helicobacter pylori user’s guide · the pytest* user’s guide is intended to provide the user...

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PYtest* 14C-UREA BREATH TEST FOR HELICOBACTER PYLORI

USER’S GUIDE

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CONTENTS

INTRODUCTION............................................................................................................................................................................. 5PACKAGE INSERT: PYtest* CAPSULES .....................................................................................................................6 – 10PACKAGE INSERT: PYtest* KIT ....................................................................................................................................11 – 14PYtest* KIT PROGRAM .....................................................................................................................................................15 – 17

PROVIDER PURCHASE PROGRAM FORM ................................................................................................................................ 16THE BALLOON LABEL ....................................................................................................................................................................17

PYtest* FREQUENTLY ASKED QUESTIONSGENERAL

Are there any special purchasing requirements for the PYtest*? ........................................................................................ 18How does the PYtest* work? ...................................................................................................................................................... 18How are the kits returned to Halyard Health for analysis and how soon will I get a result? ......................................... 18Can I use any balloon to collect the patient’s breath? .......................................................................................................... 18Can a patient use a method other than a balloon to collect the breath sample? ........................................................... 18Does Halyard Health provide safety traps? .............................................................................................................................. 18What should be done if the patient is not able to fully inflate the balloon with one breath? ....................................... 18What happens if a balloon is only half-filled? .......................................................................................................................... 18What happens if a balloon has a leak? ...................................................................................................................................... 18What are confounding factors for the PYtest*? ...................................................................................................................... 19What must a patient do prior to the PYtest*? .......................................................................................................................... 19What medications are considered to be Proton-Pump Inhibitors? .................................................................................... 19Are H2 Blockers considered a confounding factor? .............................................................................................................. 19What is an H2 Blocker? ................................................................................................................................................................. 19What medications are considered to be H2 Blockers? ......................................................................................................... 19Are antacids considered to be a confounding factor? .......................................................................................................... 19What is an antacid? ....................................................................................................................................................................... 19What are names of commonly used antacids? ....................................................................................................................... 19How soon can the test be repeated? ........................................................................................................................................ 19What happens if the patient feels the capsule is stuck in her/his throat? ......................................................................... 19Are any of the chemicals involved in the PYtest* hazardous (flammable or caustic)? ................................................... 19

SAMPLE COUNTING How is analysis performed?......................................................................................................................................................... 19PYtest* breath sample analysis illustrations .............................................................................................................................20Can a breath sample be counted immediately after collection? .........................................................................................21I have a sample with a result between 50 and 300 DPM. How long should I wait to recount? ...................................21Is there special interfacing software available for particular models of liquid scintillation counters (LSCs)? ............21Is the printout from my LSC sufficient to substantiate a diagnosis? ...................................................................................21Are there any LSCs that cannot be used? .................................................................................................................................21Will a “Well Counter” work to analyze the samples? ...............................................................................................................21We have a scintillation counter in our department. Does this mean we have a liquid scintillation counter? ...........21Should my LSC be recertified or checked by the manufacturer if it has not been used in the last year?...................21Where can I get a LSC? .................................................................................................................................................................21Do I need a quench curve? ..........................................................................................................................................................21What do I need to do for quality control of the counter? .....................................................................................................21Do you have any tips for breath sample counting? ................................................................................................................21Sample preparation ........................................................................................................................................................................21Sample counting, analysis and reporting ................................................................................................................................. 22Same efficiency for all breath samples ..................................................................................................................................... 22Quench Curve ................................................................................................................................................................................ 22Quality Control ............................................................................................................................................................................... 22Which liquid scintillation fluids are compatible with PYtest* Breath Collection Fluid? .................................................. 22Which liquid scintillation fluids are not recommended for use with PYtest* Breath Collection Fluid? ...................... 22

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INTERPRETATION AND RESULTS What are the cut-off points for Positive and Negative results? ........................................................................................... 23What is the definition of indeterminate? .................................................................................................................................. 23What causes an indeterminate result? ...................................................................................................................................... 23What is suggested for retesting a patient with an indeterminate result? .......................................................................... 23Does the test result need to be confirmed by serology or other methods of testing? .................................................. 23If I discover a patient has taken a confounding medication, but the result of the test is still positive, is this really a positive test? ...................................................................................................................................................... 23What does it mean if I discover a patient had a confounding factor and the result is negative? ................................ 23

RADIATION SAFETY What is the risk from the 14C? ......................................................................................................................................................24What is the dose to the people performing the test? Are they at risk? .................................................................... 24 – 25

WASTE DISPOSAL How do I dispose of the vials after they are counted, or how do I dispose of the BCF/LSF? ....................................... 25 Do I need a special license to store the waste? ...................................................................................................................... 25What do I do with the packaging? (boxes, capsule package, balloon, etc.) ..................................................................... 25

NATIONAL DRUG CODEWhat is the NDC # for the PYtest*? ........................................................................................................................................... 25

RADIOACTIVE MATERIAL ISSUES Do we need to have a CLIA license to perform analysis of this test at our site? .............................................................26Do I need a Radioactive Materials License to use the PYtest*? ...........................................................................................26I work in a hospital in an Agreement State that still requires a Materials License. Is there someone in my hospital who might have a license? ..........................................................................................................26I work in private practice in an Agreement State that still requires a Materials License, but have an affiliation with a hospital. Could their license be extended to allow me to use the test? ....................................26Can I get my own license? ..........................................................................................................................................................26We don’t have a Nuclear Medicine Department, but I’ve heard of mobile nuclear medicine facilities. How does that fit in with the PYtest*? .............................................................................................................................................26Am I in an NRC-regulated state or an Agreement State? .....................................................................................................26I have a Radioactive Materials User License. What do I need to do to order the PYtest*? ............................................26Carbon-14 is not listed on my Radioactive Materials User License. What should I do to use the PYtest*? ..............26Agreement States ..........................................................................................................................................................................26Is the 14C for the PYtest* made in an accelerator, natural sources, or a reactor? ...........................................................26Are we required to check the dose of each PYtest* like other radiopharmaceuticals? .................................................26Can I contact someone at Halyard Health with questions? .................................................................................................26

PUBLICATIONS REGARDING THE PYtest* ................................................................................................................... 27

PEPTO-BISMOL IS A REGISTERED TRADEMARK OF PROCTOR AND GAMBLE COMPANYCARAFATE, ETC., AXCAN PHARMA INC.PRILOSEC, ETC., ASTRAZENECA LPPREVACID, ETC., TAP HOLDINGS INC.TAGAMET, ETC., GLAXOSMITHKLINEZANTAC, ETC., GLAXOSMITHKLINEAXID, ETC., ELI LILLY AND COMPANYPEPCID, ETC., JOHNSON & JOHNSON-MERCK CONSUMER PHARMACEUTICALS COMPANYMAALOX, ETC., NOVARTIS CONSUMER HEALTH CANADA INC.ROLAIDS, ETC., MCNEIL-PPC INC.TUMS, ETC., GLAXOSMITHKLINEMYLANTA, ETC., JOHNSON & JOHNSON-MERCK CONSUMER PHARMACEUTICALS COMPANYGELUSIL, ETC., MCNEIL-PPC INC.BIOSAFE II, ETC., BIOSAFE MEDICAL TECHNOLOGIES INC.OPTIPHASE HISAFE 3 AND SUPERMIX, ETC., PERKIN-ELMER INC.SCINTISAFE, ETC., FISHER SCIENTIFIC COMPANYACIPHEX, ETC., EISAI CO. LTDNEXIUM, ETC., ASTRAZENECA LPPROTONIX, ETC., WYETH PHARMACEUTICALS INC.

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INTRODUCTION

The PYtest* User’s Guide is intended to provide the user with supplemental information not found in the PYtest* package insert and our product brochures. This document is also intended to answer additional frequently asked questions.

