Cancer Clinical Trials: The Basics

Cancer Clinical Trials: The Basics

What Are Cancer Clinical Trials?

* Research studies involving people
* Try to answer scientific questions and find better ways to prevent, diagnose, or treat cancer

Why Are Cancer Clinical Trials Important?

* Cancer affects all of us
* Each year in the U.S.A:
o More than half a million people are expected to die of cancer — more than 1,500 people a day
o 1 of 4 deaths is from cancer
o More than 1 million new cancer cases are expected to be diagnosed

Why Are Cancer Clinical Trials Important?
* Clinical trials translate results of basic scientific research into better ways to prevent, diagnose, or treat cancer

* The more people that take part, the faster we can:
o Answer critical research questions
o Find better treatments and ways to prevent cancer

Do Many People Participate in Cancer Clinical Trials?
* Only 3 percent of U.S. adults with cancer participate in clinical trials

Types of Cancer Clinical Trials
* Treatment trials
* Prevention trials
* Early-detection trials/screening trials
* Diagnostic trials
* Quality-of-life studies/supportive care studies

Clinical Trial Phases
Phase 1 trials
* How does the agent affect the human body?
* What dosage is safe?

Phase 2 trials
* Does the agent or intervention have an effect on the cancer?

Phase 3 trials
* Is the new agent or intervention (or new use of a treatment) better than the standard?
* Participants have an equal chance to be assigned to one of two or more groups

Randomized Trials
Participants have an equal chance to be assigned to one of two or more groups:
o One gets the most widely accepted treatment (standard treatment)
o The other gets the new treatment being tested, which researchers hope and have reason to believe will be better than standard treatment

Randomization
Why Is Randomization Important?
* So all groups are as alike as possible
* Provides the best way to prove the effectiveness of a new agent or intervention

Cancer Treatment Trials
* What new treatments can help people who have cancer?
* What is the most effective treatment for people who have cancer?
Placebos are almost never used:
* Placebos are used only when no standard treatment exists
* Patients are told of this possibility before deciding to take part

Cancer Prevention Trials
* Evaluate the effectiveness of ways to reduce the risk of cancer
* Enroll healthy people at high risk for developing cancer

Cancer Prevention Trials
* Action studies
* Agent studies
(“taking something”)—also called “chemoprevention studies”

Chemoprevention Trials
* Phase 3 chemoprevention trials compare a promising new agent with either a:
o Standard agent
o Placebo

Clinical Trial Protocol
* A recipe or blueprint
* Strict scientific guidelines:
o Purpose of study
o How many people will participate
o Who is eligible to participate
o How the study will be carried out
o What information will be gathered about participants
o Endpoints

Benefits of Participation
Possible benefits:
o Patients will receive, at a minimum, the best standard treatment
o If the new treatment or intervention is proven to work, patients may be among the first to benefit
o Patients have a chance to help others and improve cancer care
Risks of Participation
Possible risks:
o New treatments or interventions under study are not always better than, or even as good as, standard care
o Even if a new treatment has benefits, it may not work for every patient
o Health insurance and managed care providers do not always cover clinical trials

Patient Protection
* There have, unfortunately,
been past abuses in patient
protection
* Federal regulations ensure
that people are told about the benefits, risks, and purpose of research before they agree to participate

How Are Patients’ Rights Protected?
* Informed consent
* Scientific review
* Institutional review boards (IRBs)
* Data safety and monitoring boards

Informed consent:
* Purpose
* Procedures
* Risks and potential benefits
* Individual rights
* Scientific review
* Institutional review boards (IRBs) are required by Federal law for trials that are:
o Federally funded
o Subject to FDA regulation

Data and safety monitoring boards:
* Ensure that risks are minimized
* Ensure data integrity
* Stop a trial if safety concerns arise or objectives have been met

Sometimes patients:
* Don’t know about clinical trials
* Don’t have access to trials
* May be afraid or suspicious of research
* Can’t afford to participate
* May not want to go against physician’s wishes

