Intravenous Fluid for the Treatment of Emergency Department Patients With Migraine Headache: A Randomized Controlled Trial.

STUDY OBJECTIVE: The objective of this pilot study is to assess the feasibility and necessity of performing a large-scale trial to measure the effect of intravenous fluid therapy on migraine headache pain. METHODS: This was a single-center, pilot randomized controlled trial. We randomized adult emergency department migraine headache patients to receive 1 L of normal saline solution during 1 hour (fluid group) or saline solution at 10 mL/hour for 1 hour (control group). All patients received intravenous prochlorperazine and diphenhydramine at the start of fluid administration. Participants and outcome assessors were blinded; nurses administering the intervention were not. Outcomes were assessed at 60 and 120 minutes, and 48 hours. The primary outcome was the difference in the verbal pain rating (on a scale of 0 to 10) between 0 and 60 minutes. Key secondary outcomes included additional clinical endpoints, the rate of protocol completion, and the effectiveness of blinding. RESULTS: Fifty patients consented to participate; one withdrew, leaving 25 patients randomized to the fluid group and 24 in the no fluid group. The mean improvement in 0- to 60-minute pain score was 4.5 (95% confidence interval 3.7 to 5.3) in the fluid group and 4.9 (95% confidence interval 3.5 to 6.2) in the control group. Primary outcome data were collected for 49 of 50 enrolled patients, and only one participant correctly identified the group assignment. CONCLUSION: This pilot study showed no statistically significant treatment effect from fluid administration, but does not exclude the possibility of a clinically important treatment effect. The study protocol and approach to blinding are both feasible and effective.

Occult Suicidality and Psychiatric Disease Among Emergency Department Patients with Low-acuity Chief Complaints.

INTRODUCTION: Patients presenting to emergency departments (ED) are often screened for suicidality, even when their chief complaint does not involve mental health concerns. Patient receptiveness to ED-based mental health screening and intervention is unknown, particularly among patients with low-acuity chief complaints, who often prioritize rapid evaluation and discharge. METHODS: This cross-sectional study included adults with low-acuity chief complaints presenting to an urban, academic ED in the Northeastern United States during daytime and evening hours, from 2015 to 2016. Participants completed validated mental health screening instruments, including the Suicide Behaviors Questionnaire-Revised and the Patient Health Questionnaire-4. Participants were also asked to rate the importance of addressing mental health concerns during their ED visit. RESULTS: We approached 1,688 patients, and 816 (48.4%) consented to participate in the study. Of these, 27% screened positive for anxiety and 25% screened positive for depression. Even among patients with no prior depression history, 17% were at high risk of depression. Eleven percent of participants were at high risk for suicidal behavior, including 5% of those with no reported history of depression or bipolar disorder. Thirty-five percent of patients at risk for suicide and 53% of those at high risk of depression thought it was important or very important to address these issues during the ED visit. CONCLUSION: Symptoms of mental health disorders were common among this group of ED patients presenting with low-acuity chief complaints. Patients often desired to address these mental health concerns as part of their ED visit.

Risk Factors for Malnutrition among Older Adults in the Emergency Department: A Multicenter Study.

BACKGROUND: Among older adults, malnutrition is common, often missed by healthcare providers, and influences recovery from illness or injury. OBJECTIVE: To identify modifiable risk factors associated with malnutrition in older patients. DESIGN: Prospective cross-sectional multicenter study. SETTING: 3 EDs in the South, Northeast, and Midwest. PARTICIPANTS: Non-critically ill, English-speaking adults aged ≥65 years. MEASUREMENTS: Random time block sampling was used to enroll patients. The ED interview assessed malnutrition using the Mini Nutritional Assessment Short-Form. Food insecurity and poor oral health were assessed using validated measures. Other risk factors examined included depressive symptoms, limited mobility, lack of transportation, loneliness, and medication side effects, qualified by whether the patient reported the risk factor affected their diet. The population attributable risk proportion (PARP) for malnutrition was estimated for each risk factor. RESULTS: In our sample (n = 252), the prevalence of malnutrition was 12%. Patient characteristics associated with malnutrition included not having a college degree, being admitted to the hospital, and residence in an assisted living facility. Of the risk factors examined, the PARPs for malnutrition were highest for poor oral health (54%; 95% CI 16%, 78%), food insecurity (14%; 95% CI 3%, 31%), and lack of transportation affecting diet (12%; 95% CI 3%, 28%). CONCLUSION: Results of this observational study identify multiple modifiable factors associated with the problem of malnutrition in older adults.

