Jane P. Gagliardi

Native Valve Infective Endocarditis in Elderly and Younger Adult Patients: Comparison of Clinical Features and Outcomes with Use of the Duke Criteria and the Duke Endocarditis Database

The effect of age on the presentation and outcome of infective endocarditis (IE) is unclear. Many of the available data are based on analyses of mixed populations of patients including intravenous drug users or those with prosthetic valve endocarditis or native valve IE. We used the Duke criteria to compare the characteristics of 44 episodes of definite native valve IE in elderly patients (> 64 years old) with the characteristics of 64 similarly defined episodes of native valve IE in younger, nonintravenous-drug-using adult patients (> 29 years and < 60 years old). Our data suggest that the clinical presentation, characteristics, and outcome of native valve IE are similar for elderly patients and younger adult patients, although elderly patients were hospitalized an average of 12 days longer. Although we found that the occurrence of renal failure and cerebral embolism during an episode of IE was associated with higher rates of death (odds ratios, 4.8 and 4.0, respectively), age was not a significant contributor to mortality.

Defining the Role of Baclofen for the Treatment of Alcohol Dependence

The pharmacological properties of baclofen, a GABAB receptor agonist, have led to investigation of its use for the off-label treatment of alcohol dependence. Literature examining the role of baclofen in alcohol dependence suggests that it may be a useful medication in the treatment armamentarium with an additional benefit of promoting abstinence and reducing alcohol-associated cravings and anxiety. We conducted a systematic review of prospective, randomized controlled trials comparing baclofen with placebo for the treatment of alcohol dependence. Four randomized controlled trials were identified but only three met criteria for inclusion. The excluded trial was a post hoc analysis of data collected from an original trial whose primary outcome did not fit our inclusion criteria and was terminated prior to completion. Compared with placebo, subjects randomized to baclofen experienced higher rates of abstinence and lower anxiety scores; the effect of baclofen was statistically significant in two trials assessing patients with more severe alcohol dependence and non-significant in a trial of outpatients receiving concomitant manualized psychotherapy. Baclofen appeared to be safe, well tolerated and to have low addiction liability even in the setting of moderate-to-severe liver cirrhosis, a known complication of alcohol dependence. Though baclofen may hold promise, the different outcomes and sample populations of the three studies highlight the need for more research to better understand the appropriate target patient population to benefit from this medication. Questions still remain about optimal dosing and duration. There is not enough evidence to support the use of baclofen as a first-line treatment option, except for those alcohol-dependent patients with moderate-to-severe liver cirrhosis in whom other pharmacological treatments are not safe or practical.

Clinical effectiveness of baclofen for the treatment of alcohol dependence: a review

Baclofen, an agonist at the B subunit of gaba-aminobutyric acid receptor, possesses pharmacologic properties that may confer utility for the treatment of alcohol dependence. Research suggests that not only can it be useful in promoting maintenance of alcohol abstinence but also it may play a key role in decreasing alcohol cravings and anxiety often associated with alcohol dependence. To assess the benefit of baclofen for alcohol dependence, a review of the literature was conducted to identify published data investigating this off-label treatment. Four randomized controlled trials to date have been published and were included in this review. Although primary outcomes differ between studies, patients randomized to baclofen experience higher rates of abstinence from alcohol than those taking placebo in two of the trials. Secondary analyses indicate that baclofen is safe in patients with alcohol dependence, including those with moderate to severe liver cirrhosis, and may provide beneficial anxiolytic effects. Despite some positive data, the largest available randomized controlled trial failed to find any differences between baclofen and placebo. In all studies, individuals with severe medical comorbidities, seizure disorders, and psychiatric disorders were excluded from trials, which may limit external validity. In summary, there may be beneficial effects from using baclofen for the treatment of alcohol dependence; however, limited conclusions can be drawn from the small number of studies currently available for review. Larger well-designed trials are needed to further define baclofen’s role for the treatment of alcohol dependence.

