Category Archives: Research

Efficacy of Nimodipine Administration on Vasospasm after Subarachnoid Hemorrhage

I reviewed three articles on the efficacy of Nimodipine administration on vasospasm after subarachnoid hemorrhage in order to produce improved clinical outcomes.

Efficacy of Nimodipine Administration on Vasospasm after Subarachnoid Hemorrhage

Although the outcomes for these patients continues to remain poor, the current evidence suggests that calcium antagonist like Nimodipine can play an integral part of providing the best possible care for this populuation subset. The authors demonstrate that continuous local intra-arterial nimodipine administration (CLINA) is both safe and effective in helping reverse vasospasm and prevent delayed ischemic neurological deficit commonly associated with subarachnoid hemorrhage. They show that intra-arterial nimodipine administration shows good vessel widening effects against vasospasm. Additionally, the authors observed a positive correlation between the degree of blood vessel expansion and the improvement in clinical symptoms.

Here are the three main articles referenced in the paper. Unfortunately, only the first article is available without a fee.

  1. Angiographic Features and Clinical Outcomes of Intra-Arterial Nimodipine Injection in Patients with Subarachnoid Hemorrhage-Induced Vasospasm
  2. Continuous intra-arterial infusion of nimodipine at the onset of resistant vasospasm in aneurysmal subarachnoidal hemorrhage – A technical resport ($)
  3. Continuous Local Intra-arterial Nimodipine Administration in Severe Symptomatic Vasospasm after Subarachnoid Hemorrhage ($)

Here are the supporting related references, and fortunately most of them are available without a fee.

  1. American Association of Neurological Surgeons – Cerebral Aneurysm
  2. American Association of Neuroscience Nurses – Care of the Patient with Aneurysmal Subarachnoid Hemorrhage
  3. Guidelines for the management of aneurysmal subarachnoid hemorrhage: a statement for healthcare professionals from a special writing group of the Stroke Council, American Heart Association
  4. The Chocrane Library – Calcium Antagonists in Aneurysmal Subarachnoid Hemorrhage ($)
  5. Intra-Arterial Nimodipine for Severe Cerebral Vasospasm after Aneurysmal Subarachnoid Hemorrhage: Influence on Clinical Course and Cerebral Perfusion
  6. The role of transcranial Doppler ultrasonography in the diagnosis and management of vasospasm after aneurysmal subarachnoid hemorrhage ($)
  7. Inflammation and cerebral vasospasm after subarachnoid hemorrhage ($)
  8. Angiographic Features and Clinical Outcomes of Intra-Arterial Nimodipine Injection in Patients with Subarachnoid Hemorrhage-Induced Vasospasm
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Healthcare Informatics – Privacy vs. Openness

In today’s world when we have such great technology and people, why are we so worried about privacy and hiding the very information that can help us so very much.

I understand that there should always be a choice available to each and every one of us on whether we share our data or not. Protecting patients involved in research from harm and preserving their rights is essential to ethical research. Furthermore, in the National Academies Committee on Health Research and the Privacy of Health Information: The HIPAA Privacy Rule section “The Value and Importance of Health Information Privacy” stated in the subsection entitled “Patient Attitudes About Privacy in Health Research” that “ideally, there would be empirical evidence regarding the privacy value of all the specific Privacy Rule provisions that impact researchers, but there are only limited data on this topic from the consumer/patient perspective.” Yet, as everyone is aware health research is vital to the benefit of improving healthcare at both societal and personal levels. Has the pendulum has swung to far in the opposite direction, towards privacy and security? Does society need to reconsider how and why we are doing things that might be doing more harm than good in its current state. Health Information Privacy is and will continue to be an extremely important topic. For a detailed discussion on Public Health Protection and Privacy of Medical Records see the following excerpt from: Wendy E. Parmet, Public Health Protection and the Privacy of Medical Records, 16 Harvard Civil Rights-Civil Liberties Law Review 265-304 (Summer, 1981) (171 Footnotes). Further information on this is also found in the Harvard Journal of Law & Technology Volume 25, Number 1 Fall 2011, Much Ado About Data Ownership.

