Patients who received intravenous magnesium sulfate for acute asthma exacerbation in the emergency department had decreased hospital admissions and no serious adverse effects.

Otitis media with effusion (OME), one of the most common diseases in early childhood, is a self-limited illness1 with an estimated recurrence rate of 50% within 24 months2 . OME is characterized by an accumulation of fluid in the middle ear without symptoms or signs of acute infection.3 In most cases OME causes mild hearing impairment for a short period. OME in the pediatric population can lead to diminished hearing which in theory could hinder early learning. Some studies have shown an association with adult hearing loss as well.4 In one study, for instance, OME and recurrent otitis media before the age of 3 were weakly associated with worse classroom concentration, mathematical skills, oral performance and reading skills5 .

No one was helped (no difference in mortality rate between the two strategies) 1 in 3 were helped (transfusion avoided with a restrictive strategy) No one was helped (no difference in mortality rate between the two strategies) 36% lower risk of blood transfusion with a restrictive strategy Blood transfusion is a common treatment of anemia due to chronic disease or acute blood loss.1 However, there continues to be uncertainty concerning the appropriate threshold for transfusion. A restrictive protocol could decrease blood administered, transmissible infections, transfusion reactions, volume overload, and utilization of a limited commodity. However, anemia may result in decreased oxygen delivery, which could lead to metabolic dysfunction and increased cell death.2 Determining an appropriate transfusion threshold is thus an important objective. A previous Cochrane review3 found that the use of restrictive thresholds decreased transfusions compared to liberal thresholds. No difference in secondary outcomes, including 30-day mortality, hospital length of stay, cardiac events, and myocardial infarction, was noted. Here we summarize an updated Cochrane review of 31 trials and 12,587 adult participants.4 Included studies were randomized trials that assigned patients to either liberal or restrictive transfusion thresholds, typically defined as a hemoglobin level of 9 to 10 or 7 to 8 g/dL, respectively. The primary outcome was 30-day mortality. Secondary outcomes included the proportion of participants transfused, number of units transfused, cardiac events, nonfatal and fatal myocardial infarction, renal failure, and congestive heart failure. The authors found no difference in 30-day mortality between liberal and restrictive transfusion protocols (relative risk [RR] = 0.97, 95% confidence interval [CI] = 0.8 to 1.2). However, 84% of the subjects assigned to liberal thresholds received a blood transfusion, compared to 48% of the restrictive group subjects, an absolute reduction of 36% (NNT of 3 for avoiding red blood cell transfusion). The liberal threshold also resulted in 1.3 more units being transfused per participant than the restrictive threshold. There was no difference between the two groups in cardiac events, myocardial infarction, congestive heart failure, rebleeding, sepsis, pneumonia, thromboembolism, or renal failure. Subgroup analysis of 30-day mortality was also performed and two subgroup results are of particular note. The first consisted of patients with an acute myocardial infarction, for whom two studies found that 30-day mortality was numerically (although not statistically) higher in the restrictive than in the liberal group, with low numbers of deaths (9/78 vs. 2/76) and low numbers overall in the analysis (n = 154). On the other hand, participants with acute gastrointestinal bleeding in three studies had a significantly lower mortality with the restrictive protocol than with the liberal protocol (RR = 0.65, 95% CI = 0.43-0.97, n = 1522, NNT = 37). This Cochrane review was a comprehensive and important update to the prior review, but several important caveats should be kept in mind. These include the potential for biases due to lack of blinding, statistical heterogeneity in the secondary outcomes, and differences among study methodologies. The intervention examined in this study, the administration of blood, makes blinding difficult, increasing risk of bias because only one trial blinded participants to treatment. Another concern is statistical heterogeneity. While the primary outcome had low heterogeneity, some secondary outcomes, including the risk of receiving blood transfusion, showed heterogeneity. Finally, important methodologic differences between the studies could have affected the validity of the findings. One important example is differing restrictive transfusion thresholds. Half of the studies used a restrictive threshold of 7 g/dL, while the other half used 8 g/dL. A transfusion threshold of 7 g/dL was more common in studies of intensive care unit (ICU) patients. Study populations varied widely, and different transfusion thresholds may affect different patients and conditions differently. This is apparent in the subgroup analysis where there were signals of possible benefit and harms. Subgroup analysis of patients with acute gastrointestinal bleeding demonstrated benefit with the restrictive protocol, while analysis of patients with acute myocardial infarction demonstrated possible harm. The implication of these findings is unclear, although they suggest areas for research. While there was no difference in mortality or adverse outcomes, restrictive transfusion criteria did decrease transfusions, a potential benefit we see as important based on resource utilization and harm risks associated with transfusion. Of note, a systematic review published in 2020 evaluated the effects of a restrictive compared to a liberal hemoglobin threshold in intensive care patients and supports the findings of the Cochrane review.4 Eight randomized controlled trials and 3,415 subjects were included and no significant difference was found in short-term mortality, length of hospital stay, length of ICU stay, or ischemic events. Because there was no evidence suggesting benefits with the routine use of a liberal transfusion threshold and because a liberal transfusion threshold leads to greater blood administration, we have assigned a color recommendation of black (harms > benefits). In summary, routine use of a liberal hemoglobin threshold demonstrated no clear medical benefit or harm in regard to 30-day mortality and morbidity outcomes. However, the liberal threshold did lead to increased utilization of blood products, which could pose a risk of infection and transfusion reactions.