In all cases concerning regulatory issues, local, state and Federal policies must be followed. Standard Operating Procedures should also be followed at your site. Halyard Health advises that you consult with Radiation and Chemical Safety Offices at your location, as well as with Compliance, Quality and Regulatory sources.

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PACKAGE INSERT: PYtest* CAPSULES

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Results were reported as disintegrations per minute (DPM). Analysis for accuracy used the ten minute breath sample. A breath sample DPM <50 was defined as a negative result. DPM ≥200 was defined as a positive result. DPM in the range of 50-199 was classified as indeterminate.

STUDY 1:

Of 186 patients who had histopathology and CLOtest* (80 men, 106 women), 53 were infected with H. pylori as determined by agreement between histology and CLOtest*. The study results are summarized below:

Table 1: Study #1 (n=186, Indeterminate results included)

Histology and CLOtest*

H. pylori Positive Negative Total

PYtest*

(DPM 10 min.)

Positive 51 8 59 ppv. 86%

Indeterminate 1 8 9

Negative 1 117 118 npv. 99%

Total 53 133 186

sensitivity specificity

96% 88%

Notes: PYtest* at 10 min. was compared to the gold standard of biopsy results in which histology and CLOtest* concurred. Patients who did not have both biopsy tests performed, or in whom the tests differed, were excluded from analysis. There was no statistical difference in test accuracy based on gender of patient.ppv = positive predictive value (true positive divided by total PYtest* positive)npv = negative predictive value (true negative divided by total PYtest* negative)

STUDY 2:Breath tests were performed on 436 outpatients attending gastroenterology practices at sites in the United States. Seventy-six patients (40 men, 36 women) who had histology and CLOtest* were evaluated. The results are summarized below:




PYtest*

(DPM 10 min.)


Indeterminate 4 2 6


Total 27 49 76


82% 96%

Notes: PYtest* at 10 min. was compared to the gold standard of biopsy results in which histology and CLOtest* concurred. Patients who did not have both biopsy tests performed, or in whom the tests differed, were excluded from analysis. There was no statistical difference in test accuracy based on gender of patient.ppv = positive predictive value (true positive divided by total PYtest* positive)npv = negative predictive value (true negative divided by total PYtest* negative)

INDICATIONS AND USAGE

PYtest* (14C-Urea Breath Test) is indicated for use in the detection of gastric urease as an aid in the diagnosis of H. pylori infection in the human stomach. The test utilizes a liquid scintillation counter for the measurement of 14CO2 in breath samples.

PYtest* (14C-Urea Capsules)

DESCRIPTION

PYtest* (14C-Urea capsules) is intended for use in the detection of gastric urease as an aid in the diagnosis of Helicobacter pylori (H. pylori) infection in the human stomach. The test utilizes a liquid scintillation counter for the measurement of 14CO2 in breath samples. The capsules are to be used when analysis is planned at the site where the sample is taken.

PYtest* capsule is a gelatin capsule for oral administration containing 1µCi of 14C labeled Urea. The urea is adsorbed on sugar spheres and colored yellow with fluorescein.

Data on 14C-Urea:

Structural Formula (14C-Urea): NH2 14CONH2

Radiation emission: beta-emission, 49 keVmean, 156 keVmax, no other emissions

External emission: No external radiation hazard. Low-energy beta emissions only. Maximum range of 0.3 mm in water.

Radiological half-life: 5,730 years

Maximum effective dose equivalent (EDE): 0.3 mrem/µCi

CLINICAL PHARMACOLOGY

The urease enzyme is not present in mammalian cells, so the presence of urease in the stomach is evidence that bacteria are present. The presence of urease is not specific for H. pylori, but other bacteria are not usually found in the stomach. The principle of the breath test is shown in Figure 1.

Figure 1: Principle of Breath Test

To detect H. pylori, Urea labeled with 14C is swallowed by the patient. If gastric urease from H. pylori is present, urea is split to form CO2 and NH3 at the interface between the gastric epithelium and lumen and 14CO2 is absorbed into the blood and exhaled in the breath.

Following ingestion of the capsule by a patient with H. pylori, 14CO2 excretion

in the breath peaks between 10 and 15 minutes and declines thereafter with a biological half-life of about 15 minutes. 14C-Urea that is not hydrolyzed by H. pylori is excreted in the urine with a half-life of approximately 12 hours. About 10% of the 14C remains in the body at 72 hours and is gradually excreted with a biological half-life of 40 days.

CLINICAL STUDIES

Two studies were performed. In both studies, patients with gastro-intestinal symptoms underwent the breath test and an endoscopy. During the endoscopy, biopsy samples were taken from the antral gastric mucosa for histological analysis (2 samples, Giemsa stain) and rapid urease test (1 sample, CLOtest*). Breath samples were mailed to the TRI-MED lab where they were read in a liquid scintillation counter.

14CO2 in breath

unchangedurea in urine

bicarbonatein bloodstream counts

scintillation(beta) counter

addscintillation fluid

transfer CO2

to counting vial

collect 2L breathin mylar balloon

NH4+

ammoniumH14 CO3

–

NH2

NH2

H. pylori

14C=O

14C-Urea inPYtest* capsule

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ADVERSE REACTIONS

No adverse reactions were reported in clinical trials.

OVERDOSAGE

Risk from radiation is negligible even with a 1,000 capsule overdose (0.3 rem). If overdose occurs, the patient may drink one glass of water (150 mL) every hour to hasten excretion of the isotope. Maximum excretion of urea is achieved at a urine output of ≥2.0 mL/min.

DOSAGE AND ADMINISTRATION

Materials Needed, but not Provided

For analysis at test site Breath sample collected into balloon (recommended method; see Figure 2)• Breath test report form• Stopwatch/Timer capable of timing an interval up to 10 minutes.• Marking pen • 1-20 mL scintillation vial • Breath transfer pump• Pipette (10 mL) for measuring fluids• Collection fluid (2.5 cc per vial)• Scintillation fluid (10 cc/vial)• 1 - Mylar collection balloon • 1 - Straw• 2 - Needles• 2 - 30 mL medicine cups• Water (40 mL)• Any gas pump that is airtight and has a flow rate between .5 and 1 liter per

minute may be used.

Figure 2: Other Components

For analysis on-site Breath sample collected into vialCaution - Halyard Health does not endorse breath sample collection by this method because patients might come into direct contact with the hyamine.

• Breath test report form• Stopwatch/Timer capable of timing an interval up to 10 minutes• Safety trap (Figure 3)• 1 - Straw • 1 - 20 mL scintillation vial• Marking pen• Pipette (10 mL) for measuring fluids• Collection fluid (2.5 cc/vial)• Scintillation fluid (10 cc/vial)

CONTRAINDICATIONS

None

WARNINGS

None

PRECAUTIONS

General: After the patient ingests the 14C-Urea capsule, the sample collected for test purposes is for in vitro diagnostic use only.

A false-positive test could occur in patients who have achlorhydria. Very rarely, a false-positive test may occur due to urease associated with Helicobacters other than H. pylori (i.e., Helicobacter heilmanni).

LIMITATIONS OF THE TEST:

• The test has been evaluated in outpatients before elective endoscopy.

• Test results should be evaluated with clinical signs and patient history when diagnosing H. pylori infection.

• The performance characteristics of the test have not been established for monitoring the efficacy of antimicrobial therapies for the treatment of H. pylori infection.

• A negative result does not completely rule out the possibility of H. pylori infection. If clinical signs and patient history suggest H. pylori infection, repeat the PYtest* or use an alternative diagnostic method.

RADIOACTIVITY:

Persons concerned about very low doses of radioactivity may postpone the test or may decide to use an alternative means of diagnosis. The test produces radiation exposure equal to 24 hours of normal background. In animal experiments, such low doses of radiation do not carry measurable risk.

