Monday, July 15, 2019

On Sabbatical

Hello Readers,

My research responsibilities have expanded, which is a good thing, but requires that I scale back other commitments, including Lit Bits. Alas...

Not to leave you without resources, I suggest the following to help you keep abreast of the medical literature:
Best,

David
KP and the CREST Network

Monday, June 17, 2019

Lit Bits: June 17, 2019

From the recent medical literature...


1. ICU admissions reduce mortality among patients with STEMI: retrospective cohort study.

Valley TS, et al. BMJ. 2019 Jun 4;365:l1927.

OBJECTIVE:
To evaluate the effect of intensive care unit (ICU) admission on mortality among patients with ST elevation myocardial infarction (STEMI).

DESIGN:
Retrospective cohort study.

SETTING:
1727 acute care hospitals in the United States.

PARTICIPANTS:
Medicare beneficiaries (aged 65 years or older) admitted with STEMI to either an ICU or a non-ICU unit (general/telemetry ward or intermediate care) between January 2014 and October 2015.

MAIN OUTCOME MEASURE:
30 day mortality. An instrumental variable analysis was done to account for confounding, using as an instrument the additional distance that a patient with STEMI would need to travel beyond the closest hospital to arrive at a hospital in the top quarter of ICU admission rates for STEMI.

RESULTS:
The analysis included 109 375 patients admitted to hospital with STEMI. Hospitals in the top quarter of ICU admission rates admitted 85% or more of STEMI patients to an ICU. Among patients who received ICU care dependent on their proximity to a hospital in the top quarter of ICU admission rates, ICU admission was associated with lower 30 day mortality than non-ICU admission (absolute decrease 6.1 (95% confidence interval -11.9 to -0.3) percentage points). In a separate analysis among patients with non-STEMI, a group for whom evidence suggests that routine ICU care does not improve outcomes, ICU admission was not associated with differences in mortality (absolute increase 1.3 (-0.9 to 3.4) percentage points).

CONCLUSIONS:
ICU care for STEMI is associated with improved mortality among patients who could be treated in an ICU or non-ICU unit. An urgent need exists to identify which patients with STEMI benefit from ICU admission and what about ICU care is beneficial.


2. Derivation, Validation, and Potential Treatment Implications of Novel Clinical Phenotypes for Sepsis

Seymour CW, et al. JAMA. 2019;321(20):2003-2017.

Key Points
Question  Are clinical sepsis phenotypes identifiable at hospital presentation correlated with the biomarkers of host response and clinical outcomes and relevant for understanding the heterogeneity of treatment effects?

Findings  In this retrospective analysis using data from 63 858 patients in 3 observational cohorts, 4 novel sepsis phenotypes (α, β, γ, and δ) with different demographics, laboratory values, and patterns of organ dysfunction were derived, validated, and shown to correlate with biomarkers and mortality. In the simulations using data from 3 randomized clinical trials involving 4737 patients, the outcomes related to the treatments were sensitive to changes in the distribution of these phenotypes.

Meaning  Four novel clinical phenotypes of sepsis were identified that correlated with host-response patterns and clinical outcomes and may help inform the design and interpretation of clinical trials.

IMPORTANCE:
Sepsis is a heterogeneous syndrome. Identification of distinct clinical phenotypes may allow more precise therapy and improve care.

OBJECTIVE:
To derive sepsis phenotypes from clinical data, determine their reproducibility and correlation with host-response biomarkers and clinical outcomes, and assess the potential causal relationship with results from randomized clinical trials (RCTs).

DESIGN, SETTINGS, AND PARTICIPANTS:
Retrospective analysis of data sets using statistical, machine learning, and simulation tools. Phenotypes were derived among 20 189 total patients (16 552 unique patients) who met Sepsis-3 criteria within 6 hours of hospital presentation at 12 Pennsylvania hospitals (2010-2012) using consensus k means clustering applied to 29 variables. Reproducibility and correlation with biological parameters and clinical outcomes were assessed in a second database (2013-2014; n = 43 086 total patients and n = 31 160 unique patients), in a prospective cohort study of sepsis due to pneumonia (n = 583), and in 3 sepsis RCTs (n = 4737).

EXPOSURES:
All clinical and laboratory variables in the electronic health record.

MAIN OUTCOMES AND MEASURES:
Derived phenotype (α, β, γ, and δ) frequency, host-response biomarkers, 28-day and 365-day mortality, and RCT simulation outputs.

RESULTS:
The derivation cohort included 20 189 patients with sepsis (mean age, 64 [SD, 17] years; 10 022 [50%] male; mean maximum 24-hour Sequential Organ Failure Assessment [SOFA] score, 3.9 [SD, 2.4]). The validation cohort included 43 086 patients (mean age, 67 [SD, 17] years; 21 993 [51%] male; mean maximum 24-hour SOFA score, 3.6 [SD, 2.0]). Of the 4 derived phenotypes, the α phenotype was the most common (n = 6625; 33%) and included patients with the lowest administration of a vasopressor; in the β phenotype (n = 5512; 27%), patients were older and had more chronic illness and renal dysfunction; in the γ phenotype (n = 5385; 27%), patients had more inflammation and pulmonary dysfunction; and in the δ phenotype (n = 2667; 13%), patients had more liver dysfunction and septic shock. Phenotype distributions were similar in the validation cohort. There were consistent differences in biomarker patterns by phenotype. In the derivation cohort, cumulative 28-day mortality was 287 deaths of 5691 unique patients (5%) for the α phenotype; 561 of 4420 (13%) for the β phenotype; 1031 of 4318 (24%) for the γ phenotype; and 897 of 2223 (40%) for the δ phenotype. Across all cohorts and trials, 28-day and 365-day mortality were highest among the δ phenotype vs the other 3 phenotypes (P less than .001). In simulation models, the proportion of RCTs reporting benefit, harm, or no effect changed considerably (eg, varying the phenotype frequencies within an RCT of early goal-directed therapy changed the results from more than 33% chance of benefit to  more than 60% chance of harm).

