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The Inequality and Health Disparity seen with the COVID-19 Pandemic Is Similar to Past Pandemics

Posted in and Bioethics, Coronavirus Gene Expression, COVID-19, Economic Impact of Coronavirus Pandemic, Health Care System by Country, Health Economics and Outcomes Research, Health Law & Patient Safety, Healthcare costs and reimbursement, Healthcare Reform, Income Disparity, Infectious Disease Immunodiagnostics, number of asymptomatic infections, Population Health Management, Population Health Management, Genetics & Pharmaceutical, SARS-CoV-2, Seasonality & Environmental Factors in Resurgence, Treatment Protocols for COVID-19, United States, Vaccinology, Viral diseases, Virus Infective Acute Respiratory Syndrome: SARS-CoV, Women Health, tagged , , , , , , , , , , on July 20, 2020| Leave a Comment »

The Inequality and Health Disparity seen with the COVID-19 Pandemic Is Similar to Past Pandemics

Curator: Stephen J. Williams, PhD

2019-nCoV-CDC-23311

It has become very evident, at least in during this pandemic within the United States, that African Americans and poorer communities have been disproportionately affected by the SARS-CoV2 outbreak . However, there are many other diseases such as diabetes, heart disease, and cancer in which these specific health disparities are evident as well :

Diversity and Health Disparity Issues Need to be Addressed for GWAS and Precision Medicine Studies

Personalized Medicine, Omics, and Health Disparities in Cancer:  Can Personalized Medicine Help Reduce the Disparity Problem?

Disease like cancer have been shown to have wide disparities based on socioeconomic status, with higher incidence rates seen in poorer and less educated sub-populations, not just here but underdeveloped countries as well (see Opinion Articles from the Lancet: COVID-19 and Cancer Care in China and Africa) and graphics below)

 

 

 

 

 

 

 

 

 

 

In an article in Science by Lizzie Wade, these disparities separated on socioeconomic status, have occurred in many other pandemics throughout history, and is not unique to the current COVID19 outbreak.  The article, entitled “An Unequal Blow”, reveal how

in past pandemics, people on the margins suffered the most.

Source: https://science.sciencemag.org/content/368/6492/700.summary

Health Disparities during the Black Death Bubonic Plague Pandemic in the 14th Century (1347-1351)

During the mid 14th century, all of Europe was affected by a plague induced by the bacterium Yersinia pestis, and killed anywhere between 30 – 60% of the European population.  According to reports by the time the Black Death had reached London by January 1349 there had already been horrendous reports coming out of Florence Italy where the deadly disease ravished the population there in the summer of 1348 (more than half of the city’s population died). And by mid 1349 the Black Death had killed more than half of Londoners.  It appeared that no one was safe from the deadly pandemic, affecting the rich, the poor, the young, the old.

However, after careful and meticulous archaeological and historical analysis in England and other sites, revealed a distinct social and economic inequalities that predominated and most likely guided the pandemics course throughout Europe.   According to Dr. Gwen Robbins Schug, a bio-archaeologist at Appalachian State University,

Bio-archaeology and other social sciences have repeatedly demonstrated that these kinds of crises play out along the preexisting fault lines of each society.  The people at greatest risk were often those already marginalized- the poor and minorities who faced discrimination in ways that damaged their health or limited their access to medical care even in pandemic times.

At the start of the Black Death, Europe had already gone under a climactic change with erratic weather.  As a result, a Great Famine struck Europe between 1315-17.  Wages fell and more people fell into poverty while the wealthiest expanded their riches, leading to an increased gap in wealth and social disparity.  In fact according to recordkeeping most of Englanders were living below the poverty line.

Author Lizzie Wade also interviewed Dr. Sharon, DeWitte, a biological anthropologist at University of South Carolina, who looks at skeletal remains of Black Death victims to get evidence on their health status, like evidence of malnutrition, osteoporosis, etc.   And it appears that most of the victims may have had preexisting health conditions indicative of poorer status.  And other evidence show that wealthy landowners had a lower mortality rate than poorer inner city dwellers.

1918 Spanish Flu

Socioeconomic and demographic studies have shown that both Native American Indians and African Americans on the lower end of the socioeconomic status were disproportionately affected by the 1918 Spanish flu pandemic.  According to census records, the poorest had a 50% higher mortality rate than wealthy areas in the city of Oslo.  In the US, minors and factory workers died at the highest rates.  In the US African Americans had already had bouts with preexisting issues like tuberculosis and may have contributed to the higher mortality.  In addition Jim Crow laws in the South, responsible for widespread discrimination, also impacted the ability of African Americans to seek proper medical care.

From the Atlantic

Source: https://www.theatlantic.com/politics/archive/2016/05/americas-health-segregation-problem/483219/

America’s Health Segregation Problem

Has the country done enough to overcome its Jim Crow health care history?

VANN R. NEWKIRK II

MAY 18, 2016

Like other forms of segregation, health-care segregation was originally a function of explicitly racist black codes and Jim Crow laws. Many hospitals, clinics, and doctor’s offices were totally segregated by race, and many more maintained separate wings or staff that could never intermingle under threat of law. The deficit of trained black medical professionals (itself caused by a number of factors including education segregation) meant that no matter where black people received health-care services, they would find their care to be subpar compared to that of whites. While there were some deaths that were directly attributable to being denied emergency service, most of the damage was done in establishing the same cumulative health disparities that plague black people today as a societal fate. The descendants of enslaved people lived much more dangerous and unhealthy lives than white counterparts, on disease-ridden and degraded environments. Within the confines of a segregated health-care system, these factors became poor health outcomes that shaped black America as if they were its genetic material.

 

https://twitter.com/time4equity/status/1175080469425266688?s=20

 

R.A.HahnaB.I.TrumanbD.R.Williamsc.Civil rights as determinants of public health and racial and ethnic health equity: Health care, education, employment, and housing in the United States.

SSM – Population Health: Volume 4, April 2018, Pages 17-24

Highlights

  • Civil rights are characterized as social determinants of health.
  • Four domains in civil rights history since 1950 are explored in—health care, education, employment, and housing.
  • Health care, education, employment show substantial benefits when civil rights are enforced.
  • Housing shows an overall failure to enforce existing civil rights and persistent discrimination.
  • Civil rights and their enforcement may be considered a powerful arena for public health theorizing, research, policy, and action.

 

For more articles on COVID-19 Please go to our Coronovirus Portal

https://pharmaceuticalintelligence.com/coronavirus-portal/

 

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Placenta lacks molecules required for COVID-19 infection

Posted in Allergy and Infectious Diseases, Biochemical pathways, Biomarkers & Medical Diagnostics, Biotechnology, Cancer Researchers Fighting COVID-19, Clinical Diagnostics, Coronavirus Gene Expression, COVID-19, Economic Impact of Coronavirus Pandemic, Enzymes and isoenzymes, Infectious Disease & New Antibiotic Targets, Infectious Disease Immunodiagnostics, number of asymptomatic infections, Placenta, SAR-Cov-2 a vasculotropic (blood vessels) RNA Virus, Serology tests for coronavirus antibodies, Treatment Protocols for COVID-19, Virus Infective Acute Respiratory Syndrome: SARS-CoV, tagged , , , , , on July 16, 2020| Leave a Comment »

Placenta lacks molecules required for COVID-19 infection

Reporter and Curator: Dr. Sudipta Saha, Ph.D.

The pandemic of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected more than 10 million people, including pregnant women. To date, no consistent evidence for the vertical transmission of SARS-CoV-2 has been found. The placenta serves as the lungs, gut, kidneys, and liver of the fetus. This fetal organ also has major endocrine actions that modulate maternal physiology and, importantly, together with the extraplacental chorioamniotic membranes shield the fetus against microbes from hematogenous dissemination and from invading the amniotic cavity.

 

Most pathogens that cause hematogenous infections in the mother are not able to reach the fetus, which is largely due to the potent protective mechanisms provided by placental cells (i.e. trophoblast cells: syncytiotrophoblasts and cytotrophoblasts). Yet, some of these pathogens such as Toxoplasma gondii, Rubella virus, herpesvirus (HSV), cytomegalovirus (CMV), and Zika virus (ZIKV), among others, are capable of crossing the placenta and infecting the fetus, causing congenital disease.

 

The placental membranes that contain the fetus and amniotic fluid lack the messenger RNA (mRNA) molecule required to manufacture the ACE2 receptor, the main cell surface receptor used by the SARS-CoV-2 virus to cause infection. These placental tissues also lack mRNA needed to make an enzyme, called TMPRSS2, that SARS-CoV-2 uses to enter a cell. Both the receptor and enzyme are present in only miniscule amounts in the placenta, suggesting a possible explanation for why SARS-CoV-2 has only rarely been found in fetuses or newborns of women infected with the virus, according to the study authors.

 

The single-cell transcriptomic analysis presented by the researchers provides evidence that SARS-CoV-2 is unlikely to infect the placenta and fetus since its canonical receptor and protease, ACE2 and TRMPSS2, are only minimally expressed by the human placenta throughout pregnancy. In addition, it was shown that the SARS-CoV-2 receptors are not expressed by the chorioamniotic membranes in the third trimester. However, viral receptors utilized by CMV, ZIKV, and others are highly expressed by the human placental tissues.

