One-Minute Telegram Archive

Last updated: August 15, 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

Monkeypox infection: New perspectives on the current monkeypox outbreak?

One-Minute Telegram 56-2022-1/3

  • Research question: How is the monkeypox virus transmitted, and what are the symptoms and outcomes of an infection in the current outbreak?
  • Study design: international case series
  • Study population: 528 symptomatic patients with PCR-confirmed monkeypox virus infection
  • Methods: Data were collected at 43 sites in 16 countries between April and June 2022 using a case-report spreadsheet.
  • Main results
    • Patient characteristics
    • Suspected mode of transmission: sexual activity in 95% of cases
    • Median incubation period: 7 days (range: 3–20 days)
    • Clinical features at presentation included:
    • 13% of patients required hospitalization, most commonly for pain management.
    • Severe courses were rare, and no patients died.
    • Clinical presentation was similar in HIV-positive and HIV-negative patients.
  • Limitations include
    • Variability in the PCR testing methods across the different sites
    • Only patients who sought medical care were included, potentially leading to selection bias.
  • Study funding: None disclosed

The take-home message?
This study showed that during the current outbreak, now considered a Public Health Emergency in the US [1], monkeypox has disproportionally affected men who have sex with men and that the clinical presentation (rash and/or anogenital and mucosal lesions) and disease course were similar regardless of HIV status. Approximately 1 in 10 patients required hospitalization, mostly for pain management, and no deaths were reported.

  • Title of study: Monkeypox virus infection in humans across 16 countries — April–June 2022 [2]
  • Authors: Thornhill JP et al.
  • Journal: NEJM

Doubling the dose of levonorgestrel-based emergency contraception to improve efficacy in individuals with obesity

One-Minute Telegram 56-2022-2/3

The take-home message?
Doubling the dose of levonorgestrel-based emergency contraception showed no benefits with regard to preventing or delaying ovulation in individuals with obesity. Previous studies have suggested that ulipristal acetate may be more effective as emergency contraception in this population. [3]

Vitamin D for fracture prevention

One-Minute Telegram 56-2022-3/3

The take-home message?
In this randomized controlled trial, supplementation of vitamin D did not reduce the risk of bone fractures in a general population of men aged ≥ 50 years and women aged ≥ 55 years.

  • Title of study: Supplemental vitamin D and incident fractures in midlife and older adults [6]
  • Authors: LeBoff MS et al.
  • Journal: NEJM

Do weekend warriors benefit from exercise as much as those who work out more regularly?

One-Minute Telegram 55-2022-1/3 - Exercising only on the weekend - being a “weekend warrior” - is a convenient option for achieving the World Health Organization's recommended levels of moderate to vigorous physical activity (MVPA), but does the number of activity sessions per week impact the health benefits?

This prospective, survey-based cohort study followed 350,978 adults (mean age 41.4 years, 50.8% women, 67.8% non-Hispanic White) for a median of 10.4 years and their data was linked to their National Death Index records.

Based on self-reported physical activity, participants were classified as either physically inactive (MVPA < 150 minutes/week) or physically active (≥ 150 minutes/week of moderate activity or ≥ 75 minutes/week of vigorous activity). The physically active group was further subdivided into a regularly active group (≥ 3 sessions/week) and a weekend warrior group (1–2 sessions/week).

Compared to the inactive group, both the regularly active group (HR, 0.85; 95% CI, 0.83–0.88) and the weekend warrior group (0.92; 0.83–1.02) had reduced all-cause mortality rates, though the reduction in the weekend warrior group was nonsignificant. However, differences in the rates of all-cause and cause-specific mortality between the regularly active and weekend warrior groups were nonsignificant.

Limitations include that activity levels were self-reported and therefore may not have accurately reflected the participants’ actual activity levels, that the number of deaths in the weekend warrior group was low, which may have limited the study’s power to detect a reduction in mortality in this group, and that residual confounding cannot be ruled out.