Below is a Ted video of John Wilbanks entitled “Let’s pool our medical data.” In it he eloquently discusses the topic of balancing both our privacy and the many benefits of opening and sharing our medical data.

Performing a medical or genomic experiment on a human requires informed consent and careful boundaries around privacy. But what if the data that results, once scrubbed of identifying marks, was released into the wild? At WeConsent.us, John Wilbanks thinks through the ethical and procedural steps to create an open, massive, mine-able database of data about health and genomics from many sources. One step: the Portable Legal Consent for Common Genomics Research (PLC-CGR), an experimental bioethics protocol that would allow any test subject to say, “Yes, once this experiment is over, you can use my data, anonymously, to answer any other questions you can think of.” Compiling piles of test results in one place, Wilbanks suggests, would turn genetic info into big data–giving researchers the potential to spot patterns that simply aren’t viewable up close.

A campaigner for the wide adoption of data sharing in science, Wilbanks is also a Senior Fellow with the Kauffman Foundation, a Research Fellow at Lybba and supported by Sage Bionetworks

“All too many observations lie isolated and forgotten on personal hard drives and CDs, trapped by technical, legal and cultural barriers.” – Nature, September 2009

The idea of creating a commons open framework is not a new topic. The idea of a commons as a knowledge bank, a form of communication and community, and a worldview perspective have been around for a while. Here are just a few examples of current commons or open frameworks.

  1. NIH – ERA Commons
  2. Creative Commons
    1. Creative Commons jurisdiction ports

However, the ideas of openness and sharing information are rarely discussed topics in healthcare. When compared to the enormity of talks, policies, classes, etc. given on HIPAA privacy and security, research patents, and competition in general. Therefore, to further expand this idea we need to adopt some of the work done on this idea from the Computer Science industry that not only embraces these ideas, concepts, and philosophies, but is pioneering and leading the charge behind the ideas surrounding big data. The Internet is one of the most amazing commons ever created.  Who can imagine life without it anymore?

In Sir Tim Berners Lee Ted talk he proposes a web for open, linked data that could do for numbers what the Web did for words, pictures, video: unlock our data and reframe the way we use it together, which sounds a lot like the main theme or main philosophy from John Wilbanks talk above.

In the 1980s, scientists at CERN were asking themselves how massive, complex, collaborative projects — like the fledgling LHC — could be orchestrated and tracked. Tim Berners-Lee, then a contractor, answered by inventing the World Wide Web. This global system of hypertext documents, linked through the Internet, brought about a massive cultural shift ushered in by the new tech and content it made possible: AOL, eBay, Wikipedia, TED.com…
Berners-Lee is now director of the World Wide Web Consortium (W3C), which maintains standards for the Web and continues to refine its design. Recently he has envisioned a “Semantic Web” — an evolved version of the same system that recognizes the meaning of the information it carries. He is also a senior researcher at MIT’s Computer Science and AI Lab.

“It’s hard to overstate the impact of the global system he created. It’s almost Gutenbergian.” – Time

Here are some other related talks that follow along this similar methodology and philosophy:

  1. Don Tapscott: Four principles for the open world
  2. Thomas Goetz: It’s time to redesign medical data
  3. Clay Shirky: How the Internet will (one day) transform government

To bring the focus back to the healthcare industry or more specifically to healthcare informatics , Shah from the Stanford SOM, in his paper titled “Translational bioinformatics embraces big data,” reviews the latest trends and major developments in translational bioinformatics in the past year (2011-2012). His key take-home points are:

  1. Translational informatics is ready to revolutionize human health and healthcare using large-scale measurements on individuals.
  2. Data-centric approaches that compute on massive amounts of data (often called “Big Data”) to discover patterns and to make clinically relevant predictions will gain adoption.
  3. Research that bridges the latest multimodal measurement technologies with large amounts of electronic healthcare data is increasing; and is where new breakthroughs will occur.