CONCLUSIONS AND RELEVANCE:
In this retrospective analysis of data sets from patients with sepsis, 4 clinical phenotypes were identified that correlated with host-response patterns and clinical outcomes, and simulations suggested these phenotypes may help in understanding heterogeneity of treatment effects. Further research is needed to determine the utility of these phenotypes in clinical care and for informing trial design and interpretation.


3. Ketamine Corner

A. Subdissociative‐dose Ketamine Is Effective for Treating Acute Exacerbations of Chronic Pain

Lumanauw DD, et al. Acad Emerg Med. 2019 Mar 22 [Epub ahead of print]

BACKGROUND:
Subdissociative-dose ketamine (SDDK) is used to treat acute pain. We sought to determine if SDDK is effective in relieving acute exacerbations of chronic pain.

METHODS:
This study was a randomized double-blind placebo-controlled trial conducted May 2017 to June 2018 at a public teaching hospital (ClinicalTrials.gov #NCT02920528). The primary endpoint was a 20-mm decrease on a 100-mm visual analog scale (VAS) at 60 minutes. Power analysis using three groups (0.5 mg/kg ketamine, 0.25 mg/kg ketamine, or placebo infused over 20 minutes) estimated that 96 subjects were needed for 90% power. Inclusion criteria included age over 18 years, chronic pain over 3 months, and acute exacerbation (VAS ≥ 70 mm). Pain, agitation, and sedation were assessed by VAS at baseline and 20, 40, and 60 minutes after initiation of study drug. Telephone follow-up at 24 to 48 hours used a 10-point numeric rating scale for pain.

RESULTS:
A total of 106 subjects were recruited, with three excluded for baseline pain less than 70 mm. After randomization, 35 received 0.5 mg/kg ketamine, 36 received 0.25 mg/kg ketamine, and 35 received placebo. Three subjects receiving 0.5 mg/kg withdrew during the infusion due to adverse effects, and one subject in each group had incomplete data, leaving 97 for analysis. Initial pain scores (91.9 ± 8.9 mm), age (46.5 ± 12.6 years), sex distribution, and types of pain reported were similar. Primary endpoint analysis found that 25 of 30 (83%) improved with 0.5 mg/kg ketamine, 28 of 35 (80%) with 0.25 mg/kg ketamine, and 13 of 32 (41%) with placebo (p = 0.001). More adverse effects occurred in the ketamine groups with one subject in the 0.25 mg/kg group requiring a restraint code for agitation. A total of 89% of subjects were contacted at 24 to 48 hours, and no difference in pain level was detected between groups.

CONCLUSION:
Ketamine infusions at both 0.5 and 0.25 mg/kg over 20 minutes were effective in treating acute exacerbations of chronic pain but resulted in more adverse effects compared to placebo. Ketamine did not demonstrate longer-term pain control over the next 24 to 48 hours.

B. Psychiatric Outcomes of Patients With Severe Agitation Following Administration of Prehospital Ketamine

Lebin JA, et al. Acad Emerg Med. 2019 Mar 15 [Epub ahead of print]

BACKGROUND:
Ketamine is an emerging drug used in the management of undifferentiated, severe agitation in the prehospital setting. However, prior work has indicated that ketamine may exacerbate psychotic symptoms in patients with schizophrenia. The objective of this study was to describe psychiatric outcomes in patients who receive prehospital ketamine for severe agitation.

METHODS:
This is a retrospective cohort study, conducted at two tertiary academic medical centers, utilizing chart review of patients requiring prehospital sedation for severe agitation from January 1, 2014, to June 30, 2016. Patients received either intramuscular (IM) versus intravenous (IV) ketamine or IM versus IV benzodiazepine. The primary outcome was psychiatric inpatient admission with secondary outcomes including ED psychiatric evaluation and nonpsychiatric inpatient admission. Generalized estimating equations and Fisher's exact tests were used to compare cohorts.

RESULTS:
During the study period, 141 patient encounters met inclusion with 59 (42%) receiving prehospital ketamine. There were no statistically significant differences between the ketamine and benzodiazepine cohorts for psychiatric inpatient admission (6.8% vs. 2.4%, difference = 4.3%, 95% CI = -2% to 12%, p = 0.23) or ED psychiatric evaluation (8.6% vs. 15%, difference = -6.8%, 95% CI = -18% to 5%, p = 0.23). Patients with schizophrenia who received ketamine did not require psychiatric inpatient admission (17% vs. 10%, difference = 6.7%, 95% CI = -46% to 79%, p = 0.63) or ED psychiatric evaluation (17% vs. 50%, difference = -33%, 95% CI = -100% to 33%, p = 0.55) significantly more than those who received benzodiazepines, although the subgroup was small (n = 16). While there was no significant difference in the nonpsychiatric admission rate between the ketamine and benzodiazepine cohorts (35% vs. 51%, p = 0.082), nonpsychiatric admissions in the benzodiazepine cohort were largely driven by intubation (63% vs. 3.8%, difference = 59%, 95% CI = 38% to 79%, p less than 0.001).

CONCLUSIONS:
Administration of prehospital ketamine for severe agitation was not associated with an increase in the rate of psychiatric evaluation in the emergency department or psychiatric inpatient admission when compared with benzodiazepine treatment, regardless of the patient's psychiatric history.

4. We do extraordinary things for our patients in what we think are ordinary shifts

“Any job where we do our best and use our skills to care for those we love and provide a service to others is a societal good.”

“A job in which we actually help people survive illness and injury, actually guide them through difficult social situations, one in which we ease suffering and make death less terrifying is worth celebrating. That's a gift to our patients and to ourselves.”

Leap E. Life in Emergistan: Just Another Day in the ED, Saving Lives. Emerg Med News 2019;41(5):5.


5. Severe Hypertension in Pregnancy Demands Prompt Treatment

Maternal deaths associated with preeclampsia and subsequent stroke can be averted with rapid administration of antihypertensives.

Judy AE, et al. Systolic Hypertension, Preeclampsia-Related Mortality, and Stroke in California. Obstet Gynecol. 2019 Jun;133(6):1151-1159.