Dexmedetomidine for the Treatment of Alcohol Withdrawal Syndrome: Rationale and Current Status of Research

Dexmedetomidine is currently used in the US in the treatment of alcohol withdrawal syndrome (AWS) in the intensive care unit (ICU) setting, although data to support this practice are limited. Dexmedetomidine targets the noradrenergic system, an important but frequently overlooked secondary mechanism in the development of AWS, and, in doing so, may reduce the need for excessive benzodiazepine use which can increase the risk of γ-aminobutyric acid (GABA)-mediated deliriogenesis and respiratory depression. The purpose of this narrative review is to evaluate available literature reporting on the safety and efficacy of dexmedetomidine for AWS in the ICU setting. An English-language MEDLINE search (1966 to July 2013) was performed to identify articles evaluating the efficacy and safety of dexmedetomidine for AWS. Case series, case reports and controlled trials were evaluated for topic relevance and clinical applicability. Reference lists of articles retrieved through this search were reviewed to identify any relevant publications. Studies focusing on the safety and efficacy of dexmedetomidine for AWS in humans were selected. Studies were included if they were published as full articles; abstracts alone were not included in this review. Eight published case studies and case series were identified. Based on a limited body of evidence, dexmedetomidine shows promise as a potentially safe and possibly effective adjuvant treatment for AWS in the ICU. Prospective, well-controlled studies are needed to confirm the safety and efficacy of the use of dexmedetomidine in AWS.

Examination of baseline risk factors for QTc interval prolongation in patients prescribed intravenous haloperidol.

AbstractBackground: Intravenous haloperidol can increase the risk for corrected QT interval (QTc) prolongation, torsades de pointes (TdP) and sudden death. There are a number of risk factors reported in the literature for QTc prolongation and TdP with intravenous haloperidol. Objective: The purpose of this study was to determine the prevalence of baseline risk factors for QTc prolongation and TdP in hospitalized medical inpatients prescribed intravenous haloperidol. Methods: This is a retrospective cohort study of medically ill hospitalized inpatients prescribed intravenous haloperidol between 30 June 2007 and 1 January 2010. Records were ascertained for the presence of baseline risk factors for QTc prolongation and TdP. Results: A total of 175 subjects were identified as receiving intravenous haloperidol during the study period. Mean age was 62.9±19.1 years, and 48.6% of subjects were female. At baseline, 85.7% of subjects had ≥1 risk factor for QTc prolongation and TdP, with the majority of these subjects (58.0%) having between two and five risk factors. Of the total study sample, 74.9% had a baseline ECG; mean QTc value was 457 msec (± 40.8 msec). Greater than 50% of subjects had a sex-specific QTc value higher than the increased risk threshold of 450 msec in males or 460 msec in females at baseline. Following intravenous haloperidol administration, 46.9% of subjects had a follow-up ECG obtained within 24 hours. At the time of intravenous haloperidol administration, 93.1% of subjects had a potassium value available and 62.9% had a magnesium value. Approximately 30% of subjects had either a potassium or magnesium value below the normal laboratory range. Of the 175 subjects, 43.4% were taking ≥1 concomitant QTc prolongation medication at the time of intravenous haloperidol administration. Conclusions: Consistent with previously published reports, patients in this study prescribed intravenous haloperidol had multiple risk factors, both modifiable and non-modifiable, at baseline for QTc prolongation and TdP. The modifiable risk factors may be important targets of interventions aimed at optimizing the safety of the use of intravenous haloperidol, while the non-modifiable risk factors may warrant closer scrutiny with consideration of alternative therapies and continuous monitoring.

