Investigator-Initiated Studies: Two Stories from the NIH
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The document discusses two investigator-initiated studies funded by the National Heart, Lung, and Blood Institute (NHLBI). The first story describes a study that found reopening occluded arteries in patients who had a heart attack over 24 hours prior did not reduce risk of death or heart attack and was difficult to conduct due to physician bias in favor of the procedure and slow funding and recruitment. The second story discusses a study that found certain blood thinning drugs can prevent heart attacks and strokes, despite initial resistance from the medical community. The document advocates for continued government funding of investigator-initiated clinical trials to evaluate new treatments while managing conflicts of interest.
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2) Multivariate analysis identified female sex, younger age, presence of peripheral artery disease, and use of a 6-French sheath as independent predictors of RAO.
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2) A 30-year-old Saudi lady seen for migraines and borderline hypertension who underwent a cardiac procedure.
3) A 13-year-old patient who had a cardiac procedure.
4) A 25-year-old staff member with a cardiac history.
Adh
Here are my thoughts on the discussion questions:
Q1. The study found that the no-AC cohort had lower rates of hemorrhagic and thrombotic complications compared to the AC cohort, though the difference was not statistically significant.
Q2. The traditional approach is to anticoagulate patients on VA-ECMO based on ELSO guidelines to target an ACT of 180-220 seconds. This study evaluated a non-traditional approach of not routinely anticoagulating patients in the first 24 hours.
Q3. You're right that not reporting coagulation data for the no-AC cohort limits reliability. Without knowing coagulation status, it's difficult to fully evaluate thrombotic risk in that group
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Journal club may 2016
This study evaluated a novel transcatheter interatrial shunt device for treating heart failure with preserved ejection fraction (HFPEF). 64 patients underwent successful implantation of the device. At 6 months follow up, 71% of patients had a reduction in pulmonary capillary wedge pressure at rest or during exercise compared to baseline. The procedure was well tolerated with no safety issues. The results suggest the device may help reduce left atrial pressure and improve functional status for patients with HFPEF, though the study had limitations as an open-label single-arm trial with short follow up.
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This document discusses prosthetic heart valve thrombosis (PHVT), including its diagnosis and management guidelines. PHVT occurs more commonly in mechanical heart valves compared to bioprosthetic valves. The incidence is higher in developing countries and contributes significantly to late mortality after heart valve surgery. Guidelines vary in their recommendations for treating PHVT, with some advocating surgery for all cases while others recommend thrombolytic therapy. Recent studies have explored newer, lower dose thrombolytic regimens that achieve similar efficacy but lower risks of complications compared to older regimens. Definitive diagnosis of PHVT involves transesophageal echocardiography to assess thrombus size and differentiate thrombus from pannus, while transthoracic echocardiography
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Title: Sense of Smell
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Describe the primary categories of smells and the concept of odor blindness.
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Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
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Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
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Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
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Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
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Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
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25% of the population with heightened sensitivity to taste, especially bitterness
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TEST BANK For Community Health Nursing A Canadian Perspective, 5th Edition by...
TEST BANK For Community Health Nursing A Canadian Perspective, 5th Edition by...
Investigator-Initiated Studies: Two Stories from the NIH
- 1. Investigator-Initiated Studies: Two Stories from the NIH Michael S Lauer, MD, FACC, FAHA Director, Division of Cardiovascular Sciences NHLBI/NIH January 11, 2012 Disclosures: None
- 2. First Story: Occluded Artery after MI http://www.circulation.or.kr/info/case/200904/fig1.gif http://www.indiastudychannel.com/attachments/Resources/82666-221135-Coronary%20Angiogram.jpg
- 3. Observational Findings Lamas GA et al. Circulation 1995;92:1101-9
- 4. OAT Timeline 9/30/99 OAT Starts 6/15/98-8/02/99 OAT Pilot enrollment 12/30/05 OAT Recruitment Completed Total: 2166 07/2001 TOSCA-2 begins 08/2002 OAT-EP begins 12/2003 OAT-NUC begins AHA 6/1/1998 1st NHLBI submission 3/1/1999 2nd NHLBI submission NHLBI Workshop on Coronary Revascularization 1st OAT Steering Committee 151 409 485 523 382 196 Enrolled patients per year 20 Many thanks to Dr. Judith Hochman 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006
- 8. The Findings and Response ACC/AHA STEMI Guideline: “PCI of a totally occluded infarct artery greater than 24 hours after STEMI is not recommended in asymptomatic patients…[who] do not have evidence of severe ischemia.” Hochman JS. N Engl J Med 2006;355:2395-407 Antman EM et al. JACC 2008;51:210-47
- 9. A More Recent Story Ridker PM. J Throm Haemost 2009;7(S 1):332-9 Ridker PM et al. N Engl J Med 2008;359:2195-207