Important: The Presence of Anti-HLA Donor-Specific Antibodies in Lung Allograft Recipients Does Not Correlate With C4d Immunofluorescence in Transbronchial Biopsy Specimens

Jordan A. Roberts, Roberto Barrios, Philip T. Cagle, Yimin Ge, Hidehiro Takei, Abida K. Haque, Kevin M. Burns, Geoffrey A. Land, Smaroula Dilioglou, and David W. Bernard (2013) The Presence of Anti-HLA Donor-Specific Antibodies in Lung Allograft Recipients Does Not Correlate With C4d Immunofluorescence in Transbronchial Biopsy Specimens. Archives of Pathology & Laboratory Medicine In-Press.

Early Online Release

The Presence of Anti-HLA Donor-Specific Antibodies in Lung Allograft Recipients Does Not Correlate With C4d Immunofluorescence in Transbronchial Biopsy Specimens

Jordan A. Roberts , MD; Roberto Barrios , MD; Philip T. Cagle , MD; Yimin Ge , MD; Hidehiro Takei , MD; Abida K. Haque , MD; Kevin M. Burns , MD; Geoffrey A. Land , PhD; Smaroula Dilioglou , PhD; David W. Bernard , MD, PhD

From the Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, Texas (Drs Roberts, Barrios, Cagle, Ge, Takei, Haque, Burns, Land, Dilioglou, and Bernard); and the Department of Pathology, Weill Cornell Medical College of Cornell University, Houston, Texas (Drs Barrios, Cagle, Ge, and Takei).

Context.—C4d immunofluorescence (IF) is a surrogate for development of donor-specific antibodies (DSAs) against human leukocyte antigen (HLA) class I and II antigens in kidney and heart biopsy specimens for monitoring of antibody-mediated (humoral) allograft rejection (AMR). Use of C4d IF in monitoring of lung allografts has shown conflicting results.

Objective.—To determine if C4d IF can be used as a reliable marker for AMR and if it correlates with the presence of DSAs and histologic findings on biopsy.

Design.—All transbronchial biopsies in lung allograft recipients, performed at our institution in a 3-year period, were reviewed. A cohort of 92 patients with 110 corresponding biopsies met the inclusion criteria of (1) having a resulted DSA within 2 weeks of biopsy and (2) having C4d immunofluorescence studies performed and confirmed.

Results.—Twenty-nine patients (31.5%) were positive for DSAs and 63 patients (68.5%) did not develop DSAs. Positive C4d capillary IF was seen in 18 of 110 total biopsy specimens (16.4%). Eight of these biopsy samples were from patients positive for DSAs and 10 were from patients negative for DSAs. The correlation coefficient between the presence of DSAs and C4d IF was 0.1628 (P = .09).

Conclusions.—A significant proportion of DSA-positive patients had negative C4d IF results and frequently have no histologic changes on biopsy specimens. DSA-negative patients can be positive for C4d and may show the same histologic changes as reported for DSA-positive patients. Diagnosis of AMR in lung may require a collaborative approach combining clinical data, DSA status, and histology.

HER2 by immunohistochemistry and FISH in Breast Cancer: Impact of the 2007 ASCO/CAP criteria

Kurt A. Schalper, Sudha Kumar, Pei Hui, David L. Rimm, and Peter Gershkovich (2013) A Retrospective Population-Based Comparison of HER2 Immunohistochemistry and Fluorescence In Situ Hybridization in Breast Carcinomas: Impact of 2007 American Society of Clinical Oncology/College of American Pathologists Criteria. Archives of Pathology & Laboratory Medicine In-Press.

Early Online Release

A Retrospective Population-Based Comparison of HER2 Immunohistochemistry and Fluorescence In Situ Hybridization in Breast Carcinomas: Impact of 2007 American Society of Clinical Oncology/College of American Pathologists Criteria

Kurt A. Schalper , MD, PhD; Sudha Kumar , BE, MOT; Pei Hui , MD, PhD; David L. Rimm , MD, PhD; Peter Gershkovich , MD, MHA

From the Department of Pathology, Yale School of Medicine, New Haven, Connecticut (Drs Schalper, Kumar, Hui, Rimm, and Gershkovich) and Servicio de Anatomia Patologica, Clinica Alemana de Santiago, Chile (Dr Schalper).

Context.—In 2007 the American Society of Clinical Oncology/College of American Pathologists made new recommendations for HER2 testing and redefined HER2 positivity.

Objective.—To analyze results from simultaneous HER2 testing with immunohistochemistry and fluorescence in situ hybridization (FISH) in 2590 invasive breast carcinomas between 2002 and 2010, using 2 scoring systems.