Asymptomatic bacteriuria, occurring in 2-15% of pregnancies, is generally defined as at least one urine culture showing >100,000 colony-forming units (CFUs)/mL in the absence of fever or symptoms of urinary tract infection.1 Escherichia coli is the most commonly associated pathogen, comprising up to 80% of isolates.

No one was harmed (no serious or life-threatening adverse events) 1 in 9 were harmed (experienced neuropsychological adverse events) No one was harmed (no serious or life-threatening adverse events) 11% higher risk of neuropsychological adverse events compared to the opioid group A total of 870 adult patients who presented to the ED with acute pain from traumatic and nontraumatic causes, in two meta-analyses comprising a total of 11 trials Acute pain is one of the most common complaints in the emergency department (ED). With recent efforts to find effective nonopioid analgesics, ketamine has surfaced as a potential option for ED analgesia.1-3 While ketamine is typically used as a sedative agent, several studies have shown that when it is administered in subdissociative doses, both as a stand-alone agent and as an adjunct to opioids, it may also provide analgesia.4 Two recently published meta-analyses compared ketamine with opioid analgesics in adult ED patients with acute pain. The patient-level meta-analysis, by Karlow et al.,5 included randomized controlled trials that directly compared a single bolus, slow push, or slow infusion of a subdissociative intravenous (IV) dose of ketamine with a single IV dose of opioid/opiate analgesia. This comprised three studies that included a total of 261 adult ED patients. The primary outcome studied was the change in patient-reported pain scores after administration of ketamine (dose range = 0.3 to 0.5 mg/kg IV) or morphine (dose = 0.1 mg/kg IV). The pooled estimate for the mean difference in reported pain score reduction between the ketamine and morphine groups was 0.42 (95% confidence interval [CI] = −0.70 to 1.54). Because of heterogeneity in the methods and timing of pain assessment and in event assessment, adverse events were reported as raw data. Ketamine was associated with a higher rate of adverse events than morphine in all of the individual studies. However, the only reported acute life-threatening adverse event was decreased oxygen saturation, which was reported in a single patient in the opioid trial arms and in none of the patients in the ketamine groups. Ghate et al.6 performed a systematic review and meta-analysis comparing low-dose ketamine with opioids in adults with acute pain in the ED. The authors included eight studies (six RCTs and two observational studies), with a total of 609 ED patients. The major outcome studied was change in patient-reported pain scores 30 minutes after treatment. Both low-dose ketamine (dose range = 0.1 to 0.6 mg/kg IV/SC/IM) and morphine (dose = 0.1 mg/kg IV or 0.5 mg hydromorphone IV) appeared to provide some level of analgesia in individual studies (compiled data were not reported), but no significant difference was demonstrated between the two agents. The study also reported rates of neuropsychological adverse events of 15.4% in the ketamine group and 4.4% in the opioid group (relative risk [RR] = 3.44, 95% CI = 1.81 to 6.55, absolute risk difference [ARD] = 11%, number needed to harm [NNH] = 9) Neuropsychological events were defined as agitation, hallucination, dysphoria, and confusion. The meta-analysis by Ghate et al. included more studies than the meta-analysis by Karlow et al. and a larger sample of patients (n = 609). However, the former included two observational studies, raising concern about the validity of the results and the appropriateness of pooling the data. The studies included in Ghate et al. varied significantly in the dose (0.1 to 0.6 mg/kg) and route of administration (IV/SC/IM) of ketamine, as well as in the use of adjunctive analgesia (one study’s protocol included a dose of midazolam with ketamine). The incorporated studies also varied in the choice of the compared opioid, with one study utilizing 0.5 mg IV hydromorphone and the others 0.1 mg/kg IV morphine. Regarding the meta-analysis by Karlow et al., the clinical heterogeneity among the included trials is a major limitation. One of the studies included only patients with long-bone fractures, while the other two included patients with musculoskeletal pain and abdominal pain, raising the question of whether specific etiologies of pain may respond differently to specific analgesics. Patients receiving ketamine appeared to have more acute adverse events, but it was difficult to draw conclusions about harm endpoints because of the small sample size. Neither of the two meta-analyses included data on the rate of administration of the medications, which has been shown to correlate with adverse side effects.7 It must also be noted that pain control commonly requires redosing and titration. Comparing a single dose of opioid analgesia to a single dose of ketamine thus might not be appropriate for determining the efficacy of either for pain control. In addition, this meta-analysis included only patients with acute pain; the efficacy of ketamine in patients with chronic pain (e.g., chronic back pain) is not addressed here. Finally, the small sample size of the included trials and the meta-analyses limits the validity of the findings. In summary, ketamine appears to be comparable to opioids for acute pain control. However, because of the small sample size of the meta-analyses and limitations of the included trials, we have assigned a color recommendation of yellow (unclear if benefits) to this intervention. Larger high-quality studies are needed to further support the routine use of ketamine for pain control in the ED.

