27 September 2009

The Randomized Controlled Trial



The Randomized Controlled Trial
By: Rakhi Naik, MD

Eltrombopag for Thrombocytopenia in Patients with Cirrhosis Associated with Hepatitis C

STUDY OUTLINE
* Hypothesis: Eltrombopag can increase platelet counts in patient with hepatitis C cirrhosis.
* Design: Randomized controlled trial
* Setting: Multicenter trial in US & Europe
* Participants: 74 patients w/Hepatitis C cirrhosis
* Data Collection: Measurement of platelet counts before and after eltrombopag administration for 4 weeks; measurement of platelet counts after standard hepatitis C treatment with peg-interferon/ribavirin
* Outcome: Platelet counts, safety

BACKGROUND
* Chronic liver disease secondary to hepatitis C cirrhosis is often associated with significant thrombocytopenia.
* Thrombocytopenia in chronic hepatitis C infection is multifactorial in origin & is thought to be caused by:
o splenic sequestration (2/2 portal hypertension/hypersplenism)
o decreased thrombopoetin production (2/2 impaired hepatic synthetic function)
o bone marrow suppression (2/2 direct toxic effect of the hepatitis virus itself).

* Platelet counts below 75,000 are often not eligible for treatment with pegylated interferon & ribavirin because treatment itself leads to cytopenias in almost 100% of cases.

BACKGROUND
* Eltrombopag is an oral thrombopoetin receptor agonist that increases megakaryocyte proliferation and differentiation in animal models.

* Research questions:
o Can eltrombopag increase platelet levels in patients with untreated chronic hepatitis C cirrhosis?
o Can continued use of eltrombopag during hepatitis C treatment reduce treatment-related thrombocytopenia?
o What dose of eltrombopag is most effective for achieving these goals?

METHODS

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From mice To Men



From mice To Men

Jumpstarting A Laboratory Research Career
December 6, 2007
By: Elizabeth M. Jaffee, M.D.
The Dana and Albert “Cubby” Broccoli Professor of Oncology


Issues to Consider
* Stay where you trained or go elsewhere
* Identifying mentors
* Deciding on a research focus
* Leveraging small grants, getting the big one
* Building a team to work for you
* Balancing the work versus home life

Should you stay where you trained or should you take your first job at another institution?
* Pros for staying
o Implies you have a supportive mentor
o Implies you have a project of interest to others in your institution
o Experience with the institutional systems
o Experience with who might be good colleagues
* Start Up Time Is Shorter
* Pros for leaving
o Cuts the apron strings so that you are not in competition with your mentor at same place
o Likely to get more space and resources due to negotiations
o Likely able to get good students with less competition in your field
* No Identity Complex

Identify a mentor(s) for the most difficult stage in your career

* Cheer leader, promoter, encourager
* Sounding board for fine tuning ideas
* Devil’s advocate whose not afraid to give you the opposite view
* Editor of paper’s, grants, and presentations
* Guidance counselor to help you navigate through tough issues
* Referral Agent who sends you qualified student/postdoctoral fellow applicants
* Introduces you to leaders in your field
Your parent in the workplace

Develop A Five-Year Plan
Time interval goal between Assistant and Associate Professor
* What research questions do you want to focus on?
* What do you need to get you to where you want to be at 5-years
* Is it feasible now? At 1, 2, 3, and 4 years later?
* Revisit each year with your mentor to make sure you are on track
* How many grants and papers do you plan to submit?

Considerations in choosing how to focus your research
* Choose areas that make you want to come to work
o Desire, Desire, Desire!
* Choose a 5-year plan that will help you develop an identity separate from your mentor’s
* Consider several related areas - one high risk and and one or more low risk
* Choose areas that have more than one funding source

Grants: If only it were the 1990’s Again!
* Apply for more than one
o Can submit same grant to several funding agencies or similar ones that overlap
* Apply for career development grants first
* Pursue institutional grants and foundations if appropriate
* Spend 3 or more months writing your first grant
o Have a draft available 1-2 months before due date
o Ask mentor and other colleagues to review
o Have a scientist in a related but different field read the grant for clarity of presentation of ideas
* Go for the R01 by the end of the 5-year plan

Building a Team That Works For You, Literally!
* Learn to lead
o You will make mistakes - learn from them
o Take leadership development courses
o Listen to your team
o Show trust and faith in your team members!
o Mistakes are made by all of us. Be forgiving and continue to trust.
o Don’t let emotions or sense of insecurity get in the way of doing the right thing for your team (we all have this starting at all stages of our career).
* Lead by example
* Identify individuals you can influence
o Make sure they have the personality to take direction from you
o Make sure they have qualities you value
o Make sure you can lead them to be the best they can be

Get the right people on the bus!
Key Point

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Insect Sting Allergy and Venom Immunotherapy



Insect Sting Allergy and Venom Immunotherapy
By: David B.K. Golden, M.D.
Johns Hopkins University, Baltimore


History of Reaction to Insect Stings (Skin Test Positive Patients)

No reaction
Large Local
Cutaneous Systemic
Anaphylaxis

Severe swelling 24 hrs after a sting should be treated with:
A. Antibiotics C. Antihistamine E. Epinephrine
B. Prednisone D. Venom immunotherapy

Venom immunotherapy:
A. Is not necessary (“He’ll outgrow it”) B. Is dangerous
C. is only partially effective D. Is forever E. None of the above

Diagnosis of Insect Sting Allergy (Indications for Venom Immunotherapy)
Symptoms and Signs of Insect Sting Anaphylaxis in Adults and Children
Symptoms or Sign
Cutaneous only
Urticaria/angioedema
Dizziness/hypotension
Dyspnea/wheezing
Throat tightness/
Hoarseness
Loss of consciousness

Epidemiology of Venom Allergy

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