Design.—Cases between 2002 and 2006 were scored by using original US Food and Drug Administration criteria (N = 1138) and those between 2007 and 2010 were evaluated according to American Society of Clinical Oncology/College of American Pathologists criteria (N = 1452). Concordance between testing methods and clinicopathologic associations were determined.

Results.—Overall concordance between immunohistochemistry/FISH in the 9-year period was 96.2% (κ = 0.82), and positive concordance was lower. After 2007, the proportion of HER2/neu-positive and HER2/neu-negative cases was not significantly changed when using immunohistochemistry (10.5% versus 8.9%, P = .22 and 69.4% versus 63%, P = .13, respectively), but the number of equivocal cases was higher (19.9% versus 28%, P < .001). While the proportion of negative cases by FISH remained unchanged after 2007 (86.5% versus 88.2%, P = .76), the number of positive cases was lower (13.4% versus 9.2%, P < .001). In addition, 38 cases (2.6%) were FISH equivocal, 16 of which were also equivocal by immunohistochemistry. Overall, immunohistochemistry/FISH concordance was 95.9% between 2002 and 2006 (κ = 0.82) and 96.4% after 2007 (κ = 0.82). However, an approximately 13% lower positive assay concordance was noted in the last period.

Conclusions.—Application of American Society of Clinical Oncology/College of American Pathologists recommendations is associated with comparable overall immunohistochemistry/FISH concordance, reduced positive concordance, and increased equivocal results.

"The sublimity and the beauty of the world as described by modern science do not rest, for Dworkin, on the elegance and the simplicity of its equations and on the striking symmetries it has uncovered."

Can You Have ReligionWithout God?

By  MOSHE HALBERTAL

"The sublimity and the beauty of the world as described by modern science do not rest, for Dworkin, on the elegance and the simplicity of its equations and on the striking symmetries it has uncovered. For Dworkin, its sublimity flows from the inevitability and integrity ascribed to it by an Einstein-like stance. In this respect, the aesthetic qualities of the Spinozistic universe resemble the features that make a work of art beautiful and arresting. Any change in color or line in a great painting will affect its totality; every feature in it is intrinsically necessary. When the beauty of a painting dawns on us, it has a compelling power of inevitability; it arrests our will. If, as I believe, what distinguishes the religious sensibility from the strictly secular is not the concept of God but the category of the holy, such works of art are like the sacred. Their integrity and inevitability are inherent to them; they are not ours to mess with. It is for this reason that the destruction of a work of art feels sacrilegious, and that certain aspects of modern technological hubris are, for the ecological sensibility, not only wrong but also sinful. Religion without God does not endorse any form of worship, but it certainly calls for reverence.' 

Acta Inform Med. 2013;21(3):156-9. doi: 10.5455/aim.2013.21.156-159.

At what level of collective equipoise does a randomized clinical trial become ethical for the members of institutional review board/ethical committees?

Mhaskar R, B Bercu B, Djulbegovic B.

Source

Clinical Translational Science Institute, Center for Evidence-based Medicine and Health Outcomes Research, Tampa, FLorida, USA ; Department of Internal Medicine, Division of Evidence-based Medicine and Health Outcomes Research University of South Florida, Tampa, FLorida, USA.

Abstract

BACKGROUND:

The conduct of a randomized controlled trial (RCT) is deemed ethical only if we are in state of "equipoise" as to which treatment would be most beneficial for the patients. Individual equipoise applies to an individual clinician or a member of ethical, institutional review board (IRB), whilst collective equipoise refers to the profession as a whole. It is argued that physicians are not bound by the equipoise but their actions are directed by the confines of the expert opinion. Experts can agree or disagree in various proportions on the merit of a given treatment. Hence, the collective equipoise will be often incomplete. In turn, the opinions of content expert in the field of the proposed trial influence the IRB members' decision regarding trial approval.

METHODS:

We conducted a survey of IRB members at University of South Florida and the IRB members attending the bioethics conference organized in Clearwater, Florida, USA. The survey was made available as hard copy (paper based) and included six hypothetical scenarios outlining clinical trials targeted at measuring the collective equipoise. We defined the collective equipoise as the situation when survey participants were equally split (50:50) in their decision regarding whether a proposed clinical trial would be ethical to conduct. The opinion of 100 experts in the field expressed as proportion of experts favoring treatment A vs. B in each of the five scenarios was made available to the participants.

