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One-Minute Telegram Archive 2020

Last updated: January 16, 2023

Introductiontoggle arrow icon

This article contains a collection of content written 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.

For the One-Minute Telegram, AMBOSS has partnered with QxMD to bring you seamless access to the medical literature that we review. Read by QxMD can serve as your own personalized medical and scientific journal, allowing you to keep up with the latest new research that impacts your practice in minutes per day. Read is integrated with full-text holdings at thousands of institutions around the globe, including Harvard, Yale, and the Massachusetts General Hospital. Read by QxMD is available for all mobile devices (iOS and Android) and accessible via all web browsers. See “Tips and links” below to try it out.

See also our current One-Minute Telegram Archive, our One-Minute Telegram Archive 2022 and our One-Minute Telegram Archive 2021

Q4 2020toggle arrow icon

Edition 15 - December 12, 2020toggle arrow icon

Ho-ho-holiday edition: The pounds of Christmas past, present, and future – and will Santa have to postpone his trip this year?

One-Minute Telegram 15-2020-1/4

Hey Santa, will you bring us presents this year? – A recent opinion article looks into how COVID-19 might affect Santa’s work! Many important questions were asked: Would Santa be a high-risk patient, being a bit overweight (and 1,750 years old)? Would he need a negative COVID-19 test from each household before entering? Does he need special protection equipment? Does he need to self-quarantine after each trip? The author recommends that Santa proceed with his visits, seeing how someone without a history of having had influenza is unlikely to be affected by COVID-19, but it was Dr. Anthony Fauci who confirmed what we hoped for all along: Santa has innate immunity! It seems Christmas won’t be canceled, and, oh boy, are we merry! [1][2]

A Holiday souvenir – If you have ever put on a few pounds during the holiday season, you are in good company! A study conducted in the US, Germany, and Japan recorded the weight of 2,924 participants for one year using wireless scales. In the three countries, participants experienced the largest weight increase in the ten days following Christmas. The upside: half the weight gain was swiftly lost afterward. The downside: the other half remained until the summer or beyond. On a lighter note, another study showed that weight monitoring and education on the physical activity calorie equivalent (PACE) of traditional holiday fare could prevent weight gain during the end-of-year festivities. So it might be worthwhile to hang up some motivational posters beside the stockings! [3][4]

Gaming the system – If weight monitoring is not your thing, you could also consider asking Santa for a gaming console this year! Researchers evaluated the health of 2,459 e-sport players and found that, contrary to popular assumptions, gamers were more likely to have normal weight compared to the general population. They were also more commonly nondrinkers and nonsmokers (their hands are too busy!). This notwithstanding, e-sports rarely provide much in the way of physical activity, and 80.3% of the participants were not meeting the WHO physical activity guidelines – which is about the same amount as the general population. So enjoy a much deserved game break this holiday season, but then perhaps get moving to your favorite holiday tunes! [5]

The take‑home message?

There is still joy to be found this holiday season! Your friends here at AMBOSS encourage you to take a moment and reflect on something or someone that makes you smile, not least that you are the 2020 person of the year!
[6]

Let’s keep our spirits and motivation high as we carry this honor into the new year and stay mindful of the CDC’s advice: spread holiday cheer, not COVID! [7]

What is the risk factor in COVID-19: obesity or its comorbidities?

One-Minute Telegram 15-2020-2/4 - That obesity increases the risk of death from COVID-19 is well established, but whether this is due to the increased fat mass itself or rather conditions secondary to obesity (e.g., cardiovascular disease) has not been extensively studied. [8]

This retrospective cohort study included data from 2,466 hospitalized SARS-CoV-2 PCR-positive adult patients. Patients were classified using BMI and divided into three classes: class 1 (30 to < 35), class 2 (35 to < 40), and class 3 (≥ 40). The median hospital stay was 7 days, 533 patients (22%) were intubated and 627 (25%) died.

There was an increased risk for death or intubation in all three obesity classes, and the association persisted after controlling for the effects of age, sex, race/ethnicity, smoking status, and chronic comorbidities (e.g., diabetes, hypertension, pulmonary diseases). The risk was lower in individuals with class 1 obesity (adjusted HR 1.1; 95% CI, 0.9–1.4) compared to class 2 (1.3; 0.98–1.7) and class 3 obesity (1.6; 1.1–2.1). However, this effect was seen only in patients under 65 years of age but not in those aged 65 years or more (P for interaction = 0.042).

Limitations include that BMI was missing for 28% of the cohort (multiple imputation for missing BMI data was used), increasing the risk of bias.

The take‑home message?

Obesity is an independent risk factor for intubation or death in patients with COVID-19 regardless of race, ethnicity, and comorbidities, but only in patients younger than 65 years of age. Physicians and policymakers should keep this in mind when considering prevention strategies (e.g., vaccination allocation) and management of COVID-19 patients (e.g., hospitalization). Further research is required to determine the mechanism for this association (e.g., specific cytokines).

Anticoagulation for patients with bioprosthetic mitral valves: is it time for a DOAC?

One-Minute Telegram 15-2020-3/4 - In 2011, a landmark trial demonstrated that rivaroxaban was noninferior to warfarin in preventing cardioembolic events in nonvalvular atrial fibrillation without increasing bleeding rates. However, a notable limitation of this trial was that patients with prosthetic heart valves were not included. [10]

The present study set out to fill this knowledge gap by evaluating the outcomes of 1005 patients with a bioprosthetic valve and atrial fibrillation or flutter and indications for anticoagulation. Patients were randomized at least 48 hours after undergoing mitral-valve surgery to either 15–20 mg of rivaroxaban (n = 500) or warfarin treatment (n = 505) with the aim of achieving an INR of 2–3. The maximum follow-up was 12 months.

The primary outcomes of mean time until death, major cardiovascular events, or major bleeding did not differ significantly between the groups (P < 0.001 for noninferiority). Patients in the rivaroxaban group had similar or better secondary outcomes at 12 months compared to the warfarin group:

Limitations include the open-label design. The secondary outcomes should also be interpreted with caution due to the low rate of events in each group. These findings cannot be extrapolated to patients with non-bioprosthetic valves or those with mitral stenosis.

The take‑home message?

This industry-sponsored study demonstrates that rivaroxaban is noninferior to warfarin in the treatment of atrial fibrillation in patients with bioprosthetic mitral valves, giving physicians the option to begin treatment with rivaroxaban at an early stage after surgery without the need for INR monitoring. Future studies are needed to examine the effects of rivaroxaban in patients with bioprosthetic aortic valves and mechanical valves.

Early IV nitrate treatment for acute heart failure: should we or shouldn’t we?

One-Minute Telegram 15-2020-4/4 - Management of acute heart failure (AHF) can differ depending on the guideline or consensus statement. While the ACC Expert Consensus recommends reserving IV nitrates for patients with refractory congestive symptoms after initial treatment, the ESC guideline favors the early use of IV nitrates in patients with pulmonary congestion or edema. [12][13]

This cross-over trial conducted in France designed a nitrate care bundle in order to improve ESC guideline adherence and to assess the benefit of early nitrate use. The study included 503 patients aged 75 years and older who presented to the emergency department (ED) with AHF (worsening dyspnea and other signs of congestion) and randomly assigned them to one of two groups:

  • An intervention group in which patients received early IV nitrate boluses, moderate doses of IV furosemide, and management of precipitating factors (e.g., atrial fibrillation, infection) in the ED (n = 200)
  • A control group in which patient received “usual care” at the discretion of the emergency physician (n = 303)

Patients in the intervention group compared to the control group received a higher dose of IV nitrates within 4 hours of treatment (median difference 23.8 mg; 95% CI, 13 to 34.1 mg), a lower dose of diuretics (median difference -13.1 mg; -25 to -0,9 mg), and proportionately more frequent treatment of precipitating factors in the ED (adjusted difference 31.1%; 14.3–47.9%). While the care bundle did improve guideline adherence, there was no significant difference between the two groups in survival rates, all-cause mortality, readmission, length of hospital stay, or acute kidney injury at 30 days.

Limitations include the open-label design, that nitrate dosages were variable, and that the control group treatment was not standardized. The study’s exclusion of patients below the age of 75 years limits the generalizability of the results, and longer-term outcomes were not recorded.

The take‑home message?

Early use of IV nitrates in elderly patients with AHF is not superior to “standard of care” in achieving short-term treatment goals. However, further research will be needed to identify effective treatments and to support the development of accepted guidelines.

Edition 14 - November 28, 2020toggle arrow icon

Pills vs. scalpels: appendicitis treatment revisited

One-Minute Telegram 14-2020-1/3 - The vast majority of patients with appendicitis undergo appendectomy, yet antibiotics may be just as safe and effective. Past studies have supported surgery, while others have advocated antibiotic therapy. [15][16]

To test this hypothesis further, a US-based, randomized trial included 1,552 adults with appendicitis:

On day 30, a health-related quality of life score (EQ-5D score) [17] of the antibiotics group was not inferior to that of the surgery group. However, 29% of the patients in the antibiotics group would undergo an appendectomy by day 90 (41% of patients with an appendicolith and 25% without). There were no deaths, and the rate of serious adverse events did not differ significantly between the two groups, but patients in the antibiotics group had significantly more complications (8.1 vs. 3.5%). When excluding patients with appendicoliths, the rate of complications was similar between the groups (3.7 vs. 3.5%); emergency department visits and hospitalizations after treatment allocation were more frequent in the antibiotics group.

Limitations of this study include that outcomes > 90 days are not available, this study was not blinded, and antibiotic regimes were not standardized.

The take‑home message?

Results from this study suggest that antibiotic therapy is non inferior to surgical intervention for the treatment of acute appendicitis. However, further studies are needed to develop appropriate selection criteria to help minimize complication rates and the need for subsequent appendectomies.

Admit patient to home: virtual hospitals for patients with COVID-19

One-Minute Telegram 14-2020-2/3 - Hospitals have been struggling to conserve their resources amid the pandemic, but natural constraints, especially in the workforce, constitute a limit to these efforts.