Why Do So Few Cancer Patients Participate in Clinical Trials?
Doctors might:
* Lack awareness of appropriate clinical trials
* Be unwilling to “lose control” of a person’s care
* Believe that standard therapy is best
* Be concerned that clinical trials add administrative burdens

NCI Information Resources

Cancer Clinical Trials: The Basics.ppt

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Surgical Preparation and Instrument Care

Surgical Preparation and Instrument Care

Sanitation, Disinfection and Sterilization

Learning Outcomes
After this section is completed you should be able to:
List the classes of pathogenic organisms in order of their resistance to destruction
Differentiate between sanitation, disinfection and sterilization
List the different ways that microbial control methods destroy or inhibit pathogenic organisms

After this section is completed you should be able to:
List the five categories of physical methods of microbial control
Name and describe the physical methods of microbial control
Identify the level of microbial control achieved with each of the physical methods
State an example of the application of each of the physical methods of microbial control

List the properties of the “ideal chemical agent” for microbial control
Name and describe the classes of microbial control chemicals
Identify the level of microbial control achieved by the chemical classes

List the advantages and disadvantages of the autoclave in animal care facilities
Explain the function of the autoclave
Compare and contrast the different autoclaves

Describe the preparation of each of the following for processing in the autoclave: linen packs, pouch packs, hard goods, liquids and contaminated objects
List the guidelines for loading the autoclave chamber
Compare the three different autoclave cycles

List and define the five methods of quality control for sterilization
List and define the two methods of quality control for disinfection

Section Outline
Levels of microbial resistance
Degrees of microbial control
How microbial control methods work
Methods of microbial control
Autoclave
Quality control for sterilization and disinfection

Overarching Principle
The objective in sanitation, sterilization and disinfection is to control microorganisms, or pathogens, in the environment, thus protecting patients and staff from contamination and disease, and thereby promoting optimal healing and wellness.

The Ever Present Danger
Improper application of the methods of sanitation, sterilization and disinfection can lead to microbial resistance and increase the risk of nosocomial infection

Levels of Microbial Resistance
Pathogens
Microorganisms that cause disease
Viruses
Bacteria
Fungi
Protozoan
Prions
Different classes of pathogens vary in their resistance to destruction by chemical methods

Protozoan Cysts
Bacterial Spores
Non-enveloped virus
TB organisms
Enveloped viruses
Fungi
Vegetative bacteria


Most Resistant
Least Resistant
Levels of Microbial Resistance
Microbial control
Is achieved by using methods of sanitation, disinfection and sterilization
Microbial control
Done to a degree that is practical, efficient and cost effective

Levels of Microbial Resistance
Sterility is used only when necessary

In many situations sanitation and disinfection create acceptable levels of microbial control

Degrees of Microbial Control
Sterilization is the elimination of all life from an object
Complete microbial control
Asepsis is a condition in which no living organisms are present
Free of infection or infectious material

Degrees of Microbial Control
Sanitation: The state of being clean and conducive to health.

Disinfection: To cleanse so as to destroy or prevent the growth of disease-carrying microorganisms

Degrees of Microbial Control
Disinfection, sanitation and cleaning remove most microorganisms
Most disinfectants are microbiocidal
Microbes are killed
Some disinfectants are bacteriostatic
Microbial growth is inhibited

Degrees of Microbial Control
Disinfectants can be classified according to their spectrum of activity
Bacteriocidal
Bacteriostatic
Sporocidal
Virucidal
Fungicidal

How Microbial Control Methods Work
Mode of Action
Different physical and chemical methods destroy or inhibit microbes in several ways
Damage cell walls or membranes
Interfere with cell enzyme activity or metabolism
Destroy microbial cell contents through oxidation, hydrolysis, reduction, coagulation, protein denaturation or the formation of salts

Efficacy of Microbial Control
The effectiveness of all microbial control methods depends on the following factors:
Time
Most methods have minimum effective exposure times
Temperature
Most methods are more effective as temperature increases

