Popul Health Manag. 2016 Jan 29. [Epub ahead of print]

Describing Total Population Health: A Review and Critique of Existing Units.

Baehr A1,2, Holland T3, Biala K4,5, Margolis GS4, Wiebe DJ2,6, Carr BG4,7.

Author information

• 11 Office of Disease Prevention and Health Promotion , U.S. Department of Health and Human Services, Rockville, Maryland.
• 22 Perelman School of Medicine at the University of Pennsylvania , Philadelphia, Pennsylvania.
• 33 GAP Solutions, Inc. (Contractor) Supporting the Office of the Assistant Secretary for Preparedness and Response , U.S. Department of Health and Human Services, Washington, DC.
• 44 Emergency Care Coordination Center , Office of the Assistant Secretary for Preparedness and Response, U.S. Department of Health and Human Services, Washington, DC.
• 55 U.S. Department of Agriculture, Food and Nutrition Service , Alexandra, Virginia.
• 66 Department of Biostatistics and Epidemiology, University of Pennsylvania , Philadelphia, Pennsylvania.
• 77 Sidney Kimmel Medical College, Thomas Jefferson University , Philadelphia, Pennsylvania.

Abstract

Total population health is a key tenet of health care reform efforts, evident in initiatives such as the National Quality Strategy, shifts toward population-based payments, and community benefit requirements for tax-exempt hospitals. Representing total population health in a way that guides best practices and establishes shared accountability for geographic communities, however, remains a challenge in part because of differences in how stakeholders define populations. To better understand the landscape of potential denominators for population health, this study examined a selection of relevant geographic units. The approach included a comprehensive review of health services and public health research literature as well as recent pertinent health policy documents. Units were characterized based on whether they: exhibit "breadth" of coverage across the whole US population; are "accurate" or grounded in health care utilization patterns; are "actionable" with mechanisms for implementing funding and regulation; and promote "synergism" or effective coordination of public health and health care activities. Although other key components of a total population health unit may exist and no single identified unit possesses all of the aforementioned features, several promising candidates were identified. Specifically, healthcare coalitions link health care and public health domains to care for a geographic community, but their connection to utilization is not empiric and limited funding exists at the coalition level. Although Accountable Care Organizations do not uniformly incorporate public health or facilitate coordination across all payers or providers, they represent an effective mechanism to increase collaboration within health care systems and represent a potential building block to influence total population health.

"The revised 2013 ASCO/CAP guidelines can potentially lead to more patients being eligible for trastuzumab therapy..."

Tse Hui Lim, Alvin Soon Tiong Lim, Aye Aye Thike, Sim Leng Tien, and Puay Hoon Tan (2016) Implications of the Updated 2013 American Society of Clinical Oncology/College of American Pathologists Guideline Recommendations on Human Epidermal Growth Factor Receptor 2 Gene Testing Using Immunohistochemistry and Fluorescence In Situ Hybridization for Breast Cancer. Archives of Pathology & Laboratory Medicine: February 2016, Vol. 140, No. 2, pp. 140-147.

ORIGINAL ARTICLES

Implications of the Updated 2013 American Society of Clinical Oncology/College of American Pathologists Guideline Recommendations on Human Epidermal Growth Factor Receptor 2 Gene Testing Using Immunohistochemistry and Fluorescence In Situ Hybridization for Breast Cancer

Tse Hui Lim, MSc; Alvin Soon Tiong Lim, PhD; Aye Aye Thike, MMedSci; Sim Leng Tien, MD, FRCPA; Puay Hoon Tan, MD, FRCPath

From the Department of Pathology, The Academia, Singapore General Hospital, Singapore.

Reprints: Tse Hui Lim, MSc, Cytogenetics Laboratory, Department of Pathology, The Academia, Diagnostics Tower, Level 9, Singapore General Hopsital, 20 College Rd, Singapore 169856 (e-mail: lim.tse.hui@sgh.com.sg).

The authors have no relevant financial interest in the products or companies described in this article.

Context.— Human epidermal growth factor receptor 2 (HER2/neu) amplification is used as a predictive marker for trastuzumab treatment in breast cancer. Both immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) testing algorithms have been based on the 2007 American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines. In late 2013, the guidelines were updated with new scoring criteria.

Objective. —To assess the impact of the revised ASCO/CAP recommendations on both IHC and FISH results by using the dual-color HER2/neu and centromeric FISH probes.