This US-based study investigated whether treatment for COVID-19 from home in a virtual hospital setting could replace in-patient treatment for low-risk patients. 1477 patients with PCR-confirmed nonsevere COVID-19 pneumonia (ATS/IDSA criteria) and an adequate home environment were included. [19] Patients were evaluated in person and admitted for treatment to one of two individually staffed virtual floors, depending on their DSCRB-65 prognostic score: [20]

  • A virtual observation unit (VOU) for patients with a DSCRB-65 of 0, where a registered nurse (RN) provided daily virtual symptom monitoring (n = 1293; median stay = 11 days)
  • A virtual acute care unit (VACU) for patients with a modified DSCRB-65 score between 1 and 3, with daily virtual visits from physicians and RNs plus home visits from clinicians at the beginning of the study and, then, as needed (n = 184; median stay = 12 days).

All patients could communicate 24/7 with an RN. Additionally, VACU patients were given a home monitoring kit that included a blood pressure cuff, pulse oximeter, and thermometer. Of all the patients, 3% (VOU) and 13% (VACU) required subsequent hospitalization and, of those, 5% (VOU) and 0% (VACU) died. If subsequent hospitalization was indicated, patients were admitted immediately.

A limitation of this study is the restricted generalizability, as this health network was experienced in setting up virtual environments and, therefore, capable of setting up a virtual hospital based on existing infrastructure.

The take‑home message?

This study suggests that for most low-risk patients with COVID-19 pneumonia, treatment at home via a virtual hospital is a viable option, freeing up hospital resources and reducing SARS-CoV-2 exposure in the process. While the immediate creation of similar care models may be logistically challenging, they could become an important part of health care in the future.

  • Title of study: Insights from rapid deployment of a “virtual hospital” as standard care during the COVID-19 pandemic [21]
  • Authors: Sitammagari et al.
  • Journal: Annals of Internal Medicine
  • AMBOSS links: COVID-19, Pneumonia

GFR formulas are just estimates, but can we estimate better?

One-Minute Telegram 14-2020-3/3 - Current equations used to estimate a patient’s glomerular filtration rate (eGFR), namely the CKiD for children aged 1–16 years and the CKD-EPI for adults , can produce inaccurate or inconsistent results, particularly in adolescents and young adults. Other formulas have been developed, but their performance is not clearly superior; e.g., the FAS equation showed improved accuracy across different ages but overestimated GFR in patients with low serum creatinine levels and in those with chronic kidney disease. [22][23]

The aim of this study was to develop a formula that combines the strengths of the FAS and CKD-EPI equations, providing more accurate results regardless of age and kidney function. Data from 19,629 patients over the age of 2 years was used to develop the new European Kidney Function Consortium (EKFC) equation and validate it internally and externally. The gold standard was a measured GFR (mGFR) that was established by either plasma clearance or urinary clearance of exogenous filtration markers in all patients.

In comparison to the CKD-EPI, CKiD, and FAS equations, the eGFR calculated with the EKFC formula was closest to the mGFR in all age groups (except 2–4 years) and in all subgroups of kidney function (lower bias). In patients aged 2–4 years, the EKFC highly underestimated the mGFR (> 10 ml/min).

A self-reported limitation of this study was that it included only white individuals, possibly limiting the use of the formula in other populations (it could underestimate the mGFR because of differences in creatinine generation). However, some physicians argue against stratification of GFR formulas based on race and rather encourage researchers to focus on finding other markers for creatinine generation. [24][25]

The take‑home message?

The new EKFC equation may provide a more accurate estimate of GFR across age and kidney function in comparison to previously recommended equations, but it too has its limitations: GFR estimates may be underestimated in young children and in those people with higher baseline creatinine generation.

Edition 13 - November 14, 2020toggle arrow icon

Robots vs. residents: who can interpret chest x-rays better?

One-Minute Telegram 13-2020-1/3 - The idea that artificial intelligence (AI) can be used to help close the gap between unequally distributed healthcare resources is far from new, and the application of AI in the interpretation of radiologic imaging is an area of particular research interest. [27][28]

Three board-certified radiologists labeled 1,998 AP frontal chest radiographs according to 72 prespecified findings: anatomical (e.g., consolidations, pneumothorax, masses), devices (e.g., cardiac pacer and wires), technical (e.g., rotated x-ray), and tubes and lines (e.g., correctly or incorrectly positioned central intravascular lines). These interpretations served as the gold standard for this study.

Five third-year radiology residents from different US academic medical centers were then tested against a previously trained and validated AI deep learning model in interpreting a set of approximately 400 images per resident versus all 1,998 of these images, respectively. The mean image-based sensitivity to detect the labeled findings was similar for the residents and the AI model (72 vs. 71.6%, P = 0.66). The mean specificity was higher for the AI model compared to the residents (98 vs. 97.3%, P < 0.001), as was the positive predictive value (73 vs. 68.2%, P = 0.001). Overall, the AI algorithm performed better than the residents in more prevalent, less complex findings (e.g., cardiomegaly, pulmonary edema, hyperaeration) but worse in less prevalent, more complex ones (e.g., masses, nodules, enlarged hilum).

An important limitation was that the AI model was tested against only five radiology residents.

The take‑home message?

An AI algorithm may perform similarly to radiology residents in evaluating AP chest radiographs when compared to board-certified radiologists. Developing well trained AI algorithms may be worth pursuing as a tool to aid experienced radiologists with initial interpretation, potentially increasing efficiency and reducing health care costs in the process.

COVID-19: Are people willing to get vaccinated?

One-Minute Telegram 13-2020-2/3 - There are over one hundred vaccine candidates currently being tested for their safety and effectiveness worldwide, and it seems we are getting closer to finding a good candidate (Pfizer and BioNTech), but acceptance is a major concern. A recent survey study suggests that the willingness of US adults to receive a COVID-19 vaccine is affected by various factors, including not only questions of efficacy and risk but also by political partisanship and where the vaccine was produced. But what about the rest of the world? [30][31][32]

A survey conducted in 19 countries asked 13,426 participants selected at random, first, whether they would take a generally available vaccine if proven safe and effective and, second, whether they would take a vaccine if recommended by their employer. Results showed an overall willingness to receive a COVID-19 vaccine as follows:

  • 71.5% “completely agree” or “somewhat agree;” 14.2% “neutral/no opinion;” 14.2% “somewhat disagree” or “completely agree”
  • Lowest acceptance rate was 54.9% (Russia); highest acceptance rate was 88.6% (China); US acceptance rate was 75.4%

Positive responses increased with age (highest in participants ≥ 65 years), residency in a country with a high incidence and with higher mortality rates due to COVID-19, and in individuals who trusted their government. Positive responses decreased with low income (lowest in participants earning < 2 USD/day) and low level of education. Willingness to take an employer-recommended vaccine was lower overall (61.4%), with younger participants (18–24 years) being more willing to follow such a recommendation than older ones.

The take‑home message?

COVID-19 vaccine acceptance is likely highly variable, depending on country, demographics, and trust in government. The information gathered in this survey can help in the development of communication strategies to increase willingness in different population groups.

  • Title of study: A global survey of potential acceptance of a COVID-19 vaccine [33]
  • Authors: Lazarus et al.
  • Journal: Nature Medicine
  • AMBOSS links: COVID-19

Push it fast or push it slow: for hyponatremia, which is the best way to go?

One-Minute Telegram 13-2020-3/3 - Hypertonic saline for the treatment of symptomatic hyponatremia can be administered as a rapid intermittent bolus (RIB) or as a slow continuous infusion (SCI), but robust data on whether they are equally safe and effective remains scarce.

This open-label randomized trial included 178 adult patients that presented with hypotonic hyponatremia, a serum sodium (sNa) ≤ 125 mmol/L (mean 118 mmol/L), and moderately severe symptoms (e.g., nausea, drowsiness) or severe symptoms (e.g., seizures, coma). The patients were randomized according to the SALSA trial protocol to treatment with 3% NaCl as an SCI (n = 91) or a RIB (n = 87). Baseline features (e.g., causes of hyponatremia, baseline sNa, and clinical features) were similar in both groups. [34]

Overcorrection, defined as a sNa ≥ 12 or 18 mmol/L within 24 or 48 hours respectively, occurred at a similar rate in both groups (17.2 vs. 24.2%, P = 0.26). Fewer patients in the RIB group required sNa-relowering treatment (41.4 vs. 57.1%, P = 0.04), and more patients in the RIB group achieved their 24-hour target correction rate within the first hour of treatment (32.2 vs. 17.6%, P = 0.02). However, there was little difference in the efficacy with which the target sNa was reached at 24 or 48 hours or in the improvement of symptoms between the groups; no patients developed osmotic demyelination syndrome.

The exclusion criteria limit the generalizability of the results to other populations (e.g., pregnant patients and those with anuria, hypotension, or uncontrolled diabetes).

The take‑home message?

Both RIB and SCI of hypertonic saline are safe and effective treatments for patients with symptomatic hyponatremia. The use of RIB is supported by current guideline recommendations and comes with the advantage of requiring less sodium correction calculation. However, the results require further validation for patient groups not included in this study. [35]

  • Title of study: Risk of overcorrection in rapid intermittent bolus vs slow continuous infusion therapies for patients with symptomatic hyponatremia. [36]
  • Authors: Baek et al.
  • Journal: JAMA Internal Medicine
  • AMBOSS links: Hyponatremia

Edition 12 - October 31, 2020toggle arrow icon

Halloween edition: Brain-eating worms, a return from the dead, and drool, oh my!

One-Minute Telegram 12-2020-1/4

#1 - Worms without borders: Australia is home to what we guess are 90% of the world's most terrifying critters, but sometimes you just can't get enough of a ghould thing. A young woman was evaluated for recurrent headaches and visual symptoms. A brain MRI showed a cystic lesion in her right occipital lobe suspicious for a neoplasm or abscess. However, things took a turn for the good … before they took a turn for the horrible! The lesion was resected and it was not cancer (yay!) but, as a PCR test later revealed, a TAENIA SOLIUM LARVA (no!!!). The worm is not endemic to Australia, and the woman had no history of travelling abroad. Further investigations failed to establish how T. solium found its way to Australia, but our best guess is global worming.

