Research Highlights

Movie stars lead glamorous lives, attract enormous attention, and inspire popular lifestyle trends. Angelina Jolie, in particular, has been Hollywood’s highest paid actress in multiple years, cited as one of the world’s most beautiful women, married to perhaps the sexiest man alive, and empowered as a formidable marketing force. Her latest movie, Maleficent, generated total revenues greater than $700 million, an amount that could fund an entire medical center for more than a year. Her humanitarian efforts include being appointed Goodwill Ambassador for the United Nations High Commissioner for Refugees and channeling millions of dollars toward funding worthwhile charities. Many clinicians, scientists, and politicians might dream about having the influence of Angelina Jolie. On May 14, 2013, Angelina Jolie disclosed in an editorial titled ‘‘My Medical Choice’’ that she had tested positive for a breast cancer gene (BRCA1) and undergone prophylactic bilateral mastectomies with breast reconstruction. The immediate reaction led to widespread public attention including front-page stories in mainstream media and a doubling of subsequent referrals for BRCA1 genetic counseling at some hospitals. Her disclosure is also credited for helping shape the US Supreme Court deliberations on June 13, 2013, disallowing patents for isolated genes and potentially prohibitively expensive gene testing. In our opinion, no single study in medical decision science is likely to receive this amount of instant high-profile media attention. In the present issue of the journal, Seth Noar and colleagues provide a rigorous analysis tracking online search activity before and after the Angelina Jolie disclosure. The methods involved accessing the Google Trends database from January 1, 2010, to December 31, 2013, for daily searches related to breast cancer genetics and treatment queries (along with other relevant search terms). The findings indicated a large temporary surge in queries about genetics and treatment, a modest increase in queries about general information and risk assessment, and a rapid return to baseline after about 1 week. The implication is that Angelina Jolie spurred significant informationseeking about breast cancer genetic testing for a short time. The lack of sustained activity also underscores the fleeting nature of fame and public attention. Researchers in other fields might apply the same methods for informing their own studies of acute illnesses, chronic diseases, medical treatments, or unforeseen crises. The Google Trends database allows single or multiple combined word searches to organize each investigation toward relevant items. The resulting data are numerical, longitudinal, reproducible, accessible, immediate, and free. Another strength is the ability to stratify online trends by geographic region and thereby avoid selective reporting from a few outliers. A downside, however, is the need for statistical sophistication since the actual data are normalized as ‘‘relative search volume,’’ which hides the actual count of people involved (a restriction that protects the proprietary interests of Google Inc.). This type of research has been termed infodemiology and defined as the science examining the determinants and distribution of health information on the Internet. The general design involves monitoring Received 1 October 2014 from the Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada (JB, DAR); Evaluative Clinical Sciences, Sunnybrook Research Institute, Toronto, Ontario, Canada (JB, DAR); Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada (JB, DAR); Institute for Health Policy Management and Evaluation, Toronto, Ontario, Canada (DAR); Division of General Internal Medicine, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada (DAR); and Center for Leading Injury Prevention Practice Education & Research (DAR). Dr. Redelmeier is supported by the Canada Research Chair in Medical Decision Sciences. Revision accepted for publication 16 October 2014.

Farheen Mussani, BHSc, MD, Dermatology Centre, Sunnybrook Health Sciences Centre, University of Toronto, Ontario. Jane Wu, BHSc, MD, Dermatology Centre, Sunnybrook Health Sciences Centre, University of Toronto, Ontario. The authors declare no conflicts of interest. Correspondence concerning this article should be addressed to Farheen Mussani, BHSc, MD, University of Toronto, Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Toronto, Ontario, Canada M4N 3M5. E-mail: [email protected]