Efficacy of Microbial Control
The effectiveness of all microbial control methods depends on the following factors:
Concentration and Preparation
Chemical methods require appropriate concentrations of agent
Disinfectants may be adversely affected by mixing with other chemicals
Organisms
Type, number and stage of growth of target organisms

Efficacy of Microbial Control
The effectiveness of all microbial control methods depends on the following factors:
Surface
Physical and chemical properties of the surface to be treated may interfere with the method’s activity
Some surfaces are damaged by some methods

Efficacy of Microbial Control
The effectiveness of all microbial control methods depends on the following factors:
Organic debris or other soils
Will dilute, render ineffective or interfere with many control methods
Method of application
Items may be sprayed, swabbed or immersed in disinfectants
Cotton and some synthetic materials may reduce chemical activity

Methods of Microbial Control
Physical Methods
Chemical Methods

Physical Methods
Dry Heat
Oxidation
Moist Heat
Denatures microbial protein
Radiation
Damages cell enzyme systems and DNA
Filtration
Traps organisms that are too large to pass through the filter
Ultrasonic Vibration
Coagulates proteins and damages cell walls

Dry Heat
Incineration
Material or object is exposed to a hot fire
Object must become red hot as in the inoculation loops used in microbiology
Used to dispose of tissue or carcasses
Efficacy: complete sterilization

Dry Heat
Hot Air Oven
Sterility requires 1 hour of exposure @ 170° C(340° F)
Powders and non-aqueous liquids like paraffin or Vaseline
Used in some animal care facilities and useful in domestic applications (e.g. the kitchen oven)
Efficacy: complete sterilization

Dry Heat
Drying
Most organisms require humidity to survive and grow
More commonly used to prevent spoiling and preserve foodstuffs (e.g. raisins)
Efficacy: incomplete sterilization

Moist Heat
Hot Water
Used to clean and sanitize surfaces
Addition of detergents increases efficacy by emulsifying oils and suspending soils so they are rinsed away
Efficacy: incomplete sterilization

Moist Heat
Boiling
Requires 3 hours of boiling to achieve complete sterilization
Boiling for 10 minutes will destroy vegetative bacteria and viruses but not spores
Addition of 2% calcium carbonate or sodium carbonate will inhibit rust and increase efficacy
Useful for field work
Efficacy: may be complete sterilization

Moist Heat
Steam
Similar to boiling because the temperature is the same
Exposure to steam for 90 minutes kills vegetative bacteria but not spores
Efficacy: incomplete sterilization

Moist Heat
Steam under pressure
Pressure increases the boiling point such that the temperature of the water becomes much higher that 100° C (212° F)
The autoclave utilizes steam under pressure to achieve sterilization
This is the most efficient and inexpensive method of sterilization for routine use
Efficacy: complete sterilization

Radiation
Ultraviolet (UV)
Low energy UV radiation is a sterilant when items are placed at a close range
UV radiation has no penetrating ability
Used to sterilize rooms
Very irritating to eyes
Efficacy: may be complete sterilization

Radiation
Gamma radiation
Ionizing radiation produced from a Cobalt 60 source
Good penetrating ability in solids and liquids
Used extensively in commercial preparation of pharmaceuticals, biological products and disposable plastics
Efficacy: complete sterilization

Filtration
Fluid filtration
Forced through a filter with either positive or negative pressure
Filter is most commonly a synthetic screen filter with micropore openings
Used to sterilize culture media, buffers and pharmaceuticals
Pore size of 0.45µm removes most bacteria
Microplasmas and viruses require 0.01µm to 0.1µm
May be used in conjunction with a pre-filter
Efficacy: can be complete sterilization

Filtration
Air filtration
Examples of usage: surgical masks, laboratory animal cages and air duct filters
Fibrous filters made of various paper products are effective for removing particles from air
Efficacy is influenced by air velocity, relative humidity and electrostatic charge
Efficacy: can be complete sterilization