Acute bronchitis is a lower respiratory tract infection, most commonly viral, that accounts for a significant number of health care visits. This review discusses the benefits and harms of antibiotics for acute bronchitis or acute productive cough.

How to cite this article: Hillenkamp J, Wolfson A. Inhaled steroids for asthma after emergency department discharge. 2020;2(1):57-59. doi: 10.17267/2675-021Xevidence.v2i1.2696 Submitted 01/01/2020 Accepted 04/06/2020 Published 05/26/2020 J. Évid-Based Healthc., Salvador, 2020 June;2(1):57-59 Doi: 10.17267/2675-021Xevidence.v2i1.2696 | ISSN: 2675-021X Inhaled steroids for asthma after emergency department discharge Critical Appraisal of Evidence

Chronic obstructive pulmonary disease (COPD), currently the fourth leading cause of death worldwide, is characterized by respiratory symptoms and airflow limitation often caused by long-term exposure to noxious particles or gases, most commonly tobacco.1, 2 Symptoms include dyspnea, cough, and sputum production, and episodes of acute worsening are termed exacerbations. The most common cause of exacerbations is infection, and treatments may include antibiotics, bronchodilators, and systemic corticosteroids. The latter are believed to decrease lower airway obstruction by reducing airway edema. The Cochrane Review3 summarized here analyzed 16 randomized trials of 1,787 subjects (mean age = 68 years, 80% male) comparing corticosteroid to placebo for COPD exacerbation. Patients with COPD of any severity were recruited from outpatient, inpatient, critical care, or emergency department (ED) settings for “acute functional deterioration” consistent with exacerbation. Corticosteroids were oral prednisone or intravenous prednisolone, methylprednisolone, or hydrocortisone. The length of treatment varied from 3 to 19 days; only one study extended beyond 14 days. The three primary outcomes analyzed were treatment failure (≤30 days), relapse (>30 days), and 30-day mortality. Secondary outcomes included length of hospital stay, adverse effects, and hyperglycemia. Treatment failure was defined as an increase in pharmacologic treatment, hospital admission, or return ED visit. The analysis involved nine studies and showed a significant decrease with corticosteroids (odds ratio [OR] = 0.48, 95% confidence interval [CI] = 0.35 to 0.67, absolute risk difference [ARD] = 12.2%, number needed to treat [NNT] = 9, quality of evidence = high). Analysis of three studies comparing oral to parenteral corticosteroids showed no significant difference. Relapse between 1 and 4 months was reported in five studies showing no significant difference between corticosteroid and placebo groups. Thirty-day mortality was assessed in 11 studies and also showed no difference. A secondary endpoint, hospital stay, was reported in two studies and showed a mean decrease of 1.22 days (95% CI = −2.26 to − 0.18) among those in the general inpatient setting treated with corticosteroids. Finally, utilizing eight studies, the Cochrane Review also reported on adverse effects with corticosteroid use. These included a composite of hyperglycemia, GI bleeding, dyspepsia, weight gain, depression, anxiety, psychiatric disorder, insomnia, delirium, secondary infection, and ventilatory associated pneumonia. The effects occurred twice as frequently with corticosteroids as compared to placebo (OR = 2.33, 95% CI = 1.59 to 3.43, ARD = 19.6%, NNH = 6, quality of evidence = high). The quality of the trials included in the Cochrane Review was judged to be good overall. For studies assessing primary endpoints and adverse effects, heterogeneity was minimal, while in two studies reporting hospital length of stay there was substantial heterogeneity. It should be noted that this analysis included studies of ED patients, hospital inpatients, and ICU patients, clinically a very heterogenous group. Although all patients suffered from the same disease process, the effect of corticosteroids may well vary over the spectrum of disease severity. This is an area where further studies would be beneficial. Among the 16 studies included, there was significant variation in corticosteroids used, doses prescribed, and duration of treatment. However, in the most recent 2020 Gold Report1 5 to 7 days of corticosteroid treatment is considered adequate. Moreover, while the meta-analysis showed no survival benefit of corticosteroids, there appeared to be a clear benefit in preventing treatment failure. One in six patients who received corticosteroids experienced adverse effects; however, severity of the events were not described. Subgroup analysis revealed that one in seven were noted to be hyperglycemic though this resolved with cessation of the drug. Short-term hyperglycemia is not a meaningful patient-centered effect. It is reasonable to expect that the difference in the reported composite outcome would not persist if hyperglycemia were not included. In conclusion, the Cochrane Review discussed here quantifies reported harms and benefits associated with corticosteroids in acute COPD exacerbation. Short-course corticosteroids reduced short-term (2- to 30-day) treatment failure, and patient-centered adverse events appeared to be uncommon. In critical care settings, and with use of intravenous corticosteroids, the adverse event profile may be more significant, although these data are limited. We have thus assigned a color recommendation of green (benefits> harms) to the use of corticosteroids in the treatment of acute exacerbations of COPD.