Design.— Retrospective analysis of 590 invasive carcinomas with concurrent IHC and dual-color HER2/neu and centromeric 17 (CEP17) FISH results, based on 2007 ASCO/CAP guidelines, was conducted from July 2011 to June 2013. With the revised guidelines, patients were recategorized and concordance rates between the 2 assays were recalculated.

Results. —Overall concordance rates for FISH and IHC decreased from 94.9% to 93.8% with reclassification. Negative FISH cases decreased from 79.1% to 69.3%. However, equivocal FISH cases were significantly increased from 0.7% to 9.5%, leading to more retesting. Both positive IHC and FISH cases were also noted to be increased, leading to more patients being eligible for trastuzumab treatment, especially those patients with concurrent HER2/neu and CEP17 polysomy. Approximately 1% of patients with initial FISH negative results were reclassified as having positive results when both the ratios and average copy number of HER2/neu were considered under the revised guidelines.

Conclusions.— The revised 2013 ASCO/CAP guidelines can potentially lead to more patients being eligible for trastuzumab therapy but additional retesting is to be expected owing to an increased number of equivocal FISH cases.

Nurs Ethics. 2016 Jan 27. pii: 0969733015623096. [Epub ahead of print]

Religion, Judaism, and the challenge of maintaining an adequately immunized population.

Greenberger C1.

Author information

• 1Jerusalem College of Technology, Israel greenber@jct.ac.il.

Abstract

A slow but steady trend to decline routine immunization has evolved over the past few decades, despite its pivotal role in staving off life-threatening communicable diseases. Religious beliefs are among the reasons given for exemptions. In the context of an overview of various religious approaches to this issue, this article addresses the Jewish religious obligation to immunize. The latter is nested in the more general obligation to take responsibility for one's health as it is essential to living a morally productive life. Furthermore, the individual's responsibility extends to supporting communal health by contributing to herd immunity. Judaism embraces evidence-based information regarding immunization safety and efficacy and holds the resulting professional guidelines to be religiously binding. From a Jewish perspective, government bodies need to weigh respect for individual autonomy to refrain from immunization against preserving public safety, such that waiving autonomy should be reserved for immediately life-threatening situations. Nurses' knowledge and understanding of the Jewish legal approach as explicated in this article and those of other religions in which similar principles apply (such as Islam and Christianity) can enrich their awareness of how revering God can go hand in hand with an obligation to prevent illness for the self and the community by immunizing.

ENDING CHILDHOOD OBESITY IS A GLOBAL CHALLENGE

BY SANIA NISHTAR AND PETER GLUCKMAN ON 1/30/16 AT 7:02 AM

"The increase in obesity in low- and middle-income countries across Africa and Asia—which is truly alarming—threatens to negate the increased life expectancy seen over the last decade and significantly contributes to rising deaths, diseases and reduced quality of life for those affected."

Philip T. Cagle, MD: The Archives of Pathology and Laboratory Medicine: Pioneering Spirit Continues After 90 Years

Philip T. Cagle (2016) Pioneering Spirit Continues After 90 Years. Archives of Pathology & Laboratory Medicine: February 2016, Vol. 140, No. 2, pp. 115-115.

EDITORIAL

Pioneering Spirit Continues After 90 Years

Philip T. Cagle, MD

From the Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, Texas.

Corresponding author: Philip T. Cagle, MD, Department of Pathology and Genomic Medicine, Houston Methodist Hospital, 6565 Fannin Street, Main Building, Room 227, Houston, Texas 77030 (e-mail: pcagle@houstonmethodist.org).

Wal-Mart closings to leave food deserts in some areas of U.S.

Wal-Mart closings to leave food deserts in some areas of U.S.

"In Wichita, the Wal-Mart that opened four years ago became a community hub in a shopping plaza that previously had been a haven for prostitution and gang shootings, said Pastor Kevass Harding, whose Dellrose United Methodist Church is near the store.

The store hired workers from the neighborhood. Residents — many of whom are elderly — could walk just blocks to get their medicines at Wal-Mart's pharmacy, as well as fresh produce and meat."

J Med Ethics. 2016 Feb;42(2):100-3. doi: 10.1136/medethics-2015-103213.

HIV status: the prima facie right not to know the result.

Chan TK.

