One-Minute Telegram Archive

Last updated: May 23, 2022

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This article contains a collection of content written during 2022 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 2021, and our One-Minute Telegram Archive 2020

The aspirin debate rages on: 2022 USPSTF updated recommendations

One-Minute Telegram 50-2022-1/3 - The USPSTF has updated its 2016 recommendations after commissioning a systematic review and microsimulation of outcomes on hypothetical cohorts (stratified by age, sex, and CVD risk level) to determine the benefits and harms of aspirin (ASA) use for the primary prevention of atherosclerotic cardiovascular disease (ASCVD) and colorectal cancer (CRC). [1]

Cardiovascular disease: Outcomes were based on data from 11 RCTs and 1 pilot trial (n = 134,870).

USPSTF recommendation for initiation of low-dose ASA to prevent ASCVD

Colorectal cancer

  • There was limited RCT evidence to support an association between low-dose ASA and decreased CRC incidence (OR, 1.07; 0.92–1.24; n=4 trials) or mortality (OR, 1.36; 0.97–1.91; n=2 trials).
  • Findings were highly variable depending on the duration of follow-up.
  • The evidence regarding the benefit of low-dose ASA in reducing CRC incidence or mortality was inconclusive.

The take-home message?

This 2022 USPSTF update reduces the age range and grade of recommendation for using low-dose ASA in the primary prevention of ASCVD. Starting low-dose aspirin is not recommended in adults ≥ 60 years. Based on evidence of a small net benefit, low-dose ASA may be considered on an individual basis in adults 40–59 years with a 10-year ASCVD risk ≥ 10% and a low risk of bleeding. Whether low-dose ASA reduces the risk of CRC remains unclear.

One-size-fits-none: age and BMI thresholds for diabetes screening

One-Minute Telegram 50-2022- 2/3 - Diabetes mellitus is more prevalent, more likely to be undiagnosed, and more likely to result in adverse outcomes in Black, Hispanic, and Asian Americans compared to White Americans. The current USPSTF recommendation on prediabetes and type 2 diabetes is to screen all adults aged 35–70 years with a BMI ≥ 25 kg/m2. [5]

This cross-sectional study included data from 19,335 nonpregnant adults aged 18–70 years from the National Health and Nutrition Examination Survey (NHANES). The authors used a logistic regression model to estimate the prevalence of diabetes at various BMI levels among individuals in different self-identified racial/ethnic groups.

The estimated prevalence of diabetes in individuals with a BMI ≥ 25 kg/m2 at 35 years of age was:

  • Asian Americans: 3.8% (95% CI, 2.8–5.1%)
  • Black Americans: 3.5% (2.7%-4.7%)
  • Hispanic Americans: 3.0% (2.1%-4.2%)
  • White Americans: 1.4% (1.0–2.0%)

Assuming a prevalence of 1.4% is an acceptable threshold to begin screening for diabetes, the equivalent BMI (in kg/m2) to begin screening at age 35 was estimated as follows:

  • Asian Americans: 20 (range, <18.5–23)
  • Black Americans: < 18.5 (<18.5–23)
  • Hispanic Americans: 18.5 (<18.5–24)
  • White Americans: 25

Limitations include that socioeconomic, cultural, genetic, and other factors could not be considered based on the available information. Furthermore, the prevalence threshold for screening for diabetes has not been clearly established.

The take-home message?

This cross-sectional study demonstrated that Asian, Black, and Hispanic Americans have a higher prevalence of diabetes mellitus at younger ages and lower BMIs than White Americans. Prospective research is needed to explore the possible benefits of more individualized screening thresholds to reduce racial/ethnic disparities in diabetes care.

  • Title of study: Diabetes screening by race and ethnicity in the United States: equivalent body mass index and age thresholds [6]
  • Authors: Aggarwal R et al.
  • Journal: Ann Intern Med.
  • AMBOSS Links: Diabetes mellitus

A new drug combination to treat obesity in adolescents

One-Minute Telegram 50-2022-3/3 - The combination of phentermine (PHEN) and topiramate (TPM) has been approved for use in adults with overweight or obesity since 2012, but it remains unclear whether it is also safe and effective for adolescents. [7]

In this multicenter randomized, double-blind, placebo-controlled trial, 227 adolescents with obesity were stratified by age group and sex and assigned in a 1:1:2 ratio to receive placebo (n = 56), mid-dose PHEN/TPM (7.5 mg/46 mg; n=54), or top-dose PHEN/TPM (15 mg/96 mg; n = 113) once daily for 56 weeks. All participants were counseled to follow a diet and lifestyle modification program.

  • Primary endpoint
    • Efficacy: mean percent change in BMI at week 56
      • Placebo: + 3.34 (± 1.44)
      • Mid-dose PHEN/TPM: - 4.78 (± 1.30)
      • Top-dose PHEN/TPM: - 7.11 (± 1.01)
  • Secondary endpoints
  • Safety endpoints
    • At least one adverse event was reported by 51.8% of participants in the placebo group, 37.0% in the mid-dose group, and 52.2% in the top-dose group.
    • Seven participants stopped the study early due to adverse events (3 in the placebo group, 1 in the mid-dose group, and 3 in the top-dose group).

Limitations include a high drop-out rate (mainly due to loss to follow-up rate and voluntary withdrawal from the study), which the authors attribute to the study having been conducted during the initial wave of the COVID-19 pandemic.

The take-home message?
This industry-sponsored study demonstrated that PHEN/TPM, when used as an adjunct to lifestyle therapy, provided a safe treatment option for reducing BMI, waist circumference, and other metabolic parameters in adolescents with obesity.