#2 - A patient declared dead comes back to life: With everything that has gone on in 2020, patients returning from the dead should be no surprise. A recently published report described the case of a woman who presented with acute brainstem and cerebellar stroke as well as an acute abdomen. She underwent an exploratory laparotomy and externalization of a ventriculoperitoneal shunt, during which she went into cardiac arrest. She was declared dead after 30 minutes of CPR. But 20 minutes later, the OR staff noticed that the patient was showing signs of life. Surgery was restarted, and the patient was transferred (alive) to the ICU. Unlike in horror films, the Lazarus phenomenon is rarely seen in medicine and as far as the literature shows, none of those returning from the dead have gone on to attack the living.

#3 - A new organ in the back of your nose: Ever wonder why your snot goes down so smoothly? Well, researchers have found a previously unknown organ in the posterior nasopharynx that helps you wash it down! The structures were discovered during PET/CT scans performed on patients with prostate or urethral cancer (n=100). Tracer uptake was similar to that in the salivary gland, and histological studies in 2 human cadavers confirmed characteristics of a salivary gland. We imagine them putting on their best Dr. Frankenstein impressions and shouting: "IT'S sALIVEa!" They proposed the name “tubarial salivary glands,” but we would have liked to see something more topical, like "spit pits" or "drool pools." They moreover recommended avoiding radiotherapy in this area to prevent xerostomia and dysphagia – and we agree: wouldn’t want anything to come between us and our mountains of candy!

The take‑home message?
Reality can be stranger than fiction. Happy Halloween!

Original studies

COVID-19 death rates: Are we missing the full story?

One-Minute Telegram 12-2020-2/4 - When estimating the true medical impact of COVID-19, reported deaths secondary to a SARS-CoV-2 infection may only tell part of the story. Undocumented deaths due to the virus and those not directly related to the virus but rather to healthcare-related disruptions caused by the pandemic (e.g., stay-at-home orders) may be more difficult to ascertain.

In this study, researchers calculated the expected number of deaths in the US for this past summer using a forecasting model based on historical data that they adjusted for seasonality and annual trends, excluding the impact of an unforeseen pandemic. This number was then compared to death certificate data and population counts obtained from the National Center for Health Statistics and the US Census Bureau.

There was a total of 1,336, 561 deaths recorded between March 1 and August 1 of this year, approximately 20% more than the number of expected deaths (1,111,031; 95% CI, 1,110,364–1,111,697). One-third of the excess deaths were recorded in three states: NJ, NY, and MA. Of these excess deaths, 67% could be directly attributed to COVID-19. There was also a significant increase in the deaths attributed to heart disease and Alzheimer disease or dementia.

The results of this study are influenced by the assumptions underlying the statistical model and some data was only preliminary. Accordingly, outcomes are subject to change.

The take‑home message?
Death rates in the US appear to be significantly higher this year, and approximately two-thirds of these excess deaths can be attributed to COVID-19. Whether the remaining excess deaths were due to undocumented SARS-CoV-2 infections or to disruptions in the health care system affecting uninfected patients remains unclear.

  • Title of study: Excess deaths from COVID-19 and other causes, March–July 2020 [40]
  • Authors: Woolf et al.
  • Journal: JAMA
  • AMBOSS links: COVID-19

Time is precious: point-of-care testing for SARS-CoV-2

One-Minute Telegram 12-2020-3/4 - Point-of-care (POC) tests can reduce the time to diagnosis, potentially saving hospital resources and limiting chains of infection. An interventional nonrandomized trial examined how much time an FDA-approved, highly sensitive and specific POC test can save in comparison to the laboratory-based PCR tests previously used in patients with suspected COVID-19. [41][42]

This UK-based study included adults with suspected COVID-19 who presented to an acute care facility (clinic or emergency department), required inpatient treatment, and were tested within 24 hours of presentation with either the POC test (n = 499) or the laboratory-based PCR test (n = 555). The median time to results was 1.7 hours (IQR, 1.6–1.9) in the POC group, compared to 21.3 hours (16.0–27.9 hours) in the PCR group. The median time from presentation to arrival in a definitive COVID-19-positive or negative ward was 8.0 hours (6.0–15.0 hours) in the POC group and 28.8 hours (23.5–38.9 hours) in the PCR group. Of note, COVID-19 prevalence was higher in the POC group than in the PCR group (39 vs. 28%, P < 0.001), as were hospital admissions (73 vs. 57%, P < 0.001) and ICU admissions (13 vs. 8%, P = 0.004).

Because this study was not blinded, there may have been a selection bias for those patients receiving the POC vs. laboratory-based PCR tests. Those patients with a higher likelihood of having the disease may have selectively received the POC test and also received expedited clinical care.

The take‑home message?
POC testing for SARS-CoV-2 may save significant time in the management of hospitalized patients. These gains speak in favor of POC instead of centralized PCR testing to improve health care efficiency during the pandemic.

  • Title of study: Clinical impact of molecular point-of-care testing for suspected COVID-19 in hospital (COV-19POC): a prospective, interventional, non-randomised, controlled study [43]
  • Authors: Brendish et al.
  • Journal: The Lancet Respiratory Medicine
  • AMBOSS links: COVID-19

Levothyroxine and AFib in older patients: what’s the right dose?

One-Minute Telegram 12-2020-4/4 - It is well established that hyperthyroidism is associated with atrial fibrillation (AFib), but it is less clear whether high doses of levothyroxine have the same effect. Excessive doses of levothyroxine are a concern in the elderly, as treatment response in this group is particularly variable, possibly due to declining lean body mass and a high rate of comorbidities.

Prospective data from a Canadian health care database on 391,612 patients over the age of 66 with current, recent (≤ 180 days), or remote (> 180 days) use of levothyroxine was used to determine the dose at which individuals may be at risk of developing AFib; 72% were women, the mean age was 82 years. 30,560 (16.1%) patients developed AFib during follow-up and were matched with 152,800 controls who did not.

Compared to low dosages of levothyroxine (< 75 mcg/day), medium (75 mcg–125 mcg/day) and high dosages (≥ 125 mcg/day) were associated with a higher risk of developing AFib (OR 1.08; 95% CI 1.04–1.11 and OR 1.29; 95% CI 1.23–1.35, respectively). Patients with remote use had a lower risk of AFib (OR 0.56; 95% CI 0.52–0.59) compared to patients with current use.

Limitations of this study include lack of information on the indications for levothyroxine treatment, patient weight, and patient thyroid hormone levels (free T4 and TSH).

The take‑home message?

Elderly patients taking 75 mcg or more of levothyroxine per day may be at an increased risk of developing AFib compared to those taking lower doses. These results support current guidelines: avoid thyroid hormone replacement excess and monitor serum thyrotropin values in elderly patients more stringently. [44]

Edition 11 - October 17, 2020toggle arrow icon

Quality over quantity: once-weekly insulin

One-Minute Telegram 11-2020-1/3 - Insulin therapy poses a variety of challenges, including patient discomfort associated with the need for frequent self-injections.

This randomized clinical trial tested the safety and efficacy of a once-weekly insulin called icodec. Study subjects were adults with inadequately controlled T2DM (A1c 7.0–9.5%) who were previously treated with metformin, with or without a dipeptidyl peptidase 4 inhibitor. 125 patients were allocated to once-weekly icodec injections (starting dose 70 U) plus daily subcutaneous placebo (intervention group), and 122 patients were allocated to once-daily glargine U100 injections (starting dose 10 U) plus once-weekly subcutaneous placebo (control group). After 26 weeks, a similar proportion of patients in both the intervention and control groups reached an A1c level < 7% (OR 1.20; 95% CI, 0.98–2.13) or < 6.5% (OR 1.47; 0.85–2.52). Approximately 50% of patients in each group experienced adverse events (e.g., injection site reactions). Mild hypoglycemia (54–70 mg/dL blood glucose) was more frequent in the icodec group vs. the glargine group (rate ratio, 2.42; 1.50–3.88); clinically significant or severe hypoglycemia rates were similarly low in both groups.

This industry-sponsored study was underpowered to find differences between the groups and its restrictive patient selection criteria (e.g., exclusion of patients with a history of sulfonylurea use, insulin use, or A1C levels > 9.5%) may limit extrapolation to additional patient populations.

The take‑home message?

Select patients with diabetes may achieve glycemic control with the newly developed once-weekly insulin therapy compared to treatment with traditional daily injections. However, further studies are needed to confirm the researchers’ hypothesis and to determine the effects in a greater variety of patient groups.

COVID-19: Putting a number on hyperinflammation

One-Minute Telegram 11-2020-2/3 - A hyperinflammatory syndrome with similarities to cytokine storm syndromes was identified as a complication of COVID-19 early on in the pandemic, but validated criteria specific to a COVID-19-associated hyperinflammatory syndrome (cHIS) have so far been lacking. [47]

Researchers conducted a literature review and developed a clinical scale for cHIS consisting of six items: fever, hyperferritinemia, elevated D-dimer levels, cytokinemia, hematological dysfunction, and hepatic injury. Data from 299 adult patients from 22 US hospitals with PCR-confirmed SARS-CoV-2 infection was then used to validate the scale using in-hospital mortality or need for mechanical ventilation (MV) as outcomes. Median patient age was 56 years, 44% were female, 25% required MV, and 8% died. Compared to patients with a maximum cHIS score < 2, patients with a maximum score ≥ 2 were more likely to require MV (45% vs. 2%) and had a higher mortality risk (15% vs. 1%). A cHIS score ≥ 2 had a high sensitivity for MV (Se 95%; 95% CI, 88–99%) and mortality (Se 96%; 78–100%), but a low specificity for both MV (Sp 59%; 52–65%) and mortality (Sp 49%; 43–55%).