RESULTS:

The response rate of our survey was 33% (71/218). Fifty percent of the IRB members would approve an RCT addressing the efficacy of two drugs for the management of headache even if 80% of experts favor one treatment over another (median: 80%; third quartile: 80%). Similarly, half of participating IRB members would approve the study when the median distribution of equipoise among experts was 70% (70 in favor of treatment A vs. 30 in favor of treatment B) for treatment of leukemia, 60% for treatment of geriatric patients and 70% for treatment of newborns. Half of IRB members would approve the study when the median distribution of equipoise among experts was 70% for treatment for leukemia in dogs and 85% for leukemia in rats (and 25% of IRB members would approve such a study even if 100% of experts favors one treatment over another). None of the demographic features of respondents affected collective equipoise.

CONCLUSIONS:

This is the first study assessing collective equipoise among ethical committee/IRB members. Our study findings show that IRB members perceived that conduct of a trial enrolling humans is unethical when the equipoise level is beyond 80% (80:20 distribution of uncertainty). IRB members require a higher level of equipoise when it comes to testing a new drug in humans than in animals. A relatively high level of equipoise is needed for IRB members to be comfortable to approve trials involving life-threatening situations, children and elderly patients.

Int J Clin Pract. 2013 Nov;67(11):1086-8. doi: 10.1111/ijcp.12227.

Clinical and ethical challenges of palliative sedation therapy. The need for clear guidance and professional competencies.

Schildmann J, Schildmann E.

Source

Institute for Medical Ethics and History of Medicine, NRW Junior Research Group "Medical Ethics at the End of Life: Norm and Empiricism", Ruhr-University Bochum, Bochum, Germany.

Abstract

Palliative sedation therapy (PST) has become a frequent practice in end-of-life care and advocated in the literature as a less problematic alternative to practices of physician-assisted dying, such as ending patients' lives on request or assisted suicide . However, in clinical practice, patients, healthcare professionals and other parties involved in decisions about PST are facing numerous clinical and ethical challenges. This perspective aims to analyse important challenges associated with professional decision-making about PST and to explore the recommendations of guidelines, which have been published in recent years.

Radioprotectants

Int J Radiat Biol. 2013 Oct 29. [Epub ahead of print]

Radioprotectants to reduce the risk of radiation-induced carcinogenesis.

Oliai C, Yang LX.

Abstract

Purpose: Development of radioprotective agents has focused primarily on cytoprotection from relatively high doses of therapeutic radiation and nuclear disasters. Epidemiological studies and radiobiological models report the potential for stochastic effects from relatively low-dose radiation exposure. Diagnostic studies like computed tomography (CT) expose the patient to a small but significant amount of radiation, which has been reported to increase the risk for carcinogenesis. Young patients expected to undergo multiple CT studies may benefit from a protective agent given prior to CT. This review includes published data of agents that have been shown to protect against radiation-induced carcinogenesis. A discussion follows regarding the data that describes the extent of radiation exposure during CT, as well as technical modifications, which also reduce radiation exposure. 

Results/Conclusions: Most experiments have used in vivo animal models or in vitro cell lines. Ethical barriers prevent large-scale human studies, although, there are two prospective human studies from the Chernobyl nuclear accident. Collectively, all of these studies provide evidence of statistically significant reductions in radiation-induced carcinogenesis. Protection is achieved by several mechanisms, which include free radical scavenging, caloric restriction, non-steroidal anti-inflammatory agents, humoral factors, and an oxidative agent. Enhanced efficacy is achieved when targeting multiple mechanisms. The data presented provides the scientific foundation for future development of a radioprotectant that may reduce the risk of carcinogenesis from low-dose exposure when certain at-risk populations undergo diagnostic studies like CT.

From Indiana U: Ethical considerations surrounding survival benefit-based liver allocation

Liver Transpl. 2013 Oct 26. doi: 10.1002/lt.23780. [Epub ahead of print]

Ethical considerations surrounding survival benefit-based liver allocation.

Keller EJ, Kwo PY, Helft PR.

Source

Indiana University School of Medicine, Department of Medicine, Charles Warren Fairbanks Center for Medical Ethics, Indianapolis, Indiana, USA.