Filtration
Air filtration
HEPA: high efficiency particle absorption filters are 99.97% to 99.997% effective in removing particles with diameters greater that 0.3µm

Filtration
Air filtration
Surgical masks
Designed to protect the patient from the surgeon, not the surgeon from the patient
Special masks are available that are designed to protect personnel from animal pathogens
Masks must fit snugly, stay dry and be changed every 3 to 4 hours to remain effective

Ultrasonic Vibration
Cavitation
High frequency sound waves passed through a solution create thousands of cavitation “bubbles”
Bubbles contain a vacuum; as they implode or collapse, debris is physically removed from objects
Effective as an instrument cleaner
Efficacy: incomplete sterility

Chemical Methods
Many chemicals are available to sterilize, disinfect or sanitize
None is the “ideal” agent
Chemicals penetrate cell walls and react with cell components in various ways to destroy or inhibit growth
Many chemicals are disinfectants with varying levels of efficacy
Some are sterilants

Chemical Methods

Bacteria Viruses

Level Vegetative Acid-fast Spores Lipophilic Hydrophilic

High + + + + +

Medium + + 0 + +/-

Low + 0 0 +/- 0

Examples:

High: Aldehydes, VPHP, Chlorine-dioxide

Medium: Alcohols, Phenols, 7th generation Quats

Low: Quats

Ethylene oxide

Aldehydes

Vapor phase H2O2

Halogens

Phenols

7th generation quaternary

Alcohols

Chlorhexidine

Old generation quaternary

High-cidal

Activity

Low-cidal

Activity

Chemical Methods
Ideal chemical agent
Broad spectrum of activity
Does not stain or damage surfaces
Stable after application
Effective in a short time
Nonirritating and nontoxic to surfaces and tissues
Inexpensive and easy to store and use
Not affected by organic debris or other soil
Effective at any temperature
Nontoxic, nonpyrogenic and nonantigenic
Possesses residual and cumulative action

Chemical Methods
Soaps
Detergents
Quaternary ammonium compounds
Phenols
Aldehydes
Halogens
Chlorine and chlorine releasing compounds
Alcohols
Peroxygen compounds
Ethylene Oxide

Chemical Methods
Soaps
Anionic cleaning agent made from natural oils
Ineffective in hard water
Does not mix well with quats and decreases the effectiveness of halogens
Is not antimicrobial
Minimal disinfectant activity

Chemical Methods
Detergents
Synthetic soaps
Anionic, cationic or nonionic; anionic combined with cationic will lead to neutralization of both
Most are basic; a few are acidic
Emulsify grease and suspend particles in solution
May contain wetting agents

Chemical Methods
Quaternary Ammonium Compounds
Quats: Centrimide, benzalkonium chloride, Zephiran, Quatsyl-D, Germiphene
Effective against gm+ and gm- microorganisms and enveloped viruses
Low toxicity and generally nonirritating
Prolonged contact irritates epithelial tissues

Chemical Methods
Quaternary Ammonium Compounds
Inactivated by organic material, soap, hard water and cellulose fibers
Reduced efficacy in presence of organic debris, soap, detergents and hard water
Ineffective sporocide and fungicide
Bacteria not destroyed may clump together; those inside the clump are protected
Dissolves lipids in cell walls and cell membranes

Chemical Methods
Quaternary Ammonium Compounds
Organically substituted ammonium compounds
More effective in basic pH
Cationic detergent
Deodorizes


Chemical Methods
Phenols
Active against gm+ bacteria and enveloped viruses
Developed from phenol or carbolic acid
Synthetic phenols are prepared in soap solutions that are nontoxic and nonirritating
Prolonged contact may lead to skin lesions

Chemical Methods
Phenols
Toxic to cats because cats lack the inherent enzymes needed to detoxify the compound
May be toxic to rodents and rabbits
Not inactivated by organic matter, soap or hard water
Activity decreased by quats

Chemical Methods
Aldehydes
Active against gm+ and gm-, most acid fast bacteria, bacterial spores, most viruses and fungi
Considered to be a sterilant but may require prolonged contact

