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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. Sign up via the link in “Tips and Links” below.

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 [1]. 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.

  • Title of study: A Randomized Trial of Hydroxychloroquine as Postexposure Prophylaxis for Covid-19 [2]
  • Authors: Boulware et al.
  • Journal: NEJM
  • AMBOSS links: COVID-19

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 [3], 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 [4], 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 [5]
  • Authors: Studdert et al.
  • Journal: NEJM
  • AMBOSS links: Suizidalität

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 [6]. Previous research in children [7] and adults [8] 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 [9] (health care visits and hospitalization costs), and the Global Drug Facility list and local ministries of health [10] (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.

  • Title of study: Health System Costs of Treating Latent Tuberculosis Infection With Four Months of Rifampin Versus Nine Months of Isoniazid in Different Settings [11]
  • Authors: Bastos et al.
  • Journal: Annals of Internal Medicine
  • AMBOSS links: Tuberkulose

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 [12]
  • 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.

  • Title of study: Fluid Response Evaluation in Sepsis Hypotension and Shock: A Randomized Clinical Trial [13]
  • Authors: Douglas et al.
  • Journal: CHEST
  • AMBOSS links: Sepsis

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 [14]
  • 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 [15]
  • 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 [17]
  • 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 [18] and its relative safety has already been demonstrated in a phase 3 trial [19] 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 [20]
  • 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. [21], Vetter et al. [22]), 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.

  • Title of study: Neurologic Manifestations of Hospitalized Patients With Coronavirus Disease 2019 in Wuhan, China [23]
  • Authors: Mao et al.
  • Journal: JAMA Neurology
  • AMBOSS links: COVID-19

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 [24]
  • Authors: Werner et al.
  • Journal: NEJM
  • AMBOSS links: ARDS l EVALI