Abstract

The disparity between the demand for and supply of donor livers has continued to grow over the last two decades, placing greater weight on the need for efficient and effective liver allocation. Although the use of extended criteria donors has shown great potential, it remains unregulated. Schaubel et al. have recently proposed the Survival Benefit-Based Model to answers calls to increase efficiency and reduce futile transplants. However, it was previously determined that the current allocation system was not in need of modification, but rather, geographic disparities should be addressed. In contrast, we believe that a significant need exists to replace the current allocation system, complementing efforts to improve donor liver distribution. We illustrate this need by first identifying major ethical concerns shaping liver allocation and using them to identify strengths and shortcomings of the MELD/PELD system and Survival Benefit-Based Model. The latter model is found to be a promising means of improving liver allocation, incorporating a greater number of ethical principles, using a sophisticated statistical model to increase efficiency and reduce waste, minimizing bias, and paralleling developments in the allocation of other organs. However, it remains limited in its post-transplant predictive accuracy and may raise potential issues regarding informed consent. In addition, the proposed model fails to include quality of life concerns and prioritize younger patients. We feel it is time to take the next steps toward better liver allocation through not only reducing geographic disparities but also adopting a model better equipped to balance the many ethical concerns shaping organ allocation. Thus we support the development of a similar model, with suggested amendments.

Proc Natl Acad Sci U S A. 2013 Oct 28. [Epub ahead of print]

Global meta-analysis reveals no net change in local-scale plant biodiversity over time.

Vellend M, Baeten L, Myers-Smith IH, Elmendorf SC, Beauséjour R, Brown CD, De Frenne P, Verheyen K, Wipf S.

Source

Département de Biologie, Université de Sherbrooke, Sherbrooke, QC, Canada J1K 2R1.

Abstract

Global biodiversity is in decline. This is of concern for aesthetic and ethical reasons, but possibly also for practical reasons, as suggested by experimental studies, mostly with plants, showing that biodiversity reductions in small study plots can lead to compromised ecosystem function. However, inferring that ecosystem functions will decline due to biodiversity loss in the real world rests on the untested assumption that such loss is actually occurring at these small scales in nature. Using a global database of 168 published studies and >16,000 nonexperimental, local-scale vegetation plots, we show that mean temporal change in species diversity over periods of 5-261 y is not different from zero, with increases at least as likely as declines over time. Sites influenced primarily by plant species' invasions showed a tendency for declines in species richness, whereas sites undergoing postdisturbance succession showed increases in richness over time. Other distinctions among studies had little influence on temporal richness trends. Although maximizing diversity is likely important for maintaining ecosystem function in intensely managed systems such as restored grasslands or tree plantations, the clear lack of any general tendency for plant biodiversity to decline at small scales in nature directly contradicts the key assumption linking experimental results to ecosystem function as a motivation for biodiversity conservation in nature. How often real world changes in the diversity and composition of plant communities at the local scale cause ecosystem function to deteriorate, or actually to improve, remains unknown and is in critical need of further study.

1984: "...seeing privacy merely as a symptom of an informational deficiency..."

Front Genet. 2013 Sep 19;4:172. doi: 10.3389/fgene.2013.00172.

From omics and etics to policy and ethics: regulating evolution.

Hoppe N.

Source

Centre for Ethics and Law in the Life Sciences, Leibniz Universität Hannover Hannover, Germany

"This increase in density and availability of meaningful information leads to a perceivable public trend in seeing privacy merely as a symptom of an informational deficiency, i.e., there is a plausible argument that the perceived explosion in information sharing online may well lead to a desensitization, rather than an increased fear for privacy. At the same time, regulatory sciences and the disciplines looking at ethical, legal, and social implications of this type of technology doggedly adhere to their time-honored, heterogeneous and siloed methodological traditions: bar some notable exceptions, lawyers speak to lawyers, ethicists speak to ethicists, sociologists speak to sociologists. Where debate transcends disciplinary boundaries, it is often received with suspicion of the other discipline's (or country's) scholarly conventions, language, and style."

“Morality did not evolve to promote universal cooperation”

Why Can't We All Just Get Along? The Uncertain Biological Basis of Morality

Squaring recent research suggesting we're "naturally moral" with all the strife in the world

ROBERT WRIGHTOCT 23 2013



"Greene’s diagnosis is, at its foundation, Darwinian: the impulses and inclinations that shape moral discourse are, by and large, legacies of natural selection, rooted in our genes. Specifically, many of them are with us today because they helped our ancestors realize the benefits of cooperation. As a result, people are pretty good at getting along with one another, and at supporting the basic ethical rules that keep societies humming.
Anyone who doubts that basic moral impulses are innate will have Paul Bloom’s book to contend with. He synthesizes research—much of it done by him and his wife, Karen Wynn—demonstrating that an array of morally relevant inclinations show up in infants and toddlers. His list of natural moral endowments includes “some capacity to distinguish between kind and cruel actions,” as well as “empathy and compassion—suffering at the pain of those around us and the wish to make this pain go away.” Bloom’s work has also documented “a rudimentary sense of justice—a desire to see good actions rewarded and bad actions punished.”So if we’re such moral animals, why all the strife? Joshua Greene’s answer is appealingly simple. He says the problem is that we were designed to get along together in a particular context—relatively small hunter-gatherer societies. So our brains are good at reconciling us to groups we’re part of, but they’re less good at getting groups to make compromises with one another. “Morality did not evolve to promote universal cooperation,” he writes."