Chemical Methods
Aldehydes
Gluteraldehyde (Cidex)
Noncorrosive
Supplied as an acid, activated by adding sodium bicarbonate
Good for plastics, rubber, lenses in “cold sterilization”
Not inactivated by organic material or hard water
Irritating to respiratory tract and skin

Chemical Methods
Aldehydes
Formaldehyde (Formicide)
Aqueous solution 37% to 40% (w/v) formaldehyde
May be diluted with water or alcohol
Irritating to tissues and respiratory tract
A vapor phase surface disinfectant that slowly yields formaldehyde

Chemical Methods
Aldehydes
Biguanide (e.g. chlorhexidine gluconate [Hibitane, Precyde])
Active against gm+, most gm-, some lipophilic viruses and fungi
Efficient disinfectant, used mostly as an antiseptic
Some reduction of activity in presence of hard water and organic material
Immediate, cumulative and residual activity
Precipitates to an inactive form when mixed with a saline solution
Used as a surgical scrub and hand wash
Low toxicity

Chemical Methods
Halogens
Chlorine, iodine, fluorine and bromine
Active against gm+ and gm-, acid fast, all viruses and fungi
Iodine most common
Chlorine and chlorine releasing compounds

Chemical Methods
Halogens
Iodine
Used in solution with water or alcohol
Iodophors: iodine plus carrier molecule that acts to release iodine over time
Surgical scrub (Betadine): iodophor plus detergent
Tinctures and solutions: iodines and iodophors w/o detergent
Nonstaining and nonirritating
Inactivated by organic material
Aqueous forms are staining, irritating and corrosive to metals, especially if used undiluted

Chemical Methods
Halogens
Chlorine and chlorine releasing compounds (e.g. chlorine gas, chlorine dioxide)
Commonly available as sodium hypochlorite
Least expensive and most effective chemical disinfectant
Available chlorine equals oxidizing ability
Damages fabrics, corrosive to metals
Inactivated by organic debris
May require several minutes of contact to be effective
Skin and mucous membrane irritant if not diluted properly or rinsed well

Chemical Methods
Alcohols
Ethyl alcohol, isopropyl alcohol, methyl alcohol
Active against gm+ and gm- bacteria and enveloped viruses
Most effective when diluted to 60% to 70% (isopropyl), 705 to 80% (ethyl)

Chemical Methods
Alcohols
Used as a solvent for other disinfectants and antiseptics
Most commonly used skin antiseptic
Low cost and low toxicity

Chemical Methods
Alcohols
Irritating to tissues and painful on open wounds
Repeated use dries skin
Forms coagulum in presence of tissue fluid
Consists of a layer of tissue fluid whose proteins have been denatured by alcohol
Facilitates survival of bacteria under the coagulum
Fogs lenses, hardens plastics and dissolves some cements

Chemical Methods
Alcohols
Inactivated by organic debris
Ineffective after evaporation
Defatting agent

Chemical Methods
Peroxygen compounds (e.g. Peracetic acid)
Active against gm+ and gm-, acid-fast, fungi.
No virucidal activity
Classified as a sterilant but may not kill pinworm eggs

Chemical Methods
Peroxygen compounds (e.g. Peracetic acid)
Oxidizing agent
Reacts with cellular debris to release oxygen
Kills anaerobes
Applied as a 2% solution for 30 minutes at 80% humidity
Explosive and can damage iron, steel and rubber
Irritating to healthy tissues

Chemical Methods
Ethylene Oxide
Active against gm+ and gm-, lipophilic and hydrophilic viruses, fungi and bacterial spores
Classified as a sterilant
Effective sterilant for heat labile objects

Chemical Methods
Ethylene Oxide
EO is a colorless nearly odorless gas that diffuses and penetrates rapidly
Flammable and explosive
Toxic, carcinogenic and irritating to tissue