OBJECTIVE:
To describe the clinical characteristics of stroke and opportunities to improve care in a cohort of preeclampsia-related maternal mortalities in California.

METHODS:
The California Pregnancy-Associated Mortality Review retrospectively examined a cohort of preeclampsia pregnancy-related deaths in California from 2002 to 2007. Stroke cases were identified among preeclampsia deaths, and case summaries were reviewed with attention to clinical variables, particularly hypertension. Health care provider- and patient-related contributing factors were also examined.

RESULTS:
Among 54 preeclampsia pregnancy-related deaths that occurred in California from 2002 to 2007, 33 were attributed to stroke. Systolic blood pressure exceeded 160 mm Hg in 96% of cases, and diastolic blood pressure was 110 or higher in 65% of cases. Hemolysis, elevated liver enzymes, and low platelet count syndrome was present in 38% (9/24) of cases with available laboratory data; eclampsia occurred in 36% of cases. Headache was the most frequent symptom (87%) preceding stroke. Elevated liver transaminases were the most common laboratory abnormality (71%). Only 48% of women received antihypertensive treatment. A good-to-strong chance to alter outcome was identified in stroke cases 66% (21/32), with delayed response to clinical warning signs in 91% (30/33) of cases and ineffective treatment in 76% (25/33) cases being the most common areas for improvement.

CONCLUSION:
Stroke is the major cause of maternal mortality associated with preeclampsia or eclampsia. All but one patient in this series of strokes demonstrated severe elevation of systolic blood pressure, whereas other variables were less consistently observed. Antihypertensive treatment was not implemented in the majority of cases. Opportunities for care improvement exist and may significantly affect maternal mortality. 

6. Evaluating Effectiveness of Nasal Compression with Tranexamic Acid Compared with Simple Nasal Compression and Merocel Packing: A RCT

Akkan S, et al. Ann Emerg Med. 2019 May 9 [Epub ahead of print]

STUDY OBJECTIVE: The primary objective of this study is to compare the effectiveness of 3 treatment protocols to stop anterior epistaxis: classic compression, nasal packing, and local application of tranexamic acid. It also aims to determine the frequency of rebleeding after each of these protocols.

METHODS: This single-center, prospective, randomized controlled study was conducted with patients who had spontaneous anterior epistaxis. The study compared the effect of 3 treatment options, tranexamic acid with compression but without nasal packing, nasal packing (Merocel), and simple nasal external compression, on the primary outcome of stopping anterior epistaxis bleeding within 15 minutes.

RESULTS: Among the 135 patients enrolled, the median age was 60 years (interquartile range 25% to 75%: 48 to 72 years) and 70 patients (51.9%) were women. The success rate in the compression with tranexamic acid group was 91.1% (41 of 45 patients); in the nasal packing group, 93.3% (42 of 45 patients); and in the compression with saline solution group, 71.1% (32 of 45 patients). There was an overall statistically significant difference among the 3 treatment groups but no significant difference in pairwise comparison between the compression with tranexamic acid and nasal packing groups. In regard to rebleeding within 24 hours, the study found rates of 86.7% in the tranexamic acid group, 74% in the nasal packing group, and 60% in the compression with saline solution group.

CONCLUSION: Applying external compression after administering tranexamic acid through the nostrils by atomizer stops bleeding as effectively as anterior nasal packing using Merocel. In addition, the tranexamic acid approach is superior to Merocel in terms of decreasing rebleeding rates.

7. Brief Reviews from Ann Emerg Med

A. Among Low-Risk Patients, Does Functional Testing Decrease Referrals for Invasive Coronary Angiography Compared With Coronary Computed Tomographic Angiography?

Take-Home Message
Functional testing in patients with symptoms suggestive of low risk for acute coronary syndrome is associated with decreased invasive coronary angiography compared with coronary computed tomography (CT) angiography.


B. Do Mechanical Chest Compression Devices Compared With High-Quality Manual Chest Compressions Improve Neurologically Intact Survival of Patients Who Experience Cardiac Arrest?

Take-Home Message
Mechanical chest compression devices are not superior to conventional, high-quality manual chest compressions in improving survival to hospital discharge with good neurologic function.


C. Do Colloids Improve Mortality Compared With Crystalloids for Resuscitation of Critical Patients?

Take-Home Message
When used as an intravenous resuscitation fluid in critically ill adult and pediatric patients, colloids, including starches, dextrans, albumin, fresh frozen plasma, and gelatins, do not improve mortality compared with crystalloids.


D. Can Acute Uncomplicated Diverticulitis Be Safely Treated Without Antibiotics?

Take-Home Message
Antibiotic use in patients with acute uncomplicated diverticulitis is associated with an increased length of hospital stay but does not reduce overall or individual complication rates.


8. Treat Adolescents with STIs Before Discharging Them from the ED

This retrospective study found that almost half of adolescents prescribed outpatient antibiotics for pelvic inflammatory disease or chlamydia did not fill their prescriptions.

Lieberman A et al. Frequency of Prescription Filling Among Adolescents Prescribed Treatment for Sexually Transmitted Infections in the Emergency Department. JAMA Pediatr 2019 May 28 [Epub ahead of print]


Opening paragraph of study: Adolescents are disproportionately affected by sexually transmitted infections (STIs), making up nearly half of all diagnosed STIs annually,1 and are frequently diagnosed in the emergency department (ED) setting.2 Many STIs, such as gonorrhea and chlamydia, can be treated effectively with antibiotics. However, untreated, these infections can lead to serious morbidity. Although adolescents are often prescribed antibiotics to treat STIs, how often such prescriptions are actually filled by patients after ED discharge is unknown. We sought to fill this gap by investigating prescription filling for the treatment of STIs among adolescents in a real-world clinical setting.


9. A Promising Clinical Score for Identifying Low-Risk Febrile Infants in the ED

A score that includes age, highest temperature recorded in the ED, urinalysis, and absolute neutrophil count was highly sensitive for identifying infants with low probability of invasive bacterial infection.