Improving asthma care in Black and Latinx patients

One-Minute Telegram 49-2022-1/3 - Asthma disproportionately impacts Black and Latinx populations in the US. This study explored whether an intervention including one-time instruction on and free access to on-demand, symptom-triggered inhaled glucocorticoids could improve outcomes in asthma care. [9]

In this open-labeled trial, 1201 Black and Latinx adults with moderate-to-severe asthma, who were already using daily inhaled glucocorticoids, received a single instructional session on inhaler use. The participants were then randomized to an intervention group (n = 600), which added an inhaled glucocorticoid (beclomethasone dipropionate 80 μg) for acute symptom relief to usual care, and a control group (n = 601), which continued usual care only. Monthly questionnaires were used to estimate the rate of severe asthma exacerbations over 15 months.

  • Primary endpoint
    • The annualized rate of severe asthma exacerbations was lower in the intervention group (0.69 per year; 95% CI, 0.61–0.78) than in the usual care group (0.82 per year; 0.73–0.92); HR, 0.85; 0.72–0.99.
  • Secondary endpoints
    • Asthma control (assessed by the Asthma Control Test) improved more in the intervention group than in the usual care group. [10]
    • Quality of life (assessed by the Asthma Symptom Utility Index) improved more in the intervention group than in the usual care group. [11]
    • Participants in the intervention group missed fewer days of school or work (13.4; 11.9–15.2) than those in the usual care group (16.8; 14.9–18.9): rate ratio, 0.80; 0.67–0.95.

Serious adverse events did not differ between groups. The intervention group used approximately one more inhaled glucocorticoid inhaler per year and one fewer quick-reliever metered-dose inhaler compared to those in the usual care group.

Limitations include that the analysis was open-label and patient outcomes were based on self-reports.

The take-home message?

This trial demonstrated that a single instruction session followed by free, unlimited access to an inhaled glucocorticoid for symptom relief led to a significant and sustained decrease in severe asthma exacerbations over 15 months in Black and Latinx patients.

Prone positioning in nonintubated patients with COVID-19

One-Minute Telegram 49-2022-2/3 - The prone position is an established element of treatment for patients with acute respiratory distress syndrome, and it is recommended for mechanically ventilated patients with COVID-19. Previous prospective and retrospective studies on this intervention in nonintubated patients with COVID-19 have shown reduced mortality and a reduced need for intubation, but further benefits of prone positioning in this population remain an open question. [13][14][15]

This nonrandomized, controlled trial assigned nonintubated patients with COVID-19-related hypoxemia to either prone positioning (n = 258) or usual care (n = 243). Patients in the intervention group spent a median of 4.2 hours (IQR, 1.8–6.7 hours) in the prone position per day.

The primary outcome was the maximum amount of supplemental oxygen required on day 5 based on a modified WHO COVID-19 ordinal outcome scale, in which an AOR ≥ 1.0 indicated a shift toward worse outcomes. [16]

  • Odds of a worse outcome in the intervention group at day 5: AOR 1.63; 95% credibility interval, 1.16–2.31
  • Day 14: 1.29; 0.84–1.99
  • Day 28: 1.12; 0.67–1.86

Limitations include that the study was not randomized and that a higher proportion of patients were discharged within 5 days in the usual care group compared with the intervention group.

The authors speculate that prone positioning early in the disease may have led to worse outcomes by accelerating progression of lung damage, obscuring evidence of clinical deterioration, or leading to events of desaturation.

The take-home message?
In this trial of hypoxemic, awake patients with COVID-19 who were not receiving mechanical ventilation, the prone position provided no clinical benefit and may have worsened outcomes at day 5 after enrollment.

  • Title of study: Assessment of awake prone positioning in hospitalized adults with COVID-19: A nonrandomized controlled trial [17]
  • Authors: Tang Qian E at al.
  • Journal: JAMA Internal Medicine
  • AMBOSS Links: COVID-19

A care bundle to reduce bloodstream infections in hemodialysis

One-Minute Telegram 49-2022-3/3 - Patients receiving hemodialysis through a central catheter are at risk of developing catheter-related bloodstream infections (CRBSIs). Although nonrandomized clinical studies have shown a reduction in CRBSIs after implementation of care bundles, randomized trial data is lacking. [18]

This trial evaluated whether the implementation of a care bundle consisting of recommendations for catheter insertion, maintenance, and removal can reduce the rate of CRBSIs.

6364 patients were included in a stepped wedge, cluster-randomized design. 315 episodes of confirmed CRBSI occurred during the study period. There was no significant difference in the rate of CRBSI during the baseline (n = 158) and intervention (n = 157) phases of the trial (incidence rate ratio 1.37; 95% CI 0.85–2.21).

Limitations include that a third of the participating renal services deviated from the prespecified interventions and that many elements of the intervention had already been implemented into routine practice prior to the study. Accordingly, CRBSI rates were lower than expected in both groups, and the study’s power to detect the effects of the intervention may not have been sufficient.

The take-home message?
The care bundle implemented in this trial did not reduce the rate of CRBSIs in patients receiving hemodialysis through a central catheter.

Predicting severe COVID-19 in pregnant women

One-Minute Telegram 48-2022-1/3 - Pregnancy is considered a potential risk factor for a severe course of COVID-19, but individual risk assessments are not currently available, as most large trials excluded pregnant women.

This multicenter study used retrospective data collected from the beginning of the pandemic to May 2021 from 793 unvaccinated pregnant and early postpartum (within 10 days of birth) women with symptomatic COVID-19 (confirmed by PCR) to identify risk factors and develop two COvid Maternal Intensive Therapy (COMIT) models to predict ICU admission. A total of 44 participants (5.5%) were admitted to the ICU, of whom 10 died (1.3%).

  • miniCOMIT
  • fullCOMIT
  • Cut-off points with high sensitivity and specificity were selected for each model and used to classify the study population as high-risk or low-risk for severe COVID-19.
    • miniCOMIT outcomes in high-risk (46.1%) compared to low-risk women
    • fullCOMIT outcomes in high-risk (26.4%) compared to low-risk women

Limitations include that the model was only validated internally (i.e., within the same dataset) and that results may not be generalizable to vaccinated populations.