Lastly, we as a group of both providers and consumers of healthcare can help implement and drive these changes to work with and improve our healthcare system. In doing so please remember to keep these principles alive in all that you do:

  1. Without exception, we all belong to our community, and we each have an equal stake in what happens.
  2. People most affected by critical decisions must be included in the process of making them.
  3. Sufficiency and resilience are the opposite of the folly of growth.

Sepsis

INTRODUCTION

First, sepsis is a syndrome and not an individual disease. It is the 11th leading cause of death in the US. According to the Global Sepsis Alliance (GSA), “Sepsis is one of the most pressing healthcare challenges faced by the world today.”  The CDC shows sepsis hospital admissions “have grown from around 200 per 1000 inhabitants in 2000, to 340 in 2008. Also, in 2008 the costs for hospital treatment were US $14.8 billion, but these have increased by an annual rate of 11 percent.” According to Dr. Reinhardt “the main way it can be prevented is if it is recognized early and the patient receives adequate measures of treatment. Treatments, like antimicrobials and intravenous fluids must be initiated when the first signs of organ dysfunction appear. If they are given in the first few hours the survival rate may be up to 80 percent, but studies suggest with each hour of delay the mortality rate increases by five to eight percent.” (GSA – Stop Sepsis, Save Lives)

DEFINITION

Sepsis is a potentially deadly medical condition characterized by a whole-body inflammatory state (called a systemic inflammatory response syndrome or SIRS) that is triggered by an infection. The body may develop this inflammatory response by the immune system to microbes in the blood, urine, lungs, skin, or other tissues. A popular term for sepsis is blood poisoning. Severe sepsis is the systemic inflammatory response, infection and the presence of organ dysfunction. Septic Shock is the combination of sepsis with abnormally decreased blood pressure.

(Also, here is another great video about SIRS from the same source.)

PATHOPHYSIOLOGY

At this point in time, the literature richly illustrates that no single mediator / system / pathway / pathogen drives the pathophysiology of sepsis (Am J Pathol. 2007 May; 170(5): 1435–1444. doi:10.2353/ajpath.2007.060872Pathophysiology of Sepsis)

    • The basic pathophysiology of sepsis, severe sepsis, and septic shock includes:
      • Vasodilation
      • Third spacing due to capillary leak
      • Myocardial dysfunction.
    • Vascular endothelium is both a source and target of injury in SIRS / sepsis. Injury may be due to toxins such as LPS (endotoxin) or from ischemia itself. Tissue factor release leads to amplification of the inflammatory response and to DIC via the thrombin pathway. Thrombin not only catalyzes fibrin formation but also causes leukocyte adhesion which leads to further endothelial damage. As DIC progresses, clotting factors are consumed and bleeding occurs.
    • Clotting factors, pro-fibrinolytic, and anti-thrombin factors are consumed leading to loss of fibrinolysis & normal down-regulation of thrombin pathway. This phenomenon is both pro-inflammatory and pro-thrombotic.
    • Protein C depletion has been associated with increased mortality. This has led to a series of clinical trials utilizing protein C, activated protein C (APC), antithrombin III (AT-III), and tissue factor pathway inhibitor to try and disrupt this cycle. Activated protein C has in fact been shown to reduce mortality in severe sepsis in adults. Bleeding problems seems to outweigh the benefits in children.
    • Usually gram negative and usually originating in the urinary or respiratory systems
    • Frequent microbial causes of sepsis

 

IDENTIFYING SEPSIS

(Balk RA. Crit Care Clin 2000;16:337-52Surviving Sepsis Campaign 2008 SSC Guidelines)

Differentials

TREATMENT

DESPERATE MEASURES

These measures can help improve immunohomeostasis (pro/antiinflamatory mediators), improve coagulation response with decreased organ thrombosis, and provide mechanical support for organ perfusion during an acute episode, and may buy some time, but may or may not reduce mortality.

NOVEL THERAPIES

QUALITY

REVIEWS

CLINICAL TRIALS

DR. RIVERS TALK

Dr. Emmanuel Rivers gave a talk on Severe Sepsis Management via the EMCrit Blog. The talk is broken down into the three links to each of the episodes provided below.