Aronson PL, et al. Febrile Young Infant Research Collaborative. A Prediction Model to Identify Febrile Infants ≤60 Days at Low Risk of Invasive Bacterial Infection. Pediatrics. 2019 Jun 5 [Epub ahead of print]

OBJECTIVES:
To derive and internally validate a prediction model for the identification of febrile infants ≤60 days old at low probability of invasive bacterial infection (IBI).

METHODS:
We conducted a case-control study of febrile infants ≤60 days old who presented to the emergency departments of 11 hospitals between July 1, 2011 and June 30, 2016. Infants with IBI, defined by growth of a pathogen in blood (bacteremia) and/or cerebrospinal fluid (bacterial meningitis), were matched by hospital and date of visit to 2 control patients without IBI. Ill-appearing infants and those with complex chronic conditions were excluded. Predictors of IBI were identified with multiple logistic regression and internally validated with 10-fold cross-validation, and an IBI score was calculated.

RESULTS:
We included 181 infants with IBI (155 [85.6%] with bacteremia without meningitis and 26 [14.4%] with bacterial meningitis) and 362 control patients. Twenty-three infants with IBI (12.7%) and 138 control patients (38.1%) had fever by history only. Four predictors of IBI were identified (area under the curve 0.83 [95% confidence interval (CI): 0.79-0.86]) and incorporated into an IBI score: age less than 21 days (1 point), highest temperature recorded in the emergency department 38.0-38.4°C (2 points) or ≥38.5°C (4 points), absolute neutrophil count ≥5185 cells per μL (2 points), and abnormal urinalysis results (3 points). The sensitivity and specificity of a score ≥2 were 98.8% (95% CI: 95.7%-99.9%) and 31.3% (95% CI: 26.3%-36.6%), respectively. All 26 infants with meningitis had scores ≥2.

CONCLUSIONS:
Infants ≤60 days old with fever by history only, a normal urinalysis result, and an absolute neutrophil count less than 5185 cells per μL have a low probability of IBI.
I recommend that you also read the editorial (subscription only) by Nate Kuppermann of the PECARN and UC Davis. Kuppermann N, et al. Prediction Models for Febrile Infants: Time for a Unified Field Theory. Pediatrics 2019 June [Epub ahead of print] https://pediatrics.aappublications.org/content/early/2019/06/03/peds.2019-1375

10. Images in Clinical Practice

Thigh Pain Associated With Diarrhea

Woman With Red Eyes

Woman With Cirrhosis and Shortness of Breath

Man With Finger Pain and Swelling

Man With Chronic Back Pain

Young Male With Scrotal Pain

11. Ultrasound Corner

A. How to Perform an Ultrasound-Guided Transversus Abdominis Plane (TAP) Block for Appendicitis Pain

Nagdev A, et al. ACEP Now. May 17, 2019

Over the past few years, emergency physicians have begun implementing multimodal strategies for acute pain, reducing the use of opioids. Ultrasound-guided single-injection nerve blocks have slowly become accepted for targeted pain relief over the past decade in the emergency department for hip fractures, rib fractures, deltoid abscess drainage, and other conditions.1–3 Currently, point-of-care ultrasound (POCUS) fellowships require ultrasound-guided nerve blocks as part of the training curriculum to ensure future leaders will provide the next generation of emergency physicians the knowledge to offer optimal pain management.4,5

Over the past decade, our group has been fortunate to work in a hospital that values interdepartmental collaboration to optimize patient care. More often than not, long delays for patients admitted for surgical pathology (such as acute appendicitis) lead to repeated rounds of intravenous opioid analgesics that ultimately fail to achieve adequate pain control and feature side effects. This led our group to think of alternative methods for pain control in this population rather than standard intravenous opioid regimens.

The ultrasound-guided transversus abdominis plane (TAP) block is a well-established regional anesthetic block used by anesthesiologists for perioperative pain control of the anterior abdominal wall.6,7 At our center, after computed tomography (CT) confirmation of appendicitis, ED-performed TAP blocks have been instituted as an alternative analgesic option for alleviating pain from this common diagnosis. This additive analgesic (in addition to other intravenous agents) has proved effective in our small cohort of patients, who have demonstrated reduced pain scores and need for additional pain medications while awaiting definitive surgical intervention.8


B.  TEE During CPR Is Associated With Shorter Compression Pauses Compared With Transthoracic Echocardiography.

Fair J 3rd, et al. Ann Emerg Med. 2019 Jun;73(6):610-616.

Editor’s Capsule Summary
What is already known on this topic

Bedside ultrasonography can be helpful to identify some reversible conditions in the setting of cardiac arrest, and transesophageal echocardiography can be used to assess real-time adequacy of chest compressions.

What question this study addressed

This retrospective case series of 25 patients addressed whether transesophageal echocardiography is associated with briefer pulse check interruptions of chest compressions compared with transthoracic echocardiography or no bedside ultrasonography during cardiac arrest resuscitation.

What this study adds to our knowledge

Transesophageal echocardiography is associated with briefer pauses during pulse checks than transthoracic echocardiography or no echocardiography.

How this is relevant to clinical practice

There is the unproven possibility that transesophageal echocardiography may benefit resuscitation of cardiac arrest because of briefer pulse checks’ possibly leading to less neurologic compromise in cardiac arrest survivors.

STUDY OBJECTIVE:
Point-of-care ultrasonography provides diagnostic information in addition to visual pulse checks during cardiopulmonary resuscitation (CPR). The most commonly used modality, transthoracic echocardiography, has unfortunately been repeatedly associated with prolonged pauses in chest compressions, which correlate with worsened neurologic outcomes. Unlike transthoracic echocardiography, transesophageal echocardiography does not require cessation of compressions for adequate imaging and provides the diagnostic benefit of point-of-care ultrasonography. To assess a benefit of transesophageal echocardiography, we compare the duration of chest compression pauses between transesophageal echocardiography, transthoracic echocardiography, and manual pulse checks on video recordings of cardiac arrest resuscitations.

METHODS:
We analyzed 139 pulse check CPR pauses among 25 patients during cardiac arrest.