Chemical Methods
Ethylene Oxide
Used in a chamber with a vacuum
May be mixed with CO2, ether or freon
Used at temperatures of 21° to 60° C (70° to 140° F)
Works quicker at higher temperatures
Exposure times of 1 to 18 hours
Requires minimum relative humidity of 30% (40% is optimum
Items must be clean and dry and can be wrapped muslin, polyethylene, polypropylene or polyvinyl
Sterilized items must be ventilated in a designated area for 24 to 48 hours to dissipate residual EO

Autoclave
Advantages
Consistently achieves complete sterility
Inexpensive and easy to operate
Safe for most surgical instruments and equipment, drapes and gowns, suture materials, sponges and some plastics and rubbers
Safe for patients and personnel
Established protocols and quality control indicators are easy to access

Autoclave
Disadvantages
Staff may overestimate the ability of the autoclave
Sterility depends on saturated steam of the appropriate temperature having contact with all objects within the unit for a sufficient length of time
Requires a thorough understanding of techniques to ensure that the above occurs

Autoclave
Function
Heat is the killing agent
Steam is the vector that supplies the heat and promotes penetration of the heat
Pressure is the means to create adequately heated steam

Autoclave
Function
Complete sterilization of most items is achieved after 9 to 15 minutes exposure to 121° C (250° F)
Steam at sea level is 100° C (212° F) as pressure is increased the temperature of the steam increases
The minimum effective pressure of the autoclave is 15 pounds per square inch which provides steam at 121° C (250° F)
Many autoclaves attain 35 psi which creates steam temperature of 135° C (275° F)

Autoclave
Function
Exposure times must allow penetration and exposure of all surfaces to 121°C (250° F) steam
Exposure time is decreased by increasing pressure, which increases steam temperature

Steam Sterilization Temperature/
Pressure Chart

Temperature

Pressure(psi) °C °F Time(mins)

0 100 212 360

15 121 250 9-15

20 125 257 6.5

25 130 266 2.5

35 133 272 1

Autoclave
Types
Gravity displacement autoclave
Prevacuum autoclave

Autoclave
Types
Gravity displacement
Water is heated in a chamber
Continued heating creates pressure
Steam displaces air within the chamber forcing it out through a vent
Cycle timing begins when the temperature reaches at least 121°C

Autoclave
Types
Gravity displacement
After sufficient exposure time, steam is exhausted through a vent back into a reservoir
Air that has been sterilized within the jacket and then filtered is admitted back into the chamber to replace the exhausting steam
If the chamber is loaded improperly or there is insufficient steam, there will be air pockets remaining in the chamber that will interfere with steam penetration and result in non-sterile areas
The load must be dried within the autoclave

Autoclave
Types
Prevacuum
Usually a much larger and more costly machine
Equipped with a boiler to generate steam and a vacuum system
Air is taken out of the loaded chamber by means of the vacuum system
Steam at 121°C or more is introduced into the chamber
The steam immediately fills the chamber to eliminate the vacuum
Exposure time begins immediately
At completion of the cycle steam is vacuumed and replaced by hot, dry sterile air
Air pockets are eliminated and processing times are reduced due to the vacuum

Autoclave
Operation
Preparation of the load
Loading the chamber
Autoclave cycles

Autoclave
Operation
Preparation of the load
Linen packs
Pouch packs
Hard goods
Liquids
Contaminated objects

Autoclave
Linen packs
All instruments in packs are scrupulously cleaned and rinsed in de-ionized water
Instruments are disassembled and ratchets are left closed and unlocked
Appropriate lines are in good repair and freshly laundered
Disposable linens are not reused

Autoclave
Linen packs
A chemical sterilization indicator is included in every pack
Chemical sterilization indicators provide verification that the inside of the pack was exposed to appropriate sterilization temperatures for the appropriate length of time

Autoclave
Linen packs
The pack is wrapped using at least two layers of material
The shelf life of the sterilized pack varies with the type of the outer wrapping
Pack is sealed with autoclave tape and labeled with the date, contents and operator
Autoclave tape provides verification that the outside of the pack was exposed to appropriate sterilization temperatures