Cross-sectional assessment of patient attitudes towards participation in clinical trials: does making results publicly available matter?

OBJECTIVES: Previous studies have shown that a majority of patients cite altruistic motives, such as contributing to generalisable medical knowledge, as factors motivating clinical trial participation. We sought to examine the impact of making trial results publicly available on patients' willingness to participate in clinical research. DESIGN: Cross-sectional analysis using a questionnaire developed by a panel with expertise in publication bias, informed consent and survey design. SETTING: A single urban, academic emergency department (ED) in the Northeastern USA. PARTICIPANTS: 799 ED patients. OUTCOME MEASURES: We assessed (1) participants' attitudes towards clinical trial participation, and (2) the impact of whether study results would eventually be made publicly available or not on willingness to participate in a trial. RESULTS: Of 799 patients surveyed, 36% (95% CI 32% to 39%) reported that they would generally like to participate in a trial, and another 50% (95% CI 47% to 54%) reported that they would consider participation depending on study details. For the majority of participants, the publication of trial results was either important (36%; 95% CI 33% to 40%) or very important (48%; 95% CI 44% to 51%). Most (63%; 95% CI 59% to 66%) reported they would be less likely to participate in a trial if investigators had not publicly released results from a prior study. Additionally, 85% (95% CI 82% to 87%) felt that it was important or very important to receive information about the publication track record of sponsors and investigators during the informed consent process. CONCLUSIONS: The majority of patients in this sample would consider participation in a clinical trial. Patients value the public release of trial results, and believe that the informed consent process should address the possibility of non-publication.

Willingness and Ability of Older Adults in the Emergency Department to Provide Clinical Information Using a Tablet Computer.

OBJECTIVES: To estimate the proportion of older adults in the emergency department (ED) who are willing and able to use a tablet computer to answer questions. DESIGN: Prospective, ED-based cross-sectional study. SETTING: Two U.S. academic EDs. PARTICIPANTS: Individuals aged 65 and older. MEASUREMENTS: As part of screening for another study, potential study participants were asked whether they would be willing to use a tablet computer to answer eight questions instead of answering questions orally. A custom user interface optimized for older adults was used. Trained research assistants observed study participants as they used the tablets. Ability to use the tablet was assessed based on need for assistance and number of questions answered correctly. RESULTS: Of 365 individuals approached, 248 (68%) were willing to answer screening questions, 121 of these (49%) were willing to use a tablet computer; of these, 91 (75%) were able to answer at least six questions correctly, and 35 (29%) did not require assistance. Only 14 (12%) were able to answer all eight questions correctly without assistance. Individuals aged 65 to 74 and those reporting use of a touchscreen device at least weekly were more likely to be willing and able to use the tablet computer. Of individuals with no or mild cognitive impairment, the percentage willing to use the tablet was 45%, and the percentage answering all questions correctly was 32%. CONCLUSION: Approximately half of this sample of older adults in the ED was willing to provide information using a tablet computer, but only a small minority of these were able to enter all information correctly without assistance. Tablet computers may provide an efficient means of collecting clinical information from some older adults in the ED, but at present, it will be ineffective for a significant portion of this population.

Priorities of Care Among Older Adults in the Emergency Department: A Cross-sectional Study.