Specogna, AV; Patten, SB; Hill, MD; University of Calgary, Calgary, AB Background: Previous studies have examined predictors of treatment costs after Spontaneous Intracerebral Hemorrhage (ICH) in various countries and healthcare systems. Currently however, there is no clear understanding of which factors are associated with cost in any Canadian setting and thus no way of understanding how to plan ICH healthcare spending. Methods: We used a retrospective case series study design and adjusted linear regression to investigate if an association existed between the total cost of ICH hospital care in a Canadian health centre and age (years), gender (female vs. male), Charlson Comorbidity Index (0 vs. ≥1), in-hospital mortality (alive vs. dead), and having surgery (no vs. yes). Economic, treatment, and patient data were obtained from administrative sources. Total inflation-adjusted hospital cost per discharge was estimated in Canadian Dollars and log transformed for all analyses. Results: Analyses were performed using 987 consecutive ICH discharges from 1999 to 2008. The total cost of ICH hospital care was highly variable (mean cost per discharge=$25,613.96±$36,116.33; min $446.81 to max $326,275.10). Older age (β=–0.0057; 95% CI: –0.0103 to –0.0011) and death in hospital (β=–0.4859; 95% CI: –0.6357 to –0.3342) were significantly associated with lower total hospital cost per discharge. Whereas Charlson Comorbidity Index of ≥1 (β=0.6489; 95% CI: 0.5063 to 0.7916) and having surgery (β=1.3552; 95% CI: 1.1893 to 1.5210) were significantly associated with higher total hospital cost per discharge. Gender was not significantly associated with cost (β=0.0727; 95% CI: –0.0679 to 0.2134). Conclusions: To our knowledge this is the first study to examine predictors of ICH treatment costs in Canada. In a Canadian health centre, ICH treatment costs were significantly associated with patient age, level of comorbidity, in-hospital mortality, and surgical treatment. This study provides evidence that it may be reasonable to consider …

Should Bone Metastases Causing Neuropathic Pain be Treated with Single-dose Radiotherapy?

Editorial introductions.

Editorial introductions.

Impact of Cardiovascular Magnetic Resonance Assessment of Ejection Fraction on Eligibility for Cardioverter Defibrillator Implantation

Articles That May Change Your Practice: Low-dose Ketamine for Acute Pain

Why some individuals resist infection or recover quickly, whereas others experience severe disease associated with infection, is a fundamental question that medicine has struggled to answer. Pathogens and host immune factors have been extensively investigated for many infectious diseases, to address these questions. However, limited information is available concerning the influence of host genetics on the response to viral infections. Genetic determinants have the potential to play a role at numerous points during the course of viral infection, including viral attachment and entry, replication, disease progression and development of severity, and, finally, transmission. In this issue of the Journal, Albright et al. [1] propose that the severity of influenza illness may have a heritable component. To investigate this hypothesis, the authors used as a resource the Utah Population Data Base, which contains data from founding families and their descendants, comprised primarily of members of the Church of Jesus Christ of Latter-Day Saints (i.e., Mormons), thus representing a relatively ethnically homogeneous population. Albright et al. [1] estimated the relative risk (RR) of death for relatives of 4855 individuals (spanning 3 generations) who died of influenza. A substantial proportion of deaths occurred during the 1918 influenza pandemic, when a total of 1937 deaths were documented between 1918 and 1921, and 1293 additional deaths occurred between 1922–1932, followed by a dramatic decrease in the number of deaths occurring annually. The RR of death for first-degree relatives was 1.54 (P .0001). The RR was higher for spouses (1.98) and for secondand third-degree relatives (1.22 and 1.16, respectively). The timing of the deaths of third-degree relatives suggests that the deaths were not the result of a common exposure. To control for shared environment, the RR of death for spouses’ relatives was compared and was found to be lower for first-, second-, and third-degree relatives. Excess relatedness among individuals dying of influenza was estimated using the Geneological Index of Familiality, which demonstrated that relatedness among these individuals, including individuals who died during the 1918 pandemic, was greater than expected (P .001). The analysis was repeated with close relatives excluded (to control for shared environment), and the results were consistent with previous findings. Consistent results were not observed when the same analysis was repeated for individuals with diphtheria-associated deaths. For such individuals, excess relatedness was demonstrated; however, when close relationships were excluded, no excess relatedness was detected. Specific genes responsible for the host immune response have been invoked as major determinants of the clinical course of HIV-associated disease and hepatitis B and C virus infections [2, 3]. However, there is very little information with respect to genetic determinants as they relate to severe influenza. Over the past decade, a greater understanding of the immune evasion strategies of influenza virus has developed. This knowledge can be used to propose several candidate genes that may be responsible for severe illness. Clinical and animal studies indicate that cytokine dysregulation is associated with acute respiratory distress syndrome and death among hosts infected with avian influenza virus (H5N1) [4 – 6]. Toll-like receptors (TLRs), particularly TLR3 (which recognizes double-stranded RNA) and TLR7 and TLR8 (which recognize single-stranded RNA), are central to antiviral innate immunity [7]. Singlenucleotide polymorphisms in TLR genes are not uncommon and vary among populations [8]. TLR4 has been implicated in the innate immune response to respiratory syncytial virus (RSV) infection, and polymorphisms in the TLR4 gene have Received 5 July 2007; accepted 5 July 2007; electronically published 7 December 2007. Potential conflicts of interest: none reported. Financial support: W. M. Keck Foundation (to P.P.); National Institutes of Health (grant P01 AI158113 to P.P.); Northeast Biodefense Center (grant U54 AI057158 to P.P.); Center for Investigating Viral Immunity and Antagonism (grants U19 AI62623 and U01 CI 000354 [R21 to P.P.]); Ruth L. Kirschstein Physician Scientist Research Training in Pathogenesis of Viral Diseases Award (to S.M.); Sunnybrook Health Sciences Centre, University of Toronto, Canada (salary support to S.M.). Reprints or correspondence: Dr. Samira Mubareka, Dept. of Microbiology, Mount Sinai School of Medicine, 1 Gustave Levy Pl., Box 1124, New York, NY 10029 (samira.mubareka@mssm.edu). The Journal of Infectious Diseases 2008; 197:1–3 © 2007 by the Infectious Diseases Society of America. All rights reserved. 0022-1899/2008/19701-0001$15.00 DOI: 10.1086/524067 E D I T O R I A L C O M M E N T A R Y