This is a retrospective study with inherent limitations, and the relatively small sample size and low mortality rates in the validation cohort limit the generalizability of the results.

The take‑home message?

The use of a validated clinical scale that detects a hyperinflammatory state in patients with COVID-19 can help identify those patients at greatest risk of needing MV and dying. This scale requires external validation, but it could prove useful in prognostication and in identifying populations that might benefit from immunomodulatory treatments.

  • Title of study: Clinical criteria for COVID-19-associated hyperinflammatory syndrome: a cohort study [48]
  • Authors: Webb et al.
  • Journal: The Lancet Rheumatology
  • AMBOSS links: COVID-19

A lesson well learned, but so easily forgotten?

One-Minute Telegram 11-2020-3/3 - Not all residency programs adequately reassess residents after they successfully learn how to perform a procedure, such as a paracentesis, in order to ensure that they have maintained their skills.

118 US residents were enrolled in a training program to perform paracenteses in a simulation center. After simulation training, their performance was tested using the Paracentesis Competency Assessment Tool (PCAT) with two cutoff points: a Minimum Passing Standard (MPS) and an Unsupervised Practice Standard (UPS). All residents achieved an MPS, and approximately 40% achieved a UPS. Residents were then randomly allocated to reassess their competencies either at 3 and 6 months (group A, n = 60) or only once at 6 months (group B, n = 58). At 3 months, the performance of group A declined by both MPS (100 vs. 52.5%, P < 0.001) and UPS (40 vs. 13.6%, P = 0.002) metrics. At 6 months, the residents in group A who had received a reinforcing session were significantly more likely than the residents in group B to reach an MPS (89.7 vs. 46.3%, P < 0.001) or a UPS (34.5 vs. 3.7%, P < 0.001).

Study limitations include evaluating residency performance in a simulated environment and not considering the quality or quantity of paracenteses residents performed on real patients between assessments.

The take‑home message?

The ability of a resident to successfully perform a paracentesis declines significantly over time, but reinforcing sessions can improve performance results. This highlights the need for supervision as well as continuous physician training and education.

  • Title of study: See one, do one, forget one: early skill decay after paracentesis training [49]
  • Authors: Sall et al.
  • Journal: Journal of General Internal Medicine
  • AMBOSS links: Ascites

Edition 10 - October 3, 2020toggle arrow icon

Young, but not free from COVID-19 complications

One-Minute Telegram 10-2020-1/3 - Age is a major risk factor for complications in COVID-19 but a comprehensive analysis of the clinical outcomes for younger patients has been lacking so far.

Using data from the Premier Healthcare Database, researchers identified 3,222 nonpregnant adults between 18 and 34 years from a total of 63,103 adults who had been hospitalized for COVID-19 throughout the US. The mean age was 28.3 years, 57.6% were men and 57.0% were black and/or Hispanic; the median hospital stay was 4 days. Many of the patients included had cardiovascular risk factors, including obesity (36.8%), morbid obesity (24.5%), diabetes (18.2%), hypertension (16.1%), and smoking (15.9%). In total, 21% required intensive care, 10% required mechanical ventilation (MV), and 2.7% died.

Risk factors for the composite outcome of death and MV were morbid obesity (adjusted OR 2.30; 95% CI, 1.77–2.98), hypertension (OR 2.36; 1.79–3.12), and male sex (OR 1.53; 1.20–1.95).

The diagnosis of COVID-19 and the risk factors were identified using ICD codes in the database, potentially introducing error due to misclassification. The inclusion of only hospitalized patients in this study limits the generalizability of the findings to outpatient populations that could have a milder progression of disease.

The take‑home message?

The present study shows that adults under the age of 35 who are hospitalized for COVID-19 have a substantial risk of MV and death and that, as with older patient groups, the risk of complications increases with preexisting risk factors such as obesity and hypertension. In addition, the fact that the majority of patients identified in this study were black or Hispanic is consistent with previous findings that these populations are unequally vulnerable to COVID-19. [50]

Positive effects of SGLT2 inhibitors in patients with heart failure regardless of diabetes status

One-Minute Telegram 10-2020-2/3 - This meta-analysis pooled the data from the DAPA-HF (dapagliflozin) and EMPEROR-Reduced (empagliflozin) trials to examine the effects of SGLT2 inhibitors vs. placebo on mortality and hospitalizations in patients with heart failure and reduced ejection fraction (HFrEF) with or without diabetes. [52][53]

In total, 8,474 patients with symptomatic HFrEF (LVEF ≤40% and elevated NT-pro BNP) were included. Treatment with SGLT2 inhibitors vs. placebo lowered the risk of all-cause death (HR 0.87; 95% CI, 0.77–0.98), cardiovascular death (HR 0.86; 0.76–0.98), the combined risk of cardiovascular death, and first hospitalization for heart failure (HR 0.74; 0.68–0.82). It furthermore lowered the risk of the composite outcome of recurrent hospitalizations for heart failure and cardiovascular death (HR 0.75; 0.68–0.84). The effect of treatment vs. placebo on the composite cardiovascular death or HF hospitalization was similar regardless of diabetes status, age, sex, use of angiotensin receptor neprilysin inhibitor (ARNI), and baseline eGFR.

Subgroup analysis should be interpreted as hypothesis-generating because multiplicity was not accounted for, meaning that the investigators could have found an effect and/or interactions where there were none. In addition, this was a meta-analysis of only two studies and the original individual patient data was only available for one of the two.

The take‑home message?

Results from this industry-sponsored meta-analysis showed that SGLT2 inhibitors reduced the risk of mortality and hospitalization in patients with HFrEF regardless of diabetes status, age group, sex, baseline renal function, and previous treatment with ARNI.

Lower risk for orthostatic hypotension with higher-intensity hypertension treatment goals?

One-Minute Telegram 10-2020-3/3 - Orthostatic hypotension (OH) is a common cause for concern in patients starting or intensifying antihypertensive treatment, as it may lead to falls, especially in the elderly and frail population.

This systematic review and meta-analysis included data from 5 randomized trials that studied the effect of pursuing a higher-intensity BP goal vs. lower-intensity BP goals or placebo on the development of OH (defined as a drop of ≥ 20 mmHg in the SBP or ≥ 10 mmHg in the DBP when shifting from a seated to a standing position). In total, the primary studies included 18,466 patients (mean age 64.5 years, 38.9% women).

The mean postural change in SBP was similar between those with a higher-intensity vs. lower-intensity BP goal. In the pooled analysis of the 5 primary trials, intensive BP treatment goals proved to be a protective factor for OH (OR 0.93; 95 % CI, 0.86–0.99), which persisted after performing sensitivity analysis (OR 0.93; 95% CI, 0.89–0.98). The protection was not modified by the presence or absence of OH at baseline (P for interaction 0.80)

Limitations include lack of information regarding falls or syncope. Also, since patients in open-label studies may have received extra attention and a better standard of care, generalizability to real-world circumstances is limited.

The take‑home message?

This meta-analysis showed not only that higher-intensity treatment goals for arterial hypertension did not increase the risk of OH but, in fact, that they reduced it, even in patients with preexisting OH before the start of treatment. The authors hypothesize that these findings may be due to improved diastolic filling and baroreflex function but more research is required.

Q3 2020toggle arrow icon

Edition 9 - September 19, 2020toggle arrow icon

SARS-CoV-2 vaccine candidate shows promising results in phase 1–2 trial

One-Minute Telegram 9-2020-1/3 - After months of development, the much-awaited vaccines for SARS-CoV-2 are now being tested in healthy humans.

This placebo-controlled phase 1–2 trial designed by Novavax evaluated the safety and immunogenicity of the candidate NVX-CoV2373 vaccine [56] in healthy adults aged 18 to 59 years with no previous high-risk exposures to SARS-CoV-2 and a negative PCR or ELISA test. Participants were randomly allocated to receive either placebo (n = 23) or varying dosages of the vaccine with (n = 83) or without (n = 25) a matrix-M1 adjuvant. Intramuscular injections were administered 21 days apart.

After one dose, all subjects in the vaccine plus adjuvant group showed an immune response with anti-spike IgG and neutralizing antibodies similar to that found in the convalescent plasma of asymptomatic patients with confirmed COVID-19. After a second dose, their immune responses rose to levels similar to those found in the convalescent plasma of hospitalized patients with COVID-19. Furthermore, adjuvant regimens also induced antigen-specific polyfunctional CD4+ T-cell responses (mostly Th1 phenotype). No serious adverse events were reported and reactogenicity (e.g., pain, swelling, or fever) was absent or mild in the majority of participants, albeit more common in the adjuvant regimen group.

Since the participants were mostly young and healthy white individuals and follow-up was 35 days, generalizability to high-risk groups is lacking and long-term effects will need to be analyzed in future trials.

The take‑home message?

These results show that the vaccine in question had a good safety profile and short-term immunological responses similar to those in patients who had survived COVID-19. This makes it a promising candidate, but the results will require validation from the phase 2–3 trials.

COVID-19: Pregnant women at increased risk for complications

One-Minute Telegram 9-2020-2/3 - The effects of COVID–19 on pregnant women have been a worldwide concern since the start of the pandemic, and the lack of reliable data has posed a challenge for policymakers.

This living systematic review and metaanalysis included data from 77 cohorts to study the risk factors, clinical manifestations, and outcomes in pregnant and recently pregnant women with suspected or confirmed COVID–19.

The rate of COVID-19 in pregnant women who visited a hospital for any reason was 10% (11,432). In the hospital setting, affected pregnant women were less likely to report fever (OR 0.43, 95% CI 0.22 to 0.85) or myalgia (OR 0.48, 95% CI 0.45 to 0.51) than affected nonpregnant women of reproductive age, but were more likely to be admitted to the ICU (OR 1.62, 95% CI 1.33 to 1.96) and to receive invasive mechanical ventilation (IMV) (OR 1.88, 95% CI 1.36 to 2.60). Similar to other patient population groups, pregnant women with the risk factors increased age, higher body mass index, hypertension, and/or preexisting diabetes were more likely to develop severe disease. Compared to women without COVID-19, those with the disease had a higher probability of preterm birth (OR 3.01, 95% CI 1.16 to 7.85), and their newborns were admitted to the hospital more frequently (OR 3.13, 95% CI 2.05 to 4.78).