The take-home message?

This study developed two prediction models (available as online calculators) [20] to help estimate the risk of critical illness due to COVID-19 in unvaccinated pregnant and early postpartum women. Early identification of high-risk patients using these models could potentially improve clinical outcomes and hospital resource allocation.

Can any alcohol consumption be considered healthy?

One-Minute Telegram 48-2022-2/3 - As part of a Mediterranean diet, moderate alcohol consumption has long been considered cardioprotective. [22] However, residual confounding may have influenced the results of studies supporting this assumption.

This study included data from 371,463 participants from a UK database who were categorized based on their drinking habits, and data analysis related to cardiovascular disease (CVD) was conducted and adjusted for lifestyle factors (e.g., smoking frequency).

Key findings

Limitations include that the data came from a single UK database, restricting the generalizability to other populations.

The take-home message?

This study showed that even light-to-moderate alcohol consumption is a risk factor for CVD when adjusting for the beneficial effects of an otherwise healthy lifestyle, and that CVD risk increases exponentially with increasing alcohol consumption.

  • Title of study: Association of habitual alcohol intake with risk of cardiovascular disease [23]
  • Authors: Biddinger KJ et al.
  • Journal: JAMA Netw. Open

Ivermectin in COVID-19: yay or nay?

One-Minute Telegram 48-2022-3/3 - Recently, ivermectin has been used experimentally by some as an over-the-counter treatment for COVID-19; its effectiveness has also been studied in small clinical trials with conflicting results.

This double-blind, placebo-controlled trial randomized symptomatic adults with COVID-19 and at least one risk factor for disease progression to receive either ivermectin (400 mcg/kg; n = 679) or placebo (n = 679) once daily for 3 days.

The primary composite outcome was the rate of hospitalization or prolonged (> 6 hours) admission to the emergency department due to clinical worsening of COVID-19 within 28 days of randomization. For the primary outcome, no significant difference was observed between the ivermectin (14.7%) and placebo groups (16.3%), with an RR of 0.9 (95% credible interval, 0.7–1.16).

Additionally, there was no significant difference in the incidence of secondary outcomes (e.g., death from any cause) or adverse events between the two groups.

Limitations include that only one ivermectin regimen was investigated.

The take-home message?

This extensive, double-blind, placebo-controlled trial showed that a 3-day course of ivermectin did not lower the incidence of hospitalization or prolonged emergency department visits due to COVID-19 compared to placebo. These results further support the FDA recommendation [24] against using ivermectin to treat COVID-19.

How effective are vaccines against omicron?

One-Minute Telegram 47-2022-1/3 - Shortly after the emergence of the omicron variant (B.1.1.529) of SARS-CoV-2, laboratory studies suggested a weak neutralizing antibody response in vaccinated persons to this variant, but clinical evidence of this has so far been missing. This trial compared the effectiveness of different vaccines in preventing symptomatic omicron infection. [26]

This case-control study included 2,663,549 individuals older than 18 years of age presenting with symptoms consistent with COVID-19; 886,774 had a positive sequencing for the omicron variant, 204,154 had a positive sequencing for the delta variant, and 1,572,621 had a PCR test negative for SARS-CoV-2.

Vaccine effectiveness against symptomatic omicron infection was very low for AstraZeneca Vaxzevria. The mRNA vaccines (Pfizer-BioNTech Comirnaty and Moderna Spikevax) showed higher effectiveness at 2–4 weeks after vaccination (Pfizer-BioNTech 65.5%; 95% CI, 63.9–67%, Moderna 75.1%; 70.8–78.7%), but effectiveness declined significantly at 25+ weeks (Pfizer-BioNTech, 8.8%; 7.0–10.5%; Moderna, 14.9%; 3.9–24.7%).

Vaccine boosters significantly increased effectiveness against symptomatic omicron infections:

  • AstraZeneca (2 doses) plus Pfizer-BioNTech booster
    • At 2–4 weeks: 62.4% (61.8–63.0%)
    • At 10+ weeks: 39.6% (38.0–41.1%)
  • AstraZeneca (2 doses) plus Moderna booster
    • At 2–4 weeks: 70.1% (69.5–70.7%)
    • At 5–9 weeks: 60.9% (59.7–62.1%)
  • Pfizer-BioNTech (2 doses) plus Pfizer-BioNTech booster
    • At 2–4 weeks: 67.2% (66.5–67.8%)
    • At 10+ weeks: 45.7% (44.7–46.7%)
  • Pfizer-BioNTech (2 doses) plus Moderna booster
    • At 2–4 weeks: 73.9% (73.1–74.6%)
    • At 5–9 weeks: 64.4% (62.6–66.1%)
  • Moderna (2 doses) plus Pfizer-BioNTech booster
    • At 2–4 weeks: 64.9% (62.3–67.3%)
  • Moderna (2 doses) plus Moderna booster
    • At 2–4 weeks: 66.3% (63.7–68.8%)

The study also reported the vaccine's effectiveness against the delta variant, which, in comparison to effectiveness against omicron, was higher at all intervals after vaccination and for all the combinations of primary courses and booster doses investigated.

Limitations include that data was not available for primary vaccination with two different vaccines (e.g., 1st dose AstraZeneca, 2nd dose Moderna) or for the vaccineseffectiveness against severe disease, hospitalization, and death.

The take-home message?

This study shows that two doses of any vaccine have a limited and waning effect against symptomatic COVID-19 due to the omicron variant, with AstraZeneca’s Vaxzevria offering the least protection. A third dose (booster) of an mRNA-based vaccine significantly improves neutralizing activity with less waning of effect than is seen following the second dose. Fortunately, a growing body of evidence suggests that mRNA-based vaccines protect well against severe disease and death caused by any SARS-CoV-2 variant. [27]

Do balanced salt solutions provide a benefit over saline in ICU patients?