Articles That May Change Your Practice: Right Patient, Right Crew, Right Destination

Global Reluctance to Practice Evidence-based Medicine Continues in the Treatment of Uncomplicated Painful Bone Metastases Despite Level 1 Evidence and Practice Guidelines

Editorial: “Formula-Driven” Versus “Lab-Driven” Massive Transfusion Protocols: At a State of Clinical Equipoise

The aim of this study was to determine whether puberty plays a mediating role in onset of schizophrenia. The hypothesis was that there is an inverse relation between age at puberty (menarche) and age at onset in women. Competent and consenting individuals with DSM-IV-defined schizophrenia or schizoaffective disorder and their mothers underwent a 45-minute interview to ascertain age at first odd behavior, age at first psychotic symptoms, age at first hospitalization, and ages at various indices of puberty. Information about substance use, head injury, perinatal trauma, and first-degree family history of schizophrenia was also obtained. In the women (N = 35), the earlier the age at menarche, the later the ages at both the first psychotic symptoms and the first hospitalization. There was no significant association between puberty and onset in the men (N = 45). Other than gender, none of the examined variables played a role in the interaction of puberty and onset of illness. In women, early puberty (whether through hormonal or social influence) was associated with later onset of schizophrenia. This effect was not found in men; in fact, the trend was in the opposite direction.

Introduction: Currently the top 5% of complex patients consume 84% of Ontario’s Hospital and Home Care costs. There is a critical need for a dynamic, person-centred care planning process for medically complex patients with real time dialogue between ED/acute care and community care providers at care transitions. A care pathway was developed in the Sunnybrook Health Science Centre’s Emergency Department using quality improvement methodology and team. The purpose of this study is to evaluate the impact of the emergency room huddle for complex care patients on emergency doctors’ perceptions of patient safety and ED efficiency measures such as department flow and delays. Methods: Intervention - Medically complex patients with frequent ED use are now automatically flagged upon registration in the Emergency Department (ED) and an ED Care Coordination team is notified by secure email: GEM nurse, ED CCAC Care Coordinator, SW, OT/PT. The GEM nurse initiates a comprehensive patient assessment in the Emergency Department right after triage and the CCAC Care Coordinator initiates a teleconference with the patient’s family physician and community Care Coordinator with the patient’s consent. Usual physician assessment is preceded and followed by an inter-professional huddle (including the EM doctor, GEM nurse, CCAC nurse and SW, OT, PT) to ensure patient's needs, goals and team recommendations are clear. Emergency doctors who have participated in an inter-professional huddle for complex care patients are contacted via a semi-structured interview and Qualtrics surveys evaluating perceptions of patient safety and ED efficiency measures such as department flow and delays. Results: Qualitative analysis of the results will be conducted and results updated at a later date. Conclusion: Safety is enhanced through better communication between ED providers, patients, their family physicians and community care providers. It is essential that the inter-professional huddle is recognized by emergency physicians as an important element of patient safety and care. An evaluation of ED doctor’s perception of the huddle will help us understand enablers and barriers to the process and inspire further quality improvements to enhance patient care.

Acoustic Angiography: High-Resolution Contrast-Enhanced Ultrasound Imaging of the Microvasculature