The take-home message?
In this long-term prospective trial, all-cause mortality was lower in participants who achieved the recommended amount of MVPA compared to those who did not. Mortality rates did not differ significantly between those who exercised throughout the week and those who performed 1–2 sessions per week (“weekend warriors”).

  • Title of study: Association of the “weekend warrior” and other leisure-time physical activity patterns with all-cause and cause-specific mortality: a nationwide cohort study [7]
  • Authors: dos Santos M et al.
  • Journal: JAMA Internal Medicine

Updated USPSTF recommendations on dietary supplements to prevent cardiovascular disease and cancer

One-Minute Telegram 55-2022-2/3 - The USPSTF has updated its 2014 recommendations on the use of vitamin, mineral, and multivitamin supplementation for the prevention of cardiovascular disease and cancer. [8] Recommendations were based on data from 84 RCTs and 6 cohort studies that addressed the harms and benefits of supplementation.

Recommendations include:

  • Beta carotene supplements should not be used for the prevention of cardiovascular disease or cancer. Beta carotene was associated with an increased risk of lung cancer in individuals at increased risk of lung cancer.
  • Vitamin E supplements should not be used for the prevention of cardiovascular disease or cancer. Vitamin E may be associated with an increased risk of hemorrhagic stroke.
  • There is insufficient evidence to recommend for or against the use of multivitamin supplements or single- or paired-nutrient supplements (excluding beta carotene and vitamin E) for the prevention of cardiovascular disease or cancer.

Limitations include that these recommendations only apply to community-dwelling, nonpregnant adults with no known underlying health conditions, restricting generalizability to patient groups.

The take-home message?
After reviewing current evidence, the USPSTF reaffirmed its 2014 recommendations against the use of beta carotene and vitamin E supplements and again concluded that evidence is insufficient to recommend for or against other dietary supplements for the prevention of cardiovascular disease or cancer.

Uptake of hepatitis C treatment in people who inject drugs

One-Minute Telegram 55-2022-3/3 - Hepatitis C virus (HCV) infection is a curable disease that disproportionately affects people who inject drugs (PWID), but uptake of HCV treatment in this population has historically been low.

This longitudinal observational study was conducted in the US from 2006 to 2019 and included a community-based cohort of 1323 former and current PWID with detectable HCV RNA at baseline. Of those, 82% were Black, 71% male, and 66% HIV-negative. Liver cirrhosis was assessed by semiannual transient elastography. Mortality data was obtained from a national database.

  • The proportion of participants with detectable HCV RNA and cirrhosis declined from 100% and 15%, respectively, at the beginning of the study to 48% and 8%, respectively, at the end of the observation period.
  • The absence of HCV RNA was significantly associated with reduced odds of cirrhosis (OR, 0.28; 95% CI, 0.17–0.45) and reduced risk of all-cause mortality (HR, 0.54; 0.38–0.77).
  • Overall, 39% of participants reported receiving hepatitis treatment during the observation period.

Limitations include that this study was conducted in a single city, restricting generalizability. In addition, these results may lead to overestimation of treatment uptake among the general PWID population, as participation in the study likely increased the participants’ awareness of their HCV status and the availability of treatment.

The take-home message?
In this US community-based cohort study of PWID, HCV RNA was undetectable in more than half of the initially HCV-positive study participants at the end of a 13-year observation period, even though PWID have historically been uninsured or insured only with Medicaid, which may adversely affect treatment uptake. Undetectable HCV RNA correlated with a significant reduction in the odds of cirrhosis and the risk of all-cause mortality.

  • Title of study: Impact of hepatitis C treatment uptake on cirrhosis and mortality in persons who inject drugs: a longitudinal, community-based cohort study [11]
  • Authors: Cepeda JA et al.
  • Journal: Annals of Internal Medicine

Google searches for abortion pills after SCOTUS leak

One-Minute Telegram 54-2022-1/3 - On June 24, 2022, the US Supreme Court overruled the landmark 1973 Roe vs. Wade decision, shifting determination over abortion laws to state legislatures. How this decision will affect the way individuals seek information about and access to abortion remains unclear.