Defining the Role of Dexmedetomidine in the Prevention of Delirium in the Intensive Care Unit

Dexmedetomidine is a highly selective α 2 agonist used as a sedative agent. It also provides anxiolysis and sympatholysis without significant respiratory compromise or delirium. We conducted a systematic review to examine whether sedation of patients in the intensive care unit (ICU) with dexmedetomidine was associated with a lower incidence of delirium as compared to other nondexmedetomidine sedation strategies. A search of PUBMED, EMBASE, and the Cochrane Database of Systematic Reviews yielded only three trials from 1966 through April 2015 that met our predefined inclusion criteria and assessed dexmedetomidine and outcomes of delirium as their primary endpoint. The studies varied in regard to population, comparator sedation regimen, delirium outcome measure, and dexmedetomidine dosing. All trials are limited by design issues that limit our ability definitively to conclude that dexmedetomidine prevents delirium. Evidence does suggest that dexmedetomidine may allow for avoidance of deep sedation and use of benzodiazepines, factors both observed to increase the risk for developing delirium. Our assessment of currently published literature highlights the need for ongoing research to better delineate the role of dexmedetomidine for delirium prevention.

Innovation in evidence-based medicine education and assessment: an interactive class for third- and fourth-year medical students

INTRODUCTIONEvidence-based medicine (EBM) is an importantcomponent of an undergraduate medical educationcurriculum that promotes lifelong learning andcritical thinking [1]. Defined as ‘‘the conscientious,explicit, and judicious use of current best evidence inmaking decisions about the care of individualpatients’’ [2], EBM can be considered another impor-tant clinical tool, not unlike the stethoscope. Theauthors designed and assessed an innovative EBMcourse for third-year medical students to strengthenthe EBM curriculum for undergraduate medicaleducation.BACKGROUNDPrevious studies have advocated real-time teaching ofEBM during attending rounds, in a case-based formatwith role playing or with standardized patients [3–5].At the same time, brief training in literature searchingand critical appraisal skills has been shown to beeffective, and interactive workshops have beensuggested as an ideal format for medical students[6–8]. At many academic medical centers, includingthe authors’, constraints on resident and student dutyhours and increased demands for productivity fromclinical teaching faculty have made adding formalcurricula to the clinical services problematic. In aneffort to combine an interactive learning environmentwith core topics in EBM, we devised a multidisciplin-ary, case-based seminar series that is team-taughtby clinicians and a librarian and is designed to beinteractive, engaging, and clinically relevant.METHODSDesigned by a medical librarian and a physician(Schardt and Gagliardi), the EBM course is intendedto provide an interactive forum for students todevelop skills in practicing EBM in the care ofpatients. The first version of the EBM course wasoffered as a noncredit elective to 8 third-year medicalstudents in 2006 and consisted of 6 90-minute sessionsconducted over the course of the spring semester.After experimenting with a 10-session format, wesettled on 6 120-minute sessions conducted onconsecutive Thursday evenings, from 5:00 p.m. to7:00 p.m.After the third iteration of the course in 2008, itbecame a credit-bearing elective, which requiredopening it not only to third-year medical students,but also to fourth-year medical students. Since the2008/09 academic year, the EBM course has attractedapproximately forty students per year. The currentstudy with pre- and post-course assessments ofknowledge as well as attitudes was conducted duringthe 2008/09 academic year.The EBM course is designed to optimize studentreadiness and participation, faculty willingness toteach, and instructional strategies to maximize reten-tion and use of EBM skills, with key features outlinedbelow.1. Timing in the curriculumAt our institution, medical students complete theirrequired clinical clerkships during the second year.The EBM course is designed for students who arepursuing academic endeavors during the third year,which is dedicated to research. This is optimal timingbecause students have completed their requiredclinical clerkships and, therefore, have had somepatient care experience along with the opportunity toobserve and practice EBM in a variety of settings.Additionally, as they are about halfway through theirscholarly research activity year, they are cognizant ofsome of the logistical and practical issues involved indesigning and conducting scientific research.2. Course organization and facultyTable 1 shows the course outline. The introductorysession provides an overview of the EBM frameworkand the basics of study design. The subsequent foursessions are case based and teach relevant issuespertaining to the retrieval, appraisal, and applicationof studies of therapy, diagnosis, harm, and systematicreviews. The final session is designed to demonstratethe real-time application of EBM skills. Cliniciansfrom the emergency department and in-patient unitstake students through actual clinical cases they haveencountered and demonstrate how they used EBM tocontribute to their care of actual patients. Each caseusually takes five to fifteen minutes and effectivelydemonstrates that EBM can be incorporated intoclinical practice.We rely on a diverse faculty with a broad spectrumof clinical interest and experience. Facilitators areclinically based and recruited from departments anddisciplines in which they are likely to have encoun-tered many of the students in clinical settings. Inthis way, no one faculty member is responsible fordelivering of all content, students benefit fromwitnessing the use of EBM skills by a variety of