One-Minute Telegram 47-2022-2/3 - Fluid therapy in critically ill patients usually consists of balanced multielectrolyte solution (BMES) or 0.9% sodium chloride solution (saline). Whether BMES can reduce adverse outcomes compared to saline is a subject of ongoing debate. [29][30]

In this multicenter double-blinded trial, 5037 ICU patients were randomized to receive either BMES (n = 2515) or saline (n = 2522). Baseline characteristics were similar in both groups (age 61.9±16.5 years, 38.7% women, median APACHE II score = 19).

The median duration of treatment (6.0 days, IQR 3.0–10.0) and volume of fluid received in the ICU (3.9 liters, 2.0–6.7) were comparable between groups.

There was no significant difference in 90-day mortality, new renal replacement therapy, maximum creatinine levels, or the number of adverse events between the two groups.

Limitations include that administration of fluids outside the ICU was not recorded, and that outcome data was not available for a small number of patients.

Notably, a recently updated metaanalysis that incorporated the results of this study suggests a trend toward reduced mortality with the use of BMES over saline. [31]

The take-home message?

This study demonstrated no difference in 90-day mortality or the rate of new renal replacement therapy in critically ill patients who received either BMES or saline in the ICU, but further studies are needed to identify the patient groups that may benefit from the respective fluids.

  • Title of study: Balanced multielectrolyte solution versus saline in critically ill adults [32]
  • Authors: Finfer F et al.
  • Journal: NEJM
  • AMBOSS links: IV fluid therapy

How many cases of breast cancer are overdiagnosed through screening?

One-Minute Telegram 47-2022-3/3 - Screening for breast cancer can lead to overdiagnosis, defined as treatment of cancer that would not have caused symptoms within the patient’s remaining lifetime. However, the rate of overdiagnosis due to screening is currently unknown.

In this trial, the rate of overdiagnosis was estimated using data from a biennial screening program of the US Breast Cancer Surveillance Consortium (BCSC). The analysis used mathematical modeling and included 35,986 patients between the ages of 50 and 74 years who had had ≥ 1 mammogram between 2000 and 2018. 82,677 mammograms resulting in 718 breast cancer diagnoses were included in the analysis. Screening test sensitivity was estimated to be 81.4% (95% CI, 73.1–88.7%).

Of all screen-detected cancers, 15.4% (95% prediction interval 9.4–26.5%) were estimated to be overdiagnosed, with 6.1% (0.2–20.1%) being due to indolent preclinical cancer and 9.3% (5.5–13.5%) due to progressive cancer in patients who would have died of other causes before clinical cancer manifestation. The overdiagnosis rate was lowest in the first screening at age 50 (11.5%; 3.8–28.3%) and gradually increased until the last screen at age 74 (23.6%; 17.7–31.9%). Overdiagnosis at age 50 was primarily due to indolent cancer; overdiagnosis at age 74 was primarily due to progressive cancer that did not affect the patient’s longevity.

Limitations include that only patients who had received their first screening examination within the BCSC were included, leading to low event numbers that, in turn, were insufficient to fit the model to patient features or tumor subtypes.

The take-home message?

Results from this study suggest that almost 1 in 7 cases of breast cancer detected by mammography screening in patients aged 50–74 years is overdiagnosed. The risk of overdiagnosis (potentially leading to unnecessary studies and treatment) increases with patient age, mainly due to the diagnosis of progressive cancer in patients who would have died of other causes before dying of cancer.

  • Title of study: Estimation of breast cancer overdiagnosis in a U.S. breast screening cohort [33]
  • Authors: Ryser MD et al.
  • Journal: Annals of Internal Medicine

2022 updated recommendations from the Advisory Committee on Immunization Practices (ACIP)

One-Minute Telegram 46-2022-1/3 - The ACIP is composed of 15 medical and public health experts who provide recommendations to the Centers for Disease Control regarding the selection and timing of vaccines for children and adults in the United States.

Important recommendations and updates in 2022 include the following:

Other vaccination recommendations (e.g., varicella, MMR, VPH, hepatitis A) remain largely unchanged.

The take-home message?

The 2022 ACIP updated recommendations to the US immunization schedule have been released. The full updated vaccination schedule for adults and children can be found at the CDC website.

  • Title of study: Recommended adult immunization schedule, United States, 2022 [34]
  • Authors: Murthy N, et. al
  • Journal: Annals of Internal Medicine

2022 updated American College of Gastroenterology (ACG) guidelines for GERD

One-Minute Telegram 46-2022-2/3 - Gastroesophageal reflux disease (GERD) is one of the most common diseases seen in primary care. Since publication of the 2013 American College of Gastroenterology (ACG) guidelines for GERD, understanding of the disease has evolved and numerous developments in its diagnosis and management have occured.

Important recommendations and updates include the following:

  • Diagnostic testing:
  • Diet and lifestyle recommendations:
    • Avoidance of the following:
      • Meals up to 3 hours before bedtime
      • Tobacco use
      • Trigger foods (e.g., coffee, chocolate, carbonated beverages, spicy or acidic foods)
    • Weight loss (for patients with overweight)
    • Elevate the head of the bed (for nighttime GERD symptoms)
  • Medical interventions:
    • PPIs are the medication of choice.
    • PPIs should be taken 30–60 minutes prior to a meal once or twice daily.
    • Discontinuation of PPIs and reevaluation after 8 weeks of empiric treatment
    • Continuation of PPIs in patients with high grade esophagitis
  • Surgical interventions:
    • Antireflux surgery is recommended as an option for long-term therapy.
    • Roux-en-Y surgery is recommended as an option in patients with obesity.
    • Magnetic sphincter augmentation and transoral incisionless fundoplication are new additions to the guidelines if medical treatment fails.