Preclinical studies were not conducted on 14C-Urea. The estimated dose equivalent received from a single administration of PYtest* (1µCi 14C) is about 0.3 mrem.

INFORMATION FOR PATIENTS:

It is necessary for the patient to fast for 6 hours before the test. The patient should also be off antibiotics and bismuth for 1 month, and proton pump inhibitors and sucralfate for 2 weeks prior to the test. Instruct the patient not to handle the capsule directly as this may interfere with the test result. The capsule should be swallowed intact. Do not chew the capsule.

Carcinogenesis, mutagenesis, impairment of fertility: No studies have been conducted with 14C-Urea to evaluate its potential for carcinogenicity, impairment of fertility, or mutagenicity.

Drug Interactions: Antibiotics, proton pump inhibitors, sucralfate and bismuth preparations are known to suppress H. pylori. Ingestion of antibiotics or bismuth within 4 weeks and proton pump inhibitors or sucralfate within 2 weeks prior to performing the test may give false- negative results.

Pregnancy: Pregnancy category C. Animal reproduction studies have not been conducted with PYtest* (14C-Urea). It is also not known whether PYtest* can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. PYtest* should be given to a pregnant woman only if clearly needed.

Nursing mothers: It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when PYtest* is administered to a nursing woman.

Pediatric Use: Clinical studies in children have not been conducted. However, PYtest* is expected to work the same in children as in adults. While the dose (1 capsule) does not need to be adjusted, the child must be able to swallow the intact capsule and blow into a straw.

Marking Pen

Stopwatch

Collection Fluid

Pipette

Breath Pump

Needles

StrawPYtest* Balloon

ScintillationFluid

Vial

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Figure 3: Typical Safety Trap

DOSAGE

One PYtest* capsule.

PROCEDURAL NOTES:

• Inform the patient to fast for 6 hours prior to the test.

• The patient should be off antibiotics and bismuth for 1 month, and proton pump inhibitors and sucralfate for 2 weeks prior to the test.

• Have patient sitting at rest while doing the test.

• The capsule should not be handled directly as this may interfere with the test result.

• To avoid contamination by bacteria in the mouth, the capsule should be swallowed intact. Do not chew capsule.

STEP-BY-STEP PROCEDURE FOR BALLOON:

Breath Sample Collection by BalloonBefore the test 1. Label balloon and fill in breath test report form.

2. Check that all materials are present.

Minus 1 minute 1. Open the package containing the 14C-Urea capsule and tip the capsule into the empty 30 mL cup. Do not handle the capsule directly.

2. Hand the cup to the patient.3. Fill the second cup with 20 mL of lukewarm water.

0 minute 1. Ask the patient to tip the capsule directly into his/her mouth, then swallow it with the 20 mL of lukewarm water.

2. Start the stopwatch when the patient swallows the capsule.3. Discard waste (e.g., capsule packaging, used straws) according

to your facility’s regulations.

3 minutes Ask the patient to drink another 20 mL of lukewarm water (in case the capsule may have lodged in the esophagus and not yet reached the gastric mucosa).

10 minutes 1. Push a drinking straw into the neck of the balloon.2. Ask the patient to hold his/her breath for 5-10 seconds, then

blow up a balloon with a slow breath through the straw, filling the balloon completely.

3. Tie the neck of the balloon into a tight knot. 4. Check that the balloon label and the breath test report form

are completed correctly.

After sample collection

See test analysis procedure.

Breath Sample Collection by VialCaution – Halyard Health does not endorse the collection of breath samples by this method for patient safety reasons.

Before the test 1. Label vial and fill in breath test report form. Vial test label should include the patient’s name, date of sample collection and time sample is taken.

2. Check that the vial contains 2.5 mL of collection fluid (1.5 mL methanol, 1.0 mL 1 molar hyamine, two drops thymolphthalein pH indicator).

3. Check that all materials are present.

Minus 2 minutes Attach a straw to the safety trap (Figure 3).




2. Start the stopwatch when the patient swallows the capsule.3. Discard waste (e.g., capsule packaging, used straw) according



10 minutes Ask the patient to hold his/her breath for 5-10 seconds, then blow bubbles into the collection fluid via the safety trap. The patient should blow bubbles until the fluid turns clear. Put lid on vial.


See test analysis procedure.

TEST ANALYSIS PROCEDURE

General Information

• The collection fluid contains hyamine, methanol and a pH indicator. Hyamine is a corrosive caustic alkali. If you are using the vial method and collecting breath directly into the collection fluid you must supervise the patient and ensure that a safety trap is used.

• The amount of hyamine (1 mL of 1/m) and methanol (2.5 mL) in one collection vial is not sufficient to cause serious poisoning. Local irritation to skin or mucous membranes is likely when the solution is blue. After collecting CO2 the collection fluid turns clear. At this point it is less dangerous because the pH is near neutral.

• If the collection fluid splashes onto the skin or eyes, wash immediately with water. If the collection fluid is accidentally ingested, wash the mouth with water and have the patient drink 250 mL of water immediately. Consult your poison information center for further facts on hyamine.

• Scintillation fluid comes in many formulations. It is usually a mixture of toluene and various cyclic hydrocarbons. It is flammable. Biodegradable formulations do exist. Consult your supplier if you have questions.

Balloon Read On-Site:

1. Add 2.5 mL collection fluid to each vial.

2. Label the scintillation vial lid to match the label on the balloon.

3. Attach a needle to the inlet and outlet tubes on the pump.

4. Turn on pump. Allow to run for about 15 seconds.

5. Put needle from the rigid outlet tube in a vial until it makes bubbles in the collection fluid.

6. Pierce the label of a filled balloon with the other needle and hold it in a stable position. (Do not pierce the balloon anywhere else or it may tear. Do not squeeze the balloon.)

7. After 2-3 minutes the collection fluid should turn colorless.

8. After the collection fluid is colorless, remove the needles from the balloon and collection fluid and discard according to your facility protocol.

9. Change needles between patients.

Attach strawand blow here

10

40

35

30

25

20

15

10

5

0

1 3 5 8 13 20 32 50 79 126

200

316

501

794

1259

1995

3162

5012

100.0%

50.0%

30.0%

20.0%

10.0%

0.0%

40.0%

80.0%

70.0%

60.0%

90.0%

Frequ

ency

Negative (64.5%) Indeterminate(6.5%)

Positive(30%)

Cumulative %

DPM Group Gold Standard NegativeGold Standard Positive

EXPECTED VALUES

As shown in Figure 4 approximately 30% of patients tested will be positive for H. pylori.

Figure 4: Histogram showing DPM distribution for the PYtest*.

*Note: DPM groupings were calculated on a logarithmic scale. Empty DPM groupings were not included. Chart includes all patients from Studies 1 and 2. Frequency of DPM group includes samples with DPM < Group Name.

DPM = Disintegrations per minute

Gold Standard = Agreement between histology and CLOtest*

If the capsule is damaged or appears abnormal in any way, it may give inaccurate results.

HOW SUPPLIED

PYtest* Capsules, clear gelatin capsules each containing 1 µCi of 14C-Urea in unit dose packages of 1, 10 and 100.

PYtest* Kit (14C-Urea Breath Test) is also supplied as a kit containing a PYtest* Capsule and breath collection equipment.

The expiration date is printed on the capsule label.

PYtest* Capsules and Kit should be stored at 15°-30°C (59°-86°F) in an area designated by each individual institution’s regulations.

Rx Only

Please call Halyard Health at 1-844-425-9273 with any questions, or visit our web site at www.halyardhealth.com.

