Thursday, February 28, 2019

Update on emerging biomarkers in lung cancer

 2019 Jan;11(Suppl 1):S81-S88. doi: 10.21037/jtd.2019.01.46.

Update on emerging biomarkers in lung cancer.

Author information

1
Houston Methodist Hospital, Cancer Center, Houston, Texas, USA.
2
Department of Pathology, University of Mississippi Medical Center, Jackson, Mississippi, USA.
3
Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, Texas, USA.

Abstract

There has been considerable progress made in identifying oncogenic driver mutations in advanced lung cancer. The recognition that lung cancer is actually an umbrella classification that is comprised of multiple molecular subgroups has had a profound impact on how medical oncologists make treatment decisions. These mutations are clinically important as available targeted therapies can achieve significant responses and prolonged disease control. This review will summarize the current guidelines for biomarker testing and available therapeutic agents.

Obesity and the 'self-control' brain area: What is the link?

Obesity and the 'self-control' brain area: What is the link?


"Exercise has been shown to increase activity in our prefrontal cortex," suggests Lowe, "which in turn lets us better ignore food cravings, going well beyond its traditional role as merely a means of getting rid of surplus calories."

"The adoption of a single-payer system requires major trade-offs: a loss of personal and economic freedom, the loss of existing health coverage, the imposition of unprecedented federal taxation, major payment reductions for doctors and medical professionals, long waiting lists, and care delays and denials."

The National Debate over Government-Controlled Health Care


Policymakers are debating whether Congress should enact a single-payer health care system or create a system based on personal choice and market competition. The fundamental question is whether government officials or individuals and families will make the key health care decisions. The adoption of a single-payer system requires major trade-offs: a loss of personal and economic freedom, the loss of existing health coverage, the imposition of unprecedented federal taxation, major payment reductions for doctors and medical professionals, long waiting lists, and care delays and denials. Public opinion on this issue is in flux and malleable, and conservatives in Congress must offer sound, concrete policy alternatives or risk forfeiting the game and handing victory to the champions of a single-payer program.

Rebirth of the body politic

Rebirth of the body politic

Individualism is not a sufficient foundation for social life: the image of the body politic reminds us that we are all one

"Aristotle’s vision of political life combines Thucydides’ realism and Plato’s idealism. He acknowledged that humans formed themselves into political bodies to survive, but he did not believe that this fully accounted for the purpose of the city-state. ‘While it comes into existence for the sake of life, it remains in existence for the sake of the good life,’ Aristotle writes in the Politics. The state does not just secure life but renders it rich and meaningful. National parks, orchestras, symphonies, museums and libraries are some of the descendants of this idea."



Patient perspectives on use of electronic health records for research recruitment

 2019 Feb 26;19(1):42. doi: 10.1186/s12874-019-0686-z.

Patient perspectives on use of electronic health records for research recruitment.

Author information

1
Center for Biomedical Ethics and Society, Vanderbilt University Medical Center, 2525 West End Avenue, Suite 400, Nashville, TN, 37203, USA. laura.m.beskow@vanderbilt.edu.
2
Center for Biomedical Ethics and Society, Vanderbilt University Medical Center, 2525 West End Avenue, Suite 400, Nashville, TN, 37203, USA.

Abstract

BACKGROUND:

EHR phenotyping offers the ability to rapidly assemble a precisely defined cohort of patients prescreened for eligibility to participate in health-related research. Even so, stakeholders in the process must still contend with the practical and ethical challenges associated with research recruitment. Patient perspectives on these matters are particularly important given that the success of research recruitment depends on patients' willingness to participate.

METHODS:

We conducted 15 focus groups (n = 110 participants) in four counties in diverse regions of the southeastern US: Appalachia, the Mississippi Delta, and the Piedmont area of North Carolina. Based on a hypothetical study of a behavioral intervention for type 2 diabetes, we asked about the acceptability and appropriateness of direct investigator versus physician-mediated contact with patients for research recruitment, and whether patients should be asked to opt in or opt out of further contact in response to recruitment letters.

RESULTS:

For initial contact, nearly all participants said it would be acceptable for researchers to contact patients directly and three-fourths said that it would be acceptable for researchers to contact patients through their physicians. When we asked which would be most appropriate, a substantial majority chose direct contact. Themes that arose in the discussion included trust and transparency, decision-making power, the effect on research, and the effect on patient care. For response expectations, the vast majority of participants said both opt-in and opt-out would be acceptable-typically finding neither especially problematic and noting that both afford patients the opportunity to make their own decisions.