RESULTS:
Transesophageal echocardiography provided the shortest mean pulse check duration (9 seconds [95% confidence interval {CI} 5 to 12 seconds]). Mean pulse check duration with transthoracic echocardiography was 19 seconds (95% CI 16 to 22 seconds), and it was 11 seconds (95% CI 8 to 14 seconds) with manual checks. Intraclass correlation coefficient between abstractors for a portion of individual and average times was 0.99 and 0.99, respectively (P less than .001 for both).

CONCLUSION:
Our study suggests that pulse check times with transesophageal echocardiography are shorter versus with transthoracic echocardiography for ED point-of-care ultrasonography during cardiac arrest resuscitations, and further emphasizes the need for careful attention to compression pause duration when using transthoracic echocardiography for point-of-care ultrasonography during ED cardiac arrest resuscitations.


C. High-Yield Ocular Ultrasound Applications in the ED from ACEP Now




12. RBC transfusions for ED patients with GI bleeding within an integrated health system

Mark DG, et al. Am J Emerg Med 2019 June 10 [Epub ahead of print]

Study objective: To assess trends over time in red blood cell (RBC) transfusion practice among emergency department (ED) patients with gastrointestinal (GI) bleeding within an integrated healthcare system, inclusive of 21 EDs.

Methods: Retrospective cohort of ED patients diagnosed with GI bleeding between July 1st, 2012 and September 30th, 2016. The primary outcome was receipt of an RBC transfusion in the ED. Secondary outcomes included 90-day rates of RBC transfusion, repeat ED visits, rehospitalization, and all-cause mortality. Logistic regression was used to obtain confounder-adjusted outcome rates.

Results: A total of 24,868 unique patient encounters were used for the primary analysis. The median hemoglobin level in the ED prior to RBC transfusion decreased from 7.5 g/dl to 6.9 g/dl in the first versus last twelve months of the study period (p less than 0.0001). A small trend was observed in the overall adjusted rate of ED RBC transfusion (absolute quarterly change of −0.1%, R2=0.18, p=0.0001) largely attributable to the subgroup of patients with hemoglobin nadirs between 7.0 and 9.9 g/dl (absolute quarterly change of −0.4%, R2=0.38,
p less than 0.0001). Rates of RBC transfusions through 90days likewise decreased (absolute quarterly change of −0.4%, R2=0.85, p less than 0.0001) with stable to decreased corresponding rates of repeat ED visits, rehospitalizations and mortality.

Conclusion: Rates of ED RBC transfusion decreased over time among patients with GI bleeding, particularly in those with hemoglobin nadirs between 7.0 and 9.9 g/dl. These findings suggest that ED providers are willing to adopt evidence-based restrictive RBC transfusion recommendations for patients with GI bleeding.

13. Opioid Corner

A. Opioids Prescribed in 1 of 6 ED Visits by Young People

By Kelly Young. Journal Watch. May 28, 2019

One in six emergency department visits by adolescents and young adults resulted in an opioid prescription, according to a Pediatrics study.

Using 2005 to 2015 data from two national health surveys, researchers examined 47,000 visits to emergency departments and 31,000 visits to outpatient clinics among patients aged 13 to 22. Among the findings:

Nearly 15% of emergency department visits and 3% of clinic visits resulted in an opioid prescription.

Opioid prescriptions in the ED decreased slightly over time.

The prescribing rate surpassed 40% for dental problems in all ages and clavicle fracture in adolescents.

A commentator writes: "This study's findings reflect many of the unique attributes of health care use by young adults. ... Young adults seek care for acute conditions and injuries, chronic conditions, and reproductive care and receive a greater proportion of their care at emergency departments than any age group except for the elderly."


B. Factors Predicting Risk for Opioid Use Disorder

Patients with previous personality, somatoform, or psychotic disorders had a higher likelihood of developing opioid use disorder.

Klimas J et al. Strategies to Identify Patient Risks of Prescription Opioid Addiction When Initiating Opioids for Pain: A Systematic Review. JAMA Netw Open 2019 May 3 [Epub ahead of print]

IMPORTANCE:
Although prescription opioid use disorder is associated with substantial harms, strategies to identify patients with pain among whom prescription opioids can be safely prescribed have not been systematically reviewed.

OBJECTIVE:
To review the evidence examining factors associated with opioid addiction and screening tools for identifying adult patients at high vs low risk of developing symptoms of prescription opioid addiction when initiating prescription opioids for pain.

DATA SOURCES:
MEDLINE and Embase (January 1946 to November 2018) were searched for articles investigating risks of prescription opioid addiction.

STUDY SELECTION:
Original studies that were included compared symptoms, signs, risk factors, and screening tools among patients who developed prescription opioid addiction and those who did not.

DATA EXTRACTION AND SYNTHESIS:
Two investigators independently assessed quality to exclude biased or unreliable study designs and extracted data from higher quality studies. The Preferred Reporting Items for Systematic Reviews and Meta-analyses of Diagnostic Accuracy Studies (PRISMA-DTA) reporting guideline was followed.

MAIN OUTCOMES AND MEASURES:
Likelihood ratios (LRs) for risk factors and screening tools were calculated.

RESULTS:
Of 1287 identified studies, 6 high-quality studies were included in the qualitative synthesis and 4 were included in the quantitative synthesis. The 4 high-quality studies included in the quantitative synthesis were all retrospective studies including a total of 2 888 346 patients with 4470 cases that met the authors' definitions of prescription opioid addiction. A history of opioid use disorder (LR range, 17-22) or other substance use disorder (LR range, 4.2-17), certain mental health diagnoses (eg, personality disorder: LR, 27; 95% CI, 18-41), and concomitant prescription of certain psychiatric medications (eg, atypical antipsychotics: LR, 17; 95% CI, 15-18) appeared useful for identifying patients at high risk of opioid addiction. Among individual findings, only the absence of a mood disorder (negative LR, 0.50; 95% CI, 0.45-0.52) was associated with a lower risk of opioid addiction. Despite their widespread use, most screening tools involving combinations of questions were based on low-quality studies or, when diagnostic performance was assessed among high-quality studies, demonstrated poor performance in helping to identify patients at high vs low risk.

