc-10. Updated: December 2, 2020. Accessed: December 28, 2020.
  41. US FDA Emergency Use Authorization (EUA) for Pfizer-BioNTech COVID-19 Vaccine. https://www.fda.gov/emergency-preparedness-and-response/coronavirus-disease-2019-covid-19/pfizer-biontech-covid-19-vaccine. Updated: October 11, 2020. Accessed: December 28, 2020.
  42. Interim Considerations: Preparing for the Potential Management of Anaphylaxis at COVID-19 Vaccination Sites. https://www.cdc.gov/vaccines/covid-19/info-by-product/pfizer/anaphylaxis-management.html. Updated: December 16, 2020. Accessed: December 28, 2020.
  43. Polack FP, Thomas SJ, Kitchin N, et al. Safety and Efficacy of the BNT162b2 mRNA Covid-19 Vaccine. N Engl J Med. 2020 . doi: 10.1056/nejmoa2034577 . | Open in Read by QxMD
  44. COVID-19 Hospitalization and Death by Race/Ethnicity. https://www.cdc.gov/coronavirus/2019-ncov/covid-data/investigations-discovery/hospitalization-death-by-race-ethnicity.html. Updated: November 30, 2020. Accessed: December 28, 2020.
  45. Social Determinants of Health: Know What Affects Health. https://www.cdc.gov/socialdeterminants/index.htm. Updated: August 19, 2020. Accessed: December 28, 2020.
  46. Ogedegbe G, Ravenell J, Adhikari S, et al. Assessment of Racial/Ethnic Disparities in Hospitalization and Mortality in Patients With COVID-19 in New York City. JAMA Network Open. 2020; 3 (12): p.e2026881. doi: 10.1001/jamanetworkopen.2020.26881 . | Open in Read by QxMD
  47. Pendergrast TR, Jain S, Trueger NS, Gottlieb M, Woitowich NC, Arora VM. Prevalence of Personal Attacks and Sexual Harassment of Physicians on Social Media. JAMA Internal Medicine. 2021 . doi: 10.1001/jamainternmed.2020.7235 . | Open in Read by QxMD
  48. Agarwal A, Mukherjee A, Kumar G, Chatterjee P, Bhatnagar T, Malhotra P. Convalescent plasma in the management of moderate covid-19 in adults in India: open label phase II multicentre randomised controlled trial (PLACID Trial). BMJ. 2020 : p.m3939. doi: 10.1136/bmj.m3939 . | Open in Read by QxMD
  49. Joyner MJ, Carter RE, Senefeld JW, et al. Convalescent Plasma Antibody Levels and the Risk of Death from Covid-19. N Engl J Med. 2021 . doi: 10.1056/nejmoa2031893 . | Open in Read by QxMD
  50. Roberts CK, Hevener AL, Barnard RJ. Metabolic Syndrome and Insulin Resistance: Underlying Causes and Modification by Exercise Training. Comprehensive Physiology. 2013 . doi: 10.1002/cphy.c110062 . | Open in Read by QxMD
  51. Kushner RF. Weight Loss Strategies for Treatment of Obesity: Lifestyle Management and Pharmacotherapy. Prog Cardiovasc Dis. 2018; 61 (2): p.246-252. doi: 10.1016/j.pcad.2018.06.001 . | Open in Read by QxMD
  52. MorphoSys AG : MorphoSys Provides Update on Results From Partner's Phase 2b/3 RESILIENT Study of Bimagrumab. https://www.morphosys.com/media-investors/media-center/morphosys-ag-morphosys-provides-update-on-results-from-partners-phase. Updated: April 21, 2016. Accessed: February 1, 2021.