10. Turn off pump after last patient sample is transferred.

11. Double check that the label on the vial lid matches the label on the balloon.

12. Add 10 mL scintillation fluid to each vial and mix fluid.

13. Count the sample in liquid scintillation counter for 5 minutes or as directed by the liquid scintillation counter manufacturer. (Note that values of 50-300 CPM can occur immediately after the addition of the scintillation fluid due to chemiluminescence. Chemiluminescence decays rapidly over an hour or two and will reveal itself by falling counts. Read the sample repeatedly until values 10 minutes apart are similar. If DPM is still 50-300, you should allow the sample to settle for 12-24 hours before retesting).

14. Include a standard and a blank control vial in each run.

Vials Read On-Site See steps 12-14 under “Balloon read on-site.”

QUALITY CONTROL

A minimum of 1 mmol of CO2 is required to perform analysis of a breath sample. The amount of breath required to provide 1 mmol of CO2 varies depending on the amount of CO2 the patient is producing. Since a full balloon typically contains at least 1 mmol of CO2, the balloon should be completely filled.

RESULTS

Interpretation of results (10 minute sample)

<50 DPM Negative for H. pylori

50-199 DPM Indeterminate for H. pylori

≥200 DPM Positive for H. pylori

The indeterminate result should be evaluated by repeating the PYtest* or using an alternative diagnostic method. If repeat breath testing is undertaken, careful history to exclude confounding factors should be obtained. If confounding factors are identified, wait an appropriate time (refer to Table 3) before repeating the PYtest*.

The cutoff point of 50 DPM was determined to be the mean +3SD of results obtained in patients who did not have H. pylori.


Table 3: Factors which might cause sub-optimal breath test results

Factor Result Comment

Recent antibiotic or bismuth (Pepto-Bismol, etc.)

false neg. Relapse of partially treated Hp may take 1–4 weeks

Omeprazole (or other proton pump inhibitors)

false neg. These agents suppress Hp in 40% of patients. Discontinue for at least 2 weeks before performing the PYtest*.

Resective gastric surgery false neg. Isotope may empty rapidly from the stomach.

Resective gastric surgery false pos. Patient may be achlorhydric and have bacterial overgrowth (non-Hp urease).

Food in stomach (also bezoar, gastroparesis)

unknown Isotope may not come into contact with gastric mucosa. Patient may be achlorhydric and/or have bacterial overgrowth (non-Hp urease).

U.S. Patent Nos.: 4,748,113; 4,830,010

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PACKAGE INSERT: PYtest* KIT

12

PYtest* KIT (14C-UREA BREATH TEST)

DESCRIPTION

PYtest* (14C-Urea Breath Test) is a qualitative and non-invasive method for the diagnosis of Helicobacter pylori (H. pylori). To detect H. pylori, 14C-Urea supplied in a capsule is swallowed by the patient. If gastric urease from H. pylori is present, Urea is split to form CO2 and NH3. Ten minutes after the patient ingests the capsule, a breath sample is collected into a balloon. The breath sample is later transferred to collection fluid to trap the labeled CO2. The liquid sample is then analyzed in a liquid scintillation counter.

The PYtest* Kit (14C-Urea Breath Test) is designed for use with the PYtest* capsule, a gelatin capsule for oral administration containing 1 µCi of 14C labeled Urea. The urea is adsorbed on sugar spheres and colored yellow with fluorescein.

Data on 14C-Urea:

Structural Formula (14C-Urea): NH2 14CONH2

Radiation emission: beta-emission, 49 keVmean, 156 keVmax

, no other emissions

External emission: No external radiation hazard. Low-energy beta emissions only. Maximum range of 0.3 mm in water.

Radiological Half-life: 5,730 years

Maximum effective dose equivalent (EDE) : 0.3 mrem/µCi

CLINICAL PHARMACOLOGY

The urease enzyme is not present in mammalian cells, so the presence of urease in the stomach is evidence that bacteria are present. The presence of urease is not specific for H. pylori, but other bacteria are not usually found in the stomach. The principle of the breath test is shown in Figure 1.

Figure 1: Principle of Breath Test

To detect H. pylori, Urea labeled with 14C is swallowed by the patient. If gastric urease from H. pylori is present, urea is split to form CO2 and NH3 at the interface between the gastric epithelium and lumen and 14CO2 is absorbed into the blood and exhaled in the breath.

Following ingestion of the capsule by a patient with H. pylori, 14CO2 excretion

in the breath peaks between 10 and 15 minutes and declines thereafter with a biological half-life of about 15 minutes. 14C-Urea that is not hydrolyzed by H. pylori is excreted in the urine with a half-life of approximately 12 hours. About 10% of the 14C remains in the body at 72 hours and is gradually excreted with a biological half-life of 40 days.

CLINICAL STUDIES

Two studies were performed. In both studies, patients with gastrointestinal symptoms underwent the breath test and an endoscopy. During the endoscopy, biopsy samples were taken from the antral gastric mucosa for histological analysis (2 samples, Giemsa stain) and rapid urease test (1 sample, CLOtest*). Breath samples were mailed to the TRI-MED lab where they were read in a liquid scintillation counter.

Results were reported as disintegrations per minute (DPM). Analysis for accuracy used the ten minute breath sample. A breath sample DPM <50 was defined as a negative result. DPM ≥200 was defined as a positive result. DPM in the range of 50 -199 was classified as indeterminate.

Study 1:

Of 186 patients who had histopathology and CLOtest* (80 men, 106 women), 53 were infected with H. pylori as determined by agreement between histology and CLOtest*. The study results are summarized below:




PYtest*

(DPM 10 min.)


Indeterminate 1 8 9


Total 53 133 186


96% 88%

Notes: PYtest* at 10 min. was compared to the gold standard of biopsy results in which histology and CLOtest* concurred. Patients who did not have both biopsy tests performed, or in whom the tests differed, were excluded from analysis. There was no statistical difference in test accuracy based on gender of patient.

ppv = positive predictive value (true positive divided by total PYtest* positive)

npv = negative predictive value (true negative divided by total PYtest* negative)

Study 2:

Breath tests were performed on 436 outpatients attending gastroenterology practices at sites in the United States. Seventy-six patients (40 men, 36 women) who had histology and CLOtest* were evaluated. The results are summarized below:




PYtest*

(DPM 10 min.)


Indeterminate 4 2 6


Total 27 49 76


82% 96%

Notes: PYtest* at 10 min. was compared to the gold standard of biopsy results in which histology and CLOtest* concurred. Patients who did not have both biopsy tests performed, or in whom the tests differed, were excluded from analysis. There was no statistical difference in test accuracy based on gender of patient.

ppv = positive predictive value (true positive divided by total PYtest* positive)

npv = negative predictive value (true negative divided by total PYtest* negative)

INDICATIONS AND USAGE

PYtest* (14C-Urea Breath Test) is indicated for use in the detection of gastric urease as an aid in the diagnosis of H. pylori infection in the human stomach. The test utilizes a liquid scintillation counter for the measurement of 14CO2 in breath samples.

14CO2 in breath

unchangedurea in urine

bicarbonatein bloodstream counts

scintillation(beta) counter

addscintillation fluid

transfer CO2

to counting vial

collect 2L breathin mylar balloon

NH4+

ammonium H14 CO3

–

NH2

NH2

H. pylori

14C=O

14C-Urea inPYtest* capsule

13

Pediatric Use: Clinical studies in children have not been conducted. However, PYtest* is expected to work the same in children as in adults. While the dose (1 capsule) does not need to be adjusted, the child must be able to swallow the intact capsule and blow into a straw.

ADVERSE REACTIONS

No adverse reactions were reported in clinical trials.

OVERDOSAGE

Risk from radiation is negligible even with a 1,000 capsule overdose (0.3 rem). If overdose occurs, the patient may drink one glass of water (150 mL) every hour to hasten excretion of the isotope. Maximum excretion of Urea is achieved at a urine output of ≥2.0 mL/min.