Abstract

When a patient regains consciousness from Cryptococcus meningitis, the clinician may offer an HIV test (in case it has not already been done) (scenario 1) or offer to tell the patient his HIV status (in case the test has already been performed with a positive result while the patient was unconscious) (scenario 2). Youngs and Simmonds proposed that the patient has the prima facie right to refuse an HIV test in scenario 1 but not the prima facie right not to be told the HIV status in scenario 2. I submit that the claims to the right of refusal in both scenarios are similarly strong as they should both be grounded in privacy, self determination or dignity. But a conscientious agent should bear in mind that members of the public also have the right not to be harmed. When the circumstance allows, a proper balance of the potential benefits and harm for all the competing parties should guide the clinical decision as to whose right should finally prevail. Where a full ethical analysis is not possible, the presumption should favour respecting the patient's right of refusal in both scenarios.

"...13 percent of Hispanic young adult women admitted to suffering from clinical depression, compared to only 2 percent of men the same age."

Health habits, attitudes of Hispanic millennials studied

By Jenny Deam

"One of the most disturbing findings, Mallory said, was that 13 percent of Hispanic young adult women admitted to suffering from clinical depression, compared to only 2 percent of men the same age. Mallory said the number is probably much higher because that is only the number who admit to or have been diagnosed with depression."

"With PD-L1 testing it has become clear that the historically used US regulatory approach of one assay-one drug will not be sustainable."

Arch Pathol Lab Med. 2016 Jan 18. [Epub ahead of print]

Programmed Death Ligand 1 Immunohistochemistry- A New Challenge for Pathologists: A Perspective From Members of the Pulmonary Pathology Society.

Sholl LM1, Aisner DL, Allen TC, Beasley MB, Borczuk AC, Cagle PT, Capelozzi V, Dacic S, Hariri L, Kerr KM, Lantuejoul S, Mino-Kenudson M, Raparia K,Rekhtman N, Roy-Chowdhuri S, Thunnissen E, Tsao MS, Yatabe Y.

Author information

Abstract

The binding of programmed death ligands 1 and 2 (PD-L1 and PD-L2) to PD-1 blocks T-cell-mediated immune response to tumor. Antibodies that target programmed death 1 (PD-1) will block the ligand-receptor interface, thereby allowing T cells to attack the tumor and increase antitumor immune response. In clinical trials, PD-1 inhibitors have been associated with an approximately 20% overall response rate in unselected patients with non-small cell lung cancer, with sustained tumor response in a subset of patients treated by these immune checkpoint inhibitors. Facing a proliferation of PD-L1 immunohistochemistry clones, staining platforms, and scoring criteria, the pathologist must decide on the feasibility of introducing a newly approved companion diagnostic assay that may require purchase not only of a specific antibody kit but of a particular staining platform. Given the likely reality that clinical practice may, in the near future, demand access to 4 different PD-L1 antibodies coupled with different immunohistochemistry platforms, laboratories will be challenged with deciding among this variety of testing methods, each with its own potential benefits. Another immediate challenge to PD-L1 testing in lung cancer patients is that of access to adequate tumor tissue, given that non-small cell lung cancer samples are often extremely limited in size. With PD-L1 testing it has become clear that the historically used US regulatory approach of one assay-one drug will not be sustainable. One evolving concept is that of complementary diagnostics, a novel regulatory pathway initiated by the US Food and Drug Administration, which is distinct from companion diagnostics in that it may present additional flexibility. Although pathologists need to face the practical reality that oncologists will be asking regularly for the PD-L1 immunohistochemistry status of their patients' tumors, we should also keep in mind that there may be room for improvement of biomarkers for immunotherapy response. The field is rich with opportunities for investigation into biomarkers of immunotherapy response, particularly in the form of collaborative, multidisciplinary studies that incorporate oncologists, pathologists, and basic scientists. Pathologists must take the lead in the rational incorporation of these biomarkers into clinical practice.

"Motivated by an idealistic view of education and career and vulnerable to predatory, disingenuous, or at least negligent institutions, young people and their families too often take on large amounts of student debt."

Betrayed by the Dream Factory

My life and career have been scarred by the naïve exchange I made at college: an education of questionable value for a dangerous amount of debt.

By Samual Garner

"Some well-paying professions might make this amount manageable, but for a bioethicist like me, it’s been crushing. Many things had to go wrong for this to happen—or right, if you’re a school or a lender. Although the hefty amount I owe is unusual, my experience is not: Motivated by an idealistic view of education and career and vulnerable to predatory, disingenuous, or at least negligent institutions, young people and their families too often take on large amounts of student debt. No matter how much they owe, the consequences of that debt can be outsized. These young people may have to abandon their educations early; pay back far more, after interest, than they took out; manage exceptionally exploitative loan terms; shoulder serious, chronic mental distress; delay important life decisions; and participate less in the economy than they otherwise would."