 

Transcript levels do not always correlate with protein expression, but the data of the present study indicates a low likelihood of placental infection and vertical transmission of SARS-CoV-2. However, it is still possible that the expression of these proteins is much higher in individuals with pregnancy complications related with the renin-angiotensin-aldosterone system, which can alter the expression of ACE2. The cellular receptors and mechanisms that could be exploited by SARS-CoV-2 are still under investigation.

 

References:

 

https://www.nih.gov/news-events/news-releases/placenta-lacks-major-molecules-used-sars-cov-2-virus-cause-infection

 

https://pubmed.ncbi.nlm.nih.gov/32662421/

 

https://pubmed.ncbi.nlm.nih.gov/32217113/

 

https://pubmed.ncbi.nlm.nih.gov/32161408/

 

https://pubmed.ncbi.nlm.nih.gov/32335053/

 

https://pubmed.ncbi.nlm.nih.gov/32298273/

 

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From Cell Press:  New Insights on the D614G Strain of COVID: Will a New Mutated Strain Delay Vaccine Development?

Posted in BioIT: BioInformatics, NGS, Clinical & Translational, Pharmaceutical R&D Informatics, Clinical Genomics, Cancer Informatics, Biomarkers: Inflammation, Biotechnology, coronavirus, Coronavirus Gene Expression, COVID-19, COVID-19: Pandemic Surgery Guidance, Drug Development Process, Economic Impact of Coronavirus Pandemic, Immune-Mediation (independent immunopathology: lung and reticuloendothelial system), Infectious Disease & New Antibiotic Targets, number of asymptomatic infections, Pharmaceutical Discovery, Pharmaceutical Drug Discovery, Pharmaceutical R&D Investment, Population Health Management, Nutrition and Phytochemistry, SARS-CoV-2, Seasonality & Environmental Factors in Resurgence, Serology tests for coronavirus antibodies, Treatment Protocols for COVID-19, Vaccinology, Viral diseases, Virology - Vector-borne DIsease, Virus Infective Acute Respiratory Syndrome: SARS-CoV, tagged , , , , on July 3, 2020| Leave a Comment »

From Cell Press:  New Insights on the D614G Strain of COVID: Will a New Mutated Strain Delay Vaccine Development?

Reporter: Stephen J. Williams, PhD

Two recent articles in Cell Press, both peer reviewed, discuss the emergence and potential dominance of a new mutated strain of COVID-19, in which the spike protein harbors a D614G mutation.

In the first article “Making Sense of Mutation: What D614G means for the COVID-19 pandemic Remains Unclear”[1] , authors Drs. Nathan Grubaugh, William Hanage, and Angela Rasmussen discuss the recent findings by Korber et al. 2020 [2] which describe the potential increases in infectivity and mortality of this new mutant compared to the parent strain of SARS-CoV2.  For completeness sake I will post this article as to not defer from their interpretations of this important paper by Korber and to offer some counter opinion to some articles which have surfaced this morning in the news.

Making sense of mutation: what D614G means for the COVID-19 pandemic remains unclear

 

Nathan D. Grubaugh1 *, William P. Hanage2 *, Angela L. Rasmussen3 * 1Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT 06510, USA 2Center for Communicable Disease Dynamics, Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA 3Center for Infection and Immunity, Columbia Mailman School of Public Health, New York, NY 10032, USA Correspondence: grubaughlab@gmail.com

 

Abstract: Korber et al. (2020) found that a SARS-CoV-2 variant in the spike protein, D614G, rapidly became dominant around the world. While clinical and in vitro data suggest that D614G changes the virus phenotype, the impact of the mutation on transmission, disease, and vaccine and therapeutic development are largely unknown.

Introduction: Following the emergence of SARS-CoV-2 in China in late 2019, and the rapid expansion of the COVID19 pandemic in 2020, questions about viral evolution have come tumbling after. Did SARS-CoV-2 evolve to become better adapted to humans? More infectious or transmissible? More deadly? Virus mutations can rise in frequency due to natural selection, random genetic drift, or features of recent epidemiology. As these forces can work in tandem, it’s often hard to differentiate when a virus mutation becomes common through fitness or by chance. It is even harder to determine if a single mutation will change the outcome of an infection, or a pandemic. The new study by Korber et al. (2020) sits at the heart of this debate. They present compelling data that an amino acid change in the virus’ spike protein, D614G, emerged early during the pandemic, and viruses containing G614 are now dominant in many places around the world. The crucial questions are whether this is the result of natural selection, and what it means for the COVID-19 pandemic. For viruses like SARS-CoV-2 transmission really is everything – if they don’t get into another host their lineage ends. Korber et al. (2020) hypothesized that the rapid spread of G614 was because it is more infectious than D614. In support of their hypothesis, the authors provided evidence that clinical samples from G614 infections have a higher levels of viral RNA, and produced higher titers in pseudoviruses from in vitro experiments; results that now seem to be corroborated by others [e.g. (Hu et al., 2020; Wagner et al., 2020)]. Still, these data do not prove that G614 is more infectious or transmissible than viruses containing D614. And because of that, many questions remain on the potential impacts, if any, that D614G has on the COVID-19 pandemic.

The authors note that this new G614 variant has become the predominant form over the whole world however in China the predominant form is still the D614 form.  As they state

“over the period that G614 became the global majority variant, the number of introductions from China where D614 was still dominant were declining, while those from Europe climbed. This alone might explain the apparent success of G614.”

Grubaugh et al. feel there is not enough evidence that infection with this new variant will lead to higher mortality.  Both Korber et al. and the Seattle study (Wagner et al) did not find that the higher viral load of this variant led to a difference in hospitalizations so apparently each variant might be equally as morbid.

In addition, Grubaugh et al. believe this variant would not have much affect on vaccine development as, even though the mutation lies within the spike protein, D614G is not in the receptor binding domain of the spike protein.  Korber suggest that there may be changes in glycosylation however these experiments will need to be performed.  In addition, antibodies from either D614 or G614 variant infected patients could cross neutralize.

 

Conclusions: While there has already been much breathless commentary on what this mutation means for the COVID19 pandemic, the global expansion of G614 whether through natural selection or chance means that this variant now is the pandemic. As a result its properties matter. It is clear from the in vitro and clinical data that G614 has a distinct phenotype, but whether this is the result of bonafide adaptation to human ACE2, whether it increases transmissibility, or will have a notable effect, is not clear. The work by Korber et al. (2020) provides an early base for more extensive epidemiological, in vivo experimental, and diverse clinical investigations to fill in the many critical gaps in how D614G impacts the pandemic.

The link to the Korber Cell paper is here: https://www.cell.com/cell/fulltext/S0092-8674(20)30820-5

Tracking changes in SARS-CoV-2 Spike: evidence that D614G increases infectivity of the COVID-19 virus

DOI: https://doi.org/10.1016/j.cell.2020.06.043

Keypoints

  • The consistent increase of G614 at regional levels may indicate a fitness advantage

 

  • G614 is associated with lower RT PCR Ct’s, suggestive of higher viral loads in patients

 

  • The G614 variant grows to higher titers as pseudotyped virions

Summary

A SARS-CoV-2 variant carrying the Spike protein amino acid change D614G has become the most prevalent form in the global pandemic. Dynamic tracking of variant frequencies revealed a recurrent pattern of G614 increase at multiple geographic levels: national, regional and municipal. The shift occurred even in local epidemics where the original D614 form was well established prior to the introduction of the G614 variant. The consistency of this pattern was highly statistically significant, suggesting that the G614 variant may have a fitness advantage. We found that the G614 variant grows to higher titer as pseudotyped virions. In infected individuals G614 is associated with lower RT-PCR cycle thresholds, suggestive of higher upper respiratory tract viral loads, although not with increased disease severity. These findings illuminate changes important for a mechanistic understanding of the virus, and support continuing surveillance of Spike mutations to aid in the development of immunological interventions.

 

References

  1. Grubaugh, N.D., Hanage, W.P., Rasmussen, A.L., Making sense of mutation: what D614G means for the COVID-19 pandemic remains unclear, Cell (2020), doi: https:// doi.org/10.1016/j.cell.2020.06.040.
  2. Korber, B., Fischer, W.M., Gnanakaran, S., Yoon, H., Theiler, J., Abfalterer, W., Hengartner, N., Giorgi, E.E., Bhattacharya, T., Foley, B., et al. (2020). Tracking changes in SARS-CoV-2 Spike: evidence that D614G increases infectivity of the COVID-19 virus. Cell 182.
  3. Endo, A., Centre for the Mathematical Modelling of Infectious Diseases COVID-19 Working Group, Abbott, S., Kucharski, A.J., and Funk, S. (2020). Estimating the overdispersion in COVID-19 transmission using outbreak sizes outside China. Wellcome Open Res 5, 67.
  4. Hu, J., He, C.-L., Gao, Q.-Z., Zhang, G.-J., Cao, X.-X., Long, Q.-X., Deng, H.-J., Huang, L.-Y., Chen, J., Wang, K., et al. (2020). The D614G mutation of SARS-CoV-2 spike protein enhances viral infectivity and decreases neutralization sensitivity to individual convalescent sera. bioRxiv 2020.06.20.161323.
  5. Wagner, C., Roychoudhury, P., Hadfield, J., Hodcroft, E.B., Lee, J., Moncla, L.H., Müller, N.F., Behrens, C., Huang, M.-L., Mathias, P., et al. (2020). Comparing viral load and clinical outcomes in Washington State across D614G mutation in spike protein of SARS-CoV-2. Https://github.com/blab/ncov-D614G.