  53. Heymsfield SB, Coleman LA, Miller R, et al. Effect of Bimagrumab vs Placebo on Body Fat Mass Among Adults With Type 2 Diabetes and Obesity. JAMA Network Open. 2021; 4 (1): p.e2033457. doi: 10.1001/jamanetworkopen.2020.33457 . | Open in Read by QxMD
  54. Helms J, Tacquard C, et al. High risk of thrombosis in patients with severe SARS-CoV-2 infection: a multicenter prospective cohort study. Intensive Care Med. 2020; 46 (6): p.1089-1098. doi: 10.1007/s00134-020-06062-x . | Open in Read by QxMD
  55. Barnes GD, Burnett A, Allen A, et al. Thromboembolism and anticoagulant therapy during the COVID-19 pandemic: interim clinical guidance from the anticoagulation forum.. J Thromb Thrombolysis. 2020; 50 (1): p.72-81. doi: 10.1007/s11239-020-02138-z . | Open in Read by QxMD
  56. Labrecque JA, Swanson SA. Target trial emulation: teaching epidemiology and beyond.. Eur J Epidemiol. 2017; 32 (6): p.473-475. doi: 10.1007/s10654-017-0293-4 . | Open in Read by QxMD
  57. Al-Samkari H, Gupta S, Leaf RK, et al. Thrombosis, Bleeding, and the Observational Effect of Early Therapeutic Anticoagulation on Survival in Critically Ill Patients With COVID-19. Ann Intern Med. 2021 . doi: 10.7326/m20-6739 . | Open in Read by QxMD
  58. Marshall M. The lasting misery of coronavirus long-haulers. Nature. 2020; 585 (7825): p.339-341. doi: 10.1038/d41586-020-02598-6 . | Open in Read by QxMD
  59. EDITORIAL. Long COVID: let patients help define long-lasting COVID symptoms. Nature. 2020; 586 (7828): p.170-170. doi: 10.1038/d41586-020-02796-2 . | Open in Read by QxMD
  60. Carfì A, Bernabei R, Landi F. Persistent Symptoms in Patients After Acute COVID-19. JAMA. 2020; 324 (6): p.603. doi: 10.1001/jama.2020.12603 . | Open in Read by QxMD
  61. Boyd B, Solh T. Takotsubo cardiomyopathy. J Am Acad Physician Assist. 2020; 33 (3): p.24-29. doi: 10.1097/01.jaa.0000654368.35241.fc . | Open in Read by QxMD
  62. Kir D, Beer N, De Marchena EJ. Takotsubo cardiomyopathy caused by emotional stressors in the coronavirus disease 2019 (COVID‐19) pandemic era. J Card Surg. 2020; 36 (2): p.764-769. doi: 10.1111/jocs.15251 . | Open in Read by QxMD
  63. Jabri A, Kalra A, Kumar A, et al. Incidence of Stress Cardiomyopathy During the Coronavirus Disease 2019 Pandemic. JAMA Network Open. 2020; 3 (7): p.e2014780. doi: 10.1001/jamanetworkopen.2020.14780 . | Open in Read by QxMD
  64. Ghadri JR, Sarcon A, Diekmann J, et al. Happy heart syndrome: role of positive emotional stress in takotsubo syndrome. Eur Heart J. 2016; 37 (37): p.2823-2829. doi: 10.1093/eurheartj/ehv757 . | Open in Read by QxMD
  65. Crane MA, Popovic A, Stolbach AI, Ghanem KG. Reporting of sexually transmitted infections during the COVID-19 pandemic. Sex Transm Infect. 2020 : p.sextrans-2020-054805. doi: 10.1136/sextrans-2020-054805 . | Open in Read by QxMD
  66. Critically ill adults with coronavirus disease 2019 in New Orleans and care with an evidence based protocol.
  67. Janz DR, Mackey S, Patel N, et al. Critically Ill Adults With Coronavirus Disease 2019 in New Orleans and Care With an Evidence-Based Protocol. Chest. 2021; 159 (1): p.196-204. doi: 10.1016/j.chest.2020.08.2114 . | Open in Read by QxMD
  68. Global hepatitis report 2017. https://www.who.int/hepatitis/publications/global-hepatitis-report2017/en/. Updated: April 1, 2017. Accessed: March 1, 2021.
  69. Ryerson AB, Schillie S, Barker LK, Kupronis BA, Wester C. Vital Signs: Newly Reported Acute and Chronic Hepatitis C Cases - United States, 2009-2018.. MMWR Morb Mortal Wkly Rep. 2020; 69 (14): p.399-404. doi: 10.15585/mmwr.mm6914a2 . | Open in Read by QxMD
  70. HCV Guidance: Recommendations for Testing, Managing, and Treating Hepatitis C. https://www.hcvguidelines.org/. Updated: November 6, 2019. Accessed: March 1, 2021.
  71. Page K, Melia MT, Veenhuis RT, et al. Randomized Trial of a Vaccine Regimen to Prevent Chronic HCV Infection. N Engl J Med. 2021; 384 (6): p.541-549. doi: 10.1056/nejmoa2023345 . | Open in Read by QxMD
  72. Ahrén B, Masmiquel L, Kumar H, et al. Efficacy and safety of once-weekly semaglutide versus once-daily sitagliptin as an add-on to metformin, thiazolidinediones, or both, in patients with type 2 diabetes (SUSTAIN 2): a 56-week, double-blind, phase 3a, randomised trial.. Lancet Diabetes Endocrinol. 2017; 5 (5): p.341-354. doi: 10.1016/S2213-8587(17)30092-X . | Open in Read by QxMD
  73. Marso SP, Bain SC, Consoli A, et al. Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. N Engl J Med. 2016; 375 (19): p.1834-1844. doi: 10.1056/nejmoa1607141 . | Open in Read by QxMD
  74. Wilding JPH, Batterham RL, Calanna S, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021 . doi: 10.1056/nejmoa2032183 . | Open in Read by QxMD