This study analyzed Google searches for abortion medications (i.e., mifepristone, misoprostol) before and after the Supreme Court’s decision was leaked in May 2022. Searches for abortion medications spiked to 162% higher than expected (95% CI, 149–175%) immediately after the leak. The searches were significantly higher in states with more restrictive reproductive health care policies (according to the Women’s Policy Research ranking). [12]

Limitations include that the motivation for the searches and the demographics of searchers were not available.

The take-home message?

This study shows that searches for abortion medications spiked after the leak of the Supreme Court's Roe vs. Wade reversal, raising concern about the potential for an increase in medically unsupervised abortions. Further research is needed to determine how changes in abortion laws will impact the way individuals seek and attain induced abortions.

  • Title of study: Internet searches for abortion medications following the leaked Supreme Court of the United States draft ruling [13]
  • Authors: Poliak A et al.
  • Journal: JAMA Internal Medicine
  • AMBOSS Links: Induced abortion

Racial and ethnic disparities in the residency match

One-Minute Telegram 54-2022-2/3 - The US physician workforce does not reflect the demographic composition of the US. Greater diversity in the workforce may reduce health care disparities. [14][15]

This study compared the total number of applicants to the number of matched residents based on self-reported race and ethnicity in 11 competitive medical specialties. The applicants were categorized into one of three groups: Asian, White (non-Hispanic), and underrepresented in medicine (URM), which comprised African American, American Indian or Alaska Native, Hispanic, and Native Hawaiian or Pacific Islander.

  • In all 11 competitive specialties, the proportion of URM individuals among matched residents was significantly lower than their proportion among all applicants.
  • In 2 of 11 specialties, the proportion of Asian individuals among matched residents was significantly lower than their proportion among all applicants.
  • In 6 of 11 specialties, the proportion of matched White residents among matched residents was significantly higher than their proportion among all applicants.

Limitations include that changes in residency recruitment practices that may have occurred since 2018 are not reflected in this analysis and that categories of race and ethnicity provided in residency applications do not adequately reflect human diversity.

The take-home message?

In this study, candidates from ethnic and racial groups that are underrepresented in the US physician workforce were significantly less likely to match into competitive specialties for graduate medical education (GME) training. This underscores the need to reevaluate current GME recruitment strategies to increase diversity in the health care workforce.

  • Title of study: Racial and ethnic differences in resident selection in 11 specialties, 2013–2018 [16]
  • Authors: Bowe S et al.
  • Journal: JAMA

Should we rethink resuscitation in septic shock?

One-Minute Telegram 54-2022-3/3 - Fluid resuscitation is a cornerstone of the treatment for septic shock, as is reflected in the 2021 Surviving Sepsis Guidelines. However, recent observational studies suggest that fluid overload may contribute to higher sepsis-related mortality, even though the overall quality of evidence is low. [17][18][19]

In this multinational study, patients treated for septic shock in an ICU who had already received at least 1 L of intravenous fluids (IVF) were randomized within 12 hours of septic shock onset to a restrictive-fluid group (n = 770; median IVF = 1798 mL), with additional IVF given only if patients met strict predetermined clinical indications, and a standard-fluid group (n = 784; median IVF = 3811 mL), in which more liberal use of additional IVF was permitted.

The primary outcome was 90-day mortality.

  • Restrictive-fluid group: 42.3%
  • Standard-fluid group: 42.1%
  • Adjusted absolute difference: 0.1% (95% CI, - 4.7–4.9)

At 90 days, there was no difference in serious adverse events, survival without life support, and survival after discharge.

Limitations include that the study was not blinded, that data on cointerventions and hemodynamic factors were not collected, that the study was not powered to detect differences in subgroups, and that all study sites were exclusively in Europe, which may limit generalizability.

The take-home message?