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Personalized Medicine, Omics, and Health Disparities in Cancer:  Can Personalized Medicine Help Reduce the Disparity Problem?

Posted in and Bioethics, Big Data, Bio-Ethics, BioBanking, BioIT: BioInformatics, BioIT: BioInformatics, NGS, Clinical & Translational, Pharmaceutical R&D Informatics, Clinical Genomics, Cancer Informatics, Biomarkers & Medical Diagnostics, Breast Cancer - impalpable breast lesions, Cancer - General, Cancer and Current Therapeutics, CANCER BIOLOGY & Innovations in Cancer Therapy, Cancer Genomics, Cancer Informatics, Cancer Prevention: Research & Programs, Cancer Screening, Centers for Medicare & Medicaid Services, Funding Opportunities for Cancer Research, Health Care System by Country, Health Economics and Outcomes Research, Health Law & Patient Safety, HealthCare IT, Healthcare Reform, interventional oncology, TP53 - Germline mutations, Women Health, tagged , , , , , , , , , , , on April 19, 2020| Leave a Comment »

Personalized Medicine, Omics, and Health Disparities in Cancer:  Can Personalized Medicine Help Reduce the Disparity Problem?

Curator: Stephen J. Williams, PhD

In a Science Perspectives article by Timothy Rebbeck, health disparities, specifically cancer disparities existing in the sub-Saharan African (SSA) nations, highlighting the cancer incidence disparities which exist compared with cancer incidence in high income areas of the world [1].  The sub-Saharan African nations display a much higher incidence of prostate, breast, and cervix cancer and these cancers are predicted to double within the next twenty years, according to IARC[2].  Most importantly,

 the histopathologic and demographic features of these tumors differ from those in high-income countries

meaning that the differences seen in incidence may reflect a true health disparity as increases rates in these cancers are not seen in high income countries (HIC).

Most frequent male cancers in SSA include prostate, lung, liver, leukemia, non-Hodgkin’s lymphoma, and Kaposi’s sarcoma (a cancer frequently seen in HIV infected patients [3]).  In SSA women, breast and cervical cancer are the most common and these display higher rates than seen in high income countries.  In fact, liver cancer is seen in SSA females at twice the rate, and in SSA males almost three times the rate as in high income countries.

 

 

 

 

 

 

Reasons for cancer disparity in SSA

Patients with cancer are often diagnosed at a late stage in SSA countries.  This contrasts with patients from high income countries, which have their cancers usually diagnosed at an earlier stage, and with many cancers, like breast[4], ovarian[5, 6], and colon, detecting the tumor in the early stages is critical for a favorable outcome and prognosis[7-10].  In addition, late diagnosis also limits many therapeutic options for the cancer patient and diseases at later stages are much harder to manage, especially with respect to unresponsiveness and/or resistance of many therapies.  In addition, treatments have to be performed in low-resource settings in SSA, and availability of clinical lab work and imaging technologies may be limited.

Molecular differences in SSA versus HIC cancers which may account for disparities

Emerging evidence suggests that there are distinct molecular signatures with SSA tumors with respect to histotype and pathology.  For example Dr. Rebbeck mentions that Nigerian breast cancers were defined by increased mutational signatures associated with deficiency of the homologous recombination DNA repair pathway, pervasive mutations in the tumor suppressor gene TP53, mutations in GATA binding protein 3 (GATA3), and greater mutational burden, compared with breast tumors from African Americans or Caucasians[11].  However more research will be required to understand the etiology and causal factors related to this molecular distinction in mutational spectra.

It is believed that there is a higher rate of hereditary cancers in SSA. And many SSA cancers exhibit the more aggressive phenotype than in other parts of the world.  For example breast tumors in SSA black cases are twice as likely than SSA Caucasian cases to be of the triple negative phenotype, which is generally more aggressive and tougher to detect and treat, as triple negative cancers are HER2 negative and therefore are not a candidate for Herceptin.  Also BRCA1/2 mutations are more frequent in black SSA cases than in Caucasian SSA cases [12, 13].

Initiatives to Combat Health Disparities in SSA

Multiple initiatives are being proposed or in action to bring personalized medicine to the sub-Saharan African nations.  These include:

H3Africa empowers African researchers to be competitive in genomic sciences, establishes and nurtures effective collaborations among African researchers on the African continent, and generates unique data that could be used to improve both African and global health.

There is currently a global effort to apply genomic science and associated technologies to further the understanding of health and disease in diverse populations. These efforts work to identify individuals and populations who are at risk for developing specific diseases, and to better understand underlying genetic and environmental contributions to that risk. Given the large amount of genetic diversity on the African continent, there exists an enormous opportunity to utilize such approaches to benefit African populations and to inform global health.

The Human Heredity and Health in Africa (H3Africa) consortium facilitates fundamental research into diseases on the African continent while also developing infrastructure, resources, training, and ethical guidelines to support a sustainable African research enterprise – led by African scientists, for the African people. The initiative consists of 51 African projects that include population-based genomic studies of common, non-communicable disorders such as heart and renal disease, as well as communicable diseases such as tuberculosis. These studies are led by African scientists and use genetic, clinical, and epidemiologic methods to identify hereditary and environmental contributions to health and disease. To establish a foundation for African scientists to continue this essential work into the future work, the consortium also supports many crucial capacity building elements, such as: ethical, legal, and social implications research; training and capacity building for bioinformatics; capacity for biobanking; and coordination and networking.

The World Economic Forum’s Leapfrogging with Precision Medicine project 

This project is part of the World Economic Forum’s Shaping the Future of Health and Healthcare Platform

The Challenge

Advancing precision medicine in a way that is equitable and beneficial to society means ensuring that healthcare systems can adopt the most scientifically and technologically appropriate approaches to a more targeted and personalized way of diagnosing and treating disease. In certain instances, countries or institutions may be able to bypass, or “leapfrog”, legacy systems or approaches that prevail in developed country contexts.

The World Economic Forum’s Leapfrogging with Precision Medicine project will develop a set of tools and case studies demonstrating how a precision medicine approach in countries with greenfield policy spaces can potentially transform their healthcare delivery and outcomes. Policies and governance mechanisms that enable leapfrogging will be iterated and scaled up to other projects.

Successes in personalized genomic research in SSA

As Dr. Rebbeck states:

 Because of the underlying genetic and genomic relationships between Africans and members of the African diaspora (primarily in North America and Europe), knowledge gained from research in SSA can be used to address health disparities that are prevalent in members of the African diaspora.

For example members of the West African heritage and genomic ancestry has been reported to confer the highest genomic risk for prostate cancer in any worldwide population [14].

 

PERSPECTIVEGLOBAL HEALTH

Cancer in sub-Saharan Africa

  1. Timothy R. Rebbeck

See all authors and affiliations

Science  03 Jan 2020:
Vol. 367, Issue 6473, pp. 27-28
DOI: 10.1126/science.aay474

Summary/Abstract

Cancer is an increasing global public health burden. This is especially the case in sub-Saharan Africa (SSA); high rates of cancer—particularly of the prostate, breast, and cervix—characterize cancer in most countries in SSA. The number of these cancers in SSA is predicted to more than double in the next 20 years (1). Both the explanations for these increasing rates and the solutions to address this cancer epidemic require SSA-specific data and approaches. The histopathologic and demographic features of these tumors differ from those in high-income countries (HICs). Basic knowledge of the epidemiology, clinical features, and molecular characteristics of cancers in SSA is needed to build prevention and treatment tools that will address the future cancer burden. The distinct distribution and determinants of cancer in SSA provide an opportunity to generate knowledge about cancer risk factors, genomics, and opportunities for prevention and treatment globally, not only in Africa.

 