Objective To study patients who initially presented to the Emergency Department with acute renal colic to determine if patient-reported stone passage detects stone expulsion as accurately as follow-up computed tomography (CT) scan. Methods This is a secondary analysis of a multi-center prospective trial of patients diagnosed by a CT scan with a symptomatic ureteral stone <9 mm in diameter. Patient-reported stone passage, defined as capture or visualization of the stone, was compared to CT scan-confirmed passage performed 29-36 days after initial presentation. Results Four-hundred-three patients were randomized in the original study and 21 were excluded from this analysis because they were lost to follow-up or received ureteroscopic surgery. Of the 382 remaining evaluable patients, 237 (62.0%) underwent a follow-up CT scan. The mean (standard deviation) diameter of the symptomatic kidney stone was 3.8 mm (1.4). In those who reported stone passage, 93.8% (91/97) demonstrated passage of the symptomatic ureteral stone on follow-up CT. Of patients who did not report stone passage, 72.1% (101/140) demonstrated passage of their stone on follow-up CT. Conclusions For patients who report capture or visualization of a ureteral stone, a follow-up CT scan may not be needed to verify stone passage. For patients who do not capture their stone or visualize stone passage, imaging should be considered to confirm passage.

Academic Emergency MedicineVolume 27, Issue 12 p. 1358-1359 The Brass Tacks: Concise Reviews Of Published EvidenceFree Access Noninvasive Positive Pressure Ventilation for Cardiogenic Pulmonary Edema Brian M. Killeen MD, Corresponding Author Brian M. Killeen MD Killeenbm2@upmc.edu orcid.org/0000-0003-3892-2652 Department of Emergency Medicine, University of Pittsburgh, Pittsburgh, PA Address for correspondence and reprints: Brian M. Killeen, MD; e-mail: Killeenbm2@upmc.edu.Search for more papers by this authorAllan B. Wolfson MD, Allan B. Wolfson MD orcid.org/0000-0002-6101-9392 Department of Emergency Medicine, University of Pittsburgh, Pittsburgh, PASearch for more papers by this author Brian M. Killeen MD, Corresponding Author Brian M. Killeen MD Killeenbm2@upmc.edu orcid.org/0000-0003-3892-2652 Department of Emergency Medicine, University of Pittsburgh, Pittsburgh, PA Address for correspondence and reprints: Brian M. Killeen, MD; e-mail: Killeenbm2@upmc.edu.Search for more papers by this authorAllan B. Wolfson MD, Allan B. Wolfson MD orcid.org/0000-0002-6101-9392 Department of Emergency Medicine, University of Pittsburgh, Pittsburgh, PASearch for more papers by this author First published: 16 April 2020 https://doi.org/10.1111/acem.13986 The authors have no relevant financial information or potential conflicts to disclose. Editor’s Note: Brass Tacks are concise reviews of published evidence. This series is a result of collaboration between Academic Emergency Medicine and the evidence-based medicine website, www.TheNNT.com. For inquiries please contact the section editor, Shahriar Zehtabchi, MD (e-mail: shahriar.zehtabchi@downstate.edu). AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat NNT color recommendation Green (benefits > harms) Summary heading Reduces hospital mortality and endotracheal intubations Benefits in NNT 1 in 17 were helped (deaths prevented) 1 in 13 were helped (endotracheal intubations prevented) Benefits in percentages 5.9% lower risk of death 7.7% lower rate of endotracheal intubations Harms in NNT (NNH) No one was harmed Harms in percentages No one was harmed Efficacy endpoints Mortality, need for endotracheal intubation Harm endpoints Acute myocardial infarction, increased length of hospital stay Who was in the studies 2664 adult participants (>18 years of age) with respiratory distress due to acute cardiogenic pulmonary edema not requiring immediate mechanical ventilation treated either prehospital, in the ED, or in the intensive care unit NARRATIVE Acute cardiogenic pulmonary edema (ACPE) has traditionally been treated pharmacologically, with a combination of nitrates, diuretics, morphine, and inotropes. Since the introduction of noninvasive positive pressure ventilation (NIPPV), a method of providing mechanical ventilation that does not bypass the upper airway, this modality has been widely used as an important addition to the acute care of ACPE. NIPPV encompasses both CPAP (continuous positive airway pressure) and BiPAP (bilevel positive airway pressure), two slightly varied modalities of breathing support where oxygen and additional pressure are delivered most commonly through a facial mask. CPAP delivers a constant pressure throughout the respiratory cycle, while BiPAP delivers independent levels of pressure support set by the clinician for both inspiratory and expiratory phases. Noninvasive positive pressure ventilation provides multiple benefits in ACPE including improving respiratory dynamics, hemodynamic effects, and decreasing work of breathing. Beneficial respiratory effects include recruitment of additional alveolar units for gas exchange, correction of hypoxemia, reduction in hypoxia-induced pulmonary vascular resistance, and improvement in lung compliance. Hemodynamic effects are complex, however, and ultimately lead to a reduction in afterload and increased LV emptying. Decreasing work of breathing will in turn reduce myocardial oxygen demand and allow for improvement in overall cardiopulmonary dynamics. A 2013 meta-analysis of patients with ACPE found no significant differences in clinical outcomes when comparing CPAP to BiPAP.1 Common contraindications to the