Autoclave

SHELF LIFE

Wrapper Shelf-life

Dbl wrapped two layer muslin 4 wk

Dbl wrapped two layer muslin 6 mo

heat sealed in dust covers

after sterilization

Dbl wrapped two layer muslin 2 mo

tape sealed in dust covers

after sterilization

Dbl wrapped non-woven barrier 6 mo

materials (paper)

Paper/plastic peel pouches, heat sealed 1 year

Plastic-peel pouches, heat sealed 1 year

Autoclave
Linen packs
Pack should not exceed 30 X 30 X 50 cm (12 X 12 X 20 inches) in size
Pack should not exceed 5.5 kg (12 lb) in weight
Pack should not exceed 115 kg/m3 in density

Autoclave
Pouch packs
Used for single instruments, sponges, etc.
Previous guidelines apply
Pouches are heat sealed or ends are rolled and securely taped with autoclave tape
Labeled as above

Autoclave
Hard goods
Stainless steel or other hard instruments, trays, bowls, laboratory cages and other equipment may be autoclaved without wrapping
Must be physically clean and rinsed in de-ionized water
Syringes and plungers are separated before autoclaving

Autoclave
Liquids
Contained in Pyrex flasks 3 times larger than contents require
Cover loosely with applied lid or paraffin film, or place a needle through the stopper to allow air exchange
Sterility of liquids processed in the autoclave is in question
Removing liquids from the chamber is hazardous to personnel

Autoclave
Contaminated objects
Used before disposal to decontaminate syringes, culture plates, etc., that contain biohazardous waste
Place objects in a container appropriate for disposal
Special autoclavable biohazard bags are available

Autoclave
Chamber loading
Must allow free circulation of steam
Use perforated or wire mesh shelves
Linen packs have 2.5cm to 7.5cm space between
Place multiple packs on edge instead of stacking
Paper/plastic pouches are placed in specially designed baskets that support them on edge with the paper side of each package facing the plastic side of the adjacent package
Solid bowls or basins are placed upside down or on edge
Mixed loads (hard goods and wrapped goods) have wrapped goods on upper shelf

Autoclave
Autoclave cycles
Wrapped goods
Hard goods
Liquids

Autoclave
Autoclave cycles
Wrapped goods
Has “dry” cycle that allows wrapped packs to dry
Used for most surgical packs

Autoclave
Autoclave cycles
Hard goods
Has no dry cycle
Used for trays, bowls, cages, etc. that will not be maintained in a sterile condition
Also used for flash autoclaving to quickly sterilize instruments that are needed immediately

Autoclave
Autoclave cycles
Liquids
Exhausts steam more slowly than other cycles
Used for liquids that would be forced from containers during a faster exhaust cycle

Quality Control
The effectiveness of any method of microbial control must be monitored regularly
Verification of the effectiveness of microbial control should be performed at least monthly

Quality Control
Methods
Recording thermometer
Thermocouple
Chemical indicator
Biological testing
Bowie Dick test
Surface sampling
Serology

Quality Control
Methods
Recording thermometer
Displays the temperature of the autoclave chamber
Operator observes for correct temperature during cycle
Some autoclaves are equipped with printed tape of chamber temperatures during cycle

Quality Control
Methods
Thermocouple
Used in steam and dry heat sterilization chambers
Temperature sensors are placed in the part of a test pack that is most inaccessible to steam penetration

Quality Control
Methods
Chemical indicator
Paper strips impregnated with sensitive chemicals change color when conditions of sterility are met
Used with autoclaves and ethylene oxide systems
Placed deep inside packs before sterilization

Quality Control
Methods
Biological testing
Bacterial spores are exposed to autoclave or ethylene oxide and then cultured
Recommended method for verification of proper autoclave operation in veterinary clinics

Quality Control
Methods
Bowie Dick test
Tests pre-vacuumed autoclaves for complete removal of air and uniform steam penetration
Uses a pack of uniform dimensions with a cross of autoclave tape in the center