Limitations include heterogeneity between the studies considered and the fact that only patients from hospital-settings were included, limiting generalizability to other populations.

The take‑home message?

While the pregnant women in this study were less likely to develop fever or myalgia than nonpregnant women, they were more likely to have a preterm birth, be admitted to the ICU, and require IMV.

Commonly used scores for pulmonary embolism are only moderately useful in predicting short-term mortality

One-Minute Telegram 9-2020-3/3 - The clinical manifestations and resulting complications of acute pulmonary embolisms (PE) can vary substantially, highlighting the importance of clinical scores to identify high-risk patients and subsequently provide more targeted treatment.

In this multicenter US cohort study, 416 patients (mean age, 61.3 years; 49.8% men) with acute PE were stratified according to risk using the Pulmonary Embolism Severity Index (PESI) , the simplified PESI (sPESI) , the European Society of Cardiology risk score, and a modified Bova score. The baseline scores were compared for their ability to predict patient mortality at 7 and 30 days.

All-cause mortality was 6.0% within 7 days and 12.3% within 30 days. The sPESI had the highest discriminatory capabilities for 7-day mortality (AUC = 0.666; 95% CI, 0.640–0.693), while the Bova score had the lowest (AUC = 0.616; 95% CI, 0.581–0.651). The mean differences in the scores were greater for the 30-day mortality: The PESI had the highest AUC (0.694, 95% CI 0.677–0.710) and the Bova the lowest AUC (0.550; 95% CI 0.526–0.575).

Limitations include that the study’s mortality was not PE-specific and patients were only included if they were screened with one of the above-mentioned tools, which could have led to the exclusion of lower-risk PE patients.

The take‑home message?

In this study, current risk scores for PE were only moderately reliable in estimating 7-day and 30-day mortality. The necessity remains for larger studies to develop and validate risk assessment scores for patients with PE.

Edition 8 - September 05, 2020toggle arrow icon

Read the fine print: Remdesivir’s effect on moderate COVID-19 of uncertain clinical relevance.

One-Minute Telegram 8-2020-1/3 - Remdesivir has been proven to shorten time to recovery in severe COVID-19, albeit without a significant effect on overall mortality. [60]

This industry-sponsored (Gilead Sciences), multicenter randomized open-label trial studied the effects of remdesivir on moderate COVID-19, defined as radiographic evidence of pulmonary infiltrates and oxygen saturation > 94% on room air.

584 patients were randomized in a 1:1:1 ratio to 5-day remdesivir, 10-day remdesivir, and standard care. The primary outcome was the clinical status on day 11 of the study, measured on a 7-point ordinal scale (1 = death, 7 = discharge).

Patients in the 5-day remdesivir group (but not the 10-day group) were more likely to have a better clinical status on day 11 compared to the standard care group (OR = 1.65; 95% CI, 1.09-2.48; P = 0.02). However, no significant difference in the time to improvement of ≥ 1 or ≥ 2 points in the clinical scale in the remdesivir groups vs. standard care was found. Discharge rates peaked after each group's completion of remdesivir treatment.

One limitation was the nonblinded design, since completion of treatment with remdesivir may have influenced the investigator’s decision to discharge patients and, therefore, could have influenced the study outcome.

The take-home message?

While 5-day remdesivir was associated with improvement according to the clinical status scale in hospitalized patients with moderate COVID-19, the effect was not clinically significant and may have been an artifact of the nonblinded study design. Based partially on this study, the FDA has authorized remdesivir to treat all hospitalized patients with COVID-19. [61]

Should a cocktail of vitamin C, thiamine, and hydrocortisone be given to all patients with septic shock?

One-Minute Telegram 8-2020-2/3 - Previous studies that investigated the effects of vitamin supplementation in patients with sepsis have failed to show clinical benefits when compared to placebo or hydrocortisone treatment. [63][64] Recently, however, a small study reported reduced organ dysfunction after combined treatment with ascorbic acid, thiamine, and corticosteroids. [65]

The present multicenter randomized, blinded, clinical trial has attempted to replicate these results. 205 adults with septic shock were enrolled within 24 hours of starting vasopressors and randomized to receive either parenteral ascorbic acid (1500 mg), hydrocortisone (50 mg), and thiamine (100 mg) or a placebo every 6 hours for 4 days or until ICU discharge.

SOFA score , mortality, and incidence of kidney failure did not differ significantly between the treatment and the placebo group 72 hours after randomization. Subgroup analysis suggested that the intervention could have been beneficial only for patients with higher baseline SOFA scores (> 9).

Limitations include that patients with ongoing or planned corticosteroid use at the time of randomization were excluded from the study, eliminating a group of patients who were more likely to profit from the intervention.

The take-home message?

This study did not find evidence to support the routine addition of ascorbic acid, corticosteroids, and thiamine to the treatment of patients with septic shock to prevent organ dysfunction, but further investigations are needed to determine if the benefits of the intervention are restricted to certain groups of patients (e.g., such with a higher SOFA score).

For some patients with heart failure, more pills mean better outcomes, study finds

One-Minute Telegram 8-2020-3/3 - Current guidelines recommend that patients with heart failure and reduced ejection fraction (HFrEF) receive dual or triple therapy with a combination of various drugs [67]. However, adherence to these recommendations has previously been shown to be low [68].

To examine the effects of treatment and guideline adherence in real-world conditions, researchers conducted a retrospective cohort study in patients registered in the Humana Medicare Advantage Prescription Drug plan between 2008 and 2016.

17,106 patients with recently diagnosed HFrEF were included, 22% of which had received monotherapy, 41% dual therapy, and 13% triple therapy after hospital discharge, while 23% had received no medication. Compared to patients who received no medication, the composite risk of death or rehospitalization progressively decreased in patients who received monotherapy (HR 0.68; 95% CI, 0.64–0.71), followed by those who received dual therapy (HR 0.56; 95% CI, 0.53–0.59), and those who received triple therapy (HR 0.45; 95% CI, 0.41–0.50).

Since this study was based on claims data, the reasons behind giving or withholding therapy are unknown (e.g., comorbidities, clinical status). Moreover, this study did not consider social determinants of health, which may have influenced treatment choices and adherence.

The take-home message?

In patients with HFrEF, combination therapy had the highest reduction in mortality and rehospitalization risk, but only about half of patients received guideline-directed therapy, highlighting once more the importance of following guidelines.

Edition 7 - August 22, 2020toggle arrow icon

Dexamethasone for COVID‑19: the RECOVERY trial

One-Minute Telegram 7-2020-1/3 - The recent preliminary report of the RECOVERY trial [70] has helped pick up the pace in the race to find a cure for COVID-19 with its investigation of whether dexamethasone can reduce mortality in hospitalized patients. 6,425 patients were randomly assigned with a 1:2 ratio to receive either dexamethasone (6 mg oral or IV for 10 days) or standard care alone.

Overall, 28‑day‑mortality was significantly lower in the dexamethasone group (22.9%) than in the standard care group (25.7%) (rate ratio 0.83; 95% CI, 0.75–0.93). Subgroup analysis revealed that the protective effect was higher for patients on invasive mechanical ventilation (IMV) (rate ratio 0.64; 95% CI, 0.51–0.81), followed by patients receiving oxygen only (rate ratio, 0.82; 95% CI, 0.72–0.94). There was no observed positive effect on mortality in patients who were not receiving any respiratory support (rate ratio 1.19; 95% CI, 0.91–1.55). Of all patients who were not initially on IMV, those who received dexamethasone were less likely to require IMV during their hospital stay (risk ratio 0.77; 95% CI, 0.62–0.95).

The take‑home message

In this randomized control trial, treatment with dexamethasone was associated with reduced mortality in hospitalized patients with COVID‑19 receiving oxygen therapy and IMV. Further analysis is ongoing regarding cause-specific mortality and other clinical outcomes.

SARS‑CoV‑2 viral load is similar in symptomatic and asymptomatic individuals.

One-Minute Telegram 7-2020-2/3 - Many of the preventative measures recommended to stop the spread of COVID‑19 are based on the understanding that asymptomatic individuals can also transmit the virus [72]. But do asymptomatic and symptomatic individuals have the same viral load, and, if so, for the same amount of time?

Researchers in South Korea retrospectively evaluated a cohort of 303 isolated SARS‑CoV‑2‑positive patients. At the time of diagnosis, 110 (36.3%) of these patients had no symptoms and, of those, most (80.9%) remained asymptomatic throughout their isolation (median stay of 24 days).

There was no significant difference in viral load between the symptomatic and the asymptomatic patients. The median time from the first positive RT‑PCR test to a negative conversion was similar in asymptomatic and symptomatic patients (17 days vs. 19.5 days, P = 0.07).

Limitations included the possibility of sampling errors, since the samples were taken by the patients themselves, and limited generalizability of the results, since the cohort mainly included young patients (median age of 25 years) with a low proportion of comorbidities (3.9%).

The take‑home message?

Asymptomatic patients with SARS‑CoV‑2 infection had a similar viral load as patients with symptoms, and there was no difference in the time to negative conversion. The fact that asymptomatic patients can also carry a high viral load highlights the importance of widespread testing for SARS‑CoV‑2, the use of preventive measures, and the isolation of all infected individuals.

  • Title of study: Clinical course and molecular viral shedding among asymptomatic and symptomatic patients with SARS‑CoV‑2 infection in a community treatment center in the Republic of Korea [73]
  • Authors: Lee et. al
  • Journal: JAMA Internal Medicine
  • AMBOSS links: COVID-19

Can Vitamin D3 supplementation prevent depression?

One-Minute Telegram 7-2020-3/3 - Low levels of 25‑hydroxyvitamin D have been associated with a higher risk of late‑life depression [74]. However, evidence from randomized studies that would support prophylactic vitamin D3 supplementation has been lacking so far.