HT:RW

Kids need standing desks, too

"One study also looked at screen time, often used as a proxy for sedentary behavior, and found that after standing desks were put in classrooms, students spent 71 fewer minutes each day watching television and using computers."

"I routinely fool myself into thinking that I'm much more productive than I've ever been, thanks to all my electronic devices."

Is our plugged-in lifestyle kidnapping our lives?


Jerry Davich

"By the time I returned to bed – in what seemed like 15 minutes after I awoke – I glanced at the clock. It was 4:14 a.m. And my mind was racing. Ugh. Officially, I was off the clock yet I was on it for nearly two hours. Maybe the clock was on me, like a piano dropped from above.

I routinely fool myself into thinking that I'm much more productive than I've ever been, thanks to all my electronic devices. I feel more plugged in than a convention showcase of household appliances. Like an alcoholic, I could quit anytime, I tell myself."

PD-L1 and Lung Cancer

PD-L1 and Lung Cancer

Lynette M. Sholl, Dara L. Aisner, Timothy Craig Allen, Mary Beth Beasley, Alain C. Borczuk, Philip T. Cagle, Vera Capelozzi, Sanja Dacic, Lida Hariri, Keith M. Kerr, Sylvie Lantuejoul, Mari Mino-Kenudson, Kirtee Raparia, Natasha Rekhtman, Sinchita Roy-Chowdhuri, Eric Thunnissen, Ming Sound Tsao, and Yasushi Yatabe (2016) Programmed Death Ligand 1 Immunohistochemistry— A New Challenge for Pathologists: A Perspective From Members of the Pulmonary Pathology Society. Archives of Pathology & Laboratory Medicine In-Press.

Early Online Release

Programmed Death Ligand 1 Immunohistochemistry— A New Challenge for Pathologists: A Perspective From Members of the Pulmonary Pathology Society

Lynette M. Sholl, MD; Dara L. Aisner, MD; Timothy Craig Allen, MD, JD; Mary Beth Beasley, MD; Alain C. Borczuk, MD; Philip T.Cagle, MD; Vera Capelozzi, MD, PhD; Sanja Dacic, MD, PhD; Lida Hariri, MD, PhD; Keith M. Kerr, BSc, MB, ChB, FRCPath, FRCPE;Sylvie Lantuejoul, MD, PhD; Mari Mino-Kenudson, MD; Kirtee Raparia, MD; Natasha Rekhtman, MD, PhD; Sinchita Roy-Chowdhuri,MD, PhD; Eric Thunnissen, MD, PhD; Ming Sound Tsao, MD; Yasushi Yatabe, MD, PhD; for the members of the Pulmonary Pathology Society

From the Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts (Dr Sholl); the Department of Pathology, University of Colorado Cancer Center, Denver (Dr Aisner); the Department of Pathology, The University of Texas Medical Branch, Galveston (Dr Allen); the Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, New York (Dr Beasley); the Department of Pathology, Weill Cornell Medical College, New York, New York (Drs Borczuk and Cagle); the Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, Texas (Dr Cagle); the Department of Pathology, University of Sao Paulo Medical School, Sao Paulo, Brazil (Dr Capelozzi); the Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania (Dr Dacic); the Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston (Drs Hariri and Kenudson); the Department of Pathology, Aberdeen University Medical School and Aberdeen Royal Infirmary, Foresterhill, Aberdeen, Scotland, United Kingdom (Dr Kerr); the Department of Biopathology, Centre Léon Bérard, Lyon, and J Fourier University– INSERM U 823-Institut A Bonniot, Grenoble, France (Dr Lantuejoul); the Department of Pathology, Northwestern University, Feinberg School of Medicine, Chicago, Illinois (Dr Raparia); the Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York (Dr Rekhtman); the Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston (Dr Roy-Chowdhuri); the Department of Pathology, VU Medical Center, Amsterdam, the Netherlands (Dr Thunnissen); the Department of Pathology, University Health Network, Princess Margaret Cancer Centre and University of Toronto, Toronto, Ontario, Canada (Dr Tsao); and the Department of Pathology and Molecular Diagnostics, Aichi Cancer Center, Nagoya, Japan (Dr Yatabe).