In this trial, there was no difference in survival or serious adverse events in patients treated for septic shock with a restrictive fluid strategy compared to those treated with standard fluid therapy. Further prospective research is needed to determine if a restrictive fluid strategy may nevertheless be beneficial in specific subsets of patients with septic shock.

Can vitamin C reduce mortality in sepsis?

One-Minute Telegram 53-2022-1/3 - Acute vitamin C deficiency is common in critically ill patients and may contribute to oxidative organ injury and, potentially, poor outcomes. [21] A recent meta-analysis suggested a possible reduction in mortality with adjunctive high-dose vitamin C in patients with sepsis, but the treatment effects were of low certainty, emphasizing the need for further high-quality trials. [22]

This international trial included 872 patients who had been in the ICU for less than 24 hours, had a proven or suspected infection, and were receiving a vasopressor. Patients were randomized to receive either high-dose vitamin C (50 mg/kg IV; n = 435) or placebo (n = 437) every 6 hours for up to 96 hours.

On day 28 of the trial, the composite of death or persistent organ dysfunction occurred in 44.5% of patients in the vitamin C group and in 38.5% of patients in the placebo group (risk ratio, 1.21; 95% CI, 1.04—1.40).

Limitations include the lack of sufficient data and power to enable detailed subgroup analysis and that the trial was conducted in three high-income countries, and therefore the generalizability to lower-income countries may be limited.

The take-home message?

Previous research had suggested the possible benefits of high-dose vitamin C in critically ill patients. However, in this trial, its use in the treatment of ICU patients with sepsis who were receiving vasopressors was associated with higher mortality and persistent organ dysfunction when compared with placebo.

How accurate are brachial blood pressure cuff devices?

One-Minute Telegram 53-2022-2/3 - Measuring blood pressure (BP) with a brachial BP cuff device is a convenient alternative to invasive aortic BP measurement, but may lack accuracy. [24]

This cross-sectional study recruited 500 patients (29% female) due to undergo a clinically indicated coronary angiography. Patients with severe aortic stenosis or atrial fibrillation were excluded. BP was measured invasively at the end of angiography and noninvasively using an automated BP monitor, which provided brachial cuff BP and a noninvasive measure of central BP estimated from pulse waves.

Using invasive aortic systolic BP (SBP) measurements as values of reference, brachial cuff SBP was more accurate in men than in women (mean difference in men, –0.3 mm Hg; mean difference in women, –6.5 mm Hg; P < 0.001). Conversely, noninvasive measurement of central SBP (calibrated for mean arterial pressure and diastolic BP) was more accurate in women than in men.

However, 55% of the total effect of sex on brachial cuff SBP accuracy was attributable to height; the direct effect of sex on brachial cuff SBP accuracy was insignificant.

Limitations include restricted generalizability, as 94% of participants were white, 29% were female, and all participants had an indication for coronary angiography. Additionally, the trial was conducted using only a single type of device for noninvasive BP monitoring.

The take-home message?

While brachial cuff SBP measurements were found to be accurate in men, this study shows that the method was less accurate in women, mainly because of their smaller stature. Noninvasive central SBP (derived from brachial pulse waves) appeared to be the most accurate noninvasive method in women.

  • Title of study: Accuracy difference of noninvasive blood pressure measurements by sex and height [25]
  • Authors: Abbaoui Y et al.
  • Journal: JAMA Network Open
  • AMBOSS Links: Hypertension, ASCVD

Can metformin and lifestyle intervention reduce cardiovascular risk in patients with impaired glucose tolerance?

One-Minute Telegram 53-2022-3/3 - Lifestyle changes and glucose control in patients with impaired glucose tolerance result in reduced glucose levels and reduced progression to diabetes. [26] This trial addressed whether these interventions may also improve cardiovascular outcomes.

In this RCT, 3234 participants with impaired glucose tolerance were randomized into 1 of 3 groups: metformin 850 mg twice daily, placebo, or intensive lifestyle intervention aiming to reduce body weight by ≥ 7%. Participants were followed for 3 years.