World Neurosurg. 2013 Oct 7. pii: S1878-8750(13)01291-6. doi: 10.1016/j.wneu.2013.10.006. [Epub ahead of print]

Jazz Improvisation, Creativity And Brain Plasticity.

Duffau H.

Source

Department of Neurosurgery, Gui de Chauliac Hospital, Montpellier University Medical Center, 80 Av Augustin Fliche, 34295 Montpellier, France; National Institute for Health and Medical Research (INSERM), U1051 Laboratory, Team "Brain Plasticity, Stem Cells and Glial Tumors", Institute for Neurosciences of Montpellier, Montpellier University Medical Center, 34091 Montpellier, France. Electronic address: h-duffau@chu-montpellier.fr.

We present the case of a professional jazz guitarist with temporal lobe epilepsy secondary to an arteriovenous cerebral malformation. He underwent a left temporal lobectomy in 1980. Following surgery, he presented with severe retrograde amnesia as well as complete loss of musical interest and capabilities. The patient's musical abilities recovered over time and he regained his previous virtuoso status. In 2007 his medical history, neuropsychological functions, and structural MRI were examined and revealed a remarkable degree of recovery of memory and musical abilities in the context of extensive temporal lobe resection. The neuropsychological findings and neuroanatomical features of the MRI were analyzed to try to understand the high degree of recovery of both long-term memory and musical processing abilities in this musician. This case also reveals the possibility of an unusual degree of cerebral plasticity and reorganization. Additionally, it emphasizes the question of musical virtuosism. This report shows that the musical capabilities of professional musicians, in specific cases, can completely recover even when much of the left temporal lobe has been removed.

The relationship between adolescents' well-being and their wireless phone use

Environ Health. 2013 Oct 22;12(1):90. [Epub ahead of print]

The relationship between adolescents' well-being and their wireless phone use: a cross-sectional study.

Redmayne M, Smith E, Abramson MJ.

Abstract

BACKGROUND:

The exposure of young people to radiofrequency electromagnetic fields (RF-EMFs) has increased rapidly in recent years with their increased use of cellphones and use of cordless phones and WiFi. We sought to ascertain associations between New Zealand early-adolescents' subjective well-being and self-reported use of, or exposure to, wireless telephone and internet technology.

METHODS:

In this cross-sectional survey, participants completed questionnaires in class about their cellphone and cordless phone use, their self-reported well-being, and possible confounding information such as whether they had had influenza recently or had a television in the bedroom. Parental questionnaires provided data on whether they had WiFi at home and cordless phone ownership and model. Data were analysed with Ordinal Logistic Regression adjusting for common confounders. Odds ratios (OR) and 95% confidence intervals were calculated.

RESULTS:

The number and duration of cellphone and cordless phone calls were associated with increased risk of headaches (>6 cellphone calls over 10 minutes weekly, adjusted OR 2.4, CI 1.2-4.8; >15 minutes cordless use daily adjusted OR 1.74, CI 1.1-2.9)). Texting and extended use of wireless phones was related to having a painful 'texting' thumb). Using a wired cellphone headset was associated with tinnitus (adjusted OR 1.8, CI 1.0-3.3), while wireless headsets were associated with headache (adjusted OR 2.2, CI 1.1-4.5), feeling down/depressed (adjusted OR 2.0, CI 1.1-3.8), and waking in the night (adjusted OR 2.4, CI 1.2-4.8). Several cordless phone frequencies bands were related to tinnitus, feeling down/depressed and sleepiness at school, while the last of these was also related to modulation. Waking nightly was less likely for those with WiFi at home (adjusted OR 0.7, CI 0.4-0.99). Being woken at night by a cellphone was strongly related to tiredness at school (OR 4.1, CI 2.2-7.7).

CONCLUSIONS:

There were more statistically significant associations (36%) than could be expected by chance (5%). Several were dose-dependent relationships. To safeguard young people's well-being, we suggest limiting their use of cellphones and cordless phones to less than 15 minutes daily, and employing a speaker-phone device for longer daily use. We recommend parental measures are taken to prevent young people being woken by their cellphones.

"providing compassionate care for dying peers may result in transformative experiences for inmate caregivers"

J Forensic Nurs. 2013 Jan-Mar;9(1):35-44. doi: 10.1097/JFN.0b013e31827a585c.