The take-home message?

The 2022 ACG guidelines update the previous recommendations for diagnosis and medical management of GERD and provide new recommendations for its surgical and procedural management.

What are the long-term cardiovascular outcomes of COVID-19?

One-Minute Telegram 46-2022-3/3 - Although the acute cardiovascular complications of COVID-19 have been extensively studied, the long-term risks of cardiovascular disease have not been fully investigated. [36]

In this observational cohort trial, investigators analyzed data from the US Department of Veterans Affairs national health care databases to identify 153,760 individuals who survived the first 30 days following recovery from COVID-19. After this period, these individuals were assessed every 30 days for roughly one year and compared with 5,637,647 individuals without COVID-19 from the same databases.

Compared to contemporary controls, the risk of the following prespecified composite outcomes were higher in COVID-19 survivors:

Importantly, the increased risk of cardiovascular disease following COVID-19 was also demonstrated in individuals without cardiovascular risk factors or a previous history of cardiovascular disease.

Limitations include that cause of death could not be considered, as this was not included in the databases, and that the demographic composition of the dataset was predominantly white (76.78%) and male (90.31%), restricting generalizability.

The take-home message?

This trial demonstrates that individuals who recovered from COVID-19 have an increased risk of cardiovascular disease in the months following the disease. Ongoing care of individuals who have recovered from COVID-19 should include monitoring for cardiovascular disease, even if it was not present prior to the infection.

  • Title of study: Long-term cardiovascular outcomes of COVID-19 [37]
  • Authors: Xie Y, et al.
  • Journal: Nature Medicine
  • AMBOSS Links: COVID-19

Oral outpatient treatment of COVID-19 with molnupiravir

One-Minute Telegram 45-2022-1/3 - Primary prevention of COVID-19 has been hampered by disappointingly low vaccination rates, necessitating the development of medications that reduce the progression of the disease. A promising candidate is molnupiravir, a prodrug of N-hydroxycytidine (NHC) that is incorporated into viral RNA upon phosphorylation and causes errors throughout the viral genome, rendering the virus unable to replicate.

In this phase 3, double-blind trial, patients were randomized 1:1 to either molnupiravir (800 mg PO twice daily for 5 days) or a placebo within five days of mild to moderate COVID-19 symptom onset. Between May 6 and November 4, 2021, 1433 non-hospitalized, unvaccinated adults, who had at least one risk factor for severe illness (i.e., age > 60 years; cancer; obesity; diabetes; chronic lung, heart, or kidney disease) were included.

On day 29 after the beginning of treatment, patients taking molnupiravir were less likely to have been admitted to hospital or to have died (composite primary outcome) than those taking the placebo (6.8% vs. 9.7%, difference -3.0; 95% CI, -5.9 to -0.1). The number of adverse events did not differ significantly between groups. Notably, patients with SARS-CoV-2 antibodies at the beginning of the trial did not benefit.

Limitations include that only unvaccinated patients took part in this study and patients with more severe disease (i.e., those expected to require hospitalization for COVID-19 within the next 48 hours) were excluded, restricting generalizability.

The take‑home message?

This trial demonstrated the effectiveness of oral molnupiravir in lowering the risk of hospitalization and death in unvaccinated, non-hospitalized adults with mild to moderate COVID-19 and at least one risk factor for severe illness.

  • Title of study: Molnupiravir for Oral Treatment of Covid-19 in Nonhospitalized Patients [38]
  • Authors: Bernal AJ et al.
  • Journal: NEJM
  • AMBOSS Links: COVID-19

New protein-based vaccine against COVID-19: Nuvaxovid (NVX-CoV2373)

One-Minute Telegram 45-2022-2/3 - Lack of vaccine availability and vaccine hesitancy continue to curb efforts to control the COVID-19 pandemic. The development of non-mRNA vaccines that do not require special storage may help bridge the vaccination gap.

The newly developed vaccine Nuvaxovid (NVX-CoV2373) combines a recombinant spike protein assembled into nanoparticles with a saponin-based adjuvant (Matrix-M). It can be stored for up to 6 months at household refrigerator temperatures.

In this phase 3, observer-blinded, placebo-controlled trial conducted in the US and Mexico, adults > 18 years of age were randomized in a 2:1-ratio to receive two doses of NVX-CoV2373 or placebo 21 days apart. Between December 27, 2020, and February 18, 2021, 19,714 participants received at least one dose of the vaccine and 9868 received the placebo.

Per-protocol analysis of the observation period of 3 months showed the following results:

During a median safety follow-up of 2 months, adverse events were mostly mild to moderate and self-limited with a median duration of 1–2 days. In addition, none of the safety signals reported in trials with other COVID-19 vaccines (e.g., CVT, myocarditis) were observed.

Limitations include a low number of older participants, that long-term safety and efficacy results are not yet available, and that 89% of infections were due to the alpha variant of SARS-CoV-2. Accordingly, the vaccine’s effectiveness against the delta or omicron variant is still unclear.

The take‑home message?

Nuvaxovid (NVX-CoV2373) has similar efficacy against COVID-19 as existing vaccines and a good safety profile. Further studies will have to address the vaccine's efficacy against variant strains and its duration of effect.

  • Title of study: Efficacy and safety of NVX-CoV2373 in adults in the United States and Mexico [39]
  • Authors: Dunkle LM, et al.
  • Journal: NEJM
  • AMBOSS Links: COVID-19

When is major elective surgery safe after a COVID-19 infection?

One-Minute Telegram 45-2022-3/3 - Physicians are increasingly having to deal with the question of when patients with a current or recent SARS-CoV-2-infection can safely undergo elective major surgery.