 Dr Sholl received consultancy honoraria from Genentech. Dr Rekhtman received consultancy honoraria from Bristol-Myers Squibb. Dr Beasley is a member of the Genentech Scientific Advisory Board. Dr Kerr receives lecture fees and/or advisory fees from Astra-Zeneca, Roche-Genentech, Bristol-Myers Squibb, Merck, and Pfizer. Dr Tsao received consultancy honoraria from Pfizer, Merck Canada, AstraZeneca, and Roche-Genentech. Dr Thunnissen is on the Global Advisory Board for Merck and only receives cost for travel. The other authors have no relevant financial interest in the products or companies described in this article.

Reprints: Timothy Craig Allen, MD, JD, Department of Pathology, University of Texas Medical Branch, 301 University Blvd, Galveston, TX 77555 (email: tcallen@utmb.edu).

The binding of programmed death ligands 1 and 2 (PD-L1 and PD-L2) to PD-1 blocks T-cell–mediated immune response to tumor. Antibodies that target programmed death 1 (PD-1) will block the ligand-receptor interface, thereby allowing T cells to attack the tumor and increase antitumor immune response. In clinical trials, PD-1 inhibitors have been associated with an approximately 20% overall response rate in unselected patients with non–small cell lung cancer, with sustained tumor response in a subset of patients treated by these immune checkpoint inhibitors. Facing a proliferation of PD-L1 immunohistochemistry clones, staining platforms, and scoring criteria, the pathologist must decide on the feasibility of introducing a newly approved companion diagnostic assay that may require purchase not only of a specific antibody kit but of a particular staining platform. Given the likely reality that clinical practice may, in the near future, demand access to 4 different PD-L1 antibodies coupled with different immunohistochemistry platforms, laboratories will be challenged with deciding among this variety of testing methods, each with its own potential benefits. Another immediate challenge to PD-L1 testing in lung cancer patients is that of access to adequate tumor tissue, given that non–small cell lung cancer samples are often extremely limited in size. With PD-L1 testing it has become clear that the historically used US regulatory approach of one assay–one drug will not be sustainable. One evolving concept is that of complementary diagnostics, a novel regulatory pathway initiated by the US Food and Drug Administration, which is distinct from companion diagnostics in that it may present additional flexibility. Although pathologists need to face the practical reality that oncologists will be asking regularly for the PD-L1 immunohistochemistry status of their patients' tumors, we should also keep in mind that there may be room for improvement of biomarkers for immunotherapy response. The field is rich with opportunities for investigation into biomarkers of immunotherapy response, particularly in the form of collaborative, multidisciplinary studies that incorporate oncologists, pathologists, and basic scientists. Pathologists must take the lead in the rational incorporation of these biomarkers into clinical practice.

Alain C. Borczuk and Timothy Craig Allen (2016) PD-L1 and Lung Cancer: The Era of Precision-ish Medicine?. Archives of Pathology & Laboratory Medicine In-Press.

Early Online Release

PD-L1 and Lung Cancer: The Era of Precision-ish Medicine?

Alain C. Borczuk, MD; Timothy Craig Allen, MD, JD

Reprints: Timothy Craig Allen, MD, JD, Department of Pathology, University of Texas Medical Branch, 301 University Blvd, Galveston, TX 77555 (e-mail: tcallen@utmb.edu).

The success of immune checkpoint inhibitor therapy in lung cancer, both in squamous and nonsquamous non–small cell carcinoma, has led to US Food and Drug Administration approval for 2 medications that have as part of their prescribing information an associated immunohistochemistry-based companion or complementary diagnostic test for programmed death ligand 1 (PD-L1). The intense interest in drug development in this area has resulted in additional agents with associated diagnostics looming on the horizon in 2016. In the era of precision medicine, the paradigm of paired molecular target and molecular test, which serves a model of oncogenic mutation-driven cancer therapy, is challenged by the proliferation of immunohistochemistry-based tests with different antibodies, instruments, and scoring. The difficulty inherent to targeted therapy aimed at a moving target is discussed, as well as the emerging challenges to pathologists and oncologists who seek to optimize care in this complex therapeutic arena.

Keith M. Kerr and Fred R. Hirsch (2016) Programmed Death Ligand 1 Immunohistochemistry: Friend or Foe?. Archives of Pathology & Laboratory Medicine In-Press.

Early Online Release

Programmed Death Ligand 1 Immunohistochemistry: Friend or Foe?