ADDITIONAL RESOURCES

In addition, here are some more great resources related to sepsis.

  1. Advances in Sepsis
  2. Crashing Patient Severe Sepsis
  3. Development and Implementation of a Multidisciplinary Sepsis Protocol
  4. EMCrit – Severe Sepsis Resources*
  5. EM Guidlines – Sepsis
  6. Global Sepsis Alliance
  7. International Sepsis Forum
  8. MedicineNet – Sepsis
  9. Medline Sepsis
  10. Sepsis Alliance
  11. Sepsis know from day 1
  12. Stanford SOM – Septris
  13. Surviving Sepsis
    1. The Surviving Sepsis Campaign (SSC) was developed by the European Society of Critical Care Medicinethe International Sepsis Forum,and the Society of Critical Care Medicine, to help meet the challenges of sepsis and to improve its management, diagnosis, and treatment. The agreement between the three founding organizations and funding for the campaign was concluded December 31, 2008. A generous grant has been received to continue the important work of the campaign. The grant funding extends through 2013. Assistance for US hospitals interested in implementing the bundles can be obtained through the Society of Critical Care Medicine’s Paragon program.
    2. Surviving Sepsis Protocol Checklist

Additional References

  1. 2001 SCCM/ESICM/ACCP/ATS/SIS International Sepsis De?nitions Conference
  2. Cleveland Clinic – Sepsis
  3. Genetic Polymorphisms in Sepsis and Septic Shock:Role in Prognosis and Potential for Therapy
  4. New Approaches to Sepsis: Molecular Diagnostics and Biomarkers
  5. Role of oxygen debt in the development of organ failure sepsis, and death in high-risk surgical patients
  6. Oxidative stress as a novel target in pediatric sepsis management
  7. The Pathogenesis of Sepsis
  8. Rapid Treatment of Severe Sepsis
  9. Sepsis in cirrhosis: report on the 7th meeting of the International Ascites Club
  10. Thermo Scientific biomarker procalcitonin
  11. Time is tissue: Why emerging evidence on sepsis urges physicians to watch the clock
    Early volume resuscitation can help avoid organ dysfunction—if you act quickly after making a diagnosis

CONCLUSION

Sepsis poses a significant burden upon the US healthcare system, resulting in an estimated 750,000 hospital admissions, 570,000 Emergency Department visits, 200,000 deaths and $16.7 billion in medical expenditures annually, according to, the online journal article in PLOS ONE, Chronic Medical Conditions and Risk of Sepsis. Mortality rates remain high in severe sepsis, and despite recent therapeutic breakthroughs much remains to be done to advance our understanding and treatment of sepsis. Currently, anti-sepsis initiatives focus on acute care, with ED staff employing the “sepsis bundles,” a series of steps that includes aggressive administration of antibiotics, IV fluids and blood pressure-boosting medications, and management. Additionally, the  Surviving Sepsis Campaign 2012 guidelines will further suggest that in patients with elevated lactate levels as a marker of hypoperfusion, resuscitation should be targeted at normalizing lactate as rapidly as possible (grade 2C). Having said that, however, a normal lactate doesn’t indicate absence of shock. Other factors, such as the patient’s central venous oxygen saturation level, need to be considered as well. The Surviving Sepsis Campaign guidelines are sponsored by 27 medical organizations. Among them are the Society of Critical Care Medicine, ACEP, the Society of Hospital Medicine, the American College of Chest Physicians, the American Thoracic Society, the Infectious Diseases Society of America, the Surgical Infection Society, the Pediatric Acute Lung Injury and Sepsis Investigators, and a host of international groups. Hopefully, strategies will be developed to continue to improve and maximize our efforts towards ameliorating sepsis throughout the world.