use of NIPPV include cardiac or respiratory arrest, inability to cooperate or to remove own mask in an emergency, inability to tolerate or clear secretions, facial trauma, high aspiration risk, and anticipation of a prolonged duration of mechanical ventilation. Canadian and European guidelines differ in their recommendations regarding NIPPV; Canadian guidelines suggest initiating NIPPV only if hypoxia persists despite standard medical care, whereas European guidelines recommend early initiation of NIPPV for those presenting with tachypnea (RR > 25) and hypoxia (SpO2 < 90). American guidelines do not provide clear recommendations for the treatment of ACPE.2 This is an updated review utilizing the 2019 Cochrane review by Berbenetz et al.,3 which sought to evaluate the safety and effectiveness of NIPPV compared to standard medical care for adults with ACPE. The review included 24 studies with 2,664 adult participants (>18 years of age) with respiratory distress due to ACPE who did not require immediate mechanical ventilation. Patients in the included studies were randomized to standard medical care or standard medical care plus NIPPV. NIPPV included both continuous (CPAP) and bilevel (BiPAP) positive pressure support. Standard medical care was supplemental oxygen and pharmacologic treatments that included various combinations of loop diuretics, nitrates, opioids, and inotropes. The median follow-up for determining hospital mortality was 13 days and for endotracheal intubation was 1 day. In the meta-analysis, NIPPV was associated with statistically significantly lower mortality than standard care (relative risk [RR] = 0.65, 95% confidence interval [CI] = 0.51 to 0.82, absolute risk difference [ARD] = 5.9%, number needed to treat [NNT] = 17, quality of evidence = low). NIPPV was also associated with lower intubation rates (RR = 0.49, 95% CI = 0.38 to 0.62, ARD = 7.7%, NNT = 13, quality of evidence = moderate).3 The risks of myocardial infarction and increased length of stay (potential harms) were not significantly different between the groups. Two RCTs reported a shortened ICU length of stay for NIPPV. However, the quality of the pooled evidence was very low. Other risks or limitations of NIPPV such as inability to tolerate the mask, aspiration, etc., were inconsistently defined and reported in the included trials. CAVEATS Among the 24 studies included in the meta-analysis, there was some variation in what was considered the standard medical care against which NIPPV was compared. The optimal dosing of diuretics was not defined, and it is possible that the benefits of NIPPV might have been different (reduced or null), based on the clinician providing the care. In addition, the studies included in the analysis followed different protocols for intubation, and it is unclear if this affected the reduction in intubation rates appreciated in the NIPPV group. It is worth noting that patients presenting with need for immediate intubation, depressed GCS scores, hypotension, need for PCI, and evidence of infectious sources were broadly excluded from the studies. It remains to be seen if there is a certain phenotype of patient with ACPE (e.g., more severe ACC/AHA heart failure grade) who might benefit more from the initiation of NIPPV. These are all potential areas for further research. The evidence for reduced intubation was of moderate quality and for reduction in mortality and mean length of hospital stay was of low quality. Overall there was low statistical heterogeneity among studies. Not all patients with ACPE are suitable for NIPPV and the contraindications must be considered prior to initiating therapy; these contraindications include obtunded and uncooperative patients, poor mask fit, facial trauma/burns, facial/esophageal/gastric surgeries, and vomiting or inability to handle secretions. In conclusion, NIPPV in ACPE (for those not requiring immediate ETI) appears to provide beneficial effects, including reduced mortality and decreased intubation rates, without an apparent increase in clinically significant harms. We thus assign a color rating of green (benefits > harms) to this treatment. References 1Li H, Hu C, Xia J, et al. A comparison of bilevel and continuous positive airway pressure noninvasive ventilation in acute cardiogenic pulmonary Edema. Am J Emerg Med 2013; 31: 1322– 7. 2Yancy CW, Jessup M, Bozkurt B, et al. ACCF/AHA guideline for the management of heart failure. Circulation 2013; 128: 2013. 3Berbenetz N, Wang Y, Brown J, et al. Non-invasive positive pressure ventilation (CPAP or bilevel NPPV) for cardiogenic pulmonary oedema. Cochrane Database Syst Rev 2019;(6): CD005351. Volume27, Issue12December 2020Pages 1358-1359 This article also appears in:The Brass Tacks ReferencesRelatedInformation