References

  1. Rebbeck TR: Cancer in sub-Saharan Africa. Science 2020, 367(6473):27-28.
  2. Parkin DM, Ferlay J, Jemal A, Borok M, Manraj S, N’Da G, Ogunbiyi F, Liu B, Bray F: Cancer in Sub-Saharan Africa: International Agency for Research on Cancer; 2018.
  3. Chinula L, Moses A, Gopal S: HIV-associated malignancies in sub-Saharan Africa: progress, challenges, and opportunities. Current opinion in HIV and AIDS 2017, 12(1):89-95.
  4. Colditz GA: Epidemiology of breast cancer. Findings from the nurses’ health study. Cancer 1993, 71(4 Suppl):1480-1489.
  5. Hamilton TC, Penault-Llorca F, Dauplat J: [Natural history of ovarian adenocarcinomas: from epidemiology to experimentation]. Contracept Fertil Sex 1998, 26(11):800-804.
  6. Garner EI: Advances in the early detection of ovarian carcinoma. J Reprod Med 2005, 50(6):447-453.
  7. Brockbank EC, Harry V, Kolomainen D, Mukhopadhyay D, Sohaib A, Bridges JE, Nobbenhuis MA, Shepherd JH, Ind TE, Barton DP: Laparoscopic staging for apparent early stage ovarian or fallopian tube cancer. First case series from a UK cancer centre and systematic literature review. European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 2013, 39(8):912-917.
  8. Kolligs FT: Diagnostics and Epidemiology of Colorectal Cancer. Visceral medicine 2016, 32(3):158-164.
  9. Rocken C, Neumann U, Ebert MP: [New approaches to early detection, estimation of prognosis and therapy for malignant tumours of the gastrointestinal tract]. Zeitschrift fur Gastroenterologie 2008, 46(2):216-222.
  10. Srivastava S, Verma M, Henson DE: Biomarkers for early detection of colon cancer. Clinical cancer research : an official journal of the American Association for Cancer Research 2001, 7(5):1118-1126.
  11. Pitt JJ, Riester M, Zheng Y, Yoshimatsu TF, Sanni A, Oluwasola O, Veloso A, Labrot E, Wang S, Odetunde A et al: Characterization of Nigerian breast cancer reveals prevalent homologous recombination deficiency and aggressive molecular features. Nature communications 2018, 9(1):4181.
  12. Zheng Y, Walsh T, Gulsuner S, Casadei S, Lee MK, Ogundiran TO, Ademola A, Falusi AG, Adebamowo CA, Oluwasola AO et al: Inherited Breast Cancer in Nigerian Women. Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2018, 36(28):2820-2825.
  13. Rebbeck TR, Friebel TM, Friedman E, Hamann U, Huo D, Kwong A, Olah E, Olopade OI, Solano AR, Teo SH et al: Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations. Human mutation 2018, 39(5):593-620.
  14. Lachance J, Berens AJ, Hansen MEB, Teng AK, Tishkoff SA, Rebbeck TR: Genetic Hitchhiking and Population Bottlenecks Contribute to Prostate Cancer Disparities in Men of African Descent. Cancer research 2018, 78(9):2432-2443.

Other articles on Cancer Health Disparities and Genomics on this Online Open Access Journal Include:

Gender affects the prevalence of the cancer type
The Rutgers Global Health Institute, part of Rutgers Biomedical and Health Sciences, Rutgers University, New Brunswick, New Jersey – A New Venture Designed to Improve Health and Wellness Globally
Breast Cancer Disparities to be Sponsored by NIH: NIH Launches Largest-ever Study of Breast Cancer Genetics in Black Women
War on Cancer Needs to Refocus to Stay Ahead of Disease Says Cancer Expert
Ethical Concerns in Personalized Medicine: BRCA1/2 Testing in Minors and Communication of Breast Cancer Risk
Ethics Behind Genetic Testing in Breast Cancer: A Webinar by Laura Carfang of survivingbreastcancer.org
Live Notes from @HarvardMed Bioethics: Authors Jerome Groopman, MD & Pamela Hartzband, MD, discuss Your Medical Mind
Testing for Multiple Genetic Mutations via NGS for Patients: Very Strong Family History of Breast & Ovarian Cancer, Diagnosed at Young Ages, & Negative on BRCA Test
Study Finds that Both Women and their Primary Care Physicians Confusion over Ovarian Cancer Symptoms May Lead to Misdiagnosis

 

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Live Notes from @HarvardMed Bioethics: Authors Jerome Groopman, MD & Pamela Hartzband, MD, discuss Your Medical Mind

Posted in and Bioethics, Bio-Ethics, Ethics and Leadership, Health Economics and Outcomes Research, Patient Experience, Patient Experience: Personal Memories of Invasive Medical Intervantion, Patient Outlook, Patient-centered Medicine, Prescription Drugs Costs on March 27, 2020| Leave a Comment »

Live Notes from @HarvardMed Bioethics: Authors Jerome Groopman, MD & Pamela Hartzband, MD, discuss Your Medical Mind

Writer: Stephen J. Williams, Ph.D.

As part of the Harvard Medical School Series on Bioethics: author, clinician and professor Jerome Groopman, MD and Pamel Harzband, MD gave an online discussion of their book “Your Medical Mind”, a part of Harvard Medical School Center for Bioethics Program’s Critical Reading of Contemporary Books in Bioethics Series. The Contemporary Authors in Bioethics series brings together authors and the community to discuss books that explore new and developing topics in the field. This was held as an online Zoom meeting on March 26, 2020 at 5 pm EST and could be followed on Twitter using #HarvardBioethics.  A recording of the discussion will be made available at the Harvard Med School Center for Bioethics.

 

Available at Amazon: From the Amazon book description:

An entirely new way to make the best medical decisions.

Making the right medical decisions is harder than ever. We are overwhelmed by information from all sides—whether our doctors’ recommendations, dissenting experts, confusing statistics, or testimonials on the Internet. Now Doctors Groopman and Hartzband reveal that each of us has a “medical mind,” a highly individual approach to weighing the risks and benefits of treatments.  Are you a minimalist or a maximalist, a believer or a doubter, do you look for natural healing or the latest technology?  The authors weave vivid narratives of real patients with insights from recent research to demonstrate the power of the medical mind. After reading this groundbreaking book, you will know how to arrive at choices that serve you best.

 

Doctors Groopman and Hartzband began the discussion with a recapping medical research studies and medical panels, which had reported conflicting results or reversal of recommendations, respectively.  These included studies on the benefits of statin therapy in cholesterol management, studies on whether or not Vitamin D therapy is beneficial for postmenopausal women, the ongoing controversy on the frequency with which women should get mammograms, as well as the predictive value of Prostate Specific Antigen and prostate cancer screening.  The authors singled out the research reports and medical panels reviewing the data on PSA in which the same medical panel first came out in support of using PSA levels to screen for prostate cancer and then later, after reconvening, recommended that PSA was not useful for mass screenings for prostate cancer.

In fact, both authors were

completed surprised of the diametrically opposed views within or between panels given similar data presented to those medical professionals.

The authors then asked a question:  Why would the same medical panel come to a reversal of their decision and more, importantly,  why are there such disparate conclusions from the same medical data sets, leading to varied clinical decision-making.

In general, Drs. Groopman and Hartzband asked how do physicians and patients make their decisions?

To answer this they looked at studies that Daniel Bernouli had conducted to model the economic behaviors of risk aversion in the marketplace. Bernouli’s theorem correlated market expectation with probability and outcomes

expectation = probability x utility of outcome

However, in medicine, one can measure probability (or risk) but it is very hard to measure utility (which is the value or worth of the outcome).

For example, they gave an example if a person was born blind but offered a risky to regain sight, the individual values their quality of life from their own perspective and might feel that, as their life is worthwhile as it is, they would not undergo a risky procedure. However a person who had suddenly lost their sight might value sight more, and be willing to undergo a risky procedure.

Three methods are used to put a value on utility or outcome worth with regards to medical decisions

  1. linear scale (life or death; from 0 to 1)
  2. time trade off:  e.g. how much longer do I have to live
  3. standard gamble:  let’s try it

All of these methods however are flawed because one doesn’t know their future medical condition (e.g. new information on the disease) and people values and perceptions change over time.

An example of choice of methods the medical community uses to make decisions include:

  • In the United Kingdom, their system uses a time trade off method to determine value in order to determine appropriate course of action which may inadvertently, result in rationed care
  • in the United States, the medical community uses the time trade off to determine cost effectiveness

 

Therefore Drs. Groopman and Harztband, after conducing multiple interviews with patients and physicians were able to categorize medical decision making based on groups of mindsets

  1. Maximalist: Proactive behavior, wants to stay ahead of the curve
  2. Minimalist: less intervention is more; more hesitant to try any suggested therapy
  3. Naturalist:  more prone to choose natural based therapies or home remedies
  4. Tech Oriented: wants to try the latest therapies and more apt to trust in branded and FDA approved therapeutics
  5. Believer:  trust in suggestions by physician; physician trusts medical panels suggestions
  6. Doubter: naturally inquisitive and more prone to investigate risk benefits of any suggested therapy

The authors also identified many Cognitive Traps that both physicians and patients may fall into including:

  • Relative versus Absolute Numbers: for instance putting emphasis on one number or the other without regard to context; like looking at disease numbers without taking into consideration individual risk
  • Availability: availability or lack of available information; they noticed if you fall in this trap depends on whether you are a Minimalist or Maximalist
  • Framing:  for example  when people talk to others about their conditions and hear stories about others treatments, conditions .. mainly anecdotal evidence

Stories can be helpful but they sometimes increase our overestimation of risk or benefit so framing the information is very important for both the patient as well as the physician (even doctors as patients)

Both authors have noticed a big shift in US to minimalism probably because of the rising costs of healthcare.

How do these mindsets affect the patient-physician relationship?

A University of Michigan study revealed that patients who would be characterized as maximalists pushed their physicians to do more therapy and were more prone to seek outside advice.

Physicians need to understand and listen to their patients during the patients’s first visit and determine what medical mindset that this patient has.

About the authors:

Jerome Groopman, M.D. is the Dina and Raphael Recanati Professor of Medicine at Harvard Medical School, Chief of Experimental Medicine at Beth Israel Deaconess Medical Center, and one of the world’s leading researchers in cancer and AIDS. He is a staff writer for The New Yorker and has written for The New York Times, The Wall Street Journal,The Washington Post and The New Republic. He is author of The Measure of Our Days (1997), Second Opinions (2000), Anatomy of Hope (2004), How Doctors Think (2007), and the recently released, Your Medical Mind.