In this retrospective cohort study, investigators screened the COVID-19 Research Database for unvaccinated patients who had been diagnosed with COVID-19 between March 1, 2020, and May 30, 2021, and underwent major elective surgery during that time as well. [40]

The 5479 patients included were categorized into four groups, depending on the time of surgery and the time of diagnosis: pre-COVID-19 (no infection; n = 2621), peri-COVID-19 (0–4 weeks after infection; n = 780), early post-COVID-19 (4–8 weeks after infection; n = 445), and late post-COVID-19 (≥ 8 weeks after infection; n=1633).

Risk of postoperative complications compared to the pre-COVID-19 surgery cohort:

Limitations include that the study was retrospective, only unvaccinated adults were included, the onset and severity of COVID-19 infection were not reported in the database, and that postoperative mortality rates were not available.

The take‑home message?

The risk of a perioperative complication following major elective surgery is increased in patients with a recent COVID-19 infection. The risk returns to baseline 8 weeks after infection, suggesting increased patient safety if surgery can be delayed until that time.

The ACP’s new diverticulitis guidelines

One-Minute Telegram 44-2022-1/3 - The American College of Physicians (ACP) has released its first-ever guidelines on the diagnosis and management of acute left-sided colonic diverticulitis and on the use of colonoscopy after acute left-sided colonic diverticulitis. The ACP issued one recommendation and classified additional guidance as suggestions only.

Recommendation: In patients with acute left-sided colonic diverticulitis, physicians should not use mesalamine to prevent recurrent diverticulitis.


  • Use abdominal CT imaging if there is diagnostic uncertainty.
  • Treat patients with acute uncomplicated disease in an outpatient setting.
  • Abstain from antibiotic therapy in select patient groups, including those who are immunocompetent, have no signs of systemic inflammatory response, do not require hospitalization, or are not medically frail.
  • Refer patients for a colonoscopy for detection of colorectal cancer ≥ 6–8 weeks after an initial episode of complicated left-sided colonic diverticulitis has resolved (if they have not had a colonoscopy within the past 2 years).
  • Discuss elective surgery to prevent recurrent diverticulitis after initial treatment in patients who have either persistent/frequently recurring uncomplicated diverticulitis or complicated diverticulitis.

Limitations include that, due to the low quality of the evidence (i.e., there being appreciable uncertainty), the guidelines include only one recommendation (against the use of mesalamine), the rest of the statements being suggestions only.

The take‑home message?

In these first-ever ACP guidelines, the authors, citing the low quality of evidence, issued suggestions rather than recommendations for acute management and follow-up in patients with acute left-sided diverticulitis, including when to use imaging studies, antibiotics, and follow-up colonoscopy and surgery. The only recommendation based on high-quality evidence issued was that against the use of mesalamine to prevent recurrent diverticulitis.

  • Title of study: Diagnosis and Management of Acute Left-Sided Colonic Diverticulitis: A Clinical Guideline From the American College of Physicians [42]
  • Authors: Qaseem A et al.
  • Journal: Annals of Internal Medicine
  • Title of study: Colonoscopy for Diagnostic Evaluation and Interventions to Prevent Recurrence After Acute Left-Sided Colonic Diverticulitis: A Clinical Guideline From the American College of Physicians [43]
  • Authors: Qaseem A et al.
  • Journal: Annals of Internal Medicine
  • AMBOSS links: Diverticulitis

To screen or not to screen for atrial fibrillation: 2022 updated USPSTF recommendations

One-Minute Telegram 44-2022-2/3 - The USPSTF (an independent expert panel) has commissioned an update to their 2018 recommendations on screening for atrial fibrillation (Afib) in asymptomatic adults, which yielded the following main results:

Screening tests:

  • The utility of screening with a 1-time ECG for Afib compared to no screening was inconsistent. Given the low prevalence of undiagnosed subclinical Afib, screening with a 1-time ECG is likely to yield more false-positive than true-positive results.
  • Screening with continuous (for several weeks) or intermittent (twice daily for 2 weeks or 1 year) ECG may increase the probability of detecting Afib compared to no screening.

Benefits of early detection and treatment through screening:

Harms of screening:

  • Studies reviewed found no evidence of increased risk of harmful events (e.g., major bleeding, hospitalization) in the screened population compared to the control groups.
  • However, since these events were rare in both groups, the estimates were imprecise and no definitive conclusion could be reached.

Limitations include that most of the analyzed studies were from the US and Europe, reducing generalizability.

The take‑home message?

The USPSTF found that, as already in 2018, there was insufficient evidence to recommend for or against screening for asymptomatic Afib in patients aged ≥ 50 years. Of note, the American Heart Association and the American Stroke Association have previously stated that screening for Afib in patients ≥ 65 years may be useful in the primary care setting. [45]

Valentine’s Day edition: Don’t go piercing my heart!

One-Minute Telegram 44-2022-3/3 - Valentine's Day is approaching and, as tradition dictates, our thoughts will be revolving once again around sweethearts and heartache. But, as this study shows, Cupid’s leaden arrow may not be the only dart capable of breaking your heart. Researchers set out to describe the cardiac manifestations associated with Hymenoptera stings (e.g., bee, wasp, hornet) using data from electronic medical records from a tertiary care hospital in South India. Within 2 years, thirteen patients with Hymenoptera stings presented to the emergency department, six of whom had cardiac manifestations raising concern for Kounis syndrome (an acute coronary syndrome that is associated with conditions that cause mast cell activation, e.g., hypersensitivity reactions). Patients with cardiac manifestations had a mean age of 71.7 years, and all had a history of multiple bee stings. Furthermore, all patients had ECG changes and associated troponin changes, with most reporting shortness of breath. Only one patient reported chest pain. No patients had STEMI, but two patients went into cardiogenic shock. Thankfully, all patients survived. The results highlight the importance of suspecting cardiac complications in patients with Hymenoptera stings, and they put into perspective Cupid's mischievousness: a heartache is the lesser evil compared to a heart attack. [48]

The take‑home message?

