John P. Haran

A comparison of ultrasound-guided three-in-one femoral nerve block versus parenteral opioids alone for analgesia in emergency department patients with hip fractures: a randomized controlled trial.

OBJECTIVES The primary objective was to compare the efficacy of ultrasound (US)-guided three-in-one femoral nerve blocks to standard treatment with parenteral opioids for pain control in elderly patients with hip fractures in the emergency department (ED). METHODS A randomized controlled trial was conducted at a large urban academic ED over an 18-month period. A convenience sample of older adults (age ≥ 55 years) with confirmed hip fractures and moderate to severe pain (numeric rating score ≥ 5) were randomized to one of two treatment arms: US-guided three-in-one femoral nerve block plus morphine (FNB group) or standard care, consisting of placebo (sham injection) plus morphine (SC group). Intravenous (IV) morphine was prescribed and dosed at the discretion of the treating physician; physicians were advised to target a 50% reduction in pain or per-patient request. The primary outcome measure of pain relief, or pain intensity reduction, was derived using the 11-point numerical rating scale (NRS) and calculated as the summed pain-intensity difference (SPID) over 4 hours. Secondary outcome measures included the amount of rescue analgesia and occurrence of adverse events (respiratory depression, hypotension, nausea, or vomiting). Outcome measures were compared between groups using analysis of variance for continuous variables and Fishers exact test for categorical data. RESULTS Thirty-six patients (18 in each arm) completed the study. There was no difference between treatment groups with respect to age, sex, fracture type, vital signs (baseline and at 4 hours), ED length of stay (LOS), pre-enrollment analgesia, or baseline pain intensity. In comparing pain intensity at the end of the study period, NRS scores at 4 hours were significantly lower in the FNB group (p < 0.001). Over the 4-hour study period, patients in the FNB group experienced significantly greater overall pain relief than those in the SC group, with a median SPID of 11.0 (interquartile range [IQR] = 4.0 to 21.8) in the FNB group versus 4.0 (IQR = -2.0 to 5.8) in the SC group (p = 0.001). No patient in the SC group achieved a clinically significant reduction in pain. Moreover, patients in the SC group received significantly more IV morphine than those in the FNB group (5.0 mg, IQR = 2.0 to 8.4 mg vs. 0.0 mg, IQR = 0.0 to 1.5 mg; p = 0.028). There was no difference in adverse events between groups. CONCLUSIONS Ultrasound-guided femoral nerve block as an adjunct to SC resulted in 1) significantly reduced pain intensity over 4 hours, 2) decreased amount of rescue analgesia, and 3) no appreciable difference in adverse events when compared with SC alone. Furthermore, standard pain management with parenteral opioids alone provided ineffective pain control in our study cohort of patients with severe pain from their hip fractures. Regional anesthesia has a role in the ED, and US-guided femoral nerve blocks for pain management in older adults with hip fractures should routinely be considered, particularly in cases of refractory or severe pain.

All purulence is local - epidemiology and management of skin and soft tissue infections in three urban emergency departments

BackgroundSkin and soft tissue infection (SSTIs) are commonly treated in emergency departments (EDs). While the precise role of antibiotics in treating SSTIs remains unclear, most SSTI patients receive empiric antibiotics, often targeted toward methicillin-resistant Staphylococcus aureus (MRSA). The goal of this study was to assess the efficiency with which ED clinicians targeted empiric therapy against MRSA, and to identify factors that may allow ED clinicians to safely target antibiotic use.MethodsWe performed a retrospective analysis of patient visits for community-acquired SSTIs to three urban, academic EDs in one northeastern US city during the first quarter of 2010. We examined microbiologic patterns among cultured SSTIs, and relationships between clinical and demographic factors and management of SSTIs.ResultsAntibiotics were prescribed to 86.1% of all patients. Though S. aureus (60% MRSA) was the most common pathogen cultured, antibiotic susceptibility differed between adult and pediatric patients. Susceptibility of S. aureus from ED SSTIs differed from published local antibiograms, with greater trimethoprim resistance and less fluoroquinolone resistance than seen in S. aureus from all hospital sources. Empiric antibiotics covered the resultant pathogen in 85.3% of cases, though coverage was frequently broader than necessary.ConclusionsThough S. aureus remained the predominant pathogen in community-acquired SSTIs, ED clinicians did not accurately target therapy toward the causative pathogen. Incomplete local epidemiologic data may contribute to this degree of discordance. Future efforts should seek to identify when antibiotic use can be narrowed or withheld. Local, disease-specific antibiotic resistance patterns should be publicized with the goal of improving antibiotic stewardship.