DOSAGE AND ADMINISTRATION

Materials provided:

As shown in Figure 2, the PYtest* Kit contains:

• PYtest* capsule• Two 30 mL disposable cups• One drinking straw• One mylar collection balloon• One report form• One mailing box with labels**** The kit includes analysis by Halyard Health of one balloon from one patient at one time point.

Figure 2: PYtest* Kit

Materials Needed but not Provided

1. Stopwatch/Timer capable of timing an interval up to 10 minutes.

2. Water (40 mL)

DOSAGE:

One PYtest* capsule.

PROCEDURAL NOTES:

• Inform the patient to fast for 6 hours prior to the test.

• The patient should be off antibiotics and bismuth for 1 month, and proton pump inhibitors and sucralfate for 2 weeks prior to the test.

• Have patient sitting at rest while doing the test.

• The capsule should not be handled directly as this may interfere with the test result.

• To avoid contamination by bacteria in the mouth, the capsule should be swallowed intact. Do not chew capsule.

CONTRAINDICATIONS

None

WARNINGS

None

PRECAUTIONS

General: After the patient ingests the 14C-Urea capsule, the sample collected for test purposes is for in vitro diagnostic use only.

A false positive test could occur in patients who have achlorhydria. Very rarely, a false positive test may occur due to urease associated with Helicobacters other than H. pylori (i.e., Helicobacter heilmanni).

LIMITATIONS OF THE TEST:

• The test has been evaluated in outpatients before elective endoscopy.

• Test results should be evaluated with clinical signs and patient history when diagnosing H. pylori infection.

• The performance characteristics of the test have not been established for monitoring the efficacy of antimicrobial therapies for the treatment of H. pylori infection.

• A negative result does not completely rule out the possibility of H. pylori infection. If clinical signs and patient history suggest H. pylori infection, repeat the PYtest* or use an alternative diagnostic method.

• The integrity of samples in balloons sent by air transport has not been adequately determined. In studies simulating the effects of air transport for two to seven days at temperatures of -40°C, 20°C and 55°C, no balloon failures were observed. However, the data could not provide statistical determination that no changes in 14CO2 concentration took place.

• For ground transport, integrity of samples in balloons has not been determined beyond 7 days. During this time frame, concentration of labeled CO2 can decrease as much as 0.36% per day.

RADIOACTIVITY:

Persons concerned about very low doses of radioactivity may postpone the test or may decide to use an alternative means of diagnosis. The test produces radiation exposure equal to 24 hours of normal background. In animal experiments, such low doses of radiation do not carry measurable risk.

Preclinical studies were not conducted on 14C-Urea. The estimated dose equivalent received from a single administration of PYtest* (1µCi 14C) is about 0.3 mrem.

INFORMATION FOR PATIENTS:

It is necessary for the patient to fast for 6 hours before the test. The patient should also be off antibiotics and bismuth for 1 month, and proton pump inhibitors and sucralfate for 2 weeks prior to the test. Instruct the patient not to handle the capsule directly as this may interfere with the test result. The capsule should be swallowed intact. Do not chew the capsule.

Carcinogenesis, mutagenesis, impairment of fertility: No studies have been conducted with 14C-Urea to evaluate its potential for carcinogenicity, impairment of fertility, or mutagenicity.

Drug Interactions: Antibiotics, proton pump inhibitors, sucralfate, and bismuth preparations are known to suppress H. pylori. Ingestion of antibiotics or bismuth within 4 weeks and proton pump inhibitors or sucralfate within 2 weeks prior to performing the test may give false negative results.

Pregnancy: Pregnancy category C. Animal reproduction studies have not been conducted with PYtest* (14C-Urea). It is also not known whether PYtest* can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. PYtest* should be given to a pregnant woman only if clearly needed.

Nursing mothers: It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when PYtest* is administered to a nursing woman.

14

Table 4: Factors which might cause sub-optimal breath test results

Factor Result Comment

Recent antibiotic or bismuth (Pepto-Bismol, etc.)

false neg. Relapse of partially treated Hp may take 1–4 weeks

Omeprazole (or other proton pump inhibitors)

false neg. These agents suppress Hp in 40% of patients. Discontinue for at least 2 weeks before performing the PYtest*.

Resective gastric surgery false neg. Isotope may empty rapidly from the stomach.

Resective gastric surgery false pos. Patient may be achlorhydric and have bacterial overgrowth (non-Hp urease).

Food in stomach (also bezoar, gastroparesis)

unknown Isotope may not come into contact with gastric mucosa. Patient may be achlorhydric and/or have bacterial overgrowth (non-Hp urease).

EXPECTED VALUES

As shown in Figure 3 approximately 30% of patients tested will be positive for H. pylori.

Figure 3: Histogram showing DPM distribution for the PYtest*.

*Note: DPM groupings were calculated on a logarithmic scale. Empty DPM groupings were not included. Chart includes all patients from Studies 1 and 2. Frequency of DPM group includes samples with DPM < Group Name. DPM = Disintegrations per minute Gold Standard = Agreement between histology and CLOtest*If the capsule is damaged or appears abnormal in any way, it may give inaccurate results.

HOW SUPPLIED

PYtest* Kit (14C-Urea Breath Test) is supplied as a kit containing a PYtest* Capsule, a clear gelatin capsule containing 1µCi of 14C-Urea and breath collection equipment.

PYtest* Capsules are also supplied separately in unit dose packages of 1, 10 and 100.

The expiration date is printed on the capsule label.

PYtest* Capsules and Kit should be stored at 15°-30°C (59°-86°F) in an area designated by each individual institution’s regulations.

Rx Only

Please call Halyard Health at 1-844-425-9273 with any questions, or visit our web site at www.halyardhealth.com.

40

35

30

25

20

15

10

5

0

1 3 5 8 13 20 32 50 79 126

200

316

501

794

1259

1995

3162

5012

100.0%

50.0%

30.0%

20.0%

10.0%

0.0%

40.0%

80.0%

70.0%

60.0%

90.0%

Frequ

ency

Negative (64.5%) Indeterminate(6.5%)

Positive(30%)

Cumulative %

DPM Group Gold Standard NegativeGold Standard Positive

STEP-BY-STEP PROCEDURE FOR BALLOON:

Table 3: Breath Sample Collection by Balloon

Before the test 1. Label balloon and fill in breath test report form.2. Check that all materials are present.




2. Start the stopwatch when the patient swallows the capsule.3. Discard waste (e.g., capsule packaging, used straws) according



10 minutes 1. Push a drinking straw into the neck of the balloon.2. Ask the patient to hold his/her breath for 5-10 seconds, then

blow up a balloon with a slow breath through the straw, filling the balloon completely.

3. Tie the neck of the balloon into a tight knot. 4. Check that the balloon label and the breath test report form

are completed correctly.


Place the filled balloon and breath test report in the sample box and forward to Halyard Health for analysis.

QUALITY CONTROL

A minimum of 1 mM of CO2 is required to perform analysis of a breath sample. The amount of breath required to provide 1 mM of CO2 varies depending on the amount of CO2 the patient is producing. Since a full balloon typically contains at least 1 mM of CO2, the balloon should be completely filled.

Results

Interpretation of results (10 minute sample)

<50 DPM Negative for H. pylori

50-199 DPM Indeterminate for H. pylori

≥200 DPM Positive for H. pylori

The indeterminate result should be evaluated by repeating the PYtest* or using an alternative diagnostic method. If repeat breath testing is undertaken, careful history to exclude confounding factors should be obtained. If confounding factors are present, wait an appropriate time (refer to Table 4) before repeating the PYtest*.

The cutoff point of 50 DPM was determined to be the mean + 3SD of results obtained in patients who did not have H. pylori.


15

PYtest* KIT PROGRAM

Provider Purchase Program

Facilities participating in the PYtest* Provider Purchase Program purchase the kit and test analysis then bill the insurance carrier and/or patient for the test administration and analysis. In addition to supplies needed to perform the test administration, the kit includes a result form and directions for use. The results form must be completed and returned with the kit to Halyard Health.