1 in 63 were helped (clinically important gastrointestinal bleeding was prevented) when compared to placebo No one was helped (no death was prevented) when compared to placebo 1.6% lower risk of clinically important gastrointestinal bleeding (compared to placebo) No one was helped (no death was prevented) Prevention of clinically important gastrointestinal bleeding All-cause mortality Pneumonia Clostridium difficile infection (the study was unable to state a network estimate for this outcome) Stress ulceration is a term coined to explain a form of upper gastrointestinal (GI) bleeding seen in critically ill patients, who are commonly defined as individuals admitted to an intensive care unit (ICU). Stress ulceration was first noted in the 1960s when a series of postmortem examinations performed on critically ill individuals revealed gastric mucosal lesions.1 Proposed mechanisms for the formation of stress ulceration include reduced blood flow in the vicinity of ulcer formation, ischemia of the GI mucosa, and reperfusion injury.1 Earlier studies indicated that overt GI bleeding occurred in up to 25% of critically ill patients and more recent literature estimates the incidence of clinically important GI bleeding to be in the range of 1% to 4%.1, 2 The network meta-analysis discussed here3, 4 was designed to evaluate the safety and efficacy of medications commonly used for stress ulcer prophylaxis in critically ill patients with a focus on the prevention of clinically important and overt GI bleeding, all-cause mortality, the development of pneumonia, and the development of Clostridium difficile infections (CDIs). This network meta-analysis focused on both clinically important GI bleeding and overt GI bleeding.3, 4 A network meta-analysis differs from a conventional meta-analyses in that therapies that have not been directly compared with each other in randomized controlled trials could be compared (direct and indirect comparison). Clinically important GI bleeding was defined as “evidence of upper GI bleeding with any of the following: significant hemodynamic changes not explained by other causes, need for transfusion of more than two units of blood, significant decrease in hemoglobin level, evidence of bleeding on GI endoscopy, or need for surgery to control the bleeding.”3, 4 Overt GI bleeding was defined as having coffee-ground emesis or aspirate, melena, hematemesis, or hematochezia.3, 4 However, in this evidence-based review, we only report the efficacy data for clinically important bleeding. When compared to placebo, the use of proton pump inhibitors (PPIs) in critically ill patients was associated with a significant reduction in the risk of clinically important GI bleeding in this network meta-analysis (odds ratio [OR] = 0.24, 95% confidence interval [CI] = 0.10 to 0.60, absolute risk difference = 1.6%, number needed to treat [NNT] = 63, moderate-quality evidence).3, 4 However, the administration of PPIs was not associated with a significant reduction in all-cause mortality. This network meta-analysis also compared other therapies including histamine-2-receptor antagonists (H2RA) and sucralfate with PPIs. The analysis showed the following results for reduction in clinically significant GI bleeding: PPI versus H2RA (OR = 0.38, 95% CI = 0.20 to 0.73, NNT = 125, moderate-quality evidence) and PPI versus sucralfate (OR = 0.30, 95% CI = 0.13 to 0.69, NNT = 83, moderate-quality evidence).3, 4 In this network analysis, PPIs were ranked first for the prevention of clinically important GI bleeding. The authors of this study mentioned that the use of PPIs in critically ill patients is likely to be associated with a higher risk of developing pneumonia. PPIs were associated with a statistically significant increase in developing pneumonia when compared to sucralfate (OR = 1.65, 95% CI = 1.20 to 2.27, NNH = 28).3, 4 In addition, the data trended toward a higher risk of developing pneumonia when comparing PPIs to H2RAs and to placebo but these data are not statistically significant as the associated CIs cross 1.0.3, 4 The study authors expressed their concern regarding an increased risk of developing pneumonia in critically ill patients treated with PPIs by citing a potential 3.1% absolute increase.3, 4 Nevertheless, the presented data do not support an increased risk of developing pneumonia when comparing PPIs to H2RAs or to placebo. In this study, the data pertaining to the risk of developing a CDI was not sufficient for analysis.3, 4 Although this study included a total of 57 trials, only one of them reported CDIs so a network estimate for this outcome could not be made.3, 4 Overall, this large network meta-analysis found moderate-quality evidence that prophylaxis with PPIs or H2RAs reduced clinically important GI bleeding, when compared to no prophylaxis.3, 4 Additionally, PPIs appear to be more efficacious than both H2RAs and sucralfate in terms of reducing clinically important GI bleeding. In this study, PPIs were associated with an increased chance of developing pneumonia when compared to sucralfate but not when compared to H2RAs or placebo. In addition, there was insufficient data to evaluate the risk of developing a CDI. The PPIs used in the studies included in this network meta-analysis were omeprazole, pantoprazole, esomeprazole, rabeprazole, and lansoprazole and these medication were administered intravenously or orally or via nasogastric tube. A recent study published in the New England Journal of Medicine studied the use of pantoprazole versus placebo in adult ICU patients at risk for GI bleeding.5 This study concluded that the number of clinically important events (myocardial ischemia, clinically important GI bleeding, pneumonia, and CDI) and the 90-days mortality (primary outcome of the study) were similar between the study and the control groups.5 An editorial in the same journal maintained that prophylaxis with a PPI should be reserved for patients that are significantly ill and are at exceedingly high risk of deterioration from clinically significant GI bleeding.6 Although a total of 57 trials were included in the primary meta-analysis by Alhazzani et al.,3, 4 only 16 trials had a low risk of bias. Of the remaining trials, 30 had a high risk of bias and 11 had an unclear risk of bias. However, the overall quality of the evidence was rated as moderate. The categorization and diagnosis of pneumonia in this study was a limiting