OBJECTIVES: Emergency departments (EDs) are an increasingly important site of care for older adults, but little is known about the priorities of emergency care in this population. We sought to describe and rank priorities of care among older adults receiving care in the ED. METHODS: We conducted a cross-sectional study of cognitively intact patients aged 65 years and older receiving care in two U.S. EDs. Participants provided up to three open-ended responses to a single question asking what would make their ED visit successful, useful, or valuable. A literature review and patient responses were used to generate priority categories and larger metacategories. Each response was then assigned to one of the categories by independent reviewers. We report the percentage of patients identifying a priority in each category and metacategory and the relative weight of each category based on the frequency and order of priorities provided by patients. RESULTS: A total of 185 participants provided 351 priorities. Twenty-four categories and seven metacategories were identified. Sixty-two percent (N = 114) of participants reported at least one priority in the "evaluation, treatment, and outcomes" metacategory. Of these, the most common priorities included treatment of the medical problem (n = 37, 20%), accurate diagnosis (n = 36, 19%), competent staff and provider (n = 28, 15%), and desirable health outcome (n = 24, 13%). The second and third most common metacategories were "timely care" (n = 67, 36%), and "service" (n = 38, 21%). Nineteen patients (10%) expressed a desire to be discharged; one patient (1%) expressed a desire for admission. The ranking of weighted priorities were identical to the unweighted rank order by frequency. CONCLUSIONS: Among a sample of cognitively intact older ED patients, the most common priorities were related to the accuracy and efficiency of the medical evaluation. These priorities should be considered by those attempting to improve the emergency care of older adults.

Self-Reported Versus Performance-Based Assessments of a Simple Mobility Task Among Older Adults in the Emergency Department.

STUDY OBJECTIVE: Accurate information about the mobility of independently living older adults is essential in determining whether they may be safely discharged home from the emergency department (ED). We assess the accuracy of self-reported ability to complete a simple mobility task among older ED patients. METHODS: This was a cross-sectional study of cognitively intact patients aged 65 years and older who were neither nursing home residents nor critically ill, conducted in 2 academic EDs. Consenting participants were asked whether they could get out of bed, walk 10 feet, turn around, and get back in bed without assistance, and if not, whether they could perform this task with a cane, walker, or assistance. Each participant was then asked to perform the task and was provided with a mobility device or assistance as needed. RESULTS: Of 272 patients who met eligibility criteria and answered the physical task question, 161 (59%) said they could do the task unassisted, 45 (17%) said they could do it with a cane or walker, 21 (8%) said they could do it with assistance, and 45 (17%) said they would be unable to do it even with assistance. Among those who said they could do the task either with or without assistance and who were subsequently willing to attempt the task (N=172), discrepancies between self-reported ability and actual performance were common. Of those who said they could perform the task without assistance, 12% required some assistance or were unable to complete the task. Of those who said they could perform the task with a cane or walker, 48% required either assistance or were unable to perform the task. Of those who said they could perform the task with assistance, 24% were unable to perform the task even with assistance. CONCLUSION: In this sample of older adults receiving care in the ED, the accuracy of their self-reported ability to perform a simple mobility task was poor, particularly for those who reported some need for assistance. For older adults being considered for discharge who report a need for assistance with mobility, direct observation of the patient's mobility by a member of the emergency care team should be considered.

Direct alkylation of heteroaryls using potassium alkyl- and alkoxymethyltrifluoroborates.

A direct alkylation of various heteroaryls using stoichiometric potassium alkyl- and alkoxymethyltrifluoroborates has been developed. This method leads to the synthesis of complex substituted heterocycles, which have been obtained with yields up to 89%.

Efavirenz binding site in HIV-1 reverse transcriptase monomers.