The Provider Purchase Program form is divided into several sections which are described below.

PLEASE NOTE: WITHOUT COMPLETE INFORMATION, HALYARD HEALTH MAY BE UNABLE TO RETURN THE RESULTS TO YOU

Patient Information

Indicate test date, patient name, patient date of birth, ID number and any referring physician.

Please Fax Results To

Indicate the name and fax number of the person to which the results should be faxed. Without this information Halyard Health cannot return results to you. If multiple providers or facilities need patient results information, names and fax numbers must be listed directly on the result form.

Confounding Factors

The person performing the test should ask the patient the questions regarding confounding factors. Answering NO to all questions would indicate to Halyard Health that the test was performed in accordance with the package insert. There is a section later in this document that describes the confounding factors.

Lab Contact

Please indicate the lab facility contact and phone number as it may be necessary to contact the person administering test for additional information about the sample.

Return Results To

Write the name, address and organization administering test to which the hard copy of the form should be sent.

Result – Halyard Health Use Only

The final section is filled out by Halyard Health lab personnel. Data concerning the sample along with the diagnosis of negative, positive or indeterminate are shown in this section.

Please Note

Please keep the bottom (pink) copy of the form to track kits that have been returned to Halyard Health for analysis. If you call with an inquiry regarding a result, you will be asked for the bar code number at the bottom right hand corner of the report form. The other copies (white and yellow) of the form must returned with the kit to Halyard Health.

16

BAR CODE

Distributed in the USA by Halyard Sales, LLC, Alpharetta, GA 30004 In USA, please call 1-844-425-9273 • halyardhealth.com Halyard Health, Inc., 5405 Windward Parkway, Alpharetta, GA 30004 USA Halyard Belgium BVBA, Leonardo Da Vincilaan 1, 1930 Zaventem, BelgiumSponsored in Australia by Halyard Australia Pty Limited; 52 Alfred Street, Milsons Point, NSW 2061製造販売元ハリヤード・ヘルスケア・インク横浜市西区みなとみらい二丁目2番1号

*Registered Trademark or Trademark of Halyard Health, Inc., or its affiliates. © 2015 HYH. All rights reserved. 2015-09-17 15-H1-258-0-00 / 70169955

For the detection of Helicobacter pyloriShipper/UPS tracking #

Test Date First Name Last Name

/ /DOB Patient ID# Referring Dr

/ /

Without complete address information we cannot return results to you

Please FAX Results To: FAX #

Confounding factors: Answering NO to all questions indicates the test was performed per package insert.Has the Patient taken antibiotics in the last month? ..........................................................................................................( ) Yes ( ) NoHas the Patient taken Bismuth-containing medications in the last month? .......................................................................( ) Yes ( ) NoHas the Patient taken Proton-Pump inhibitors in the last two weeks? ...............................................................................( ) Yes ( ) NoHas the Patient taken Sucralfate in the last two weeks? .....................................................................................................( ) Yes ( ) NoHas the Patient had anything to eat or drink in the past 6 hours? ......................................................................................( ) Yes ( ) NoHas the Patient had resective gastric surgery? ...................................................................................................................( ) Yes ( ) NoWas the breath sample collected incorrectly? ..................................................................................................................( ) Yes ( ) No

Breath samples must be collected 10 minutes after ingestion of the capsule.Capsule ingestion time: Breath collection time:

DPM Result: POSITIVE (200+) NEGATIVE (0-49) INDETERMINATE (50-199)

Do not duplicate or photocopy this form. Contact Halyard Health for additional forms.For questions regarding results or confounding factors see the user’s guide or call 1-844-425-9273

Return Results to: Name: Lab Contact:Address: Lab Phone: City: State: Zip:

Date to Halyard Health: Date Analyzed:Date Transferred: Date Result Faxed:

Comments: Signed: Date:

PLEASE KEEP THE PINK COPY OF THIS FORM FOR YOUR RECORDS.

RESULTS - HALYARD HEALTH USE ONLY

Halyard Health - White Copy • Halyard Health - Yellow Copy • Customer - Pink Copy

PYtest*

14C-UREA BREATH TEST

17

The Balloon LabelThe patient’s name should be clearly printed on the balloon label (sample shown below).

18

Can I use any balloon to collect the patient’s breath?

Any brand of 2 liter mylar balloon should be adequate. Note: Balloons supplied by Halyard Health have passed rigorous quality control testing and are strongly recommended.

Can a patient use a method other than a balloon to collect the breath sample?

The breath sample may be collected directly into collection fluid in a scintillation vial via a safety trap. Halyard Health does not endorse this method as patient safety may be compromised.

Does Halyard Health provide safety traps?

No. We recommend samples be collected by the balloon method. If you wish to use the vial method, you will need to obtain your own safety trap.

What should be done if the patient is not able to fully inflate the balloon with one breath?

After the patient has partially inflated the balloon with his first breath, simply squeeze the straw to keep the breath in the balloon from escaping. Allow the patient to take another breath, hold it for 5–10 seconds and then again blow into the balloon. You should try to complete this process as soon as possible. The patient may take as many breaths as is needed to completely fill the balloon.

What happens if a balloon is only half-filled?

In order to perform analysis on the breath sample, 1 mM of CO2 is required.

The amount of breath required to provide 1mM of CO2 varies depending on the

amount of CO2 the patient is producing. A balloon which is half-full may or may not provide enough CO2 for analysis. Halyard Health strongly recommends the balloon be filled completely. Do not be concerned about the balloons bursting – they are very strong.

What happens if a balloon has a leak?

If you can locate the leak, put a piece of adhesive tape over it. If the leak cannot be found, an extra balloon sample should be obtained or the test repeated.

PYtest* FREQUENTLY ASKED QUESTIONS

General

Are there any special purchasing requirements for the PYtest*?

If your facility doesn’t have a nuclear medicine department, contact Halyard Health (1-844-425-9273) to place an order. If your facility has a nuclear medicine department or otherwise orders radioactive materials on a routine basis, contact that office prior to placing an order. Even though in most states the PYtest* is exempt from licensing (physicians don’t have to have a radioactive materials license to possess and use the PYtest*), facilities that have radioactive materials licenses like to keep track of the amount of radioactive material at the facility. The person who orders radioactive materials at your institution will be able to help you place the order. You may find that you don’t have to order it through them, but it’s best to make sure of that.

If you plan to analyze samples on-site, a liquid scintillation counter is required. Halyard Health offers the microCOUNT* LITE (“microCOUNT*”) liquid scintillation counter for PYtest* sample analysis. We do recognize that many sites have an existing liquid scintillation counter (non-microCOUNT*). The microCOUNT* requires daily use Quality Control and based on this, needs no annual servicing. For non-microCOUNT* users, we recommend that you verify that the counter is in good working order. Typically, those counters should be serviced at least annually. In addition, you will need to obtain a suitable container to handle the liquid scintillation media (waste). See page 25 on waste disposal for more information.

How does the PYtest* work?

The PYtest* is a qualitative and non-invasive method for the diagnosis of Helicobacter pylori (H. pylori). To detect H. pylori, 14C-Urea supplied in a capsule is swallowed by the patient. If gastric urease from H. pylori is present, urea is hydrolyzed to form H14CO3 and NH3. The H14CO3 is absorbed into the blood, converted to 14CO2 and exhaled in the breath. Ten minutes after the patient ingests the capsule, a breath sample is collected into a balloon. The breath sample is later transferred through the collection fluid to trap a standard amount of CO2. The liquid sample is then analyzed in a liquid scintillation counter to detect radio labeled CO2. The presence of a significant amount of 14CO2 in the breath sample is indicative of Hp infection. 14C-Urea that is not hydrolyzed by urease is excreted in the urine.