Subsequently, unmasked metformin was continued in the metformin group and all participants were offered less intensive lifestyle intervention. Follow-up continued for an average of 18 years.

Although both the use of metformin and lifestyle intervention reduced the rate of diabetes onset, they had no significant effect on the primary outcome (first occurrence of nonfatal myocardial infarction, stroke, or cardiovascular death) compared to placebo:

  • Metformin vs. placebo: HR, 1.03 (95% CI, 0.78–1.37)
  • Lifestyle vs. placebo: HR, 1.14 (0.87–1.50)

Limitations include that metformin adherence fell over time and that lifestyle intervention was less intensive after the initial 3 years of follow up, which may have affected the results.

The take-home message?

In this trial with a total follow-up period of 21 years, neither the use of metformin nor lifestyle intervention lead to a reduction in myocardial infarction, stroke, or cardiovascular death in patients with impaired glucose tolerance when compared with placebo.

  • Title of study: Effects of long-term metformin and lifestyle interventions on cardiovascular events in the diabetes prevention program and its outcome study [27]
  • Authors: Goldberg RB et al.
  • Journal: Circulation
  • AMBOSS Links: ASCVD, Diabetes mellitus

Mistreatment and discrimination contribute to physician burnout.

One-Minute Telegram 52-2022-1/3 - Physician burnout, defined as emotional exhaustion, depersonalization, and a feeling of low personal accomplishment, is a common phenomenon. It has a negative impact on physicians’ well-being and may also affect patient care. Mistreatment and discrimination of physicians by patients or their relatives may be factors contributing to the development of burnout. [28][29][30][31]

In this cross-sectional study utilizing a national survey, 6512 US physicians reported mistreatment and discriminatory behaviors by patients, their families, and visitors in the preceding year with the following frequencies:

  • Racially or ethnically offensive remarks: 29.4%
  • Offensive sexist remarks: 28.7%
  • Unwanted sexual advances: 20.5%
  • Refusal to allow them to provide care because of the physician’s personal attributes: 21.6%

Female and non-White physicians were significantly more likely to report mistreatment or discrimination. The experience of mistreatment or discrimination was independently associated with higher odds of burnout.

Limitations include the potential for recall and response bias and that causality and the direction of the observed associations could not be determined in this survey-based cross-sectional study.

The take-home message?
This survey-based study found that mistreatment and discrimination of physicians by patients and their relatives was common and disproportionately directed at female and non-White physicians. The experience of mistreatment and discrimination were independently associated with physician burnout.

Does tranexamic acid reduce perioperative morbidity in noncardiac surgery?

One-Minute Telegram 52-2022-2/3 -Tranexamic acid (TXA), an antifibrinolytic drug, has been shown to reduce perioperative bleeding in procedures associated with high blood loss, including cardiac surgery and cesarean section. Whether prophylactic TXA can safely reduce perioperative bleeding associated with other surgical procedures remains unclear. [33][34]

In this non-inferiority trial, patients at risk for bleeding and cardiovascular events who were scheduled for noncardiac surgery were randomly assigned to receive a 1-g intravenous bolus of TXA (n = 4757) or placebo (n = 4778) at the start and end of surgery.

Primary outcomes:

  • Composite bleeding outcome (life-threatening bleeding, major bleeding, bleeding into a critical organ): Patients in the TXA group had a lower incidence (9.1%) at 30 days compared to those in the placebo group (11.7%; HR, 0.76; 95% CI, 0.67–0.87).
  • Primary safety outcome (composite of myocardial injury, non-hemorrhagic stroke, arterial thrombosis, symptomatic venous thromboembolism): Predetermined criteria for noninferiority were not met at 30 days (TXA vs. placebo group HR 1.02; 95% CI, 0.92–1.14).

Limitations include that the study was terminated for financial reasons before recruitment was completed and that the ability to identify perioperative thrombotic complications (a potential adverse effect of TXA use) was limited.

The take-home message?
Prophylactic tranexamic acid for noncardiac surgery in patients at risk for bleeding and adverse cardiac events reduced blood loss and critical bleeding events but did not meet noninferiority criteria for cardiovascular safety.