A computerized physician order entry set designed to improve safety of intravenous haloperidol utilization: a retrospective study in agitated hospitalized patients.

BACKGROUND Intravenous haloperidol can increase the risk for corrected QT (QTc) interval prolongation, torsades de pointes (TdP) and sudden death. OBJECTIVE The purpose of this study was to examine the effects of implementation of a computerized physician order entry (CPOE) set on adherence to monitoring parameters, maximum and cumulative doses, and identification or mitigation of risk factors for QTc prolongation in patients prescribed intravenous haloperidol. METHODS A retrospective cohort study of medically ill hospitalized inpatients prescribed intravenous haloperidol was conducted. Data were collected for two distinct 1-year time periods: the pre-CPOE set period (30 June 2007 through 30 June 2008) and the post-CPOE set period (1 January 2009 through 1 January 2010). The CPOE set was implemented on 1 October 2008. RESULTS A total of 151 subjects were included; 84 subjects were in the pre-CPOE set group and 67 subjects were in the post-CPOE set group. Following CPOE set implementation, subjects in the post-CPOE group, compared with the pre-CPOE group, were more likely to receive a 24-hour cumulative dose of intravenous haloperidol <2 mg (Fishers exact test; p < 0.048), have a baseline ECG (Fishers exact test; p = 0.045), have a follow-up ECG within 24 hours of intravenous haloperidol administration (Fishers exact test; p = 0.009) and have a magnesium value assessed at the time of intravenous haloperidol administration (Fishers exact test; p = 0.004). CONCLUSION This study reports on the successful implementation of a CPOE set designed to improve the safety of intravenous haloperidol administration in medically ill patients.

Differentiating among Depression, Delirium, and Dementia in Elderly Patients

A description and explanation of the distinguishing characteristics of depression, delirium, and dementia in elderly patients. Virtual Mentor is a monthly bioethics journal published by the American Medical Association.

Prevalence of baseline lipid monitoring in patients prescribed second-generation antipsychotics during their index hospitalization: a retrospective cohort study.

BACKGROUND Second-generation antipsychotics have been found to increase a patients risk of dyslipidemia. Despite consensus statement recommendations for lipid monitoring, studies indicate that up to 90% of patients still do not have a baseline lipid panel prior to prescription of a second-generation antipsychotic. METHODS This study retrospectively examined the prevalence of baseline lipid monitoring in patients prescribed second-generation antipsychotics during their index psychiatric hospitalization at Duke University Hospital between July 1, 2005, and July 1, 2010. RESULTS Seventy patients were included in the study, with a mean age of 21.5±2.5 years. Of these patients, 22 (31.4%) had baseline lipid panels drawn during hospitalization. Lipid monitoring was statistically more frequent in males than in females (P=.01). Although not statistically significant, lipid monitoring was also more likely to occur among subjects who were African American (40%; P=.07) and with the prescription of olanzapine (50%; P=.07). About half of baseline lipid panels demonstrated either a low high-density lipoprotein or high triglycerides, indicating at least one risk factor for the metabolic syndrome. CONCLUSION This study provides alarming evidence that, even in an academic setting with active discussions among psychiatrists regarding issues of metabolic risk and appropriate monitoring, adherence to American Psychiatric Association/American Diabetes Association consensus statement recommendations on rates of baseline lipid monitoring is disappointingly low in the absence of systems to encourage or automate best practice.