The present study was a subanalysis of the VITAL trial [75] and included 18,353 adults, aged ≥ 50 years without depression or clinically relevant depressive symptoms at baseline, defined as a PHQ‑8 score ≥ 10 points (8‑item Patient Health Questionnaire depression scale). The subjects were randomized to receive vitamin D3 (2,000 IU/day) and fish oil or a placebo and followed for a median duration of 5.3 years. The trial had a 90.5% completion rate.

The incidence rate of the primary outcome of depression or clinically relevant depressive symptom events was similar between the intervention and placebo groups (12.9 vs. 13.3 per 1000 person‑years, respectively; HR = 0.97; 95% CI, 0.87 to 1.09). Also, no significant differences were observed for change in mood scores.

An important limitation of this study was that the majority of participants had normal baseline 25‑hydroxyvitamin D levels, and over 40% of all participants in both groups were already taking vitamin D3 supplements (≤ 800 IU/day) at baseline. Additionally, mood and depression variables were only documented annually, so that short‑term events may not be reflected.

The take‑home message?

This trial does not support a role for supplementation of vitamin D3 to prevent depression in the general adult population, but further prospective studies are needed to determine the benefits of supplementation for patients with 25‑hydroxyvitamin D deficiency.

  • Title of study: Effect of long‑term vitamin D3 supplementation vs placebo on risk of depression or clinically relevant depressive symptoms and on change in mood scores [76]
  • Authors: Okereke et al.
  • Journal: JAMA
  • AMBOSS links: Major depressive disorder

Edition 6 - July 25, 2020toggle arrow icon

COVID-19: Still not there yet with antibody testing

One-Minute Telegram 6-2020-1/3 - Antibody-based testing is a promising point-of-care alternative to PCR-based testing for SARS-CoV-2 infection with the additional benefit of being able to identify patients who have recovered from a subclinical infection.

International researchers have conducted a meta-analysis to evaluate the sensitivity and specificity of antibody-based tests for SARS-CoV-2 in patients with confirmed infection (either by RT-PCR or viral culture). In total, 40 studies and 29,842 individual tests were included.

The pooled sensitivities were as follows: 97.8% (95% CI, 46.2–100%) for chemiluminescent immunoassays (CLIAs); 84.3% (95% CI, 75.6–90.9%) for enzyme-linked immunosorbent assays (ELISAs); and 66.0% (95% CI, 49.3–79.3%) for lateral flow immunoassays (LFIAs), which is the method currently being marketed as a point-of-care test. Pooled specificities ranged from 96.6–99.7%. Sensitivity was higher for tests performed three weeks after symptom onset (69.9–98.9%) compared to testing during the first week of symptoms (13.4–50.3%).

Despite the promising numbers, the authors concluded that 98% of the original studies carried a high risk of patient selection bias (e.g., due to sampling techniques) and 73% carried a high or unclear risk of bias because of unclear interpretations of the tests (e.g., no prespecified cut-off values). Only a minority of the studies included outpatients, and the specificities were estimated mostly from studies with low-risk individuals in pre-epidemic settings, dramatically limiting the generalizability of the results.

The take-home message?

This meta-analysis suggests that serological testing could be useful to diagnose SARS-CoV-2 infection, particularly within three weeks of symptom onset in hospitalized patients. However, based on the poor quality of the studies included, these results need further validation, especially in the outpatient setting. Commercial LFIA kit performance was lowest among the three testing strategies and should not be used for clinical purposes at this time.

Do individualized care programs prevent falls in the elderly?

One-Minute Telegram 6-2020-2/3 - Falls are common among elderly individuals and lead to approximately 30,000 deaths each year in the US. Although efficacy trials have shown that many falls are preventable, age-adjusted mortality attributable to falls has continued to rise. [78]

Researchers in the US have now conducted a multicenter, cluster-randomized trial under real-world practice settings to test whether an individually tailored multifactorial intervention administered by specially trained nurses could reduce the frequency and medical impact of falls when compared to enhanced usual care, where patients only received information about fall prevention.

86 primary care practices were randomly allocated to provide the intervention (2,802 participants) or enhanced usual care (2,649 participants). Patients had to be over 70 years of age and at an increased risk of fall injuries. Somewhat surprisingly, there was no significant difference between the groups with regard to the time of the first serious fall (HR = 0.92, 95% CI 0.80–1.06) and the rate of all serious fall injuries, regardless of when they occurred (HR = 0.94, 95% CI 0.81–1.10). The rates of hospitalization and death did not differ significantly either.

Limitations included the underrepresentation of racial and ethnic minorities in the study cohort and the possibility of selection bias toward participants with a higher level of general education compared to the general population.

The take-home message?

A multifactorial individualized care program was not superior to general recommendations in preventing serious falls in the elderly when put into practice in a real-world setting. However, the results of this study require validation in a more diverse population.

  • Title of study: A randomized trial of a multifactorial strategy to prevent serious fall injuries [79]
  • Authors: Bhasin et al.
  • Journal: NEJM

Statins underprescribed in patients with PAD

One-Minute Telegram 6-2020-3/3 - Peripheral artery disease (PAD), coronary heart disease (CHD), and cerebrovascular disease have a similar pathophysiology involving elevated serum lipids that contribute to the formation of arterial plaques. However, the practice of prescribing lipid-lowering agents differs significantly between these conditions and it has been found to be lowest for patients with PAD. [80]

A cohort of 943,232 adult patients with a previous diagnosis of atherosclerotic cardiovascular disease (ASCVD) was retrospectively evaluated over a three-year period to estimate and compare their risk of CHD, cerebrovascular disease events, and PAD. These risks were analyzed as both separate and composite ASCVD events.

The rate of ASCVD events for patients with CHD only, cerebrovascular disease only, and PAD only were 42.2, 38.9, and 34.7 per 1,000 patient years, respectively. The PAD-only group had a threefold rate of PAD-related events (e.g., acute limb ischemia) compared to patients with CHD only (adjusted HR = 3.75; 95% CI, 3.27–4.30). The proportion of statin use was lowest in the PAD-only group compared to patients with cerebrovascular disease only or CHD only (33.9% vs. 43% and 51.7%, respectively).

Because the data was collected from health insurance claims, only patients with health insurance were included in this study, and there was risk of misclassification of statin use and history of disease.

The take-home message?

Although patients with PAD have a high risk of ASCVD events, they are prescribed statins less frequently than patients with CHD or cerebrovascular disease. These results support the current guideline recommendations to begin statins in all PAD patients. [81]

Edition 5 - July 11, 2020toggle arrow icon

Are 24-hour shifts getting a boost? The jury is still out on optimal shift length to avoid medical errors.

One-Minute Telegram 5-2020-1/3 - The effect of resident working conditions on patient safety has long been a topic of discussion in the US [83], but the question of whether or not longer working hours negatively affect patient outcomes remains controversial. [84][85]

A recent crossover trial compared the rate of serious medical errors between resident working shifts of ≤ 16 hours (intervention schedule) and resident working shifts of ≥ 24 hours (control schedule) in six pediatric ICUs over two years. Serious medical error was defined as a preventable event that caused harm or had a high potential to cause harm.

The rate of serious medical errors was significantly higher for the intervention group as a whole (RR = 1.53, P < 0.001), but there was a high degree of variability between the individual ICUs studied. A secondary analysis that was adjusted for the number of patients per resident physician (8.8 patients in the intervention schedule vs. 6.7 in the control schedule) no longer showed an association between shorter shifts and an increase in errors. Residents in the intervention schedule had fewer weekly work hours, more weekly sleep hours, and improved neurobehavioral performance compared to the control group.

Limitations of this study included wide variability in the organizational structures, patient workload, and degree of change in the number of patients per resident of the ICUs studied.

The take-home message?

Shorter resident shifts were associated with higher rates of serious medical errors, but increased daily workload (a known risk factor for mortality [86]) and higher frequency of patient handoffs may have been more important factors than shorter shift duration.

  • Title of study: Effect on patient safety of a resident physician schedule without 24-hour shifts [87]
  • Authors: Landrigan et al.
  • Journal: NEJM
  • AMBOSS links: Quality and safety

A potential role for colchicine in the treatment of COVID-19

One-Minute Telegram 5-2020-2/3 - Colchicine, an anti-inflammatory drug commonly used in the management of gout, is gaining attention for its potential to improve outcomes in patients with COVID-19. A multicenter open-label randomized clinical trial in Greece followed two groups of randomly allocated hospitalized patients, one of which received colchicine in addition to standard treatment (n=55) while the other received standard treatment only without colchicine (n=50). Eligible patients had PCR-confirmed SARS-CoV-2 infection and a temperature ≥ 37.5°C plus ≥ 2 additional symptoms of COVID-19 (e.g., anosmia, PaO2 ≤ 95 mm Hg on room air).

Measured primary endpoints were maximum cardiac troponin level, elevation of CRP, and clinical deterioration (defined as time to clinical deterioration, using the World Health Organization’s R&D Blueprint Ordinal Clinical Scale [88]) during the three weeks after the beginning of the trial or until discharge.

Only 1/55 patients in the colchicine group had clinical deterioration versus 7/50 in the control group (1.8 vs. 14%, P = 0.02). The average time without clinical deterioration was longer in the colchicine group compared to the control group (20.7 vs. 18.6 days, P = 0.03). CRP and cTn levels were similar in both groups. Apart from a slightly higher occurrence of diarrhea in the colchicine group, adverse events were similar in both groups.

This study was limited by the small sample size, lack of blinding, and the provision of medical treatment in addition to standard COVID-19 treatment and colchicine.

The take-home message?

This study suggests that colchicine may be beneficial in the treatment of COVID-19, but further research is required to confirm this observation.