Does sweetening coffee reduce its positive impact on mortality?

One-Minute Telegram 52-2022-3/3 - Moderate coffee consumption has been associated with reduced mortality, but whether adding a sweetener influences this association has not been investigated. [36]

This prospective cohort study from the UK included a total of 171,616 participants. Self-reported coffee consumption was assessed at baseline and outcomes were evaluated over a median follow-up of 7.0 years.

Participants who drank unsweetened coffee had a lower risk of all-cause mortality compared to the coffee abstainers. The association was U-shaped with the lowest risk of mortality in consumers of 2.5–4.5 drinks/day. Those who sweetened their coffee with sugar had a similar U-shaped association with reduced mortality, albeit with non-significant results at low (< 1.5 cups) and high (> 3.5 cups) daily coffee consumption. Use of artificial sweeteners was not consistently associated with reduced mortality. These results were independent of the type of coffee (instant, ground, decaffeinated) and important confounders, such as lifestyle factors.

Limitations include the possibility of unassessed residual confounders, the reliance on self-reported data potentially leading to misclassification, and that exposure, which was assessed at baseline only, may not reflect actual exposure over time. Also, the number of participants using an artificial sweetener in coffee was relatively low, diminishing the power to detect an association.

The take-home message?
This observational study contributes to the growing body of evidence that moderate coffee consumption is associated with a decreased overall mortality. This effect persisted with the use of sugar but not with the use of artificial sweeteners.

  • Title of study: Association of sugar-sweetened, artificially sweetened, and unsweetened coffee consumption with all-cause and cause-specific mortality [37]
  • Authors: Liu D et al.
  • Journal: Annals of Internal Medicine

Is all chest pain created equal?

One-Minute Telegram 51-2022-1/3 - People of color and women have worse outcomes for acute myocardial infarction (MI) than White adults and men, respectively. [38] Whether those disparities are related to differences in triage and emergency department (ED) care is unclear.

This study analyzed data from the CDC’s National Hospital Ambulatory Medical Care Survey (NHAMCS) on 4152 adults aged 18–55 with a history of ED visits for chest pain. Admission to hospital, wait times, and care received by adults in the ED were compared for women (56.8%) versus men and people of color (34.9%, of whom 89% were non-Hispanic Black) versus White individuals.

  • Women experienced longer wait times prior to provider evaluation than men (48.1 mins vs. 37.2 mins, p < 0.001)
  • Men were more likely than women to be:
    • Seen by a provider at any given time (HR, 1.15; 95% CI, 1.05–1.26)
    • Admitted to the hospital (17.9% vs. 12.4%; AOR, 1.40; 1.08–1.81)
  • People of color experienced longer wait times prior to provider evaluation than White individuals.
    • Women: 57.8 mins vs. 42.7 mins (p = 0.006)
    • Men: 44.0 mins vs 34.0 mins (p = 0.006)
  • People of color were less likely than White individuals to be seen by a provider (HR, 0.82; 0.73–0.93)

Limitations include that the authors only considered visits for chest pain, ignoring other presenting symptoms of MI; the absolute number of acute MIs was small; and there was limited data on non-Black people of color.

The take-home message?
This study demonstrated that women and people of color experience longer ED wait times and are less likely to be seen by a provider when presenting with chest pain than men and White individuals, respectively. Further study is needed to determine how these findings correlate with the worse outcomes in these groups for acute MI.

Does the COVID-19 vaccine reduce long COVID symptoms?

One-Minute Telegram 51-2022-2/3 - Long COVID can severely impact quality of life, but no effective treatments exist at this time. While evidence suggests that long COVID occurs less frequently in people who were vaccinated before infection, [40] the question of whether vaccination after infection can alter the course of long COVID remains unclear.