Dr. Pamela Hartzband is an Assistant Professor at the Harvard Medical School and Attending Physician in the Division of Endocrinology at the Beth Israel Deaconess Medical Center in Boston. She specializes in disorders of the thyroid and pituitary glands. A magna cum laude graduate of Radcliffe College, Harvard University, she received her M.D. from Harvard Medical School. She served her internship and residency in internal medicine at the Massachusetts General Hospital, and her specialty fellowships in endocrinology and metabolism at UCLA.

More articles on BioEthics and Patient experiences in this Online Open Access Journal Include:

Ethics Behind Genetic Testing in Breast Cancer: A Webinar by Laura Carfang of survivingbreastcancer.org

Tweets and Re-Tweets by @Pharma_BI ‏and @AVIVA1950 at 2019 Petrie-Flom Center Annual Conference: Consuming Genetics: Ethical and Legal Considerations of New Technologies, Friday, May 17, 2019 from 8:00 AM to 5:00 PM EDT @Harvard_Law

Innovation + Technology = Good Patient Experience

Drivers of Patient Experience

Factors in Patient Experience

Patient Experience Survey

Please also see our offering on Amazon at https://www.amazon.com/dp/B076HGB6MZ

“The VOICES of Patients, Hospital CEOs, Health Care Providers, Caregivers and Families: Personal Experience with Critical Care and Invasive Medical Procedures,”

 

 

 

 

 

 

 

 

 

 

 

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US Responses to Coronavirus Outbreak Expose Many Flaws in Our Medical System

Posted in and Bioethics, Bio-Ethics, Biomarkers: Inflammation, coronavirus, Coronavirus Gene Expression, COVID-19, COVID-19 effects on Human Heart, COVID-19: Pandemic Surgery Guidance, Economic Impact of Coronavirus Pandemic, Ethics and Leadership, Federal Budget Appropriations, Health Economics and Outcomes Research, Health Law & Patient Safety, Health Law Policy, Healthcare costs and reimbursement, Healthcare Reform, Hospital-based Medical Innovations, Immune-Mediation (independent immunopathology: lung and reticuloendothelial system), Key Opinion Leaders in eScientific Publishing - Interviews with, Law and Medicine Conflicts, Leadership, Power, Social Interlocking Connections, number of asymptomatic infections, Patents, Patient Experience, Patient Experience: Personal Memories of Invasive Medical Intervantion, Patient Outlook, Patient’s Voice: Personal Experience with Invasive Medical Procedures, Population genetics, Population Health Management, Population Health Management, Genetics & Pharmaceutical, SARS-CoV-2, Seasonality & Environmental Factors in Resurgence, Serology tests for coronavirus antibodies, Support Staff, Treatment Protocols for COVID-19, United States, Vaccinology, Virus Infective Acute Respiratory Syndrome: SARS-CoV, tagged , , , , , , , , , , , on March 25, 2020| Leave a Comment »

US Responses to Coronavirus Outbreak Expose Many Flaws in Our Medical System

Curator: Stephen J. Williams, Ph.D.

The  coronavirus pandemic has affected almost every country in every continent however, after months of the novel advent of novel COVID-19 cases, it has become apparent that the varied clinical responses in this epidemic (and outcomes) have laid bare some of the strong and weak aspects in, both our worldwide capabilities to respond to infectious outbreaks in a global coordinated response and in individual countries’ response to their localized epidemics.

 

Some nations, like Israel, have initiated a coordinated government-private-health system wide action plan and have shown success in limiting both new cases and COVID-19 related deaths.  After the initial Wuhan China outbreak, China closed borders and the government initiated health related procedures including the building of new hospitals. As of writing today, Wuhan has experienced no new cases of COVID-19 for two straight days.

 

However, the response in the US has been perplexing and has highlighted some glaring problems that have been augmented in this crisis, in the view of this writer.    In my view, which has been formulated after social discussion with members in the field ,these issues can be centered on three major areas of deficiencies in the United States that have hindered a rapid and successful response to this current crisis and potential future crises of this nature.

 

 

  1. The mistrust or misunderstanding of science in the United States
  2. Lack of communication and connection between patients and those involved in the healthcare industry
  3. Socio-geographical inequalities within the US healthcare system

 

1. The mistrust or misunderstanding of science in the United States

 

For the past decade, anyone involved in science, whether directly as active bench scientists, regulatory scientists, scientists involved in science and health policy, or environmental scientists can attest to the constant pressure to not only defend their profession but also to defend the entire scientific process and community from an onslaught of misinformation, mistrust and anxiety toward the field of science.  This can be seen in many of the editorials in scientific publications including the journal Science and Scientific American (as shown below)

 

Stepping Away from Microscopes, Thousands Protest War on Science

Boston rally coincides with annual American Association for the Advancement of Science (AAAS) conference and is a precursor to the March for Science in Washington, D.C.

byLauren McCauley, staff writer

Responding to the troubling suppression of science under the Trump administration, thousands of scientists, allies, and frontline communities are holding a rally in Boston’s Copley Square on Sunday.

#standupforscience Tweets

 

“Science serves the common good,” reads the call to action. “It protects the health of our communities, the safety of our families, the education of our children, the foundation of our economy and jobs, and the future we all want to live in and preserve for coming generations.”

It continues: 

But it’s under attack—both science itself, and the unalienable rights that scientists help uphold and protect. 

From the muzzling of scientists and government agencies, to the immigration ban, the deletion of scientific data, and the de-funding of public science, the erosion of our institutions of science is a dangerous direction for our country. Real people and communities bear the brunt of these actions.

The rally was planned to coincide with the annual American Association for the Advancement of Science (AAAS) conference, which draws thousands of science professionals, and is a precursor to the March for Science in Washington, D.C. and in cities around the world on April 22.

 

Source: https://www.commondreams.org/news/2017/02/19/stepping-away-microscopes-thousands-protest-war-science

https://images.app.goo.gl/UXizCsX4g5wZjVtz9

 

https://www.washingtonpost.com/video/c/embed/85438fbe-278d-11e7-928e-3624539060e8

 

 

The American Association for Cancer Research (AACR) also had marches for public awareness of science and meaningful science policy at their annual conference in Washington, D.C. in 2017 (see here for free recordings of some talks including Joe Biden’s announcement of the Cancer Moonshot program) and also sponsored events such as the Rally for Medical Research.  This patient advocacy effort is led by the cancer clinicians and scientific researchers to rally public support for cancer research for the benefit of those affected by the disease.

Source: https://leadingdiscoveries.aacr.org/cancer-patients-front-and-center/

 

 

     However, some feel that scientists are being too sensitive and that science policy and science-based decision making may not be under that much of a threat in this country. Yet even as some people think that there is no actual war on science and on scientists they realize that the public is not engaged in science and may not be sympathetic to the scientific process or trust scientists’ opinions. 

 

   

From Scientific American: Is There Really a War on Science? People who oppose vaccines, GMOs and climate change evidence may be more anxious than antagonistic

 

Certainly, opponents of genetically modified crops, vaccinations that are required for children and climate science have become louder and more organized in recent times. But opponents typically live in separate camps and protest single issues, not science as a whole, said science historian and philosopher Roberta Millstein of the University of California, Davis. She spoke at a standing-room only panel session at the American Association for the Advancement of Science’s annual meeting, held in Washington, D.C. All the speakers advocated for a scientifically informed citizenry and public policy, and most discouraged broadly applied battle-themed rhetoric.

 

Source: https://www.scientificamerican.com/article/is-there-really-a-war-on-science/

 

      In general, it appears to be a major misunderstanding by the public of the scientific process, and principles of scientific discovery, which may be the fault of miscommunication by scientists or agendas which have the goals of subverting or misdirecting public policy decisions from scientific discourse and investigation.

 

This can lead to an information vacuum, which, in this age of rapid social media communication,

can quickly perpetuate misinformation.

 

This perpetuation of misinformation was very evident in a Twitter feed discussion with Dr. Eric Topol, M.D. (cardiologist and Founder and Director of the Scripps Research Translational  Institute) on the US President’s tweet on the use of the antimalarial drug hydroxychloroquine based on President Trump referencing a single study in the International Journal of Antimicrobial Agents.  The Twitter thread became a sort of “scientific journal club” with input from international scientists discussing and critiquing the results in the paper.  

 

Please note that when we scientists CRITIQUE a paper it does not mean CRITICIZE it.  A critique is merely an in depth analysis of the results and conclusions with an open discussion on the paper.  This is part of the normal peer review process.

 

Below is the original Tweet by Dr. Eric Topol as well as the ensuing tweet thread

 

https://twitter.com/EricTopol/status/1241442247133900801?s=20

 

Within the tweet thread it was discussed some of the limitations or study design flaws of the referenced paper leading the scientists in this impromptu discussion that the study could not reasonably conclude that hydroxychloroquine was not a reliable therapeutic for this coronavirus strain.

 

The lesson: The public has to realize CRITIQUE does not mean CRITICISM.

 

Scientific discourse has to occur to allow for the proper critique of results.  When this is allowed science becomes better, more robust, and we protect ourselves from maybe heading down an incorrect path, which may have major impacts on a clinical outcome, in this case.

 

 

2.  Lack of communication and connection between patients and those involved in the healthcare industry

 

In normal times, it is imperative for the patient-physician relationship to be intact in order for the physician to be able to communicate proper information to their patient during and after therapy/care.  In these critical times, this relationship and good communication skills becomes even more important.