Cytokine markers as predictors of type of respiratory infection in patients during the influenza season

OBJECTIVE The objective of this study is to characterize the cytokine response among patients presenting with an influenza-like illness who are infected with the influenza virus, a bacterial pneumonia, or another viral infection. We hypothesize that there are differences in proinflammatory and anti-inflammatory cytokines in relation to cytokines associated with the humoral response during viral and bacterial respiratory infections. METHODS We enrolled adults who presented to an urban academic emergency department during the 2008 to 2011 influenza seasons with symptoms of fever and a cough. Subjects had nasal aspirates tested by viral culture, and peripheral blood drawn to quantify cytokine concentrations. Cytokine concentrations were compared between groups using the Wilcoxon rank sum test, and receiver operating characteristic curves were calculated. RESULTS A total of 80 patients were enrolled: 40 with influenza infection, 14 patients with a bacterial pneumonia as determined by infiltrate on chest x-ray, and 26 patients negative for influenza infection and infiltrate. There were differences between the bacterial pneumonia group, and all other viral infections grouped together with regard to interleukin (IL) 4 (2.66 vs 16.77 pg/mL, P < .001), IL-5 (20.57 vs 57.57 pg/mL, P = .006), IL-6 (403.06 vs 52.69 pg/mL, P < .001), granulocyte macrophage colony-stimulating factor (18.26 vs 66.80 pg/mL, P < .001), and interferon γ (0.0 vs 830.36 pg/mL, P < .001). Interleukin 10 concentrations were elevated in patients with influenza (88.69 pg/mL) compared with all other groups combined (39.19 pg/mL; P = .003). CONCLUSION Cytokines IL-4, IL-5, IL-6, granulocyte macrophage colony-stimulating factor, and interferon γ may serve as distinct markers of bacterial infection in patients with an influenza-like illness, whereas IL-10 is uniquely elevated in influenza patients.

C-reactive protein as predictor of bacterial infection among patients with an influenza-like illness

OBJECTIVE During the influenza season patients are labeled as having an influenza-like illness (ILI) which may be either a viral or bacterial infection. We hypothesize that C-reactive protein (CRP) levels among patients with ILI diagnosed with a bacterial infection will be higher than patients diagnosed with an influenza or another viral infection. METHODS We enrolled a convenience sample of adults with ILI presenting to an urban academic emergency department from October to March during the 2008 to 2011 influenza seasons. Subjects had nasal aspirates for viral testing, and serum CRP. Bacterial infection was determined by positive blood cultures, radiographic evidence of pneumonia, or a discharge diagnosis of bacterial infection. Receiver operating characteristic curve, analysis of variance, and Student t test were used to analyze results. RESULTS Over 3 influenza seasons there were 131 total patients analyzed (48 influenza infection, 42 other viral infection and 41 bacterial infection). CRP values were 25.65 mg/L (95% CI, 18.88-32.41) for influenza, 18.73 mg/L (95% CI, 12.97-24.49) for viral and 135.96 mg/L (95% CI, 99.38-172.54) for bacterial. There was a significant difference between the bacterial group, and both the influenza and other viral infection groups (P < .001). The receiver operating characteristic curve for CRP as a determinant of bacterial infection had an area under the curve of 0.978, whereby a CRP value of <20 had a sensitivity of 100% and >80 had a specificity of 100%. CONCLUSION C-reactive protein is both a sensitive and specific marker for bacterial infection in patients presenting with ILI during the influenza season.

Paecilomyces lilacinus olecranon bursitis in an immunocompromised host: case report and review

Paecilomyces lilacinus is a little-known mold that causes rare cases of invasive infections in humans regardless of their immune status. We present a unique case in an immunocompromised host with olecranon bursitis because of multidrug-resistant P. lilacinus treated with systemic ketoconazole therapy and surgical debridement. Recognition of this fungus is difficult initially because of its appearance, which can be confused with that of other fungi. Once this organism has been identified, it is recommended that antifungal susceptibility testing be obtained to guide appropriate therapy. Combination of therapeutic modalities requires case-by-case assessment. Surgical debridement and removal of prosthesis may be indicated. Although P. lilacinus can be a laboratory contaminant, in our case, causation was established as the organism grew in repeated cultures, sufficient to confirm a fungal origin for his bursitis.