factor as well.3, 4 The majority of the included trials used a combination of clinical, radiographic, and microbiologic criteria to diagnose pneumonia, but no standard was set and the definition of pneumonia varied among the studies. Also, some of the trials that analyzed sucralfate predated the widespread use of pneumonia prevention strategies in critically ill patients, thus casting doubt on the validity of the results in the context of current ICU management. An additional caveat of this study relates to CDIs.3, 4 Recent studies have suggested that PPIs are associated with an increased risk of CDI.7 The primary study only had one trial that included CDIs and thus was unable to state a network estimate for this outcome. Of the 214 randomized patients in this single trial, only one patient developed a CDI, which indicates that there is insufficient power to address this topic.8 Another limiting factor of this meta-analysis is the heterogeneity in defining GI bleeding, as each study had different inclusion criteria. It is also important to note that study subjects included in this network meta-analysis likely had different baseline risks for GI bleeding. Although this network meta-analysis includes a variety of critically ill patients in various intensive care settings, the efficacy of the PPIs might be different in higher risk subgroups of patients. In conclusion, administration of PPIs for stress ulcer prophylaxis in critically ill patients is associated with reduced clinically important upper GI bleeding without improving survival. Due to the aforementioned, we are assigning a yellow (unclear if benefits outweigh harms) color recommendation. Additional high-quality studies are needed which compare the effects of these agents to develop more robust evidence regarding the efficacy and harm endpoints discussed.

Objective: The aim of this study was to describe and characterize the analgesic and opioid use for patients discharged from the emergency department (ED) with renal colic due to ureteral stone. Methods: This is a secondary analysis of a multicenter prospective trial of ED patients diagnosed by CT scan as having a symptomatic ureteral stone <9 mm in diameter. Participants were contacted after randomization on days 2, 7, 15, 20, and 29 and reported opioid and nonopioid analgesic use and stone passage. CT scan was repeated on day 29 to 36 to confirm passage. Results: Of 403 participants, 314 (77.9%) took an analgesic after discharge and 199 (49.4%) took opioids. Opioids were more commonly used by younger patients (p = 0.04) and those with a family history of stones (p = 0.003). Stone size and tamsulosin use were not associated with analgesic utilization. Shorter time to passage and more distal stone location were associated with less analgesic and opioid use. For those who did not expel a stone, 55.0% took opioids at any time, and for those who did expel a stone, 31.9% took opioids before the stone was expelled and 15.7% took opioids at any time after the stone was expelled. Conclusions: Factors associated with increased use of analgesics in patients discharged from the ED include a longer time to stone passage, no spontaneous passage, and proximal position of the stone in the ureter. Some patients continued to use analgesics after the stone had passed, but most stopped using analgesics by day 29. The study has been registered at https://clinicaltrials.gov (NCT00382265).

Post herpetic neuralgia (PHN) is a condition of persistent, refractory pain in an area previously affected by an acute herpes zoster infection. Age remains an important risk factor for the development of PHN, with 40% of patients older than 50 years and 75% of patients 75 years and older developing PHN after an initial episode of shingles.1 Persistent pain can lead to significant long-term problems such as depression, altered activities of daily living, and anorexia.1 Prior systematic reviews have suggested that treatment with antivirals within 72 hours of the onset of rash may reduce the incidence or duration of PHN. The Cochrane systematic review discussed here is an update of a previous Cochrane review from 2009, and draws no new conclusions compared to the earlier review. The current review included 6 double-blinded randomized placebo-controlled trials and a total of 1211 patients. Five of these trials evaluated oral acyclovir, and the sixth trial evaluated famciclovir. Fifteen other studies were excluded for reasons such as a short follow-up interval, lack of placebo control, or initiation of treatment beyond 72 hours from the onset of rash. This review found no significant difference between acyclovir and placebo in the incidence of PHN at 4 months (risk ratio (RR): 0.75, 95% confidence interval (CI) 0.51 to 1.11) or at 6 months (RR: 1.05, 95% CI 0.87 to 1.27). The single study that evaluated famciclovir also failed to show reduced incidence compared to placebo. One trial comparing placebo and acyclovir with 46 participants reported statistically significant lower mean pain scores between two and six months using the VAS validated pain scale. The most common adverse drug events included nausea, vomiting, and headache, but these were not significantly different than in patients who received placebo. The Cochrane review concludes that there is high quality evidence that acyclovir does not reduce the incidence of PHN and suggests that further trials should focus on famciclovir and other antiviral agents since there is currently insufficient evidence to determine their efficacy. This article is protected by copyright. All rights reserved.