Keith M. Kerr, BSc, MB, ChB, FRCPath, FRCPE; Fred R. Hirsch, MD, PhD

Reprints: Keith M. Kerr, BSc, MB, ChB, FRCPath, FRCPE, Department of Pathology, Aberdeen Royal Infirmary, Link Building, Foresterhill, Aberdeen, Scotland AB25 2ZD, United Kingdom (e-mail: k.kerr@abdn.ac.uk).

The approval of anti–PD-1 therapies for non–small cell lung cancer has directed the spotlight on PD-L1 immunohistochemistry as the latest predictive biomarker potentially required in this disease. Several other drugs in this class will likely be approved in the future and each has been developed with a unique anti–PD-L1 immunohistochemistry test. The prospect of 5 drugs competing in the same treatment area, each possibly requiring PD-L1 immunohistochemistry testing, presents a challenge for pathologists unlike any previously faced. The key issue is whether laboratories will attempt to deliver the trial-validated assays for one or more of these treatments, or introduce instead one or more laboratory developed tests, or attempt to provide a single PD-L1 immunohistochemistry assay for all possible anti–PD-1 and anti–PD-L1 treatments that may be used. This paper discusses some of the issues, challenges, hazards, and possible solutions that have recently emerged in this most complex interface between cancer therapeutics and laboratory biomarker testing.

Lynette M. Sholl, Dara L. Aisner, Timothy Craig Allen, Mary Beth Beasley, Alain C. Borczuk, Philip T. Cagle, Vera Capelozzi, Sanja Dacic, Lida Hariri, Keith M. Kerr, Sylvie Lantuejoul, Mari Mino-Kenudson, Kirtee Raparia, Natasha Rekhtman, Sinchita Roy-Chowdhuri, Eric Thunnissen, Ming Sound Tsao, and Yasushi Yatabe (2016) Programmed Death Ligand 1 Immunohistochemistry— A New Challenge for Pathologists: A Perspective From Members of the Pulmonary Pathology Society. Archives of Pathology & Laboratory Medicine In-Press.

Early Online Release

Programmed Death Ligand 1 Immunohistochemistry— A New Challenge for Pathologists: A Perspective From Members of the Pulmonary Pathology Society

Lynette M. Sholl, MD; Dara L. Aisner, MD; Timothy Craig Allen, MD, JD; Mary Beth Beasley, MD; Alain C. Borczuk, MD; Philip T.Cagle, MD; Vera Capelozzi, MD, PhD; Sanja Dacic, MD, PhD; Lida Hariri, MD, PhD; Keith M. Kerr, BSc, MB, ChB, FRCPath, FRCPE;Sylvie Lantuejoul, MD, PhD; Mari Mino-Kenudson, MD; Kirtee Raparia, MD; Natasha Rekhtman, MD, PhD; Sinchita Roy-Chowdhuri,MD, PhD; Eric Thunnissen, MD, PhD; Ming Sound Tsao, MD; Yasushi Yatabe, MD, PhD; for the members of the Pulmonary Pathology Society

From the Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts (Dr Sholl); the Department of Pathology, University of Colorado Cancer Center, Denver (Dr Aisner); the Department of Pathology, The University of Texas Medical Branch, Galveston (Dr Allen); the Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, New York (Dr Beasley); the Department of Pathology, Weill Cornell Medical College, New York, New York (Drs Borczuk and Cagle); the Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, Texas (Dr Cagle); the Department of Pathology, University of Sao Paulo Medical School, Sao Paulo, Brazil (Dr Capelozzi); the Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania (Dr Dacic); the Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston (Drs Hariri and Kenudson); the Department of Pathology, Aberdeen University Medical School and Aberdeen Royal Infirmary, Foresterhill, Aberdeen, Scotland, United Kingdom (Dr Kerr); the Department of Biopathology, Centre Léon Bérard, Lyon, and J Fourier University– INSERM U 823-Institut A Bonniot, Grenoble, France (Dr Lantuejoul); the Department of Pathology, Northwestern University, Feinberg School of Medicine, Chicago, Illinois (Dr Raparia); the Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York (Dr Rekhtman); the Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston (Dr Roy-Chowdhuri); the Department of Pathology, VU Medical Center, Amsterdam, the Netherlands (Dr Thunnissen); the Department of Pathology, University Health Network, Princess Margaret Cancer Centre and University of Toronto, Toronto, Ontario, Canada (Dr Tsao); and the Department of Pathology and Molecular Diagnostics, Aichi Cancer Center, Nagoya, Japan (Dr Yatabe).