Immunization with cross-conserved H1N1 influenza CD4+ T-cell epitopes lowers viral burden in HLA DR3 transgenic mice

The emergence of the pandemic H1N1 strain of influenza in 2009 was associated with a unique w-shaped age-related susceptibility curve, with higher incidence of morbidity and mortality among young persons and lower incidence among older persons, also observed during the 1918 influenza pandemic. Pre-existing H1N1 antibodies were not cross-reactive with the prior seasonal vaccine, forcing influenza experts to scramble to develop a new vaccine specific for the pandemic virus. We hypothesized that response to T-cell epitopes that are cross-conserved between pandemic H1N1 and the 2008 seasonal influenza vaccine strains might have contributed to partial protection from clinical illness among older adults, despite the lack of cross-reactive humoral immunity. Using immunoinformatics tools, we previously identified hemagglutinin and neuraminidase epitopes that were highly conserved between seasonal and pandemic H1N1. Here, we validated predicted CD4+ T-cell epitopes for their ability to bind HLA and to stimulate interferon-γ production in peripheral blood mononuclear cells from a cohort of donors presenting with influenza-like illness during the 2009 pandemic and a separate cohort immunized with trivalent influenza vaccine in 2011. A limited-epitope heterologous DNA-prime/peptide-boost vaccine composed of these sequences stimulated immune responses and lowered lung viral loads in HLA DR3 transgenic mice challenged with pandemic 2009 H1N1 influenza. Cross-priming with conserved influenza T-cell epitopes such as these may be critically important to T cell-mediated protection against pandemic H1N1 in the absence of cross-protective antibodies.

Factors influencing the development of antibiotic associated diarrhea in ED patients discharged home: risk of administering IV antibiotics.

OBJECTIVE Antibiotic-associated diarrhea (AAD) and Clostridium difficile infection (CDI) are well-known outcomes from antibiotic administration. Because emergency department (ED) visits frequently result in antibiotic use, we evaluated the frequency of AAD/CDI in adults treated and discharged home with new prescriptions for antibiotics to identify risk factors for acquiring AAD/CDI. METHODS This prospective multicenter cohort study enrolled adult patients who received antibiotics in the ED and were discharged with a new prescription for antibiotics. Antibiotic-associated diarrhea was defined as 3 or more loose stools for 2 days or more within 30 days of starting the antibiotic. C difficile infection was defined by the detection of toxin A or B within this same period. We used multivariate logistic regression to assess predictors of developing AAD. RESULTS We enrolled and followed 247 patients; 45 (18%) developed AAD, and 2 (1%) developed CDI. Patients who received intravenous (IV) antibiotics in the ED were more likely to develop AAD/CDI than patients who did not: 25.7% (95% confidence interval [CI], 17.4-34.0) vs 12.3% (95% CI, 6.8-17.9). Intravenous antibiotics had adjusted odds ratio of 2.73 (95% CI, 1.38-5.43), and Hispanic ethnicity had adjusted odds ratio of 3.04 (95% CI, 1.40-6.58). Both patients with CDI had received IV doses of broad-spectrum antibiotics. CONCLUSION Intravenous antibiotic therapy administered to ED patients before discharge was associated with higher rates of AAD and with 2 cases of CDI. Care should be taken when deciding to use broad-spectrum IV antibiotics to treat ED patients before discharge home.