Care and companionship in an isolating environment: inmates attending to dying peers.

Loeb SJ, Hollenbeak CS, Penrod J, Smith CA, Kitt-Lewis E, Crouse SB.

Source

Author Affiliations: 1School of Nursing, The Pennsylvania State University, 2Department of Medicine, Penn State College of Medicine, 3Department of Surgery and Public Health Sciences, Penn State College of Medicine, 4Department of Humanities, Penn State College of Medicine, and 5State College, PA.

Abstract

The purpose of this study was to examine the values, beliefs, and perceptions of end-of-life (EOL) care held by inmates caring for peers approaching the end of their lives. The study is part of a broader participatory action research project to infuse enhanced EOL care into state prisons. Face-to-face interviews using a semistructured discussion guide were conducted with 17 male prisoners who were providing care for peers with advanced chronic illness and approaching end of life. Qualitative data were analyzed using content and thematic analyses. Key themes were getting involved, living the role, and transforming self through caring for others. As well, contextual features at the organizational, peer, and personal levels were identified, which either facilitated or impeded inmate caregiving. Provision of enhanced EOL care by inmate peers shows promise for improving prison community relations and morale, reducing suffering, and demonstrating care and compassion within the harsh prison environment. This study provides clear evidence that providing compassionate care for dying peers may result in transformative experiences for inmate caregivers. Implications for correctional nursing practice include providing training for inmate caregivers, including them in team meetings, and implementing grief support programs. Also, upholding nursing's code of ethics and watching for predatory behavior are critical.

ATS report on managing dyspnea crisis

Ann Am Thorac Soc. 2013 Oct;10(5):S98-S106. doi: 10.1513/AnnalsATS.201306-169ST.

An official american thoracic society workshop report: assessment and palliative management of dyspnea crisis.

Mularski RA, Reinke LF, Carrieri-Kohlman V, Fischer MD, Campbell ML, Rocker G, Schneidman A, Jacobs SS, Arnold R, Benditt JO, Booth S, Byock I, Chan GK,Curtis JR, Donesky D, Hansen-Flaschen J, Heffner J, Klein R, Limberg TM, Manning HL, Morrison RS, Ries AL, Schmidt GA, Selecky PA, Truog RD, Wang AC,White DB; ATS Ad Hoc Committee on Palliative Management of Dyspnea Crisis.

Abstract

In 2009, the American Thoracic Society (ATS) funded an assembly project, Palliative Management of Dyspnea Crisis, to focus on identification, management, and optimal resource utilization for effective palliation of acute episodes of dyspnea. We conducted a comprehensive search of the medical literature and evaluated available evidence from systematic evidence-based reviews (SEBRs) using a modified AMSTAR approach and then summarized the palliative management knowledge base for participants to use in discourse at a 2009 ATS workshop. We used an informal consensus process to develop a working definition of this novel entity and established an Ad Hoc Committee on Palliative Management of Dyspnea Crisis to further develop an official ATS document on the topic. The Ad Hoc Committee members defined dyspnea crisis as "sustained and severe resting breathing discomfort that occurs in patients with advanced, often life-limiting illness and overwhelms the patient and caregivers' ability to achieve symptom relief." Dyspnea crisis can occur suddenly and is characteristically without a reversible etiology. The workshop participants focused on dyspnea crisis management for patients in whom the goals of care are focused on palliation and for whom endotracheal intubation and mechanical ventilation are not consistent with articulated preferences. However, approaches to dyspnea crisis may also be appropriate for patients electing life-sustaining treatment. The Ad Hoc Committee developed a Workshop Report concerning assessment of dyspnea crisis; ethical and professional considerations; efficient utilization, communication, and care coordination; clinical management of dyspnea crisis; development of patient education and provider aid products; and enhancing implementation with audit and quality improvement.

Zombie Nation: Breaking up no longer so hard to do?

Am J Bioeth. 2013 Nov;13(11):3-17. doi: 10.1080/15265161.2013.839752.

If I could just stop loving you: anti-love biotechnology and the ethics of a chemical breakup.

Earp BD, Wudarczyk OA, Sandberg A, Savulescu J.

Source

a University of Oxford.

Abstract

"Love hurts"-as the saying goes-and a certain amount of pain and difficulty in intimate relationships is unavoidable. Sometimes it may even be beneficial, since adversity can lead to personal growth, self-discovery, and a range of other components of a life well-lived. But other times, love can be downright dangerous. It may bind a spouse to her domestic abuser, draw an unscrupulous adult toward sexual involvement with a child, put someone under the insidious spell of a cult leader, and even inspire jealousy-fueled homicide. How might these perilous devotions be diminished? The ancients thought that treatments such as phlebotomy, exercise, or bloodletting could "cure" an individual of love. But modern neuroscience and emerging developments in psychopharmacology open up a range of possible interventions that might actually work. These developments raise profound moral questions about the potential uses-and misuses-of such anti-love biotechnology. In this article, we describe a number of prospective love-diminishing interventions, and offer a preliminary ethical framework for dealing with them responsibly should they arise.