Aspirin discontinuation with continued P2Y12 inhibitors may be beneficial for select patients after PCI

One-Minute Telegram 5-2020-3/3 - Balancing the risk of bleeding against the risk of a major adverse cardiovascular event (MACE) following a percutaneous coronary intervention (PCI) remains a challenge. In this context, the main issues of controversy continue to be the duration of dual antiplatelet therapy (DAPT) and whether P2Y12 inhibitor monotherapy might be equally effective as DAPT in preventing MACE with the added benefit of fewer complications.

A recent meta-analysis of published randomized trials with follow-up times of at least 6 months examined the safety and efficacy of P2Y12 inhibitor monotherapy 1–3 months after a PCI (intervention group) compared to continued DAPT (control group). Patients who required anticoagulation were not included, and the primary outcomes were bleeding and MACE. The indication for PCI was either stable coronary artery disease or acute coronary syndrome.

Five trials fulfilled all the criteria for inclusion, providing a total study population of 32,145 patients with 16,057 patients in the intervention group and 16,088 in the control group. The risk of MACE (MI, stent thrombosis, stroke, and death as a composite endpoint or separately) was similar for both groups, but major bleeding events, as defined by a BARC type of 3 or 5 [90], was lower in the invention group compared to the control group (HR = 0.60, 95% CI 0.42–0.86).

Study limitations included significant heterogeneity across trials for the bleeding outcomes, four trials not having been blinded, and potential selection bias in the original studies toward excluding patients at higher risk for MACE.

The take-home message?

This study provides further evidence that P2Y12 inhibitor monotherapy after 1–3 months of DAPT following PCI does not result in increased risk of MACE when compared to DAPT. Furthermore, discontinuation of aspirin was associated with significantly lower risk of bleeding. Further research is needed to confirm whether these benefits also apply to higher-risk patient groups.

Q2 2020toggle arrow icon

Edition 4 - June 27, 2020toggle arrow icon

Hydroxychloroquine for COVID-19: much ado about nothing?

One-Minute Telegram 4-2020-1/3 - Hydroxychloroquine (HCQ) has been at the center of attention since the beginning of the COVID-19 pandemic. The FDA has recently revoked emergency use authorization for both chloroquine and HCQ because the potential side effects outweigh the benefits [92]. Notwithstanding the controversy over the use of HCQ to treat COVID-19, researchers in the US and Canada set out to determine if the drug could be useful in preventing the disease.

A randomized, double-blind, placebo-controlled trial tested the effectiveness of HCQ as postexposure prophylaxis (within 4 days of exposure) in 821 asymptomatic adults exposed to COVID-19. Exposure was defined as a moderate-risk (face mask but no eye shield) or high-risk (neither face mask nor eye shield) contact to an individual with confirmed COVID-19 for ≥ 10 minutes at a distance of < 6 ft. The median age of the participants was 40 years and 27.4% reported chronic health conditions. Patients were allocated 1:1 to receive either HCQ or a placebo. After the 14-day follow-up, there was no statistically significant difference in incidence between the intervention and the control groups (11.8% vs.14.3%, P = 0.35). However, side effects were more common in the HCQ group (40.1% vs. 16.8%, P < 0.001), as was lower treatment compliance (75.4% vs. 82.6%, P = 0.01).

The take-home message?

HCQ use in this trial was not effective in preventing COVID-19 in exposed patients and frequently caused side effects, adding to the growing evidence against the use of HCQ for COVID-19. Important limitations of this study were the small sample size and lack of laboratory-confirmed diagnosis.

The other epidemic: handgun ownership and suicidality

One-Minute Telegram 4-2020-2/3 - The topic of gun ownership has long polarized public opinion in the US. Firearm violence, including mass shootings and suicide, has been described as a public health crisis that requires immediate attention nationwide [94], yet resistance to stronger regulation of firearm ownership remains high.

A recently published study followed 26.3 million adults in California for an average of 6.9 years to study the effects of acquiring a handgun on suicidality. Newly registered handgun owners (n=676,425) were compared with nonowners (n=25,637,011). Gun owners were more likely to be white, male, and residents of rural areas. During the study period, 17,894 people died by suicide, 6,691 of whom died by suicide involving a firearm. Suicide rate by any method was three times higher for male handgun owners and seven times higher for female handgun owners compared with nonowners. The adjusted hazard ratio of suicide by firearm was almost eight times higher for male handgun owners and 35 times higher for female handgun owners compared to individuals who did not own a handgun. The risk was highest in the first 30 days after handgun acquisition.

The take-home message?

Handgun owners, in particular women, are at increased risk of suicide when compared with nonowners, especially in the time immediately following acquisition. This study, funded by the Fund for a Safer Future [95], the Joyce Foundation, and Stanford University, highlights the importance of evidence-based preventive strategies for gun violence in the US.

  • Title of study: Handgun ownership and suicide in California [96]
  • Authors: Studdert et al.
  • Journal: NEJM
  • AMBOSS links: Suicide

Rifampin vs. isoniazid for latent TB infection: better care at a lower cost

One-Minute Telegram 4-2020-3/3 - Tuberculosis (TB) remains one of the greatest killers worldwide, and its eradication by 2030 is one of the targets set by the UN Sustainable Development Goals [97]. Previous research in children [98] and adults [99] has shown that a 4-month rifampin regimen is equally effective in treating latent TB and has higher completion rates than the usual 9-month isoniazid regimen, but it has not become established due to the high cost per rifampin pill.

A recently published study set out to compare the health system costs of 9-month isoniazid vs. 4-month rifampin in 6,012 adults and 829 children with latent TB infection in high-, middle-, and lower-income countries. Health care use was tabulated for each participant using various sources including local unit costs (imaging and lab studies), information from the WHO CHOICE tool [100] (health care visits and hospitalization costs), and the Global Drug Facility list and local ministries of health [101] (cost of the medication).

The average costs were significantly lower in the rifampin group in all income settings compared to the isoniazid group. Routine follow-up visits accounted for a significant portion of the costs in the high- and middle-income countries. Sensitivity analysis showed that rifampin remained more cost-effective, even when compared to a shorter 6-month course of isoniazid.

The take-home message?

Although the cost per pill of rifampin is higher than that of isoniazid, the total cost of a 4-month rifampin regimen was significantly lower than that of the standard 9-month isoniazid regimen in this study. Despite limitations (e.g., estimated costs, requirement for frequent follow-up visits), this large study supports a growing body of evidence that a 4-month rifampin course is preferable to isoniazid in patients with latent tuberculosis.

Edition 3 - June 13, 2020toggle arrow icon

Differences in outcomes of black and white patients with COVID-19

One-Minute Telegram 3-2020-1/3 - Racial and ethnic disparities in health outcomes are well documented in the US and certain minorities have higher morbidity and mortality rates. A recent study has now investigated how differences in race correlate with the outcomes of COVID-19 patients in the US.

A large health care system in Louisiana conducted a multicenter, retrospective cohort study that compared hospitalizations and in-hospital deaths of black non-Hispanic and white non-Hispanic patients with COVID-19 between March 1st and April 11th, 2020.

Although black patients represented only 31% of patients within that particular health care system, they comprised 76.9% of the hospital admissions due to COVID-19, 81% of the patients requiring mechanical ventilation, and 70.6% of patients who died.

Sociodemographic differences likely contribute to these disparities, as black patients were three times as likely to be on Medicaid insurance and twice as likely to live in low-income areas than white patients. They also had higher prevalences of obesity, diabetes, hypertension, and chronic kidney disease.

The odds of hospitalization were higher for black patients after controlling for other factors, but the hazard for in-hospital death was similar for black and white patients after adjusting for demographics, comorbidities, and clinical presentation.

The take-home message?

This study shows that black patients are more likely to be hospitalized due to COVID-19 than white patients. Although being black was not independently associated with higher mortality in this study, the composition of the population tested in this health care system suggests that more black patients die of COVID-19 than white patients.

  • Title of study: Hospitalization and mortality among black patients and white patients with Covid-19 [50]
  • Authors: Price-Haywood et al.
  • Journal: NEJM
  • AMBOSS links: COVID-19

If they’re septic and you know it … raise their legs?

One-Minute Telegram 3-2020-2/3 - Fluid responsiveness is a central concern in the management of patients with sepsis. A multicenter, nonblinded, randomized trial has now investigated whether one of the simplest tests in the arsenal, the passive leg raise (PLR), might be able to better guide fluid management.

Patients were randomized 2:1 into an intervention group (n=83) and a usual care group (n=41). If the PLR test was positive (significant increase in stroke volume), patients in the intervention group received a crystalloid fluid bolus. If the test was negative, they were started on vasopressors. PLR was repeated after every fluid bolus and dose escalation of vasopressors. The control group received "usual care" to assess fluid responsiveness, though the specifics of the methods involved were not defined.

The measures applied to the intervention group resulted in a reduced positive fluid balance (mean difference = -1.37L (95% CI, -2.53, -0.021, P = 0.021)) and less necessity for renal replacement therapy (5.1% vs. 17.5%, P = 0.042) as well as less ventilator use (17.7% vs. 34.1%, P = 0.044). They were also more likely to be discharged directly home (63.9% vs. 43.9%, P = 0.035). The rates of adverse events, the ICU length of stay, and the 30-day mortality were similar in both groups.

The take-home message?

This study showed that PLR-guided fluid and vasopressor resuscitation is a safe maneuver that can significantly improve the 72-hour fluid balance and results in less need for renal replacement therapy and ventilator support than usual care.

Bullying in surgical residents

One-Minute Telegram 3-2020-3/3 - The mistreatment of medical residents is so widespread that it has been addressed by just about every medical TV show. Who can forget the infamous rants of Dr. Cox and Dr. House? As entertaining as the shows may be, actually being on the receiving end of such behavior is no enjoyable experience. A new study has shed some light on the scale and the consequences of the problem in surgical residencies.

General surgery residents in the US were asked to respond to a voluntary, confidential survey. The validated S-NAQ was used to measure how often they experienced nine specific bullying behaviors (e.g., being the subject of gossip, being shouted at) within the past academic year.