 

Recently, I have had multiple communications, either through Twitter, Facebook, and other social media outlets with cancer patients, cancer advocacy groups, and cancer survivorship forums concerning their risks of getting infected with the coronavirus and how they should handle various aspects of their therapy, whether they were currently undergoing therapy or just about to start chemotherapy.  This made me realize that there were a huge subset of patients who were not receiving all the information and support they needed; namely patients who are immunocompromised.

 

These are patients represent

  1. cancer patient undergoing/or about to start chemotherapy
  2. Patients taking immunosuppressive drugs: organ transplant recipients, patients with autoimmune diseases, multiple sclerosis patients
  3. Patients with immunodeficiency disorders

 

These concerns prompted me to write a posting curating the guidance from National Cancer Institute (NCI) designated cancer centers to cancer patients concerning their risk to COVID19 (which can be found here).

 

Surprisingly, there were only 14 of the 51 US NCI Cancer Centers which had posted guidance (either there own or from organizations like NCI or the National Cancer Coalition Network (NCCN).  Most of the guidance to patients had stemmed from a paper written by Dr. Markham of the Fred Hutchinson Cancer Center in Seattle Washington, the first major US city which was impacted by COVID19.

 

Also I was surprised at the reactions to this posting, with patients and oncologists enthusiastic to discuss concerns around the coronavirus problem.  This led to having additional contact with patients and oncologists who, as I was surprised, are not having these conversations with each other or are totally confused on courses of action during this pandemic.  There was a true need for each party, both patients/caregivers and physicians/oncologists to be able to communicate with each other and disseminate good information.

 

Last night there was a Tweet conversation on Twitter #OTChat sponsored by @OncologyTimes.  A few tweets are included below

https://twitter.com/OncologyTimes/status/1242611841613864960?s=20

https://twitter.com/OncologyTimes/status/1242616756658753538?s=20

https://twitter.com/OncologyTimes/status/1242615906846547978?s=20

 

The Lesson:  Rapid Communication of Vital Information in times of stress is crucial in maintaining a good patient/physician relationship and preventing Misinformation.

 

3.  Socio-geographical Inequalities in the US Healthcare System

It has become very clear that the US healthcare system is fractioned and multiple inequalities (based on race, sex, geography, socio-economic status, age) exist across the whole healthcare system.  These inequalities are exacerbated in times of stress, especially when access to care is limited.

 

An example:

 

On May 12, 2015, an Amtrak Northeast Regional train from Washington, D.C. bound for New York City derailed and wrecked on the Northeast Corridor in the Port Richmond neighborhood of Philadelphia, Pennsylvania. Of 238 passengers and 5 crew on board, 8 were killed and over 200 injured, 11 critically. The train was traveling at 102 mph (164 km/h) in a 50 mph (80 km/h) zone of curved tracks when it derailed.[3]

Some of the passengers had to be extricated from the wrecked cars. Many of the passengers and local residents helped first responders during the rescue operation. Five local hospitals treated the injured. The derailment disrupted train service for several days. 

(Source Wikipedia https://en.wikipedia.org/wiki/2015_Philadelphia_train_derailment)

What was not reported was the difficulties that first responders, namely paramedics had in finding an emergency room capable of taking on the massive load of patients.  In the years prior to this accident, several hospitals, due to monetary reasons, had to close their emergency rooms or reduce them in size. In addition only two in Philadelphia were capable of accepting gun shot victims (Temple University Hospital was the closest to the derailment but one of the emergency rooms which would accept gun shot victims. This was important as Temple University ER, being in North Philadelphia, is usually very busy on any given night.  The stress to the local health system revealed how one disaster could easily overburden many hospitals.

 

Over the past decade many hospitals, especially rural hospitals, have been shuttered or consolidated into bigger health systems.  The graphic below shows this

From Bloomberg: US Hospital Closings Leave Patients with Nowhere to go

 

 

https://images.app.goo.gl/JdZ6UtaG3Ra3EA3J8

 

Note the huge swath of hospital closures in the midwest, especially in rural areas.  This has become an ongoing problem as the health care system deals with rising costs.

 

Lesson:  Epidemic Stresses an already stressed out US healthcare system

 

Please see our Coronavirus Portal at

https://pharmaceuticalintelligence.com/coronavirus-portal/

 

for more up-to-date scientific, clinical information as well as persona stories, videos, interviews and economic impact analyses

and @pharma_BI

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Diversity and Health Disparity Issues Need to be Addressed for GWAS and Precision Medicine Studies

Posted in and Bioethics, Bio-Ethics, BioIT: BioInformatics, BioIT: BioInformatics, NGS, Clinical & Translational, Pharmaceutical R&D Informatics, Clinical Genomics, Cancer Informatics, Cancer Genomics, Childhood cancer, Genome Biology, Population genetics, Population Health Management, tagged , , , , , on December 22, 2019| Leave a Comment »

Diversity and Health Disparity Issues Need to be Addressed for GWAS and Precision Medicine Studies

Curator: Stephen J. Williams, PhD

 

 

From the POLICY FORUM ETHICS AND DIVERSITY Section of Science

Ethics of inclusion: Cultivate trust in precision medicine

 See all authors and affiliations

Science  07 Jun 2019:
Vol. 364, Issue 6444, pp. 941-942
DOI: 10.1126/science.aaw8299

Precision medicine is at a crossroads. Progress toward its central goal, to address persistent health inequities, will depend on enrolling populations in research that have been historically underrepresented, thus eliminating longstanding exclusions from such research (1). Yet the history of ethical violations related to protocols for inclusion in biomedical research, as well as the continued misuse of research results (such as white nationalists looking to genetic ancestry to support claims of racial superiority), continue to engender mistrust among these populations (2). For precision medicine research (PMR) to achieve its goal, all people must believe that there is value in providing information about themselves and their families, and that their participation will translate into equitable distribution of benefits. This requires an ethics of inclusion that considers what constitutes inclusive practices in PMR, what goals and values are being furthered through efforts to enhance diversity, and who participates in adjudicating these questions. The early stages of PMR offer a critical window in which to intervene before research practices and their consequences become locked in (3).

Initiatives such as the All of Us program have set out to collect and analyze health information and biological samples from millions of people (1). At the same time, questions of trust in biomedical research persist. For example, although the recent assertions of white nationalists were eventually denounced by the American Society of Human Genetics (4), the misuse of ancestry testing may have already undermined public trust in genetic research.

There are also infamous failures in research that included historically underrepresented groups, including practices of deceit, as in the Tuskegee Syphilis Study, or the misuse of samples, as with the Havasupai tribe (5). Many people who are being asked to give their data and samples for PMR must not only reconcile such past research abuses, but also weigh future risks of potential misuse of their data.

To help assuage these concerns, ongoing PMR studies should open themselves up to research, conducted by social scientists and ethicists, that examines how their approaches enhance diversity and inclusion. Empirical studies are needed to account for how diversity is conceptualized and how goals of inclusion are operationalized throughout the life course of PMR studies. This is not limited to selection and recruitment of populations but extends to efforts to engage participants and communities, through data collection and measurement, and interpretations and applications of study findings. A commitment to transparency is an important step toward cultivating public trust in PMR’s mission and practices.

From Inclusion to Inclusive

The lack of diverse representation in precision medicine and other biomedical research is a well-known problem. For example, rare genetic variants may be overlooked—or their association with common, complex diseases can be misinterpreted—as a result of sampling bias in genetics research (6). Concentrating research efforts on samples with largely European ancestry has limited the ability of scientists to make generalizable inferences about the relationships among genes, lifestyle, environmental exposures, and disease risks, and thereby threatens the equitable translation of PMR for broad public health benefit (7).

However, recruiting for diverse research participation alone is not enough. As with any push for “diversity,” related questions arise about how to describe, define, measure, compare, and explain inferred similarities and differences among individuals and groups (8). In the face of ambivalence about how to represent population variation, there is ample evidence that researchers resort to using definitions of diversity that are heterogeneous, inconsistent, and sometimes competing (9). Varying approaches are not inherently problematic; depending on the scientific question, some measures may be more theoretically justified than others and, in many cases, a combination of measures can be leveraged to offer greater insight (10). For example, studies have shown that American adults who do not self-identify as white report better mental and physical health if they think others perceive them as white (11, 12).

The benefit of using multiple measures of race and ancestry also extends to genetic studies. In a study of hypertension in Puerto Rico, not only did classifications based on skin color and socioeconomic status better predict blood pressure than genetic ancestry, the inclusion of these sociocultural measures also revealed an association between a genetic polymorphism and hypertension that was otherwise hidden (13). Thus, practices that allow for a diversity of measurement approaches, when accompanied by a commitment to transparency about the rationales for chosen approaches, are likely to benefit PMR research more than striving for a single gold standard that would apply across all studies. These definitional and measurement issues are not merely semantic. They also are socially consequential to broader perceptions of PMR research and the potential to achieve its goals of inclusion.

Study Practices, Improve Outcomes

Given the uncertainty and complexities of the current, early phase of PMR, the time is ripe for empirical studies that enable assessment and modulation of research practices and scientific priorities in light of their social and ethical implications. Studying ongoing scientific practices in real time can help to anticipate unintended consequences that would limit researchers’ ability to meet diversity recruitment goals, address both social and biological causes of health disparities, and distribute the benefits of PMR equitably. We suggest at least two areas for empirical attention and potential intervention.