When is a medical record not a medical record?

N Z Med J. 2013 Oct 18;126(1384):109-17.

Why a shared care record is an official medical record.

Gu Y, Orr M, Warren J, Humphrey G, Day K, Tibby S, Fitzpatrick J.

Source

National Institute for Health Innovation, University of Auckland, Private Bag 92019, Auckland, New Zealand. h.gu@auckland.ac.nz.

Abstract

The literature describes three categories of health records: the Official Medical Records held by healthcare providers, Personal Health Records owned by patients, and--a possible in between case--the Shared Care Record. New complications and challenges arise with electronic storage of this latter class of record; for instance, an electronic shared care record may have multiple authors, which presents challenges regarding the roles and responsibilities for record-keeping. This article discusses the definitions and implementations of official medical records, personal health records and shared care records. We also consider the case of a New Zealand pilot of developing and implementing a shared care record in the National Shared Care Planning Programme. The nature and purpose of an official medical record remains the same whether in paper or electronic form. We maintain that a shared care record is an official medical record; it is not a personal health record that is owned and controlled by patients, although it is able to be viewed and interacted with by patients. A shared care record needs to meet the same criteria for medico-legal and ethical duties in the delivery of shared care as pertain to any official medical record.

Is medical brain drain unethical?

Swiss Med Wkly. 2013 Oct 25;143:w13845. doi: 10.4414/smw.2013.13845.

Ethics and policy of medical brain drain: a review.

Kollar E, Buyx A.

Source

Emmy Noether-Group on Bioethics and Political Philosophy and Centre of Advanced Study in Bioeth-ics, University of Münster, Germany; Eszter.Kollar@ukmuenster.de.

Abstract

Health-worker migration, commonly called "medical brain drain", refers to the mass migration of trained and skilled health professionals (doctors, nurses, midwives) from low-income to high-income countries. This is currently leaving a significant number of poor countries, particularly in sub-Saharan Africa, with critical staff shortages in the healthcare sector. A broad consensus exists that, where medical brain drain exacerbates such shortages, it is unethical, and this review presents the main arguments underpinning this view. Notwithstanding the general agreement, which policies are justifiable on ethical grounds to tackle brain drain and how best to go about implementing them remains controversial. The review offers a discussion of the specific ethical issues that have to be taken into account when deciding which policy measures to prioritise and suggests a strategy of policy implementation to address medical brain drain as a matter of urgency.

From ASCO/CAP: Recommendations for Human EGFR 2 Testing in Breast Cancer: Clinical Practice Guideline Update

Antonio C. Wolff, M. Elizabeth H. Hammond, David G. Hicks, Mitch Dowsett, Lisa M. McShane, Kimberly H. Allison, Donald C. Allred, John M.S. Bartlett, Michael Bilous, Patrick Fitzgibbons, Wedad Hanna, Robert B. Jenkins, Pamela B. Mangu, Soonmyung Paik, Edith A. Perez, Michael F. Press, Patricia A. Spears, Gail H. Vance, Giuseppe Viale, Daniel F. Hayes (2013) Recommendations for Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Update. Archives of Pathology & Laboratory Medicine In-Press.

Early Online Release

Recommendations for Human Epidermal Growth Factor Receptor 2 Testing in Breast Cancer: American Society of Clinical Oncology/College of American Pathologists Clinical Practice Guideline Update

Antonio C. Wolff *, M. Elizabeth H. Hammond *, David G. Hicks *, Mitch Dowsett *, Lisa M. McShane *, Kimberly H. Allison, Donald C. Allred, John M.S. Bartlett, Michael Bilous, Patrick Fitzgibbons, Wedad Hanna, Robert B. Jenkins, Pamela B. Mangu,Soonmyung Paik, Edith A. Perez, Michael F. Press, Patricia A. Spears, Gail H. Vance, Giuseppe Viale, and Daniel F. Hayes *