Of the 6,264 S-NAQ respondents, 66.9% had experienced bullying at least once, while occasional and frequent bullying was reported by 43.8% and 18.1% of respondents respectively. Attending surgeons were the group most frequently reported to engage in bullying. The groups who most frequently reported exposure to bullying were women, divorcees, widow(er)s, members of ethnic minorities, and residents with low ABSITE scores. The study furthermore showed that frequent exposure to bullying was associated with potentially severe consequences, including attrition, burnout, and suicidal ideation.

The take-home message?

Bullying is still common in surgical training programs and a cause for concern given the mental health issues it entails. Efforts to improve surgical training should focus on addressing the issue and ensure that residents can complete their program without the added stress of bullying.

  • Title of study: Prevalence, types, and sources of bullying reported by US general surgery residents in 2019 [104]
  • Authors: Zhang et al.
  • Journal: JAMA

Edition 2 - May 30, 2020toggle arrow icon

COVID-19: Who gets the ventilators if there aren't enough to go around?

One-Minute Telegram 2-2020-1/3 - In the wake of COVID-19, many hospitals have braced themselves for the tough ethical choices arising when demand exceeds the resources available. In March 2020, the Association of Bioethics Program Directors (ABPD) conducted a voluntary survey among its 91 members in 79 US and Canadian academic medical centers to assess the selection criteria and scoring systems in place to triage patients needing ventilation.

Of the 67 responders, more than half did not have a policy in place. The most commonly reported triage criteria were presumed benefit (96.2%) and need (53.8%). Most policies used scoring systems (80.8%), the most frequently used being the Sequential Organ Failure Assessment (SOFA) score. Half of all responders used an age criterion, yet only 7.7% specified age thresholds. 38.4% of policies gave preference to health care workers. Some employed a lottery (34.6%) or first-come, first-served principle (23.1%), but none used these as their sole criterion. 69.2% permitted appeals.

The take-home message?
Less than 50% of surveyed academic medical centers have established ventilator triage policies. The selection criteria vary greatly and information on implementation is frequently lacking.

  • Title of study: Ventilator triage policies during the COVID-19 pandemic at U.S. hospitals associated with members of the association of bioethics program directors [105]
  • Authors: Antommaria et al.
  • Journal: Annals of Internal Medicine
  • AMBOSS links: COVID-19

Can metformin prevent postoperative complications in T2DM patients?

One-Minute Telegram 2-2020-2/3 - Current guidelines recommend pausing metformin for 1–2 days before major surgery because of the risk of lactic acidosis. But what do we know about the benefits of its long-term use before major surgery?

A recent retrospective cohort study set out to determine the benefits of long-term metformin use on postoperative outcomes. The researchers evaluated electronic health records of 10,088 patients with T2DM who had undergone a major surgical intervention (defined as any procedure that required general anesthesia and a postoperative hospital stay) between January 2010 and January 2016 and studied the effects of metformin use (defined as one or more prescriptions) in the 180 days prior to the procedure. 5,962 patients (59%) with preoperative metformin prescriptions were propensity score-matched with 5,460 patients (54%) who had not taken metformin.

The metformin group had a lower hazard ratio for mortality at 90 days (HR, 0.72; 95% CI, 0.55–0.95; P = 0.02) and at 5 years (HR, 0.74; 95% CI, 0.65–0.85; P < 0.001). In addition, they had lower rates of readmission at 30 days (sub-HR, 0.84; 95% CI, 0.72–0.98, P = 0.02) and 90 days (sub-HR, 0.86; 95% CI, 0.77–0.97, P = 0.01).

These results should be viewed critically since the exact dosages and durations of the metformin regimens were unknown and there is potential for residual confounding. Furthermore, the reasons why patients with T2DM were not on metformin could vary greatly (e.g., contraindications due to preexisting conditions, adverse effects, aversion to treatment).

The take-home message?
Pleiotropic effects of metformin may benefit T2DM patients after major surgery, but further studies are needed to prove a causal connection between metformin and better outcomes.

Predicting critical illness in COVID-19

One-Minute Telegram 2-2020-3/3 - Many hospitals are struggling with insufficient space and resources to treat patients with COVID-19. Early identification of patients that will progress to critical illness would enable a more adequate and efficient distribution of medical resources. Chinese researchers aimed to develop and validate a clinical risk score (COVID-GRAM ) to help predict critical illness (defined as admission to the ICU, invasive ventilation, or death) in hospitalized patients with COVID-19.

The medical records of 1,590 laboratory-confirmed hospitalized patients with COVID-19 were screened retrospectively for 72 variables, of which 10 (chest radiography abnormality, age, hemoptysis, dyspnea, unconsciousness, number of comorbidities, cancer history, neutrophil-to-lymphocyte ratio, lactate dehydrogenase, and direct bilirubin) were included in the final model as statistically significant predictors of critical illness. The score was then validated for its generalizability with 710 patients from other Chinese hospitals that were not included in the initial cohort. The area under the receiver-operator characteristic curve (AUC), which was 0.88 (95% CI, 0.84–0.93), showed good performance in discriminating between patients who developed critical illness from those who did not.


The take-home message?
The COVID-GRAM score is one of the first instruments available for predicting critical illness in COVID-19. While efforts such as this are no doubt necessary to improve clinical decision-making and resource allocation, the COVID-GRAM score still requires validation in larger patient groups outside of China.

  • Title of study: Development and validation of a clinical risk score to predict the occurrence of critical illness in hospitalized patients with COVID-19 [107]
  • Authors: Liang et al.
  • Journal: JAMA Internal Medicine
  • AMBOSS links: COVID-19

Edition 1 - May 07, 2020toggle arrow icon

Ebola drug remdesivir – emergency use authorized but effectiveness for treatment of COVID-19 still under investigation

One-Minute Telegram 1-2020-1/3 - Remdesivir, a nucleotide analog that inhibits viral RNA polymerases, has been proven to be effective against SARS-CoV-2 in vitro [108] and its relative safety has already been demonstrated in a phase 3 trial [109] in patients with Ebola.

Gilead Sciences, the producer of remdesivir, has published data on an international group of 53 patients hospitalized with COVID-19, who were selected based on undisclosed criteria. The study cohort consisted of mostly male (70%) patients within the age range of 23 to 82 years (median 64 years). 64% of the patients were receiving some form of invasive ventilation, of which 8% were on extracorporeal membrane oxygenation (ECMO), while 23% were on ambient air or low-flow oxygen.

The authors report that 68% of patients showed improvement in oxygen-support class during a median follow-up of 18 days. However, nearly one quarter of patients had serious adverse effects. The most serious adverse effects (multiple organ dysfunction, septic shock, acute kidney failure) were more commonly reported in patients already being mechanically ventilated.

The take-home message? Although the study showed clinical improvement with remdesivir in the majority of participants, its small sample size, intransparent selection criteria, and lack of a control group make any conclusions regarding the drug's therapeutic effectiveness against SARS-CoV-2 tentative at best. Moreover, adverse effects were common, in some cases even life-threatening. Sponsored studies that are currently being conducted (NCT04252664, NCT04257656) will hopefully allow for a more rigorous assessment of remdesivir, but for now it remains authorized for emergency use by the FDA based on preliminary results from the Adaptive COVID-19 Treatment Trial (NCT04280705).

  • Title of study: Compassionate use of remdesivir for patients with severe Covid-19 [110]
  • Authors: Grein et al.
  • Journal: NEJM
  • AMBOSS links: COVID-19

Neurological symptoms may precede fever and cough in COVID-19

One-Minute Telegram 1-2020-2/3 - Evidence that the loss of smell and taste may precede respiratory symptoms in COVID-19 was found early in the course of the pandemic. An observational case series from Wuhan, China, has now investigated the presence of further neurological symptoms in hospitalized patients.

The study reviewed the records of 214 patients with confirmed SARS-CoV-2 infection who were hospitalized between January 16 and February 19, 2020. Neurological symptoms were identified in about one third of the patients. Nonspecific symptoms such as dizziness (16.8%), headache (13.1%), and muscle injury (10.7%) were most frequently reported, but impaired consciousness (7.5%) and acute cerebrovascular disease (2.8%) were also seen, especially in those with severe disease. In some patients, neurological symptoms occurred early in the course of disease and in others they even manifested before respiratory symptoms developed.

This study had significant limitations, as it was a small, retrospective, observational study that relied on medical record screening. Furthermore, the study failed to corroborate the results of previous studies (Yan et al. [111], Vetter et al. [112]), which report significantly higher rates (50–75%) of loss in taste and smell during the early stages of COVID-19.

The take-home message? While not a perfect study, it does remind us to consider COVID-19 on the differential in patients presenting with neurological symptoms, as these may precede respiratory manifestations.

Vaping kills – but who is at risk?

One-Minute Telegram 1-2020-3/3 - The CDC has been tracing e-cigarette, or vaping, product use-associated lung injury (EVALI) since August 2019. It is strongly linked to vitamin E acetate, an additive sometimes found in vape cartridges, and can cause acute respiratory distress syndrome (ARDS).

Previous research has focused mainly on patients who have survived EVALI. Now, Werner et al. have compared 2,558 hospitalized patients who survived EVALI with 60 hospitalized patients who died of EVALI in the US as of January 7, 2020. The study included the entire population of patients hospitalized for EVALI in the US and, therefore, P values were not reported.

The majority of hospitalized patients were male, of non-Hispanic white ethnicity, and had reported combined or alternating use of products containing nicotine and THC. Not surprisingly, the patients who died were older and more frequently had a history of chronic respiratory and cardiac disease than those who survived. About half of the patients who died had been seen previously in an outpatient setting, suggesting that outcomes could have been improved by earlier diagnosis and treatment. Furthermore, about two-thirds of the patients who died had a preexisting mental disorder.

The take-home message? Screening outpatients for underlying cardiac and pulmonary disease and explicitly inquiring about e-cigarette or vaping use may help to identify those at risk of developing life-threatening EVALI. Also, e-smoking kills!

  • Title of study: Hospitalizations and deaths associated with EVALI [114]
  • Authors: Werner et al.
  • Journal: NEJM
  • AMBOSS links: ARDS

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