TOXNET

If you’re looking for a great toxicology resource then TOXNET is your answer. TOXNET serves as a comprehensive reference for Poison Control Centers and Emergency Departments around the United States. However, if you’re completely new to toxicology you may want to start out here first, with the NLM Toxicology Tutorials, or here at TOXLearn. For brief introduction to this superb tool, have a look at the TOXNET Brochure.

TOXNET (TOXicology Data NETwork) is a group of databases covering chemicals and drugs, diseases and the environment, environmental health, occupational safety and health, poisoning, risk assessment and regulations, and toxicology. It is managed by the Toxicology and Environmental Health Information Program (TEHIP) in the Division of Specialized Information Services (SIS) of the National Library of Medicine (NLM). A mobile version of TOXNET is available.

TOXNET provides you with a wealth of information. For instance, the Hazardous Substances Databank (HSDB) alone provides information on chemical properties and handling, the human health effects and emergency medical treatment, animal toxicity studies, metabolism, pharmacology, environmental standards and exposures, manufacturing data, lab methods and more.

Information in the TOXNET databases covers:

  • Specific chemicals, mixtures, and products
  • Chemical nomenclature
  • Unknown chemicals
  • Special toxic effects of chemicals in humans and/or animals
  • Citations from the scientific literature

Here is a great example video of “How to Navigate TOXNET” that will walk you through getting started with it.

The main reference for using TOXNET is “TOXNET and Beyond: Using the National Library of Medicine’s Environmental Health and Toxicology Portal”. In addition, the University of Cincinnati, College of Engineering created a great abbreviated “TOXNET Procedure Manual”. However, if it’s a bare bones introduction to using TOXNET check out the following SlideShare presentation.

The listing below explains the main TOXNET databases, and what they offer. However, the following link provides a more complete breakdown, of each of the specific TOXNET databases along with sample records for each.

Chemical Nomenclature and Structure

ChemIDplus®

ChemIDplus contains over 390,000 chemical records. More than 299,000 of those records include chemical structures. ChemIDplus is searchable by Name, Synonym, CAS Registry Number, Molecular Formula, Classification Code, Locator Code, Structure, and/or Physical properties. Enhanced structure display is available in ChemIDplus Advanced..

Toxicology Data

CCRIS (Chemical Carcinogenesis Research Information System)

CCRIS is developed and maintained by the National Cancer Institute (NCI). It contains over 9,000 chemical records with carcinogenicity, mutagenicity, tumor promotion, and tumor inhibition test results. Data are derived from studies cited in primary journals, current awareness tools, NCI reports, and other special sources. Test results have been reviewed by experts in carcinogenesis and mutagenesis.

CPDB (Carcinogenic Potency Database)

CPDB provides standardized analyses of the results of 6540 chronic, long-term animal cancer tests conducted since the 1950s and reported in the general published literature or by the National Cancer Institute and the National Toxicology Program. This database was developed at the University of California, Berkeley, and Lawrence Berkeley Laboratory.

CTD (Comparative Toxicogenomics Database)

The Comparative Toxicogenomics Database (CTD) elucidates molecular mechanisms by which environmental chemicals affect human disease. It contains manually curated data describing cross-species chemical-gene/protein interactions and chemical- and gene-disease relationships. CTD is developed at North Carolina State University (NCSU). The development team is located at NCSU and the Mount Desert Island Biological Laboratory (MDIBL).

GENE-TOX (Genetic Toxicology)

GENE-TOX was created by the U.S. Environmental Protection Agency (EPA) and has genetic toxicology test results on over 3,200 chemicals. Selected literature was reviewed by scientific experts for each of the test systems under evaluation.

HSDB® (Hazardous Substances Data Bank)

HSDB provides toxicity data for over 5,000 potentially hazardous chemicals. It also has information on emergency handling procedures, industrial hygiene, environmental fate, human exposure, detection methods, and regulatory requirements. The data are fully referenced and reviewed by a Scientific Review Panel.