CONCLUSIONS AND RELEVANCE:
While a history of substance use disorder, certain mental health diagnoses, and concomitant prescription of certain psychiatric medications appeared useful for identifying patients at higher risk, few quality studies were available and no symptoms, signs, or screening tools were particularly useful for identifying those at lower risk.


14. Drug Order in Rapid Sequence Intubation: Does it Matter?

Driver BE, et al. Acad Emerg Med. 2019 Mar 4 [Epub ahead of print]

BACKGROUND:
The optimal order of drug administration (sedative first vs. neuromuscular blocking agent first) in rapid sequence intubation (RSI) is debated.

OBJECTIVE:
We sought to determine if RSI drug order was associated with the time elapsed from administration of the first RSI drug to the end of a successful first intubation attempt.

METHODS:
We conducted a planned secondary analysis of a randomized trial of adult ED patients undergoing emergency orotracheal intubation that demonstrated higher first-attempt success with bougie use compared to a tracheal tube + stylet. Drug choice, dose, and the order of sedative and neuromuscular blocking agent were not stipulated. We analyzed trial patients who received both a sedative and a neuromuscular blocking agent within 30 seconds of each other who were intubated successfully on the first attempt. The primary outcome was the time elapsed from complete administration of the first RSI drug to the end of the first intubation attempt, a surrogate outcome for apnea time. We performed a multivariable analysis using a mixed-effects generalized linear model.

RESULTS:
Of 757 original trial patients, 562 patients (74%) met criteria for analysis; 153 received the sedative agent first, and 409 received the neuromuscular blocking agent first. Administration of the neuromuscular blocking agent before the sedative agent was associated with a reduction in time from RSI administration to the end of intubation attempt of 6 seconds (95% confidence interval = 0 to 11 sec).

CONCLUSION:
Administration of either the neuromuscular blocking or the sedative agent first are both acceptable. Administering the neuromuscular blocking agent first may result in modestly faster time to intubation. For now, it is reasonable for physicians to continue performing RSI in the way they are most comfortable with. If future research determines that the order of medication administration is not associated with awareness of neuromuscular blockade, administration of the neuromuscular blocking agent first may be a logical default administration method to attempt to minimize apnea time during intubation.

15. ECG alterations suggestive of hyperkalemia in normokalemic versus hyperkalemic patients

Varga C, et al. BMC Emergency Medicine 2019;19:33

BACKGROUND:
In periarrest situations and during resuscitation it is essential to rule out reversible causes. Hyperkalemia is one of the most common, reversible causes of periarrest situations. Typical electrocardiogram (ECG) alterations may indicate hyperkalemia. The aim of our study was to compare the prevalence of ECG alterations suggestive of hyperkalemia in normokalemic and hyperkalemic patients.

METHODS:
170 patients with normal potassium (K+) levels and 135 patients with moderate (serum K+ = 6.0-7.0 mmol/l) or severe (K+ over 7.0 mmol/l) hyperkalemia, admitted to the Department of Emergency Medicine at the Somogy County Kaposi Mór General Hospital, were selected for this retrospective, cross-sectional study. ECG obtained upon admission were analyzed by two emergency physicians, independently, blinded to the objectives of the study. Statistical analysis was performed using SPSS22 software. χ2 test and Fischer exact tests were applied.

RESULTS:
24% of normokalemic patients and 46% of patients with elevated potassium levels had some kind of ECG alteration suggestive of hyperkalemia. Wide QRS (31.6%), peaked T-waves (18.4%), Ist degree AV-block (18.4%) and bradycardia (18.4%) were the most common and significantly more frequent ECG alterations suggestive of hyperkalemia in severely hyperkalemic patients compared with normokalemic patients (8.2, 4.7, 7.1 and 6.5%, respectively). There was no significant difference between the frequency of ECG alterations suggestive of hyperkalemia in normokalemic and moderately hyperkalemic patients. Upon examining ECG alterations not typically associated with hyperkalemia, we found that prolonged QTc was the only ECG alteration which was significantly more prevalent in both patients with moderate (17.5%) and severe hyperkalemia (21.1%) compared to patients with normokalemia (5.3%).

CONCLUSIONS:
A minority of patients with normal potassium levels may also exhibit ECG alterations considered to be suggestive of hyperkalemia, while more than half of the patients with hyperkalemia do not have ECG alterations suggesting hyperkalemia. These results imply that treatment of hyperkalemia in the prehospital setting should be initiated with caution. Multiple ECG alterations, however, should draw attention to potentially life threatening conditions.


16. Choosing Wisely Hepatology, Eh?

Ryan Radecki’s EM Lits of Note Blog. June 12, 2019

The Choosing Wisely campaign is quite popular in theory, if not in practice – ranging widely across the specialties from Pediatric Hospital Medicine to our own, beloved, Emergency Medicine.

This list is from the Canadian Association for the Study of the Liver, and two of their five recommendations are somewhat relevant to EM. Without further ado:

A. Statement 1: Don’t order serum ammonia to diagnose or manage hepatic encephalopathy

This was their most highly ranked recommendation when members were surveyed at their annual meeting. They cite multiple confounders regarding ammonia levels, factors affecting accuracy of the measurement, and state “elevated ammonia levels do not add any diagnostic, staging, or prognostic value.” The diagnosis, they feel, ought to be made based on clinical history and response to therapy alone.

B. Statement 2: Don’t routinely transfuse fresh frozen plasma, vitamin K, or platelets to reverse abnormal tests of coagulation in patients with cirrhosis prior to abdominal paracentesis, endoscopic variceal band ligation, or any other minor invasive procedures

This is another one of my favorite pet topics – transfusion intended to “restore normal hemostasis” in a dysfunctional, but somewhat already rebalanced coagulation system. As they say, “Routine tests of coagulation do not reflect bleeding risk in patients with cirrhosis and bleeding complications of these procedures are rare.” In fact, I’ve seen several articles approaching even liver resection in the context of elevated coagulation parameters absent any major bleeding complications – so this ought certainly apply to minor procedures, including those in the Emergency Department.