 Dr Sholl received consultancy honoraria from Genentech. Dr Rekhtman received consultancy honoraria from Bristol-Myers Squibb. Dr Beasley is a member of the Genentech Scientific Advisory Board. Dr Kerr receives lecture fees and/or advisory fees from Astra-Zeneca, Roche-Genentech, Bristol-Myers Squibb, Merck, and Pfizer. Dr Tsao received consultancy honoraria from Pfizer, Merck Canada, AstraZeneca, and Roche-Genentech. Dr Thunnissen is on the Global Advisory Board for Merck and only receives cost for travel. The other authors have no relevant financial interest in the products or companies described in this article.

Reprints: Timothy Craig Allen, MD, JD, Department of Pathology, University of Texas Medical Branch, 301 University Blvd, Galveston, TX 77555 (email: tcallen@utmb.edu).

The binding of programmed death ligands 1 and 2 (PD-L1 and PD-L2) to PD-1 blocks T-cell–mediated immune response to tumor. Antibodies that target programmed death 1 (PD-1) will block the ligand-receptor interface, thereby allowing T cells to attack the tumor and increase antitumor immune response. In clinical trials, PD-1 inhibitors have been associated with an approximately 20% overall response rate in unselected patients with non–small cell lung cancer, with sustained tumor response in a subset of patients treated by these immune checkpoint inhibitors. Facing a proliferation of PD-L1 immunohistochemistry clones, staining platforms, and scoring criteria, the pathologist must decide on the feasibility of introducing a newly approved companion diagnostic assay that may require purchase not only of a specific antibody kit but of a particular staining platform. Given the likely reality that clinical practice may, in the near future, demand access to 4 different PD-L1 antibodies coupled with different immunohistochemistry platforms, laboratories will be challenged with deciding among this variety of testing methods, each with its own potential benefits. Another immediate challenge to PD-L1 testing in lung cancer patients is that of access to adequate tumor tissue, given that non–small cell lung cancer samples are often extremely limited in size. With PD-L1 testing it has become clear that the historically used US regulatory approach of one assay–one drug will not be sustainable. One evolving concept is that of complementary diagnostics, a novel regulatory pathway initiated by the US Food and Drug Administration, which is distinct from companion diagnostics in that it may present additional flexibility. Although pathologists need to face the practical reality that oncologists will be asking regularly for the PD-L1 immunohistochemistry status of their patients' tumors, we should also keep in mind that there may be room for improvement of biomarkers for immunotherapy response. The field is rich with opportunities for investigation into biomarkers of immunotherapy response, particularly in the form of collaborative, multidisciplinary studies that incorporate oncologists, pathologists, and basic scientists. Pathologists must take the lead in the rational incorporation of these biomarkers into clinical practice.

Stand more to lower your risk of obesity

"The results found that the men who met the basic guidelines for physical activity and stood one-quarter and three-quarters of the time were, respectively, 57% and 64% less likely to be obese. Although the study did not prove that standing was the main reason for the lower weight, it appears that being less sedentary and standing whenever possible can help to improve your health."

J Psychoactive Drugs. 2016 Jan 12:1-8. [Epub ahead of print]

Marijuana: A Fifty-Year Personal Addiction Medicine Perspective.

Smith DE1.

Author information

• 1a Principal, David E. Smith, M.D. & Associates , San Francisco , CA.

Abstract

As of September 2015, the cultivation, possession, and/or use of marijuana is illegal under U.S. federal law as a Schedule I narcotic; however, it is legal in four states and Washington, D.C. Forty-six states allow some form of medicinal marijuana or decriminalization. Marijuana has been used medicinally for thousands of years; Marijuana's regulation by law enforcement in the U.S., rather than the medical community, led to an almost complete halt to academic and scientific research after the 1930s. The late 1960s saw an upsurge in recreational marijuana use by middle-class youth, the majority of whom experienced minimal adverse effects aside from arrest and attendant legal complications. Since the mid-1990s, the use of medicinal marijuana for certain conditions has gained increasing acceptance. Stronger strains and formulations of marijuana pose a risk to the developing brains of adolescents. Within the addiction medicine community, there is currently no consensus on marijuana. In the East, the feeling is primarily that marijuana continue to be proscribed. In the West, where clinicians must face the realities of medicalization, decriminalization, and/or legalization, as well as widespread recreational use, there is more of a movement to minimize adverse effects, particularly on youth.