Antigen-specific H1N1 influenza antibody responses in acute respiratory tract infections and their relation to influenza infection and disease course ,

BACKGROUND Early antibody responses to influenza infection are important in both clearance of virus and fighting the disease. Acute influenza antibody titers directed toward H1-antigens and their relation to infection type and patient outcomes have not been well investigated. OBJECTIVE Using hemagglutination inhibition (HI) assays, we aimed to characterize the H1-specific antibody titers in patients with influenza infection or another respiratory infection before and after the H1N1-pandemic influenza outbreak. Among patients with acute influenza infection we related duration of illness, severity of symptoms, and need for hospitalization to antibody titers. METHODS There were 134 adult patients (average age 34.7) who presented to an urban academic emergency department (ED) from October through March during the 2008-2011 influenza seasons with symptoms of fever and a cough. Nasal aspirates were tested by viral culture, and peripheral blood serum was run in seven H1-subtype HI assays. RESULTS Acutely infected influenza patients had markedly lower antibody titers for six of the seven pseudotype viruses. For the average over the seven titers (log units, base 2) their mean was 7.24 (95% CI 6.88, 7.61) compared with 8.60 (95% CI 8.27, 8.92) among patients who had a non-influenza respiratory illness, p<0.0001. Among patients with seasonal influenza infection, titers of some antibodies correlated with severity of symptoms and with total duration of illness (p<0.02). CONCLUSION In patients with acute respiratory infections, lower concentrations of H1-influenza-specific antibodies were associated with influenza infection. Among influenza-infected patients, higher antibody titers were present in patients with a longer duration of illness and with higher severity-of-symptom scores.

Correlation of C-reactive protein to severity of symptoms in acute influenza A infection

Background: Currently there is no objective measure to determine disease severity in patients with acute influenza infection. During acute viral infections, C-reactive protein (CRP) has been shown to be elevated. Aim: To study the relationship between the symptoms of acute influenza A infection and correlate them with the level of inflammation as measured by serum CRP levels. Settings and Design: Prospective study. Materials and Methods: We enrolled a convenience sample of adults presenting to an urban academic emergency department (ED), who had positive Enzyme-linked immunosorbent assay detection of the influenza A antigen. The subjects were excluded if they had immunosuppression, liver disease or were currently taking antiviral medication. A previously validated severity of symptom (SOS) score was calculated by asking the participants to record the severity of seven symptoms associated with influenza infection. The subjects had the serum C-reactive protein (CRP) levels tested during their ED visit. Statistical Analysis: A linear regression model was used with CRP as a predictor of the SOS score. Pearsons product-moment coefficient was used to measure the dependence between the two quantities. Results: Thirty-two subjects were enrolled from January through March 2009, and of those, eight patients were excluded from the analysis, leaving 24 study subjects: 58% were women, of ages 18 to 63 years, with a mean age of 31 years (95% CI 25, 37). The mean SOS score was 14.1 ranging from 6 to 21 (95% CI 12.6, 26.4). The mean CRP score was 24.6 ranging from 0 to 64.7 (95% CI 15.8, 33.4). The correlation coefficient between the SOS score and CRP levels was r = 0.65 (P=0.00056). Conclusion: The severity of symptoms associated with acute influenza A infection correlateswith the serum CRP levels.

Elderly patients are at increased risk for treatment failure in outpatient management of purulent skin infections

Objective: Current Infectious Disease Society of America (IDSA) guidelines for the management of purulent skin or soft tissue infections do not account for patient age in treatment recommendations. The study objective was to determine if age was associated with outpatient treatment failure for purulent skin infection after adjusting for IDSA treatment guidelines. Methods: We conducted a multicenter retrospective study of adult patients treated for a purulent skin infection and discharged home from four emergency departments between April and September 2014. Patients were followed for one month to assess for treatment failure (defined as need for a change in antibiotics, surgical intervention, or hospitalization). We used multivariable logistic regression to examine the role of patient age on treatment failure adjusting for demographic variables (gender, race), comorbidities and severity of infection. Results: A total of 467 patients met inclusion criteria (mean age 37.9 years [SD 14.0], 48.2% of whom were women). Overall, 12.4% failed initial therapy. Patients 65 years and older (n = 35) were almost 4 times more likely to fail initial ED therapy in follow‐up compared with younger patients (adjusted Odds Ratio (OR) 3.87, 95% Confidence Interval (CI) 1.24–12.10). After adjustment, for every 10 years of advancing age there was a 43% increased odds of failing initial treatment (OR 1.43 95% CI 1.09–1.88). Conclusion: Elderly patients with purulent skin infections, whose providers followed the 2014 IDSA guidelines, were more likely to fail initial treatment than younger patients. This study suggests that there is a need to re‐evaluate treatment guidelines in elderly patients.