This Valentine's Day bee kind to your heart.

Is asthma a risk factor for COVID-19?

One-Minute Telegram 43-2022-1/3 - While it stands to reason that individuals with asthma are at increased risk of a severe course with COVID-19, evidence to support this assumption has been scarce. The present study sought to bridge this knowledge gap by analyzing the Scottish Early Pandemic Evaluation and Enhanced Surveillance of COVID-19 (EAVE II) database. [49]

Among the 4,421,663 individuals included in the database between March 1, 2020, and July 27, 2021, the researchers identified 561,279 adults with asthma, 39,253 (7.0%) of which had confirmed COVID-19. Of these, 4828 (12.3%) were hospitalized, 1600 (4.1%) required ICU treatment, and 1206 (3.1%) died.

The rate of hospitalization and the composite outcome of ICU admission or death were higher in patients with asthma, especially those with a recent hospitalization for an asthma attack, compared to patients without asthma. Outcomes were also found to be positively associated with the number of courses of oral corticosteroids that patients received in the preceding two years:

  • Hospitalization:
    • All asthma patients: HR 1.27 (95% CI 1.23–1.32)
    • Hospitalization in the 2 years prior: 3.01 (2.59–3.49)
    • Oral corticosteroids in the 2 years prior:
      • ≥ 3 courses 1.54 (1.46–1.61)
      • 2 courses: 1.37 (1.26–1.48)
      • 1 course: 1.30 (1.23–1.37)
      • No courses: 1.15 (1.11–1.21)
  • ICU admission and death:
    • All asthma patients: HR 1.13 (95% CI 1.05–1.22)
    • Hospitalization in the 2 years prior: 2.24 (1.56–3.20)
    • Oral corticosteroids in the 2 years prior:
      • ≥ 3 courses 1.44 (1.31–1.58)
      • 2 courses: 1.27 (1.09–1.48)
      • 1 course: 1.04 (0.93–1.16)
      • No courses: 1.06 (0.97–1.17)

Limitations include a higher rate of COVID-19 testing in adults with asthma compared to those without, which may have been caused by differences in health care seeking behaviors. Furthermore, the study did not directly assess asthma severity or control.

The take‑home message?

This national incident cohort study from Scotland provides evidence that adults with asthma are at an increased risk of SARS-CoV-2 infection-related hospitalization, ICU admission, and death, especially if they have received ≥ 2 courses of oral corticosteroids or have been hospitalized for asthma within the preceding two years.

  • Title of study: Risk of serious COVID-19 outcomes among adults with asthma in Scotland: a national incident cohort study [50]
  • Authors: Shi T et al.
  • Journal: Lancet Respiratory Medicine
  • AMBOSS Links: COVID-19

How effective is a booster with the Pfizer–BioNTech vaccine against the delta variant?

One-Minute Telegram 43-2022-2/3 - Israel has been at the forefront of COVID-19 vaccinations and has now published data on the effectiveness of a booster dose with the BNT162b2 mRNA vaccine (Pfizer-BioNTech).

Data on 4,696,865 persons aged 16 and older who had received two vaccine doses at least 5 months prior was extracted from Israel’s Ministry of Health database for the period between July 30 and October 10, 2021, during which the delta variant of SARS-CoV-2 dominated. The rate of new infections was lower in the booster group (booster received ≥ 12 days ago) by a factor of 9.0–17.2 (dependent on age group) compared to the non-booster group (i.e., those who had received only two vaccine doses) and by a factor of 4.9–10.8 compared to the early post-booster group (booster received 3–7 days ago). The rates of severe illness were lower in the booster group by a factor of 21.7 (95% CI, 10.6–44.2) in those aged 40–59 years and 17.9 (95% CI, 15.1–21.2) in those aged 60 years and older. Mortality was lower in the booster group by a factor of 14.7 (95% CI, 10.0 to 21.4) in those aged 60 years and older.

Limitations include that risk-avoidance behaviors and coexisting conditions were not registered and that the delta variant was dominant during the time period analyzed, so that information on the booster’s effectiveness against the omicron variant is not represented.

Furthermore, the time to breakthrough infection after completing immunizations was significantly shorter in individuals with immune dysfunction compared to those without immune dysfunction.

The take‑home message?

This analysis showed that a booster dose of the Pfizer–BioNTech vaccine was highly effective against the delta variant. When comparing persons who had received a third vaccine dose with those who had received only two doses, rates of infection were substantially lower across all age groups, and rates of severe illness and death were substantially lower in older age groups.

  • Title of study: Protection against COVID-19 by BNT162b2 booster across age groups [51]
  • Authors: Bar-On YM et al.
  • Journal: NEJM
  • AMBOSS Links: COVID-19

Is fosfomycin effective in treating multidrug-resistant E. coli?

One-Minute Telegram 43-2022-3/3 - The spread of multidrug-resistant (MDR) E. coli has been exacerbated by the slow pace in developing newer antibiotics. However, developing new antibiotics may not be the only solution, as researchers are also reconsidering the effectiveness of drugs, like fosfomycin, that has been on the market for years. [52]

This multicenter noninferiority clinical trial analyzed data on 143 patients with bacteremic urinary tract infections due to MDR E. coli. The patients were randomized 1:1 to receive IV fosfomycin or a comparator (ceftriaxone or meropenem for ceftriaxone-resistant isolates) and treated for 10–14 days (with the majority of patients switching to oral treatment after 4 days, as allowed per protocol).