Antonio C. Wolff, Johns Hopkins Kimmel Comprehensive Cancer Center, Baltimore; Lisa M. McShane, National Cancer Institute, Bethesda, MD; M. Elizabeth H. Hammond, University of Utah School of Medicine and Intermountain Healthcare, Salt Lake City, UT; David G. Hicks, University of Rochester Medical Center, Rochester, NY; Mitch Dowsett, Royal Marsden Hospital, London, United Kingdom; Kimberly H. Allison, Stanford University Medical Center, Stanford; Patrick Fitzgibbons, St Jude Medical Center, Fullerton; Michael F. Press, University of Southern California, Los Angeles, CA; Donald C. Allred, Washington University School of Medicine, St Louis, MO; John M.S. Bartlett, Ontario Institute for Cancer Research; Wedad Hanna, Sunnybrook Health Sciences Center, Toronto, Ontario, Canada; Michael Bilous, University of Western Sydney and Healthscope Pathology, Sydney, New South Wales, Australia; Robert B. Jenkins, Mayo Clinic, Rochester, MN; Pamela B. Mangu, American Society of Clinical Oncology, Alexandria, VA; Soonmyung Paik, National Surgical Adjuvant Breast and Bowel Project, Pitsburgh, PA; Edith A. Perez, Mayo Clinic, Jacksonville, FL; Patricia A. Spears, North Carolina State University, Raleigh, NC; Gail H. Vance, Indiana University Medical Center, Indianapolis, IN; Giuseppe Viale, University of Milan, European Institute of Oncology, Milan, Italy; and Daniel F. Hayes, University of Michigan Comprehensive Cancer Care Center, Ann Arbor, MI.

Purpose. To update the American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guideline recommendations for human epidermal growth factor receptor 2 (HER2) testing in breast cancer to improve the accuracy of HER2 testing and its utility as a predictive marker in invasive breast cancer.

Methods. ASCO/CAP convened an Update Committee that included coauthors of the 2007 guideline to conduct a systematic literature review and update recommendations for optimal HER2 testing.

Results. The Update Committee identified criteria and areas requiring clarification to improve the accuracy of HER2 testing by immunohistochemistry (IHC) or in situ hybridization (ISH). The guideline was reviewed and approved by both organizations.

Recommendations. The Update Committee recommends that HER2 status (HER2 negative or positive) be determined in all patients with invasive (early stage or recurrence) breast cancer on the basis of one or more HER2 test results (negative, equivocal, or positive). Testing criteria define HER2-positive status when (on observing within an area of tumor that amounts to >10% of contiguous and homogeneous tumor cells) there is evidence of protein overexpression (IHC) or gene amplification (HER2 copy number or HER2/CEP17 ratio by ISH based on counting at least 20 cells within the area). If results are equivocal (revised criteria), reflex testing should be performed using an alternative assay (IHC or ISH). Repeat testing should be considered if results seem discordant with other histopathologic findings. Laboratories should demonstrate high concordance with a validated HER2 test on a sufficiently large and representative set of specimens. Testing must be performed in a laboratory accredited by CAP or another accrediting entity. The Update Committee urges providers and health systems to cooperate to ensure the highest quality testing.

Published Online: October 7, 2013

Eur J Public Health. 2013 Oct 23. [Epub ahead of print]

Adolescent perceptions of cigarette appearance.

Ford A, Moodie C, Mackintosh AM, Hastings G.

Source

1 Centre for Tobacco Control Research, Institute for Social Marketing, University of Stirling, Stirlingshire FK9 4LA, UK.

Abstract

BACKGROUND:

To reduce the possibility of cigarette appearance misleading consumers about harm caused by the product, the European Commission's draft Tobacco Products Directive proposed banning cigarettes <7.5 mm in diameter. It appears however, following a plenary vote in the European Parliament, that this will not be part of the final Tobacco Products Directive. To reduce the appeal of cigarettes, the Australian Government banned the use of branding on cigarettes and stipulated a maximum cigarette length as part of the Tobacco Plain Packaging Act. We explored the role, if any, of cigarette appearance on perceptions of appeal and harm among adolescents.

METHODS:

Focus group research with 15-year-olds (N = 48) was conducted in Glasgow (Scotland) to explore young people's perceptions of eight cigarettes differing in length, diameter, colour and decorative design.

RESULTS:

Slim and superslim cigarettes with white filter tips and decorative features were viewed most favourably and rated most attractive across gender and socio-economic groups. The slimmer diameters of these cigarettes communicated weaker tasting and less harmful looking cigarettes. This was closely linked to appeal as thinness implied a more pleasant and palatable smoke for young smokers. A long brown cigarette was viewed as particularly unattractive and communicated a stronger and more harmful product.

CONCLUSION:

This exploratory study provides some support that standardising cigarette appearance could reduce the appeal of cigarettes in adolescents and reduce the opportunity for stick design to mislead young smokers in terms of harm.