CONCLUSIONS:

External validity relies heavily on researchers' success enrolling eligible patients and failure to reach accrual targets is a costly and common barrier to advancing scientific knowledge. Our results suggest that patients recognize multiple advantages and disadvantages of different research recruitment strategies and place value on the implications not just for themselves, but also for researchers and healthcare providers. Our findings, including rich qualitative detail, contribute to the body of empirical and ethical literature on improving research recruitment and suggest specific ways forward as well as important areas for future research.

Tuesday, February 19, 2019

Update on emerging biomarkers in lung cancer

 2019 Jan;11(Suppl 1):S81-S88. doi: 10.21037/jtd.2019.01.46.

Update on emerging biomarkers in lung cancer.

Author information

1
Houston Methodist Hospital, Cancer Center, Houston, Texas, USA.
2
Department of Pathology, University of Mississippi Medical Center, Jackson, Mississippi, USA.
3
Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, Texas, USA.

Abstract

There has been considerable progress made in identifying oncogenic driver mutations in advanced lung cancer. The recognition that lung cancer is actually an umbrella classification that is comprised of multiple molecular subgroups has had a profound impact on how medical oncologists make treatment decisions. These mutations are clinically important as available targeted therapies can achieve significant responses and prolonged disease control. This review will summarize the current guidelines for biomarker testing and available therapeutic agents.

Use of Immune Checkpoint Inhibitors in Mesothelioma

 2019 Feb 14;20(2):18. doi: 10.1007/s11864-019-0613-x.

Use of Immune Checkpoint Inhibitors in Mesothelioma.

Author information

1
Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, MD, USA.
2
Pulmonary and Thoracic Oncology Department, Univ Lille, CHU Lille, INSERM U1189 OncoThAI, F59000, Lille, France.
3
French National Network of Clinical Expert Centers for Malignant Pleural Mesothelioma Management (MESOCLIN), Lille, France.
4
Department of Thoracic/Head and Neck Medical Oncology, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd. Unit 432, Houston, TX, 77030, USA. astsao@mdanderson.org.

Abstract

Recent advances in immunology have extended into the mesothelioma field. To date, only Japan has given regulatory approval to salvage nivolumab in chemo-refractory mesothelioma patients. The USA has included in the NCCN guidelines that pembrolizumab (in programmed death ligand 1 (PD-L1) immunohistochemistry (IHC)-positive patients) and nivolumab with or without ipilimumab (whatever the PD-L1 status is) are accepted salvage therapies. Based on the growing body of literature, it is anticipated that checkpoint inhibitors will receive regulatory approval in the USA and Europe soon for salvage therapy. Additional research efforts will determine whether earlier stage patients and frontline unresectable patients will benefit from the addition of immunotherapy to their treatment regimens. The realm of biomarker research has lagged behind in mesothelioma. In general, mesothelioma has less tumor mutation burden than other malignancies. Most of the single-agent salvage checkpoint inhibitor trials have shown a trend correlating higher PD-L1 immunohistochemistry (IHC) with responses. However, survival data remains immature and a larger number of patient outcomes are needed to ascertain the value of PD-L1 IHC as a predictive biomarker. Incorporation of translational studies in all immunotherapy trials and especially window-of-opportunity resectable studies should be supported and instituted in all future mesothelioma trials.

"...socialism is not like good wine, which, in moderation, might not hurt and might even be beneficial. Every step in which economic freedom is cut back bears costs." #ButSocialism

Socialism has already hurt America

From U Tirana, Albania: Forbidden insanity: the systematic denial of mental health issues from a state-run psychiatry

 2018 Dec;30(4):385-389. doi: 10.24869/psyd.2018.385.

Forbidden insanity: the systematic denial of mental health issues from a state-run psychiatry.

Author information

1
Faculty of Medicine, University of Medicine in Tirana, Tirana, Albania, gvyshka@gmail.com.

Abstract

The authors discuss the issue of psychiatric care and patients during the second half of XX century in Albania, when the country was under an absolute regime of communism. Completely isolated from the rest of the world, the territory remained a prohibited area for scholars, and local authors due to censorship or self-censorship, offered very scarce information. The general feeling of the public was that of a denial of psychic disorders in total, combined with the fear that this kind of disorders has ever since provoked. Nevertheless, insanity defence was a formulation encountered with a certain frequency in Albanian judicial procedures, although forensic psychiatry was a peripheral part of an already neglected medical specialty. The entire system of psychiatric care was mainly hospital based, and shock therapies (electroconvulsive therapy, pyretotherapy, insulin coma) were normal part of the therapeutic armamentarium along with antipsychotics and social isolation. Some recently unclassified documents and some archival papers, whose exhaustive consultation needs further study, might shed light to the problems of a psychiatry, that are not substantially different from the ones encountered in the Eastern communist Europe of the same period of time.