First, we need to understand how “upstream” decisions about how to characterize study populations and exposures influence “downstream” research findings of what are deemed causal factors. For example, when precision medicine researchers rely on self-identification with U.S. Census categories to characterize race and ethnicity, this tends to circumscribe their investigation of potential gene-environment interactions that may affect health. The convenience and routine nature of Census categories seemed to lead scientists to infer that the reasons for differences among groups were self-evident and required no additional exploration (9). The ripple effects of initial study design decisions go beyond issues of recruitment to shape other facets of research across the life course of a project, from community engagement and the return of results to the interpretation of study findings for human health.

Second, PMR studies are situated within an ecosystem of funding agencies, regulatory bodies, disciplines, and other scholars. This partly explains the use of varied terminology, different conceptual understandings and interpretations of research questions, and heterogeneous goals for inclusion. It also makes it important to explore how expectations related to funding and regulation influence research definitions of diversity and benchmarks for inclusion.

For example, who defines a diverse study population, and how might those definitions vary across different institutional actors? Who determines the metrics that constitute successful inclusion, and why? Within a research consortium, how are expectations for data sharing and harmonization reconciled with individual studies’ goals for recruitment and analysis? In complex research fields that include multiple investigators, organizations, and agendas, how are heterogeneous, perhaps even competing, priorities negotiated? To date, no studies have addressed these questions or investigated how decisions facilitate, or compromise, goals of diversity and inclusion.

The life course of individual studies and the ecosystems in which they reside cannot be easily separated and therefore must be studied in parallel to understand how meanings of diversity are shaped and how goals of inclusion are pursued. Empirically “studying the studies” will also be instrumental in creating mechanisms for transparency about how PMR is conducted and how trade-offs among competing goals are resolved. Establishing open lines of inquiry that study upstream practices may allow researchers to anticipate and address downstream decisions about how results can be interpreted and should be communicated, with a particular eye toward the consequences for communities recruited to augment diversity. Understanding how scientists negotiate the challenges and barriers to achieving diversity that go beyond fulfilling recruitment numbers is a critical step toward promoting meaningful inclusion in PMR.

Transparent Reflection, Cultivation of Trust

Emerging research on public perceptions of PMR suggests that although there is general support, questions of trust loom large. What we learn from studies that examine on-the-ground approaches aimed at enhancing diversity and inclusion, and how the research community reflects and responds with improvements in practices as needed, will play a key role in building a culture of openness that is critical for cultivating public trust.

Cultivating long-term, trusting relationships with participants underrepresented in biomedical research has been linked to a broad range of research practices. Some of these include the willingness of researchers to (i) address the effect of history and experience on marginalized groups’ trust in researchers and clinicians; (ii) engage concerns about potential group harms and risks of stigmatization and discrimination; (iii) develop relationships with participants and communities that are characterized by transparency, clear communication, and mutual commitment; and (iv) integrate participants’ values and expectations of responsible oversight beyond initial informed consent (14). These findings underscore the importance of multidisciplinary teams that include social scientists, ethicists, and policy-makers, who can identify and help to implement practices that respect the histories and concerns of diverse publics.

A commitment to an ethics of inclusion begins with a recognition that risks from the misuse of genetic and biomedical research are unevenly distributed. History makes plain that a multitude of research practices ranging from unnecessarily limited study populations and taken-for-granted data collection procedures to analytic and interpretive missteps can unintentionally bolster claims of racial superiority or inferiority and provoke group harm (15). Sustained commitment to transparency about the goals, limits, and potential uses of research is key to further cultivating trust and building long-term research relationships with populations underrepresented in biomedical studies.

As calls for increasing diversity and inclusion in PMR grow, funding and organizational pathways must be developed that integrate empirical studies of scientific practices and their rationales to determine how goals of inclusion and equity are being addressed and to identify where reform is required. In-depth, multidisciplinary empirical investigations of how diversity is defined, operationalized, and implemented can provide important insights and lessons learned for guiding emerging science, and in so doing, meet our ethical obligations to ensure transparency and meaningful inclusion.

References and Notes

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  12. C. P. Jones et al Ethn. Dis. 18, 496 (2008).
  13. C. C. Gravlee, A. L. Non, C. J. Mulligan
  14. S. A. Kraft et al Am. J. Bioeth. 18, 3 (2018).
  15. A. E. Shields et al Am. Psychol. 60, 77 (2005).
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Human personalized autologous cell therapy for Parkinson’s Disease

Posted in Autologous Cell Therapy, Biological Engineering, Biological Networks, Biomarkers & Medical Diagnostics, Biotechnology, Cell Biology, Cell Biology, Signaling & Cell Circuits, Cell Processing System in Cell Therapy Process Development, cell-based therapy, Cerebrovascular and Neurodegenerative Diseases, Competition in regenerative stem cell science, Genomic Endocrinology, hNPCs, Innovations in Neurophysiology & Neuropsychology, Neurodegenerative Diseases, Neurohumoral Transmission, Neurological Diseases, Neuronal Circuits, Neuroscience, Parkinson's disease dyskinesia levodopa, Patient-centered Medicine, Personal Health Applications: Tech Innovations serves HealhCare, Personalized and Precision Medicine & Genomic Research, Signaling & Cell Circuits, stem cell biology and patient-specific, Stem Cells for Regenerative Medicine, tagged , , , , on December 2, 2019| Leave a Comment »

Reporter and Curator: Dr. Sudipta Saha, Ph.D.

 

Parkinson’s Disease (PD), characterized by both motor and non-motor system pathology, is a common neurodegenerative disorder affecting about 1% of the population over age 60. Its prevalence presents an increasing social burden as the population ages. Since its introduction in the 1960’s, dopamine (DA)-replacement therapy (e.g., L-DOPA) has remained the gold standard treatment. While improving PD patients’ quality of life, the effects of treatment fade with disease progression and prolonged usage of these medications often (>80%) results in side effects including dyskinesias and motor fluctuations. Since the selective degeneration of A9 mDA neurons (mDANs) in the substantia nigra (SN) is a key pathological feature of the disease and is directly associated with the cardinal motor symptoms, dopaminergic cell transplantation has been proposed as a therapeutic strategy.

 

Researchers showed that mammalian fibroblasts can be converted into embryonic stem cell (ESC)-like induced pluripotent stem cells (iPSCs) by introducing four transcription factors i.e., Oct4, Sox2, Klf4, and c-Myc. This was then accomplished with human somatic cells, reprogramming them into human iPSCs (hiPSCs), offering the possibility of generating patient-specific stem cells. There are several major barriers to implementation of hiPSC-based cell therapy for PD. First, probably due to the limited understanding of the reprogramming process, wide variability exists between the differentiation potential of individual hiPSC lines. Second, the safety of hiPSC-based cell therapy has yet to be fully established. In particular, since any hiPSCs that remain undifferentiated or bear sub-clonal tumorigenic mutations have neoplastic potential, it is critical to eliminate completely such cells from a therapeutic product.

 

In the present study the researchers established human induced pluripotent stem cell (hiPSC)-based autologous cell therapy. Researchers reported a platform of core techniques for the production of mDA progenitors as a safe and effective therapeutic product. First, by combining metabolism-regulating microRNAs with reprogramming factors, a method was developed to more efficiently generate clinical grade iPSCs, as evidenced by genomic integrity and unbiased pluripotent potential. Second, a “spotting”-based in vitro differentiation methodology was established to generate functional and healthy mDA cells in a scalable manner. Third, a chemical method was developed that safely eliminates undifferentiated cells from the final product. Dopaminergic cells thus produced can express high levels of characteristic mDA markers, produce and secrete dopamine, and exhibit electrophysiological features typical of mDA cells. Transplantation of these cells into rodent models of PD robustly restored motor dysfunction and reinnervated host brain, while showing no evidence of tumor formation or redistribution of the implanted cells.

 

Together these results supported the promise of these techniques to provide clinically applicable personalized autologous cell therapy for PD. It was recognized by researchers that this methodology is likely to be more costly in dollars and manpower than techniques using off-the-shelf methods and allogenic cell lines. Nevertheless, the cost for autologous cell therapy may be expected to decrease steadily with technological refinement and automation. Given the significant advantages inherent in a cell source free of ethical concerns and with the potential to obviate the need for immunosuppression, with its attendant costs and dangers, it was proposed that this platform is suitable for the successful implementation of human personalized autologous cell therapy for PD.