This observational cohort study included data on 28,356 individuals aged 18–69 years who had participated in the UK Office for National Statistics COVID-19 Infection Survey and had received at least one dose of a COVID-19 vaccine after infection. Activity-limiting long COVID was reported by 4747 individuals (16.7%). Long COVID symptom trajectories were estimated before and after vaccination.

The odds of activity-limiting long COVID after vaccination and prior to vaccination were:

  • First dose: OR, 0.877 (95% CI, 0.805–0.955)
  • Second dose: OR, 0.909 (0.844–0.979)

Limitations include the observational design of the study and that the presence of long COVID was determined by survey reporting alone.

The take-home message?
This study demonstrated an association between vaccination after COVID-19 and reduction in long COVID symptoms. While an observational study cannot prove causality between COVID-19 vaccination and reduction in long COVID symptoms, it adds to the robust body of evidence for the benefits of vaccination against COVID-19 even following infection.

Are glucocorticoids a safe and effective treatment for IgA nephropathy?

One-Minute Telegram 51-2022-3/3 - While immunomodulators are commonly used to treat IgA nephropathy, questions regarding the safety and efficacy of immunosuppression remain. [42]

In this international, double-blind randomized controlled trial, 503 adults with biopsy-proven IgA nephropathy, > 1 g/day proteinuria, and an eGFR 20–120 mL/min/1.73 m2 were randomized 1:1 after ≥ 3 months of optimal care to receive methylprednisolone (n = 257) or placebo (n = 246). The initial cohort of patients in the methylprednisolone group (n = 136) received a dose of 0.6–0.8 mg/kg/day (max. dose 48 mg/day) for 2 months followed by a 6–8 month taper. The study was temporarily halted due to concerns about serious infections among participants in the methylprednisolone group. Subsequently, a reduced-dose cohort was enrolled (0.4 mg/kg/day, max. dose = 32 mg/day; n = 121). Patient follow-up continued for a minimum of 2 years.

Composite primary outcome
Annual event rate of 40% decline in eGFR, end-stage renal disease, and death due to kidney failure

  • Methyprednisolone: 7.3 (95% CI, 5.7–9.4)
  • Placebo: 12.1 (9.7–15.1)
  • HR, 0.53 (0.39–0.72)
    • Full dose: HR, 0.58 (0.41–0.81)
    • Reduced dose: HR, 0.27 (0.11–0.65)

Secondary outcomes
Compared to the placebo group, treatment-group participants experienced:

  • Slower rates of decline in eGFR
  • Lower rates of kidney failure requiring dialysis or transplant
  • Unsustained reduction in proteinuria (in g/day)
  • No difference in mortality

Serious adverse events were higher in the methylprednisolone group than in the placebo group, especially in the participants with the higher dose protocol.

Limitations include that the trial was paused, that the protocol was modified due to adverse events, and that the majority of participants came from a single country (China).

The take-home message?
In this RCT of individuals with IgA nephropathy, the use of methylprednisolone reduced the composite outcome of reduced eGFR, end-stage renal disease, and kidney disease-related death but was associated with an increased risk of serious adverse events. The 2021 KDIGO guideline urges extreme caution in the use of glucocorticoids in IgA nephropathy. [43]

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). [45]

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. [49]

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 [50]
  • 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. [51]

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. [53]

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. [54]
    • Quality of life (assessed by the Asthma Symptom Utility Index) improved more in the intervention group than in the usual care group. [55]
    • 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. [57][58][59]

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. [60]

  • 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 [61]
  • 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. [62]

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) [64] 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. [66] 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 [67]
  • 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 [68] 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. [70]

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. [71]

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. [73][74]

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. [75]

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 [76]
  • 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 [77]
  • 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 [78]
  • 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. [80]

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 [81]
  • 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 [82]
  • 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 [83]
  • 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. [84]

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 [86]
  • 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 [87]
  • 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. [89]

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. [92]

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. [93]

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 [94]
  • 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 [95]
  • 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. [96]

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. [98] 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. [101]

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 [102]
  • Authors: Lee CS et al.
  • Journal: JAMA Internal Medicine
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