How are the kits returned to Halyard Health for analysis and how soon will I get a result?

When you place your order, you have the option of returning the kits to Halyard Health by 2nd day Priority Mail or by 2nd day UPS. There is no additional charge for either of these methods.

In either case we will fax a result to you within 24 hours of the sample being received at Halyard Health. Saturday, Sunday and certain holidays are not counted as part of the 24 hours. Be sure to complete the “Please Fax Results To:” section or we will be unable to fax the result to you.

If you choose to have kits returned by 2nd day Priority Mail, please keep in mind that Priority Mail is not guaranteed. This means that it might take longer than two days for the kit to reach us. U.S. Mail is also not delivered on Federal holidays.

If you choose to have kits returned by 2nd day UPS, all you need to do is enter your name and address in the section entitled “Shipment From” and sign and date the form. You do not have to complete sections 3, 4, 5, 6 and 7 regarding shipping charges. Once you have completed the UPS shipping document, please tear off the top copy and keep it for your records in case the shipment needs to be traced. If you do not have a regular UPS pickup, you can either call 1-800-PICK-UPS to schedule a pickup or drop the kit in a UPS drop box.

If you are using UPS return kits, please write the UPS tracking number on the appropriate form described on page 15, or attach the top copy of the UPS form to the pink copy of the form which you keep. Note: If you do not keep a record of the UPS tracking number and your kit is lost, there is no way to track or recover it.

19

What medications are considered to be H2 Blockers?

(list may not be comprehensive)

Generic Name U.S. Trade Name Cimetidine Tagamet Famotidine Pepcid Nizatidine Axid Ranitidine Zantac

Are antacids considered to be a confounding factor?

No.

What is an antacid?

Antacids are medications which neutralize the acid secreted by the gastric parietal cells.

They are not able to block acid production like PPIs or H2 Blockers.

What are the names of commonly used antacids?

Maalox, Rolaids, Tums, Mylanta, Gelusil, and many more.

How soon can the test be repeated?

The test may be repeated after six hours if the patient is fasting and has no other confounding factors.

What happens if the patient feels the capsule is stuck in her/his throat?

You may give the patient an additional 20 mL of water right away and then the standard 20 mL three minutes after capsule ingestion. Use common sense and give the patient enough water to ensure that the capsule is in the stomach, but do not have them drink a whole glass of water. Too much water may prevent the capsule from dissolving in contact with the lining of the stomach, possibly causing a false negative result.

Are any of the chemicals involved in the PYtest* hazardous (flammable or caustic)?

If you are using the PYtest* kits (and therefore not performing analysis), the answer is No.

If you are analyzing the breath sample on-site, you must bubble the breath through breath collection fluid and add liquid scintillation cocktail. The collection fluid contains benzethonium hydroxide, methanol and a pH indicator. Benzethonium hydroxide is a corrosive alkali. After collecting CO2 the collection fluid turns clear. At this point, it is closer to neutral (pH~9) and is no longer considered corrosive.

Because of the methanol content, the breath collection fluid is also flammable. This fact remains even after the liquid scintillation fluid is added, it should be collected in an appropriate waste receptacle (typically a bottle or carboy) and disposed of in accordance with your facility’s regulations. Note: The collection fluid is not corrosive after it has turned clear. Please see page 25 on waste disposal for more information.

If you are using the vial method and collecting breath directly into the collection fluid, you must supervise the patient and ensure that a safety trap is used to prevent the patient from ingesting the collection fluid. The amount of collection fluid in one collection vial is not sufficient to cause serious poisoning. Local irritation to skin or mucous membranes is likely when the solution is blue. If the collection fluid splashes on the skin or eyes, wash immediately with water. If the collection fluid is accidentally ingested, wash the mouth with water and have the patient drink a minimum of 250 mL of water immediately. Consult your poison information center for further facts on benzethonium hydroxide. Halyard Health does not endorse the direct collection method of trapping CO2.

SAMPLE COUNTING

How is analysis performed?Please see the picture description of transfer and analysis of the PYtest* on the next page.

What are confounding factors for the PYtest*? What must a patient do prior to the PYtest*?

The following items are confounding factors for the PYtest*. Any of the following confounding factors could lead to a false-negative result:

Antibiotics - Antibiotics are medications given to treat bacterial infection. Patients should not have the test performed if they have taken antibiotics in the last month. You may get a false negative result since antibiotics have a bactericidal effect on H. pylori.

Bismuth - Bismuth is a medication used to treat abdominal discomfort. In the past it was believed to be effective because it provided a protective coating between the stomach lining and acid. We now know that bismuth suppresses H. pylori. Patients should be off all bismuth drugs for one month prior to the breath test. The most common form of bismuth available in the U.S. is Pepto Bismol. Patients should not have the test performed if they have taken bismuth in the last month. You may get a false negative result since bismuth has a bactericidal effect on H. pylori.

Sucralfate - Patients should not have the test performed if they have taken sucralfate in the last 2 weeks. The trade name for sucralfate is Carafate. Sucralfate is a medication given to treat ulcers. In the past it was felt that sucralfate worked because it provided a protective barrier between the ulcer and stomach acid. It is now known that sucralfate suppresses the growth of H. pylori. You may get a false negative result since sucralfate suppresses the growth of H. pylori .

Nonfasting - Patients should be fasting for 6 hours prior to the test. This means nothing to eat or drink. Food in the stomach may prevent the urease, from H. pylori, from contacting the 14C-Urea in the PYtest* capsule. Without this contact the chemical reaction cannot take place and a false negative result may occur.

Proton-Pump Inhibitors - Proton-pump inhibitors (PPI) are medications given to treat ulcers. They are useful in treating ulcers because they inhibit acid production. Antibiotics are also more effective in killing H. pylori when combined with PPI’s. Patients should not have the test performed if they have taken a proton-pump inhibitor in the last 2 weeks. You may get a false negative result since PPI’s have a bactericidal effect on H. pylori.

Resective Gastric Surgery - This may cause a false negative result by the surgically altered stomach allowing the capsule to quickly pass through thereby reducing the time for the urea and urease to be in contact. Additionally, this type of surgery may cause a false positive result due to urease-producing bacterial overgrowth from the duodenum appearing in the stomach and giving an H. pylori-like response to the PYtest* when indeed it is due to another type of bacterium. For these reasons, it is recommended that the PYtest* should not be used on patients that have undergone resective gastric surgery.

What medications are considered to be Proton-Pump Inhibitors?

(list may not be comprehensive)

Generic Name U.S. Trade Name Rabeprazole Aciphex Esomeprazole Nexium Lansoprazole Prevacid Omeprazole Prilosec Pantoprazole Protonix

Are H2 Blockers considered a confounding factor?

No.

What is an H2 Blocker?

H2 blockers are medications which inhibit gastric acid secretion by competing with histamine H2 receptors.

20

Add 2.5 mL collection fluid to a vial. Attach a needle to the inlet and outlet on the pump.

Turn on pump, run for 15 seconds. Insert outlet needle into vial, observe bubbles. Insert inlet needle into balloon label.

Bubble the breath through the Breath Collection Fluid until it turns colorless.

Remove needles from tubing and discard safely.

Add 10 mL liquid scintillation fluid to the vial. Cap vial and shake.

Count the sample in a liquid scintillation counter for 5 minutes.

PYtest* BREATH SAMPLE ANALYSIS

21

Can a breath sample be counted immediately after collection?

The sample may be counted immediately. If a sample gives a result of 50-300 disintegrations per minute (DPM) the sample should be counted again several hours later since chemical activity called chemiluminescence can temporarily produce false counts on the order of 100 DPM.

I have a sample with a result between 50 and 300 DPM. How long should I wait to recount?