Quality Control
Methods
Surface sampling
Surface to be tested is swabbed with a sterile applicator and transferred to a suitable media plate for growth
Surface or item is rinsed with a sterile solution, which is examined for contamination
“Contact plate” of media is touched to the surface and incubated
Recommended method for ensuring proper disinfection of surgical suites in veterinary clinics

Quality Control
Methods
Serology
The presence of viruses in the environment is monitored by serological testing of animals to determine the presence of antibodies
Animals maintained for this purpose are referred to as sentinel animals

Surgical Preparation and Instrument Care.ppt

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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

* 22 centers in the United States & Europe were involved in recruitment.
* Inclusion criteria:
o 18 years of age or older
o Presence of serum HCV antibody levels
o Detectable serum HCV RNA levels
o Compensated liver disease (which is not defined explicitly)
o Thrombocytopenia with platelet levels between 20,000-70,000.
o Evidence of cirrhosis defined as: liver biopsy c/w cirrhosis, radiographic evidence of cirrhosis, or endoscopic evidence of varices

* Exclusion criteria:
o Pregnancy
o History of thrombosis
o HIV co-infection
o Hepatitis B co-infection

METHODS
Patients randomly assigned to placebo or eltrombopag (30mg, 50mg, 75mg daily) x 4 weeks
Any patient with plt count >70k or >100k was eligible for treatment with peg-interferon α-2a or peg-interferon α-2b, respectively. The decision to treat was left to the physician & patient.
Patients continued with their previous dose of eltrombopag during treatment.
Study designed by GlaxoSmithKline & academic principal investigator.
Daily eltrombopag doses were held if platelet count rose >200,000 and would be resumed when counts dropped to around 100,000

RESULTS
Approximate bilirubin (converted) 1.5+/- 1mg/dL. INR and creatinine not reported.
5 of total 74 patient listed here were excluded for baseline plt counts >75k but were ultimately eligible for the treatment phase.
Uneven number of patients in each arm because this was a mulicenter trial & not all sites contributed to all 4 arms.

RESULTS
Only 18 patients completed treatment. Only 1 placebo patient completed tx even though 7 were eligible.
Median platelet values prior to inferon treatment and % responders had significant p values compared to placebo

RESULTS
Pre-treatment platelet values, especially in the 50mg and 75mg eltrombopag arms, were statistically significant.
Platelet levels decreased with hep C treatment in all arms. P values for the eltrombopag groups vs. placebo were not statistically significant.
More patients in the eltrombopag arms completed treatment.

CONCLUSIONS/ IMPLICATIONS
* Eltrombopag increases platelet counts in a dose-dependent manner in patients with untreated chronic hepatitis C cirrhosis.
* Eltrombopag can be used to boost platelet counts in patients being considered for peg-interferon & ribavirin treatment.

STRENGTHS
* Clinical relevance: Thrombocytopenia is a very common complication of hepatitis C infection and ineligibility for treatment is a significant public health concern.
* Efficacy: Eltrombopag is extremely effective in increasing pre-interferon platelet counts (i.e. the study was able to demonstrate efficacy even though the sample size was low).
* Ease of use: Eltrombopag can be taken orally and has an easy daily dosing schedule.
* Safety: Eltrombopag has minimal side effects, which do not seem to be dose-dependent, and are not associated with significant morbidity.

WEAKNESSES
* Small sample size, especially in interferon treatment group (underpowered)
* Failed to standardize the protocol for initiation and cessation of interferon treatment phase.

* Lack of generalizability
o The investigators may have referred only patients with cirrhosis without portal hypertension to the study in order to select for a group who was more likely to benefit from treatment.
o Similarly, HCV viral loads were not taken into account.
* ? Clinical utility
o Could not ultimately answer question of whether pre-treatment with eltrombopag resulted in successful clearance of hepatitis C with treatment (i.e. whether the fact that more patients can receive interferon treatment actually leads to more patients who benefit from treatment).

The Randomized Controlled Trial.ppt

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