Background: Although "spear tackling" is known to be a risk factor for cervical spine injury due to axial loading of the neck, and although this technique was officially banned from American football in 1976, football-associated cervical spine injuries continue to be reported. This case highlights the importance of recognizing high-risk mechanisms for cervical spine injury, and specifically the danger of spear tackling among football players at all levels. Case Report: A 16-year-old male high school football player presented to the pediatric emergency department for a neck injury sustained after spear tackling during a football game. He had no neurologic symptoms and met the NEXUS criteria for omitting x-ray evaluation. However, the description of spear tackling as the mechanism of injury led to the ordering of cervical radiographs, which revealed a C5 fracture. The patient was ultimately taken to the operating room for internal fixation, with a final surgical diagnosis of a C5 teardrop fracture. On outpatient follow-up at 1 year, the patient has had no neurologic sequelae. Why Should an Emergency Physician Be Aware of This?: This case serves as a reminder that all evaluations of trauma patients should begin with an attempt to determine, as precisely as possible, the mechanism that was in play at the time of injury. The reassurance provided by a normal physical examination may be misleading. Spear tackling is not an uncommonly encountered cause of injury in American football, despite the practice being prohibited since a rule change in 1976. Continued education and increased awareness of the association of axial load injury with spear tackling may make it possible to avoid missing a potentially devastating cervical spine injury. (C) 2018 Elsevier Inc. All rights reserved.

Acute bacterial conjunctivitis is an infective condition frequently resulting in mucopurulent ocular discharge, bulbar and palpebral injection, and discomfort. It may be difficult to differentiate between viral and bacterial conjunctivitis on clinical grounds, and swabbing eyes for cultures is not considered clinically practical. Therefore, although most cases are self-limited, antibiotics are typically given based on the belief that they decrease time to recovery, reduce sight-threatening complications, and reduce the rate of relapse. This review, an update of a previous Cochrane review from 2006, included 11 randomized control trials totaling 3,673 patients with bacterial conjunctivitis, whereas the prior review included five randomized control trials and 1,034 patients. The review included trials that made the diagnosis of bacterial conjunctivitis based on either clinical or microbiologic grounds.1 Clinical criteria required varied but generally included ocular discharge and conjunctival injection. Two of the trials required microbiologically proven bacterial conjunctivitis with the remainder making the diagnosis on clinical grounds. The primary outcomes of this review included both clinical and microbiologic cure rates.1 How cure was assessed varied between trials but, in general, it was defined by absence of symptoms or microbiologic eradication. Data analysis from the trials indicated improved early (2- to 5-day) clinical cure rate of 40% (risk ratio [RR] = 1.36, 95% confidence interval [CI] = 1.15–1.61) and microbiologic cure (RR = 1.55, 95% CI = 1.37–1.76). At 6 to 10 days (considered the “late” time point) antibiotics continued to show clinical benefit in clinical and microbiologic cure (RR = 1.21, 95% CI = 1.10–1.33; and RR = 1.37, 95% CI = 1.24–1.52 respectively). The absolute risk difference for early and late clinical cure were 11 and 9%, respectively, corresponding to NNTs of 9 and 11.1 Among subjects in the placebo groups, 30% achieved clinical cure by day 5, and 41% of cases had resolved by days 6 to 10. No serious outcomes were reported in either placebo groups or treatment groups.1 Of the 11 included trials, two primary care–based trials were judged by the reviewers to be of high quality, with the remainder graded as being of poor quality. Nine of the 11 studies were judged to have a high risk of bias. Two of the 11 trials were done at primary care sites, and the remainder were performed at specialty care sites, suggesting the possibility of referral bias.1 Interestingly, the natural history of bacterial conjunctivitis could not be inferred from the trials, as some of the trials used placebo eye drops containing an antiseptic that when applied three to four times a day was likely to have some clinical effect. Moreover, all of the included studies utilized different antibiotic regimens, which was a major contributor to the high degree of heterogeneity of the trials. Of note, the majority of the more recent trials utilized fluoroquinolones. Other factors contributing to heterogeneity included patient age, method of diagnosis, and definition of outcome measures. There was no recommendation regarding which antibiotic or duration of treatment was superior. Also of note, only two of the trials required microbiologic evidence to make the diagnosis of bacterial conjunctivitis, while the remainder allowed for bacterial conjunctivitis to be diagnosed clinically. This is a potential limitation of the study as it is possible that other forms of conjunctivitis were being treated. In this review, 30% of the placebo groups achieved clinical cure by day 5, and 41% had resolved at 6 to 10 days. This suggests that the benefits of antibiotics were reflected in the rate of resolution of conjunctivitis but not in a reduction in complications, since no serious outcomes were reported in treatment or placebo groups.1 Given that complications such as orbital cellulitis are rare, however, a larger trial would be necessary to assess the efficacy of antibiotics in terms of reduction in complications. In conclusion, despite the limited existing evidence (mostly poor quality with high risk of bias) the demonstration of consistent positive outcomes supports the use of topical antibiotics to treat bacterial conjunctivitis. The risk of adverse events associated with this treatment appear to be minimal. Therefore, we have assigned a color rating of green (benefits > harms) to this treatment. Editor's Note: Brass Tacks are concise reviews of published evidence. This series is a result of collaboration between Academic Emergency Medicine and the evidence-based medicine website, www.TheNNT.com. For inquiries please contact the section editor, Shahriar Zehtabchi, MD ([email protected]).