J Med Ethics. 2016 Jan 12. pii: medethics-2015-103310. doi: 10.1136/medethics-2015-103310. [Epub ahead of print]

Should junior doctors strike?

Toynbee M1, Al-Diwani AA1, Clacey J2, Broome MR3.

Author information

• 1Warneford Hospital, Oxford Health NHS FT, Oxford, UK Department of Psychiatry, University of Oxford, Oxford, UK.
• 2Warneford Hospital, Oxford Health NHS FT, Oxford, UK.
• 3Warneford Hospital, Oxford Health NHS FT, Oxford, UK Department of Psychiatry, University of Oxford, Oxford, UK Faculty of Philosophy, University of Oxford, Oxford, UK Division of Mental Health and Wellbeing, Warwick Medical School, University of Warwick, Coventry, UK.

Abstract

An impasse in negotiations between the Department of Health (DoH) and the British Medical Association in November this year led to an overwhelming vote for industrial action (IA) by junior doctors. At the time of writing, a last minute concession by DoH led to a deferment of IA to allow further negotiations mediated by the Advisory, Conciliation and Arbitration Service. However, IA by junior doctors remains a possibility if these negotiations stall again. Would the proposed action be ethically justifiable? Furthermore, is IA by doctors ever ethically defendable? Building on previous work, we explore important ethical considerations for doctors considering IA. The primary moral objection to doctors striking is often claimed to be risk of harm to patients. Other common arguments against IA by doctors include breaching their vocational responsibilities and possible damage to their relationship with patients and the public in general. These positions are in turn countered by claims of a greater long-term good and the legal and moral rights of employees to strike. Absolute restrictions appear to be hard to justify in the modern context, as does an unrestricted right to IA. We review these arguments, find that some common moral objections to doctors striking may be less relevant to the current situation, that a stronger contemporary objection to IA might be from a position of social justice and suggest criteria for ethically permissible doctor IA.

"Can step counters counter obesity? You answer."

Dare to Be 100: Actual Causes of Death

"My acknowledged obsession is with physical activity which I believe to be the panacea that we seek. How do we get people to move more? The editors of a major finance journal called me and asked my opinion whether the popular activity monitors are doing any public health good. My answer was prosaic in asserting that if they can assist in encouraging a more active lifestyle that is a value. But the truth of course is that most of them are consigned to the bedside drawer and languish there. Certainly our epidemic of obesity smirches our intelligence. Can step counters counter obesity? You answer."

"People with obesity have a 50% greater risk of developingcolorectal cancer than lean people."

How obesity promotes colorectal cancer

"People with obesity have a 50% greater risk of developingcolorectal cancer than lean people.

Researchers, led by Dr. Scott Waldman, PhD, of Thomas Jefferson University in Philadelphia, PA, carried out mouse studies to investigate the link between obesity and colorectal cancer."

Keith M. Kerr and Fred R. Hirsch (2016) Programmed Death Ligand 1 Immunohistochemistry: Friend or Foe?. Archives of Pathology & Laboratory Medicine In-Press.

Early Online Release

Programmed Death Ligand 1 Immunohistochemistry: Friend or Foe?

Keith M. Kerr, BSc, MB, ChB, FRCPath, FRCPE; Fred R. Hirsch, MD, PhD

Reprints: Keith M. Kerr, BSc, MB, ChB, FRCPath, FRCPE, Department of Pathology, Aberdeen Royal Infirmary, Link Building, Foresterhill, Aberdeen, Scotland AB25 2ZD, United Kingdom (e-mail: k.kerr@abdn.ac.uk).

The approval of anti–PD-1 therapies for non–small cell lung cancer has directed the spotlight on PD-L1 immunohistochemistry as the latest predictive biomarker potentially required in this disease. Several other drugs in this class will likely be approved in the future and each has been developed with a unique anti–PD-L1 immunohistochemistry test. The prospect of 5 drugs competing in the same treatment area, each possibly requiring PD-L1 immunohistochemistry testing, presents a challenge for pathologists unlike any previously faced. The key issue is whether laboratories will attempt to deliver the trial-validated assays for one or more of these treatments, or introduce instead one or more laboratory developed tests, or attempt to provide a single PD-L1 immunohistochemistry assay for all possible anti–PD-1 and anti–PD-L1 treatments that may be used. This paper discusses some of the issues, challenges, hazards, and possible solutions that have recently emerged in this most complex interface between cancer therapeutics and laboratory biomarker testing.