 

References:

 

https://www.jci.org/articles/view/130767/pdf?elqTrackId=2fd7d0edee744f9cb6d70a686d7b273b

 

https://www.ncbi.nlm.nih.gov/pubmed/31714896

 

https://www.ncbi.nlm.nih.gov/pubmed/23666606

 

https://www.ncbi.nlm.nih.gov/pubmed/27343168

 

https://www.ncbi.nlm.nih.gov/pubmed/21495962

 

https://www.ncbi.nlm.nih.gov/pubmed/28083784

 

https://www.ncbi.nlm.nih.gov/pubmed/20336395

 

https://www.ncbi.nlm.nih.gov/pubmed/28585381

 

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Impaired antibody development is promoted by chronic viral infection

Posted in Adaptive Immune Response to Biomaterials and Tissue Repair, Allergy and Infectious Diseases, Antibody Responses Predict Antigen Exposure, Autoimmune Inflammatory DIseases, “Antibody–enzyme conjugates”, Biotechnology, Cell Biology, Cell Biology, Signaling & Cell Circuits, Cell Processing System in Cell Therapy Process Development, combination immunotherapies., Diagnostic Immunology, Human Antibody Response, Human Circulating Antibody Repertoire, Human Immune System in Health and in Disease, Human Naive B Cell Repertoire, Immune Engineering, Immune Modulatory, Immuno-Oncology & Genomics, Immunodiagnostics, Immunology, Immunotherapy, Infectious Disease & New Antibiotic Targets, Infectious Disease Immunodiagnostics, Innovation in Immunology Diagnostics, Monoclonal antibody therapy, Monoclonal Immunotherapy, Protection Against Autoimmune Disease, Signaling & Cell Circuits, Synergistic Innate and Adaptive Immunotherapy, Synthetic Immunology: Hacking Immune Cells, Universal Immune Cell Therapies (uICT), Viral diseases, tagged , , , , on December 1, 2019| Leave a Comment »

Reporter and Curator: Dr. Sudipta Saha, Ph.D.

 

Effective humoral immune responses to infection and immunization are defined by high-affinity antibodies generated as a result of B cell differentiation and selection that occurs within germinal centers (GC). Within the GC, B cells undergo affinity maturation, an iterative and competitive process wherein B cells mutate their immunoglobulin genes (somatic hypermutation) and undergo clonal selection by competing for T cell help. Balancing the decision to remain within the GC and continue participating in affinity maturation or to exit the GC as a plasma cell (PC) or memory B cell (MBC) is critical for achieving optimal antibody avidity, antibody quantity, and establishing immunological memory in response to immunization or infection. Humoral immune responses during chronic infections are often dysregulated and characterized by hypergammaglobulinemia, decreased affinity maturation, and delayed development of neutralizing antibodies. Previous studies have suggested that poor antibody quality is in part due to deletion of B cells prior to establishment of the GC response.

 

In fact the impact of chronic infections on B cell fate decisions in the GC remains poorly understood. To address this question, researchers used single-cell transcriptional profiling of virus-specific GC B cells to test the hypothesis that chronic viral infection disrupted GC B cell fate decisions leading to suboptimal humoral immunity. These studies revealed a critical GC differentiation checkpoint that is disrupted by chronic infection, specifically at the point of dark zone re-entry. During chronic viral infection, virus-specific GC B cells were shunted towards terminal plasma cell (PC) or memory B cell (MBC) fates at the expense of continued participation in the GC. Early GC exit was associated with decreased B cell mutational burden and antibody quality. Persisting antigen and inflammation independently drove facets of dysregulation, with a key role for inflammation in directing premature terminal GC B cell differentiation and GC exit. Thus, the present research defines GC defects during chronic viral infection and identify a critical GC checkpoint that is short-circuited, preventing optimal maturation of humoral immunity.

 

Together, these studies identify a key GC B cell differentiation checkpoint that is dysregulated during chronic infection. Further, it was found that the chronic inflammatory environment, rather than persistent antigen, is sufficient to drive altered GC B cell differentiation during chronic infection even against unrelated antigens. However, the data also indicate that inflammatory circuits are likely linked to perception of antigen stimulation. Nevertheless, this study reveals a B cell-intrinsic program of transcriptional skewing in chronic viral infection that results in shunting out of the cyclic GC B cell process and early GC exit with consequences for antibody quality and hypergammaglobulinemia. These findings have implications for vaccination in individuals with pre-existing chronic infections where antibody responses are often ineffective and suggest that modulation of inflammatory pathways may be therapeutically useful to overcome impaired humoral immunity and foster affinity maturation during chronic viral infections.

 

References:

 

https://www.biorxiv.org/content/10.1101/849844v1

 

https://www.ncbi.nlm.nih.gov/pubmed/25656706

 

https://www.ncbi.nlm.nih.gov/pubmed/27653600

 

https://www.ncbi.nlm.nih.gov/pubmed/26912368

 

https://www.ncbi.nlm.nih.gov/pubmed/26799208

 

https://www.ncbi.nlm.nih.gov/pubmed/23001146

 

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scPopCorn: A New Computational Method for Subpopulation Detection and their Comparative Analysis Across Single-Cell Experiments

Posted in Advanced Computing Platform, Artificial Intelligence Applications in Health Care, Artificial Intelligence in Health Care - Tools & Innovations, Artificial Intelligence in Medicine - Applications in Therapeutics, Big Data & Analytics, BioIT: BioInformatics, BioIT: BioInformatics, NGS, Clinical & Translational, Pharmaceutical R&D Informatics, Clinical Genomics, Cancer Informatics, Biotechnology, Cancer Genomics, Cardiovascular Pharmacogenomics, Cell Biology, Clinical Genomics, Computational Biology/Systems and Bioinformatics, Data Science, Genome Biology, Genomic Analysis of EKG Electrophysiology Genomics, Genomic Endocrinology, Genomic Expression, Genomic Testing: Methodology for Diagnosis, Genomics Pharmacy, Immuno-Oncology & Genomics, Nutrigenomics, Personalized and Precision Medicine & Genomic Research, Pharmacogenomics, Preimplantation Genetic Diagnosis and Reproductive Genomics, Reproductive Andrology, Embryology, Genomic Endocrinology, Preimplantation Genetic Diagnosis and Reproductive Genomics, RNA Biology, RNA Biology, Cancer and Therapeutics, Single Cell Genomics, Single-cell sequencing, Uncategorized, tagged , , , , , on July 16, 2019| Leave a Comment »

scPopCorn: A New Computational Method for Subpopulation Detection and their Comparative Analysis Across Single-Cell Experiments

Reporter and Curator: Dr. Sudipta Saha, Ph.D.

4.2.5

4.2.5   scPopCorn: A New Computational Method for Subpopulation Detection and their Comparative Analysis Across Single-Cell Experiments, Volume 2 (Volume Two: Latest in Genomics Methodologies for Therapeutics: Gene Editing, NGS and BioInformatics, Simulations and the Genome Ontology), Part 4: Single Cell Genomics

Present day technological advances have facilitated unprecedented opportunities for studying biological systems at single-cell level resolution. For example, single-cell RNA sequencing (scRNA-seq) enables the measurement of transcriptomic information of thousands of individual cells in one experiment. Analyses of such data provide information that was not accessible using bulk sequencing, which can only assess average properties of cell populations. Single-cell measurements, however, can capture the heterogeneity of a population of cells. In particular, single-cell studies allow for the identification of novel cell types, states, and dynamics.

One of the most prominent uses of the scRNA-seq technology is the identification of subpopulations of cells present in a sample and comparing such subpopulations across samples. Such information is crucial for understanding the heterogeneity of cells in a sample and for comparative analysis of samples from different conditions, tissues, and species. A frequently used approach is to cluster every dataset separately, inspect marker genes for each cluster, and compare these clusters in an attempt to determine which cell types were shared between samples. This approach, however, relies on the existence of predefined or clearly identifiable marker genes and their consistent measurement across subpopulations.

Although the aligned data can then be clustered to reveal subpopulations and their correspondence, solving the subpopulation-mapping problem by performing global alignment first and clustering second overlooks the original information about subpopulations existing in each experiment. In contrast, an approach addressing this problem directly might represent a more suitable solution. So, keeping this in mind the researchers developed a computational method, single-cell subpopulations comparison (scPopCorn), that allows for comparative analysis of two or more single-cell populations.

The performance of scPopCorn was tested in three distinct settings. First, its potential was demonstrated in identifying and aligning subpopulations from single-cell data from human and mouse pancreatic single-cell data. Next, scPopCorn was applied to the task of aligning biological replicates of mouse kidney single-cell data. scPopCorn achieved the best performance over the previously published tools. Finally, it was applied to compare populations of cells from cancer and healthy brain tissues, revealing the relation of neoplastic cells to neural cells and astrocytes. Consequently, as a result of this integrative approach, scPopCorn provides a powerful tool for comparative analysis of single-cell populations.

This scPopCorn is basically a computational method for the identification of subpopulations of cells present within individual single-cell experiments and mapping of these subpopulations across these experiments. Different from other approaches, scPopCorn performs the tasks of population identification and mapping simultaneously by optimizing a function that combines both objectives. When applied to complex biological data, scPopCorn outperforms previous methods. However, it should be kept in mind that scPopCorn assumes the input single-cell data to consist of separable subpopulations and it is not designed to perform a comparative analysis of single cell trajectories datasets that do not fulfill this constraint.

Several innovations developed in this work contributed to the performance of scPopCorn. First, unifying the above-mentioned tasks into a single problem statement allowed for integrating the signal from different experiments while identifying subpopulations within each experiment. Such an incorporation aids the reduction of biological and experimental noise. The researchers believe that the ideas introduced in scPopCorn not only enabled the design of a highly accurate identification of subpopulations and mapping approach, but can also provide a stepping stone for other tools to interrogate the relationships between single cell experiments.

References:

https://www.sciencedirect.com/science/article/pii/S2405471219301887

https://www.tandfonline.com/doi/abs/10.1080/23307706.2017.1397554

https://ieeexplore.ieee.org/abstract/document/4031383

https://genomebiology.biomedcentral.com/articles/10.1186/s13059-016-0927-y

https://www.sciencedirect.com/science/article/pii/S2405471216302666

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