No doubt the uptake of these recommendations will be highly variable among hospitals and specialty groups, but lists like these are great tools with which to start the conversation.

The hyperlinked essay here: https://www.emlitofnote.com/?p=4477


17. Minor Blunt Thoracic Trauma in the ED: Sensitivity and Specificity of Chest Ultralow-Dose CT Compared With Conventional Radiography.

Macri F, et al. Ann Emerg Med. 2019 Jun;73(6):665-670.

STUDY OBJECTIVE:
To evaluate the diagnostic performance of chest ultralow-dose computed tomography (CT) compared with chest radiograph for minor blunt thoracic trauma.

METHODS:
One hundred sixty patients with minor blunt thoracic trauma were evaluated first by chest radiograph and subsequently with a double-acquisition nonenhanced chest CT protocol: reference CT and ultralow-dose CT with iterative reconstruction. Two study radiologists independently assessed injuries with a structured report and subjective image quality and calculated certainty of diagnostic confidence level.

RESULTS:
Ultralow-dose CT had a sensitivity and specificity of 100% compared with reference CT in the detection of injuries (187 lesions) in 104 patients. Chest radiograph detected abnormalities in 82 patients (79% of the population), with lower sensitivity and specificity compared with ultralow-dose CT (P less than .05). Despite an only fair interobserver agreement for ultralow-dose CT image quality (κ=0.26), the diagnostic confidence level was certain for 95.6% of patients (chest radiograph=79.3%). Ultralow-dose CT effective dose (0.203 mSv [SD 0.029 mSv]) was similar (P=.14) to that of chest radiograph (0.175 mSv [SD 0.155 mSv]) and significantly less (P less than .001) than that of reference CT (1.193 mSv [SD 0.459 mSv]).

CONCLUSION:
Ultralow-dose CT with iterative reconstruction conveyed a radiation dose similar to that of chest radiograph and was more reliable than a radiographic study for minor blunt thoracic trauma assessment. Radiologists, regardless of experience with ultralow-dose CT, were more confident with chest ultralow-dose CT than chest radiograph.

18. Vital Signs = Vital

Ryan Radecki. EM Lit of Note. June 3, 2019

That is how the authors frame it, after all: “‘Vital signs are vital’ is a common refrain in emergency medicine.”

And, these authors add to the body of work further exploring this axiom. In this simple, retrospective data analysis, they evaluate all adult visits to their Emergency Department to determine the effect of abnormal vital signs at disposition on short-term outcomes.

For discharges, about 3% of their cohort returned to the same ED within 72 hours. Only a handful – a little less than 15% – had any vital sign abnormalities at discharge. And, yes, those with vital sign abnormalities were slightly more likely to return than those who did not, with relative risk ratios centered generally around 1.2. Then, a little more than a quarter of patients were admitted on their return visit – and, again, vital sign abnormalities increased the likelihood of subsequent admission by a small amount. In this case, fever was more likely than the other abnormal vital signs to tip the scales towards admission.

Similarly, an analysis of inpatient visits and subsequent escalations in care noted vital sign abnormalities exhibited a greater risk of upgrade, with RRs centered around 2.

Overall, however, the vast majority of patients who were either admitted or discharged with abnormal vital signs did well. Abnormal vital signs are always worth recognizing and dedicating a bit of cognitive effort, but the aren’t strong enough predictors of subsequent outcomes to drive changes in management.

Hodgson NR, et al. Association of Vital Signs and Process Outcomes in Emergency Department Patients. West J Emerg Med. 2019 May; 20(3): 433–437.


19. How Quality Discharge May Reduce Return ED Visits

Sabbatini AK, et al. Capturing Emergency Department Discharge Quality With the Care Transitions Measure: A Pilot Study. Acad Emerg Med. 2019 Jun;26(6):605-609.

BACKGROUND:
Recent attention has been given to developing measures to capture the quality of ED transitions of care. We examined the utility of a patient-reported measure of transitional care, the Care Transitions Measure-3 (CTM-3), in the ED setting and its association with outcomes of care after ED discharge.

METHODS:
A telephone survey was conducted of a convenience sample of patients 14 days after discharge from two emergency departments (EDs) in an academic health system. Patients responded to three statements using a four-point agreement scale (strongly disagree, disagree, agree, strongly agree): 1) "The hospital staff took my preferences and those of my family or caregiver into account when deciding what my health care needs would be"; 2) " When I left the ER, I had a good understanding of the things I was responsible for in managing my health"; and 3) "When I left the hospital, I clearly understood the purpose for taking each of my medications." Patients were also queried about outcomes after ED discharge that are known to be related to ED care transitions including medication adherence, completion of recommended follow-up, and return visits to the ED. Multivariable logistic regression was used to determine the association between the CTM-3 score (on a 100-point scale) and outcomes of interest.

RESULTS:
Among 1,832 patients called, 576 were reached by phone, and 410 consented and completed our survey, representing a 22.4% response rate of patients we attempted to call. A 10-point increase in the CTM-3 score (better care experiences) was associated with a 12% decrease in the odds of having an ED return visit (adjusted odds ratio [AOR] = 0.88, 95% confidence interval [CI] = 0.77-1.00) and a 45% increase in the odds of taking prescribed medications as recommended (AOR = 1.45, 95% CI = 1.12-1.87). There was no association between CTM-3 score and completion of follow-up.

CONCLUSIONS:
The CTM-3 is associated with outcomes of care after an ED visit, including ED return visits and medication adherence, and may have utility as a patient-reported measure of ED transitions of care.


20. Challenge of immune-mediated adverse reactions in the ED

Daniels GA, et al. Emerg Med J. 2019 May 21 [Epub ahead of print]

Multiple drugs of a new class of cancer treatments called immune checkpoint inhibitors, which work by enabling the immune system to attack tumour cells, have been approved for a variety of indications in recent years. Immune checkpoints, such as cytotoxic T-lymphocyte antigen-4 and programmed death-1, are part of the normal immune system and regulate immune activation. Treatment with inhibitors of these checkpoints can significantly improve response rates, progression-free survival and overall survival of patients with cancer; it can also result in adverse reactions that present similarly to other conditions.