In the intention-to-treat analysis, the primary outcome of clinical and microbiological cure 5 to 7 days after the end of treatment was reached by 68.6% of patients treated with fosfomycin and 78.1% of patients treated with a comparator drug, resulting in a risk difference of -9.4% (1-sided 95% CI, -21.5% to ∞; P = 0.1) that failed to meet the prespecified noninferiority criterion of less than -7% risk difference. However, the rates of clinical and microbiological failure with fosfomycin vs. comparator were similar (14.3% vs. 19.7%, P = 0.19), and the failure to meet noninferiority was mainly due to a higher rate of adverse event-related discontinuations among patients treated with fosfomycin (8.5% vs. 0%, P = 0.006). The most serious adverse event was heart failure which occurred in 6 patients (4 of whom required drug discontinuation) who were all aged over 80 years old and had a medical history of either chronic heart failure or chronic kidney disease.

Limitations include the small sample size and the lack of blinding.

The take‑home message?

In this randomized clinical trial, fosfomycin narrowly missed noninferiority criteria when compared to ceftriaxone and meropenem in the treatment of patients with bacteremic urinary tract infections due to multidrug-resistant E. coli. However, the data suggest that fosfomycin may be an effective alternative to ceftriaxone or meropenem in select patients, e.g., those with allergies to other antibiotics or low risk of sodium overload from intravenous fosfomycin.

How effective are mRNA vaccines in preventing hospitalizations due to the omicron variant?

One-Minute Telegram 42-2022-1/3 - Population-based studies have suggested that the omicron (B.1.1.529) variant can evade immunity from prior infection and vaccination. [54] Whether this influences the hospitalization rates due to COVID-19 is an important question that investigators are just beginning to answer.

This retrospective study was conducted in a South African population and was based on healthcare data. The effectiveness of the BNT162b2 vaccine against hospitalizations was estimated during the period when the delta variant was predominant (September 1 to October 31; proxy delta period) and during the period when the omicron variant was predominant (November 15 to December 7; proxy omicron period).

In total, 133,437 PCR tests were considered during the proxy delta period, and 78,173 tests were considered during the proxy omicron period.

  • Overall test positivity (independently of vaccination status):
    • 24.4% during the proxy omicron period
    • 6.4% during the proxy delta period
  • Test positivity among the fully immunized (≥ 14 days after the second dose of BNT162b2 vaccine):
    • 33% during the proxy omicron period
    • 8.2% during the proxy delta period
  • Proportion of hospitalized patients with a positive PCR who were fully immunized:
    • 28.2% during the proxy omicron period
    • 8.3% during the proxy delta period
  • Vaccine effectiveness to prevent hospitalization:
    • 70% (95% CI, 62 to 76) during the proxy omicron period
    • 93% (95% CI, 90 to 94) during the proxy delta period

Limitations include that this study analyzed a single community (restricting generalizability), and that it did not include information on the severity of the disease in those patients who were hospitalized.

The take‑home message?

In this population-based, retrospective study, two doses of the BNT162b2 (Pfizer–BioNTech) vaccine was 70% effective in preventing hospitalization during the omicron period, which was lower than the estimated effectiveness during the delta period (93%). This highlights the importance of booster dosages and development of variant-specific vaccines.

Breakthrough infections after SARS-CoV-2 vaccination in patients with immune dysfunction

One-Minute Telegram 42-2022-2/3 - Persons with a weakened immune system were excluded from the initial SARS-CoV-2 vaccine effectiveness trials. To bridge this evidence gap, this retrospective cohort study analyzed the risk for breakthrough infections in partially and fully vaccinated patients with immune disorders (i.e., HIV infection, multiple sclerosis, rheumatoid arthritis, solid organ transplant, and bone marrow transplantation) from December 10, 2020, to October 14, 2021.
Data were obtained from the National Covid Cohort Collaborative (N3C), which provided information on 664,722 partially and fully vaccinated individuals. Out of this sample, a total of 35,512 patients with an immune disorder were identified.

  • The overall breakthrough infection rate (IR) in fully immunized individuals was 5.0 per 1000 person-months.
  • Compared to individuals with full vaccination and without immune dysfunction, the overall incidence of breakthrough infection was higher in individuals with an immune dysfunction:

Furthermore, the time to breakthrough infection after completing immunizations was significantly shorter in individuals with immune dysfunction compared to those without immune dysfunction.

Limitations include that vaccinations received outside the hospital setting may have been underreported.

The take‑home message?

This trial provides evidence that vaccinated individuals with compromised immune systems are at higher risk for breakthrough infections with SARS-CoV-2. This emphasizes the importance of mask-wearing and social distancing, and the need to investigate additional measures such as booster vaccinations in this population.

Does cataract surgery decrease the risk of dementia?

One-Minute Telegram 42-2022-3/3 - Visual impairment may contribute to cognitive decline in older individuals, but whether surgery to restore vision can delay the onset of dementia has not been thoroughly investigated. [57]

In this prospective, longitudinal nonrandomized cohort study, 3038 participants aged 65 years or older with cataract or glaucoma and no signs of dementia were screened every two years for the onset of dementia.

Participants who received a cataract extraction (n = 1382) had a reduced risk of dementia compared to those who did not (n = 1656; HR 0.71; 95% CI, 0.62–0.83). However, the effect was not observed in participants with glaucoma who received glaucoma surgery vs. those who did not (n = 728; HR, 1.08; 0.75–1.56).

Limitations include the nonrandomized nature of the study and the possibility of coding errors due to the indications for surgery as well as the diagnoses of cataract and glaucoma having been extracted from electronic medical records. Furthermore, 91% of study participants were self-reported White race, limiting generalizability to other populations.

The take‑home message?

While cataract surgery, which restores vision, appears to reduce the risk of dementia in older individuals, the same effect was not observed in participants who received glaucoma surgery, which does not restore vision. This corroborates the association of vision loss and dementia, suggesting new paths for prevention of cognitive decline.

  • Title of study: Association between cataract extraction and development of dementia [58]
  • Authors: Lee CS et al.
  • Journal: JAMA Internal Medicine
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