"Although no official accounting of the total atrocities committed by the K.G.B. exists, estimates place multiple millions of Russians in forced labor camps known as gulags, or to their deaths, both at home and abroad." #ButSocialism #ButCommunism

The Incomplete History Told by New York’s K.G.B. Museum

Designed to be apolitical, the attraction offers whiz-bang tech without the agency’s brutal past

"The USSR used the K.G.B. to quell dissent, by whatever violent means necessary, and run general surveillance on its citizenry as part of its efforts to maintain Communist order. During the Cold War, the K.G.B. rivaled the C.I.A. around the globe, but primarily carried out its most brutal acts behind the Iron Curtain. A 1980 U.S. intelligence report asserted that at its peak, the K.G.B. employed some 480,000 people (along with millions of informers) and infiltrated every aspect of life in the Soviet Union—one dissident Orthodox priest said in the 1970s that 'one hundred percent of the clergy were forced to cooperate with the K.G.B.'
Although no official accounting of the total atrocities committed by the K.G.B. exists, estimates place multiple millions of Russians in forced labor camps known as gulags, or to their deaths, both at home and abroad. The K.G.B. was instrumental in crushing the Hungarian Revolution of 1956 and the Prague Spring of 1968.When a collection of documents related to the K.G.B.’s work in Prague was released and examined by reporters and historians, it became abundantly clear that of all the weapons used by the agency, fear was the most pervasive. 'They considered the worst enemies those who could influence public opinion through media,' said Milan Barta, a senior researcher at Prague's Institute for Study of Totalitarian Regimes in a 2014 interview with the Washington Examiner. Unsuccessful plots by the K.G.B. included the kidnapping of novelist Milan Kundera and the silencing of other key public figures."


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Vaping Is Harm Reduction

Vaping Is Harm Reduction

The surgeon general is right on opioids, but wrong on tobacco.

Artificial Intelligence Crime

 2019 Feb 14. doi: 10.1007/s11948-018-00081-0. [Epub ahead of print]

Artificial Intelligence Crime: An Interdisciplinary Analysis of Foreseeable Threats and Solutions.

Author information

1
Oxford Internet Institute, University of Oxford, 1 St Giles, Oxford, OX1 3JS, UK.
2
Faculty of Law, University of Oxford, St Cross Building St. Cross Rd, Oxford, OX1 3UL, UK.
3
The Alan Turing Institute, 96 Euston Road, London, NW1 2DB, UK.
4
Oxford Internet Institute, University of Oxford, 1 St Giles, Oxford, OX1 3JS, UK. luciano.floridi@oii.ox.ac.uk.
5
The Alan Turing Institute, 96 Euston Road, London, NW1 2DB, UK. luciano.floridi@oii.ox.ac.uk.

Abstract

Artificial intelligence (AI) research and regulation seek to balance the benefits of innovation against any potential harms and disruption. However, one unintended consequence of the recent surge in AI research is the potential re-orientation of AI technologies to facilitate criminal acts, term in this article AI-Crime (AIC). AIC is theoretically feasible thanks to published experiments in automating fraud targeted at social media users, as well as demonstrations of AI-driven manipulation of simulated markets. However, because AIC is still a relatively young and inherently interdisciplinary area-spanning socio-legal studies to formal science-there is little certainty of what an AIC future might look like. This article offers the first systematic, interdisciplinary literature analysis of the foreseeable threats of AIC, providing ethicists, policy-makers, and law enforcement organisations with a synthesis of the current problems, and a possible solution space.

"Cognitive neuroscience investigations have begun to reveal the distributed neural networks which interact to implement moral judgment and social decision-making, including systems for reward learning, valuation, mental state understanding, and salience processing."

 2018;24(3):279-295. doi: 10.1080/1068316X.2017.1414817. Epub 2017 Dec 12.

The neuroscience of morality and social decision-making.