These immune-mediated adverse reactions (IMARs) are most commonly gastrointestinal, respiratory, endocrine or dermatologic. Although patients' presentations may appear similar to other types of cancer therapy, the underlying causes, and consequently their management, may differ. Prompt recognition is critical because, with appropriate management, most IMARs resolve and patients can continue receiving immune checkpoint inhibitor treatment. Rarely, these IMARs may be life-threatening and escape detection from the usual evaluations in the emergency environment. Given the unusual spectrum and mechanism of IMARs arising from immune checkpoint inhibitors, emergency departmentED staff require a clear understanding of the evaluation of IMARs to enable them to appropriately assess and treat these patients. Treatment of IMARs, most often with high-dose steroids, differs from chemotherapy-related adverse events and when possible should be coordinated with the treating oncologist.

This review summarises the ED presentation and management of IMARs arising from immune checkpoint inhibitors and includes recommendations for tools and resources for ED healthcare professionals.


21. The Diversity Snowball Effect: The Quest to Increase Diversity in EM: A Case Study of Highland's EM Residency Program

Garrick JF, et al. Ann Emerg Med. 2019 Jun;73(6):639-647.

Blacks, Hispanics/Latinos, American Indians, Pacific Islanders, Alaska Natives, and Native Hawaiians make up 33% of the US population. These same groups are underrepresented in medicine. In 2013, the physician workforce was 4.1% black, 4.4% Hispanic/Latino, 0.4% American Indian or Alaska Native, 11.7% Asian, and 48.9% white. Only 9.9% of emergency physicians identify as underrepresented minority (4.5% black, 4.8% Hispanic/Latino, and 0.6% American Indian/Alaska Native).

Efforts to increase the number of underrepresented minority physicians are important because previous studies show improved outcomes when the patient and physician share the same racial/ethnic background.

Starting in 2006, the faculty at the Highland EM Residency Program in Oakland, CA, began a diversification initiative to increase the number of underrepresented minority residents. The goal was to closely mirror the US population and match 30% underrepresented minorities with each incoming class. After the initiative, there was a 2-fold increase in the number of underrepresented minority residents (from 12% to 27%). This article is a review of the strategies used to diversify the Highland EM Residency Program. Most components can be applied across emergency medicine programs to increase the number of underrepresented minority residents and potentially improve health outcomes for diverse populations.

22. Micro Bits

A. Physician burnout costs US an average of $4.6B per year

A study published online in the Annals of Internal Medicine estimates that physician burnout costs the US an average of $4.6 billion per year. Researchers developed a mathematical model to calculate the cost of turnover and shorter hours linked to burnout and found that the issue costs health care organizations $7,600 per doctor per year, meaning it "makes good business sense" for institutions to address burnout, according to researcher Joel Goh.



B. Overcoming Barriers to Empathy in Health Care: How can we practice empathy when we feel stressed, over-worked, and burned out?


C. Acetaminophen May Blunt Empathy



D. Seniors who feel their life has purpose may live longer


E. Study Links Patient Appointment Times, Cancer Screening Rates: 'Decision Fatigue,' Lack of Time May Play a Role



F. How great nursing improves doctors' performance
   
Harvard Business Review
Every physician can think of a time — probably many — when a nurse has saved the day. And indeed, ample research shows that programs that foster a culture of excellent nursing have sweeping impacts throughout health care organizations. Hospitals participating in these initiatives see higher nurse satisfaction and retention, improved patient experience and safety, decreased mortality, increased revenues, and many other benefits. New research adds to this body of work, showing a positive association between nursing excellence and physicians' performance. 


G. Understanding the consequences of education inequality on cardiovascular disease


H. Will raising the minimum wage lower suicide rates?

This study examined whether increases in state minimum wages have been associated with changes in state suicide rates. In the period between 2006 and 2016, there were approximately 432,000 suicide deaths. Authors found each one-dollar increase in the real minimum wage was associated with a 1.9% decrease in the annual state suicide rate on average, an association that was seen most strongly in the years since 2011. Results indicate increasing the minimum wage could be a valuable strategy for preventing suicide.


I. Was It an Invisible Attack on U.S. Diplomats, or Something Stranger?

An “unknown energy source” has been blamed for debilitating symptoms suffered by Americans posted in Cuba. The real cause may be more surprising.

Dozens of leading neurologists, psychiatrists and psychologists, meanwhile, have offered an alternative narrative: that the diplomats’ symptoms are primarily psychogenic — or “functional” — in nature. If true, it would mean that the symptoms were caused not by a secret high-tech weapon but by the same confluence of psychological and neurological processes — entirely subconscious yet remarkably powerful — underlying hypnosis and the placebo effect. They are disorders, in other words, not of the brain’s hardware but of its software; not of objective injuries to the brain’s structure but of chronic alterations to how the brain functions, typically following exposure to an illness, a physical injury or stress. And the fact that the State Department and doctors the government selected to treat the diplomats have dismissed this explanation out of hand does not surprise these experts. After all, they say, functional neurological disorders are among the most misunderstood, debilitating and denigrated ailments known to medicine…


J. Sleeping with the TV on? Don’t do it.

Association of Exposure to Artificial Light at Night While Sleeping With Risk of Obesity in Women


K. Feel Free to Skip Breakfast Again and Again and Again: The Skeptical Cardiologist tackles the "most important meal of the day"


L. 3 interventions could prevent 94.3M deaths globally

Research published in the journal Circulation said increasing blood pressure treatment coverage by 70%, reducing sodium intake by 30% and eliminating trans fat consumption could prevent 94.3 million deaths globally by 2040. "Successful global implementation would require increased investment in health care capacity and quality of care in the primary health care sector, and increased efforts to reduce sodium and eliminate trans fat intake through regulation and health promotion campaigns as well," the authors wrote.



M. CDC Says Bats Are Main Source Of Human Rabies In US


N. Special Report: Stop Doing ‘Everything’

Doctors systematically overestimate the benefits and underestimate the harm of interventions to patients and their families.