Haz-Map®

Haz-Map is an occupational health database designed for health and safety professionals and for consumers seeking information about the adverse effects of workplace exposures to chemical and biological agents. The main links in Haz-Map are between chemicals and occupational diseases. These links have been established using current scientific evidence. In Haz-Map, chronic occupational diseases are linked to both jobs and industries, while acute diseases and infectious diseases are linked only to jobs. Cancers are not linked to jobs, industries or findings.

Household Products Database

The Household Products Database has information on the potential health effects of chemicals contained in common products used inside and around the home. Products can be searched by brand name, product type, manufacturer, ingredient/chemical name, and by health effects. The record for each product shows the ingredients as reported in the manufacturer’s Material Safety Data Sheet (MSDS) and includes more information such as handling, disposal, and health effects.

IRIS (Integrated Risk Information System)

IRIS is developed by the U.S. Environmental Protection Agency (EPA). It contains carcinogenic and non-carcinogenic health risk information on over 500 chemicals. IRIS risk assessment data has been reviewed by EPA scientists and represents EPA consensus.

ITER (International Toxicity Estimates for Risk)

ITER data focuses on hazard identification and dose-response assessment for human health. The database provides a table of comparisons of international risk assessment information and explains differences in risk values derived by different organizations. It is compiled by Toxicology Excellence for Risk Assessment (TERA) and contains over 650 chemical records. Data is extracted from each of the included agencies’ assessments and contains links to the documentation for the source.

LactMed (Drugs and Lactation)

A database of drugs and other chemicals to which breastfeeding mothers may be exposed. It includes information on the levels of such substances in breast milk and infant blood, and the possible adverse effects in the nursing infant. Statements of the American Academy of Pediatrics concerning a drug’s compatibility with breastfeeding are provided, as are suggested therapeutic alternatives to those drugs where appropriate. All data are derived from the scientific literature and fully referenced.

Toxics Release Inventory (TRI)

TRI is a set of publicly available databases containing information on releases of specific toxic chemicals and their management as waste, as reported annually to the EPA by U.S. industrial and federal facilities. This inventory was established under the Emergency Planning and Community Right to Know Act of 1986 (EPCRA). TRI’s data, beginning with the 1987 reporting year, covers air, water, land, and underground injection releases, as well as transfers to waste sites. In agreement with the Pollution Prevention Act of 1990, source reduction and recycling data is also included in TRI.

TOXMAP

TOXMAP is a Geographic Information System (GIS) using maps of the United States to show the amount and location of toxic chemicals released into the environment. Data is derived from the EPA’sToxics Release Inventory (TRI), which provides information on the releases of toxic chemicals into the environment as reported annually by industrial facilities around the United States. TOXMAP also contains information from the EPA’s Superfund Program.

Toxicology Literature

TOXLINE®

TOXLINE provides bibliographic information (1965 to present) covering the biochemical, pharmacological, physiological, and toxicological effects of drugs and other chemicals. It contains over 4 million references, most with abstracts, indexing terms, and Chemical Abstracts Service (CAS) Registry Numbers. The toxicology subset of MEDLINE/PubMed is part of TOXLINE. TOXLINE also contains references from specialized journals, government reports, and meeting abstracts.

Developmental and Reproductive Toxicology Database (DART)

DART covers the scientific literature on reproductive and developmental toxicology. DART is managed by NLM and funded by the EPA, the National Institute of Environmental Health Sciences (NIEHS) and NLM. DART contains references to reproductive and developmental toxicology literature published since 1965.

Medical Blogs and Podcasts

Here is a link to the many (200+) medical blogs and podcasts that I follow using Google Reader, and that you can easily subscribe to as well.There is a great deal of fantastic content created on all of these sources, check them out!

Also, here is a YouTube video showing how to create your own Google Reader Bundle similar to the one I created.

Free Evidence Based Practice Sites

Here are a few selected free database resources that support Evidence Based Practices to help with your research projects.

  1. Agency for Healthcare Research and Quality
  2. Agency for Healthcare Research and Quality – National Guideline Clearinghouse
  3. National Institute of Nursing Research
  4. The Cochrane Collaboration
  5. Trip Database
  6. Virginia Henderson International Nursing Library’s
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