Author information

1
Department of Psychology, University of Chicago, Chicago, IL, USA.
2
Department of Psychiatry and Behavioral Neuroscience, University of Chicago Medicine, Chicago, IL, USA.

Abstract

Across cultures humans care deeply about morality and create institutions, such as criminal courts, to enforce social norms. In such contexts, judges and juries engage in complex social decision-making to ascertain a defendant's capacity, blameworthiness, and culpability. Cognitive neuroscience investigations have begun to reveal the distributed neural networks which interact to implement moral judgment and social decision-making, including systems for reward learning, valuation, mental state understanding, and salience processing. These processes are fundamental to morality, and their underlying neural mechanisms are influenced by individual differences in empathy, caring and justice sensitivity. This new knowledge has important implication in legal settings for understanding how triers of fact reason. Moreover, recent work demonstrates how disruptions within the social decision-making network facilitate immoral behavior, as in the case of psychopathy. Incorporating neuroscientific methods with psychology and clinical neuroscience has the potential to improve predictions of recidivism, future dangerousness, and responsivity to particular forms of rehabilitation.

"It can never be said that the identity of the patient whose best interests are at stake evaporates (so eliminating the legal or ethical subject) when that person ceases to be conscious. Nor can it be said that the best interests of an unconscious person do not mandate continued biological existence."

 2019 Feb 14. pii: medethics-2018-105250. doi: 10.1136/medethics-2018-105250. [Epub ahead of print]

It is never lawful or ethical to withdraw life-sustaining treatment from patients with prolonged disorders of consciousness.

Author information

1
Faculty of Law, University of Oxford, Oxford, UK.
2
Green Templeton College, University of Oxford, Oxford, UK.

Abstract

In English law there is a strong (though rebuttable) presumption that life should be maintained. This article contends that this presumption means that it is always unlawful to withdraw life-sustaining treatment from patients in permanent vegetative state (PVS) and minimally conscious state (MCS), and that the reasons for this being the correct legal analysis mean also that such withdrawal will always be ethically unacceptable. There are two reasons for this conclusion. First, the medical uncertainties inherent in the definition and diagnosis of PVS/MCS are such that, as a matter of medical fact, it can never be established, with the degree of certainty necessary to rebut the presumption, that it is not in the patient's best interest to remain alive. And second (and more controversially and repercussively), that even if permanent unconsciousness can be unequivocally demonstrated, the presumption is not rebutted. This is because there is plainly more to human existence than consciousness (or consciousness the markers of which can ever be demonstrated by medical investigations). It can never be said that the identity of the patient whose best interests are at stake evaporates (so eliminating the legal or ethical subject) when that person ceases to be conscious. Nor can it be said that the best interests of an unconscious person do not mandate continued biological existence. We simply cannot know. That uncertainty is legally conclusive, and (subject to resource allocation questions and views about the relevance of family wishes and the previously expressed wishes of the patient) should be ethically conclusive.

'Medicare for All' would require obesity laws ("The country under single-payer will make former Mayor Michael Bloomberg's soda taxes and food-nannying look like child's play.") #nannystate #GovernmentIsPower

'Medicare for All' would require obesity laws


"It seems impossible for any real iteration of "Medicare for All" to succeed without massive amounts of regulation on lifestyle and health choices, or even effective obesity taxes. If the public owns the risk pool of "Medicare for All," then voters will surely demand to mitigate risk as much as possible.
The country under single-payer will make former Mayor Michael Bloomberg's soda taxes and food-nannying look like child's play. Everything from your sugar consumption to your alcohol would become a matter of public regulation, and the public would not only have the power but also the moral right to regulate how people live."

Interpathologist Diagnostic Agreement for Non-Small Cell Lung Carcinomas Using Current and Recent Classifications

 2018 Dec;142(12):1537-1548. doi: 10.5858/arpa.2017-0481-OA. Epub 2018 Apr 30.

Interpathologist Diagnostic Agreement for Non-Small Cell Lung Carcinomas Using Current and Recent Classifications.