Efavirenz (EFV) is a potent nonnucleoside reverse transcriptase inhibitor (NNRTI) used in the treatment of AIDS. NNRTIs bind in a hydrophobic pocket located in the p66 subunit of reverse transcriptase (RT), which is not present in crystal structures of RT without an inhibitor. Recent studies showed that monomeric forms of the p66 and p51 subunits bind efavirenz with micromolar affinity. The effect of efavirenz on the solution conformations of p66 and p51 monomers was studied by hydrogen-deuterium exchange mass spectrometry (HXMS) and Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS). HXMS data reveal that five peptides, four of which contain efavirenz contact residues seen in the crystal structure of the RT-EFV complex, exhibit a reduced level of exchange in monomer-EFV complexes. Moreover, peptide 232-246 undergoes slow cooperative unfolding-refolding in the bound monomers, but at a rate much slower than that observed in the p66 subunit of the RT heterodimer [Seckler, J. M., Howard, K. J., Barkley, M. D., and Wintrode, P. L. (2009) Biochemistry 48, 7646-7655]. These results suggest that the efavirenz binding site on p66 and p51 monomers is similar to the NNRTI binding pocket in the p66 subunit of RT. Nanoelectrospray ionization FT-ICR mass spectra indicate that the intact monomers each have (at least) two different conformations. In the presence of efavirenz, the mass spectra change significantly and suggest that p51 adopts a single, more compact conformation, whereas p66 undergoes facile, electrospray-induced cleavage. The population shift is consistent with a selected-fit binding mechanism.

Efavirenz binding to HIV-1 reverse transcriptase monomers and dimers.

Efavirenz (EFV) is a nonnucleoside reverse transcriptase inhibitor (NNRTI) of HIV-1 reverse transcriptase (RT) used for the treatment of AIDS. RT is a heterodimer composed of p66 and p51 subunits; p51 is produced from p66 by C-terminal truncation by HIV protease. The monomers can form p66/p66 and p51/p51 homodimers as well as the p66/p51 heterodimer. Dimerization and efavirenz binding are coupled processes. In the crystal structure of the p66/p51-EFV complex, the drug is bound to the p66 subunit. The binding of efavirenz to wild-type and dimerization-defective RT proteins was studied by equilibrium dialysis, tryptophan fluorescence, and native gel electrophoresis. A 1:1 binding stoichiometry was determined for both monomers and homodimers. Equilibrium dissociation constants are approximately 2.5 microM for both p66- and p51-EFV complexes, 250 nM for the p66/p66-EFV complex, and 7 nM for the p51/p51-EFV complex. An equilibrium dissociation constant of 92 nM for the p66/p51-EFV complex was calculated from the thermodynamic linkage between dimerization and inhibitor binding. Binding and unbinding kinetics monitored by fluorescence were slow. Progress curve analyses revealed a one-step, direct binding mechanism with association rate constants k(1) of approximately 13.5 M(-1) s(-1) for monomers and heterodimer and dissociation rate constants k(-1) of approximately 9 x 10(-5) s(-1) for monomers. A conformational selection mechanism is proposed to account for the slow association rate. These results show that efavirenz is a slow, tight-binding inhibitor capable of binding all forms of RT and suggest that the NNRTI binding site in monomers and dimers is similar.

Kinetics of association and dissociation of HIV-1 reverse transcriptase subunits.

The biologically active form of HIV-1 reverse transcriptase (RT) is the p66/p51 heterodimer. The process of maturation of the heterodimer from precursor proteins is poorly understood. Previous studies indicated that association of p66 and p51 is very slow. Three techniques, a pre-steady-state activity assay, intrinsic tryptophan fluorescence, and a FRET assay, were used to monitor the dimerization kinetics of RT. Kinetic experiments were conducted with purified p66 and p51 proteins in aqueous buffer. All three techniques gave essentially the same results. The dissociation kinetics of p66/p51 were first-order with rate constants (k(diss)) of approximately 4 x 10(-6) s(-1) (t(1/2) = 48 h). The association kinetics of p66 and p51 were concentration-dependent with second-order rate constants (k(ass)) of approximately 1.7 M(-1) s(-1) for the simple bimolecular association reaction. The implications of slow dimerization of p66/p51 for the maturation process are discussed. A reaction-controlled model invoking conformational selection is proposed to explain the slow protein-protein association kinetics.

Separation of protein oligomers by blue native gel electrophoresis.

Native gel electrophoresis is used as a tool to assess structural differences in proteins. This article presents an application to separate oligomeric forms of proteins such as human immunodeficiency virus type 1 (HIV-1) reverse transcriptase monomers and homodimers. Technical difficulties encountered with various native gel techniques and ways to circumvent them are described.