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One-Minute Telegram Archive

Introduction

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.

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Q4 2020

Edition 11 - October 17, 2020

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. [2]

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 [3]
  • 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 [4]
  • Authors: Sall et al.
  • Journal: Journal of General Internal Medicine
  • AMBOSS links: Ascites

Edition 10 - October 3, 2020

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. [5]

  • Title of study: Clinical outcomes in young US adults hospitalized with COVID-19 [6]
  • Authors: Cunningham et al.
  • Journal: JAMA Internal Medicine
  • AMBOSS links: COVID-19

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. [7][8]

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.

  • Title of study: Effects of intensive blood pressure treatment on orthostatic hypotension [10]
  • Authors: Juraschek et al.
  • Journal: Annals of Internal Medicine
  • AMBOSS links: Hypertension

Q3 2020

Edition 9 - September 19, 2020

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 [11] 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, 2020

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. [15]

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. [16]

  • Title of study: Effect of remdesivir vs standard care on clinical status at 11 days in patients with moderate COVID-19 [17]
  • Authors: Spinner et al.
  • Journal: JAMA
  • AMBOSS links: COVID‑19

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. [18][19] Recently, however, a small study reported reduced organ dysfunction after combined treatment with ascorbic acid, thiamine, and corticosteroids. [20]

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 [22]. However, adherence to these recommendations has previously been shown to be low [23].

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.

  • Title of study: Real‐world analysis of guideline‐based therapy after hospitalization for heart failure [24]
  • Authors: Wirtz et al.
  • Journal: JAHA
  • AMBOSS links: Congestive heart failure

Edition 7 - August 22, 2020

Dexamethasone for COVID‑19: the RECOVERY trial

One-Minute Telegram 7-2020-1/3 - The recent preliminary report of the RECOVERY trial [25] 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.

  • Title of study: Dexamethasone in hospitalized patients with covid‑19 — preliminary report [26]
  • Authors: The RECOVERY Collaborative Group
  • Journal: NEJM
  • AMBOSS links: COVID‑19, Glucocorticoids

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 [27]. 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 [28]
  • 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 [29]. 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 [30] 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 [31]
  • Authors: Okereke et al.
  • Journal: JAMA
  • AMBOSS links: Major depressive disorder

Edition 6 - July 25, 2020

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.

  • Title of study: Diagnostic accuracy of serological tests for covid-19: systematic review and meta-analysis [32]
  • Authors: Bastos et al.
  • Journal: BMJ
  • AMBOSS links: COVID-19

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. [33]

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 [34]
  • 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. [35]

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. [36]

Edition 5 - July 11, 2020

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 [38], but the question of whether or not longer working hours negatively affect patient outcomes remains controversial. [39][40]

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 [41]) 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 [42]
  • 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 [43]) 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.

  • Title of study: Effect of colchicine vs. standard care on cardiac and inflammatory biomarkers and clinical outcomes in patients hospitalized with coronavirus disease 2019 [44]
  • Authors: Deftereos et al.
  • Journal: JAMA
  • AMBOSS links: COVID-19

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 [45], 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 2020

Edition 4 - June 27, 2020

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 [47]. 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 [49], 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 [50], 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 [51]
  • 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 [52]. Previous research in children [53] and adults [54] 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 [55] (health care visits and hospitalization costs), and the Global Drug Facility list and local ministries of health [56] (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, 2020

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 [5]
  • 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 [59]
  • Authors: Zhang et al.
  • Journal: JAMA

Edition 2 - May 30, 2020

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 [60]
  • 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 [62]
  • Authors: Liang et al.
  • Journal: JAMA Internal Medicine
  • AMBOSS links: COVID-19

Edition 1 - May 07, 2020

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 [63] and its relative safety has already been demonstrated in a phase 3 trial [64] 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 [65]
  • 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. [66], Vetter et al. [67]), 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 [69]
  • Authors: Werner et al.
  • Journal: NEJM
  • AMBOSS links: ARDS
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last updated 10/20/2020
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