Author information

1
From the Department of Pathology & Laboratory Medicine, University of North Carolina School of Medicine, Chapel Hill (Drs Funkhouser Jr and Banks); Lineberger Comprehensive Cancer Center, UNC, Chapel Hill, North Carolina (Drs Funkhouser Jr, Hayes, Nikolaishvilli-Feinberg, and Grilley-Olson; Messrs Moore and Jo; and Ms Eeva); the Department of Medicine, UNC School of Medicine, Chapel Hill, North Carolina (Drs Hayes and Grilley-Olson); the Department of Computer Sciences, University of Wisconsin, Madison (Mr Funkhouser III); the Department of Biostatistics, UNC School of Public Health, Chapel Hill, North Carolina (Dr Fine); Medical Affairs, Ventana Medical Systems, Tucson, Arizona (Dr Banks); Unit of Pathology, Scientific Institute for Research and Health Care, San Giovanni Rotondo, Italy (Dr Graziano); the Department of Pathology, VA Medical Center, Durham, North Carolina (Dr Boswell); the Department of Medical Biosciences, Pathology, Umeå University Hospital, Umeå, Sweden (Dr Elmberger); the Department of Pathology, Kaiser-Permanente Hospital, Santa Clara, California (Dr Raparia); the Department of Pathology, Piedmont Medical Center, Rock Hill, South Carolina (Dr Hart); the Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts (Dr Sholl); the Department of Pathology, Suburban Hospital, Bethesda, Maryland (Dr Nolan); the Department of Pathology, Mayo Clinic, Rochester, Minnesota (Dr Fritchie); the Department of Pathology, VA Medical Center, Dayton, Ohio (Dr Pouagare); the Department of Pathology, University of Texas Medical Branch, Galveston (Dr Allen); the Department of Pathology, Rex Hospital, Raleigh, North Carolina (Dr Volmar); the Department of Pathology, Medical College of Georgia, Augusta (Drs Biddinger and Kleven); the Department of Pathology, Flagstaff Medical Center, Flagstaff, Arizona (Dr Papez); the Department of Pathology, VA Medical Center, Charleston, South Carolina (Dr Spencer); the Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York (Dr Rekhtman); the Department of Pathology, Massachusetts General Hospital, Boston (Drs Mino-Kenudson and Hariri); and the Department of Pathology & Genomic Medicine, Houston Methodist Hospital, Houston, Texas (Drs Driver and Cagle). Dr Allen is currently located at the Department of Pathology at University of Mississippi Medical Center, Jackson.

Abstract

CONTEXT.—:

Measurement of interpathologist diagnostic agreement (IPDA) should allow pathologists to improve current diagnostic criteria and disease classifications.

OBJECTIVES.—:

To determine how IPDA for pathologists' diagnoses of non-small cell lung carcinoma (NSCLC) is affected by the addition of a set of mucin and immunohistochemical (IHC) stains to hematoxylin-eosin (H&E) alone, by recent NSCLC reclassifications, by simplification of these classifications, and by pathologists' practice location, pulmonary pathology expertise, practice duration, and lung carcinoma case exposure.

DESIGN.—:

We used a Web-based survey to present core images of 54 NSCLC cases to 22 practicing pathologists for diagnosis, initially as H&E only, then as H&E plus mucin and 4 IHC stains. Each case was diagnosed according to published 2004, 2011, and 2015 NSCLC classifications. Cohen's kappa was calculated for the 231 pathologist pairs as a measure of IPDA.

RESULTS.—:

Twenty-two pathologists diagnosed 54 NSCLC cases by using 4 published classifications. IPDA is significantly higher for H&E/mucin/IHC diagnoses than for H&E-only diagnoses. IPDA for H&E/mucin/IHC diagnoses is highest with the 2015 classification. IPDA is estimated higher after collapse of stated diagnoses into subhead or dichotomized classes. IPDA for H&E/mucin/IHC diagnoses with the 2015 World Health Organization classification is similar for community and academic pathologists, and is higher when pathologists have pulmonary pathology expertise, have more than 6 years of practice experience, or diagnose more than 100 new lung carcinoma cases per year.

CONCLUSIONS.—:

Higher IPDA is associated with use of mucin and IHC stains, with the 2015 NSCLC classification, and with pathologists' pulmonary pathology expertise, practice duration, and frequency of lung carcinoma cases.

Ohio hospital to close after 105 years

Ohio hospital to close after 105 years



Belmont Community Hospital, a 99-bed hospital in Bellaire, Ohio, will close April 5.
The hospital opened as Bellaire City Hospital in 1914 and was acquired by Wheeling (W.Va.) Hospital in 1996.

"To acknowledge the reality of moral life is to recognize that the world contains such things as kindness, as foolishness, as mean-spiritedness."

Iris Murdoch and the power of love

Anil Gomes considers Murdoch’s view that morality is real and that, with the right conceptual resources, we can perceive it