The 50-300 DPM sample needs to be recounted to eliminate any potential chemiluminescence effects. This effect normally fades very quickly. A good recount time is 30 minutes after the initial count. If the result is still within the 50-300 DPM range, you can wait another 30 minutes or simply count the sample the next day. Halyard Health uses a conservative policy for recounting such samples which is to recount them 24 hours after the first count. Note: Samples outside the 50-300 DPM range need not be recounted. Also note that these are only guidelines and you should use your own judgement in counting.

I thought the indeterminate range is 50-199 DPM. Why is the upper range for recounting 300 DPM instead of 199 DPM?

The indeterminate range is 50-199 DPM. However, it has been our experience that the chemiluminescence observed in PYtest* sample is on the order of 100 DPM or less. Therefore, if you have an initial count of 299 DPM, then that could actually be an indeterminate sample after the activity due to chemiluminescence is removed. Therefore, we recommend recounting samples that give 50-300 DPM on initial count to rule out a change in clinical classification.

Is there special interfacing software available for particular models of liquid scintillation counters (LSCs)?

You should contact the manufacturer of your LSC regarding software. The microCOUNT* does not require a software interface.

Is the printout from my LSC sufficient to substantiate a diagnosis?

The results from the printout (in DPM) should be transferred onto a PYtest* result form or equivalent. A physician should then interpret the result and sign and date the form. It is good practice to sign and date the result from the counter.

Are there any LSCs that cannot be used?

All traditional LSCs are acceptable if they are operating properly. The microCOUNT* has been tested and found suitable for use with the PYtest*. There are several other LSCs on the market which are suitable for use with the PYtest*.

Will a “Well Counter” work to analyze the samples?

No. Well counters count gamma-emitting radionuclides and high-energy beta emitters. Carbon-14 used in the PYtest* is a weak beta-emitter. Well counters can work with high-energy beta-emitters such as P-32 or Sr-85. They detect the Bremsstrahlung radiation (low-energy x-rays) caused from the high-energy beta particles. The low energy and low activity of the PYtest* samples make this impossible. The user can try to use it, but it is highly unlikely it will work.

We have a scintillation counter in our department. Does this mean we have a Liquid Scintillation Counter?

Maybe. There are a number of types of scintillation counters or scintillation detectors. There are scintillation cameras, well counters, probes, and other devices that count radiation based on the process of scintillation using solid scintillators. These detectors can be confused with liquid scintillation counters. A liquid scintillation counter is needed to analyze the PYtest*.

Should my LSC be recertified or checked by the manufacturer if it has not been used in the last year?

If you have a microCOUNT*, it does not need to be serviced on an annual basis since it needs to be calibrated each day it is used. Other liquid scintillation counters that do not require daily calibration should be serviced on a periodic basis (at least once a year). Halyard Health also recommends frequent quality control checks be performed on your instrument to ensure proper operation.

Where can I get a LSC?

Halyard Health has developed a small single sample counter called the microCOUNT*. It is relatively inexpensive, and takes up little room.

Do I need a quench curve?

No, but you may want to use one if your LSC can use one to convert sample activities to DPM. The options are listed below.

If you have a traditional (multi-sample) LSC, and have a quench set and want to have automatic quench correction: This is recommended if you have an LSC that can store a quench curve, and if you have a quench set and/or can accurately prepare one yourself. The quench curve allows the automatic conversion of counts per minute (CPM) to disintegrations per minute (DPM) by dividing the CPM value (either background corrected or not) by the sample efficiency.

If you have a traditional (multi-sample) LSC, and DO NOT have or DO NOT want to make a quench set: You can purchase a standard set. This allows you to count both samples, record the background value, calculate the efficiency for the PYtest* counting geometry, and calculate the DPM by hand. This does not require LSC configuration skills or pipetting skills and is a simple way to get started.

If you have a microCOUNT*: The microCOUNT* utilizes a constant efficiency calculated from daily quality control of counting a standard and background set. Results are reported in DPM.

What do I need to do for quality control of the counter?

Halyard Health recommends that you count a standard and background each day it is used and keep track of the instrument performance. If the background and efficiency values start to drift, have the instrument serviced.

If you have an LSC other than a microCOUNT*, we also recommend having the instrument serviced annually by a trained technician. Since the microCOUNT* requires calibration each time it is used, annual servicing is not needed.

Do you have any tips for breath sample counting?

Sample Preparation

Ten mL liquid scintillation fluid (LSF) should be added to each vial following breath collection. The vials should be capped and the contents mixed after adding LSF. There are many brands of LSF, some of which are chemically incompatible with breath collection fluid. LSFs that have been tested at Halyard Health (both compatible and incompatible) are listed on page 22. A rule of thumb to use with a new LSF is that if the sample does not turn clear after shaking a few seconds or separates into two phases after several hours, that scintillant is likely to be incompatible with the breath collection fluid. We recommend using a biodegradable LSF for aqueous samples. These LSFs typically have maximum 14C efficiencies (without breath collection fluid) of 80-90%, unlike toluene-based LSFs which have maximum efficiencies of greater than 90%. Please remember that the breath collection fluid reduces the counting efficiency of the cocktail by around 10%.

22

Sample counting, analysis and reporting

After adding the scintillation fluid, the samples are counted for five minutes. Samples with activity in the 50-300 DPM range should be counted again several hours later since chemical activity called chemiluminescence can temporarily produce false counts on the order of 100 DPM.

Results should always be reported in disintegrations per minute (DPM). The use of DPM instead of CPM removes instrument variability, allowing for a “common ground” between laboratories. To convert CPM to DPM, use the following formula:

(Sample CPM - Background CPM)

DPM =

EfficiencyWhere:

Sample CPM = CPM of sample

Background CPM = CPM of breath sample from person who has not received 14C-Urea

Efficiency = efficiency of counter for breath test samples using your LSF (liquid scintillation fluid)

To use the above formula, two pieces of information must be known, the background and efficiency of the breath samples for your liquid scintillation counter (LSC). The background sample is obtained by preparing and counting a sample from someone who has not received 14C-Urea. The same sample may be used indefinitely. Halyard Health currently has shelf-life data on background samples approximately two years old.

You also must know the efficiency of breath samples in the LSC. The efficiency can be determined using one of the three following ways:

Same efficiency for all breath samples

Since all samples have the same constituents (vial, breath collection fluid, CO2, and liquid scintillation fluid), there is little sample-to-sample variation in the efficiency. Therefore, a back-ground breath sample can be prepared, a known amount of 14C added to that sample, and the efficiency determined by dividing the number of CPM from counting the sample by the known number of DPM in the sample. This efficiency is then used for all samples with the same constituents (also known as counting geometry). If one of the components is changed (different brand of LSF, poly vials instead of glass, etc.) you may wish to prepare a new standard. We have noticed very small (<5%) efficiency variations from sample to sample, and also for different types of cocktails and vials.

Quench curve

Some LSCs have the capability to store a quench curve for automatically calculating sample efficiency. The quench curve may be set up by the manufacturer of the LSC or by the user by preparing known amounts of 14C and quenching agents to a series of vials and counting them. The preparation and use of quench curves is beyond the scope of this document. Should you wish to prepare or use a quench curve with PYtest* breath samples, contact the technical support group of the manufacturer of your LSC.

Quality Control

Quality Control (QC) for your liquid scintillation counter is important to obtain reliable results. The recommended QC routine is very simple and will provide confidence that the LSC is working properly. The QC program should be performed every day that you count breath samples. The QC program consists of counting a background sample (described above) and a standard of known activity. The standard counted can be the sample used in the “Same efficiency for all breath samples” section above.

Alternatively, the standard set for the liquid scintillation counter may be used for monitoring operability. This is typically an unquenched sample which has an efficiency of 90-100%. The number of 14C DPM in the vial should be printed on the vial, and the efficiency can be calculated by dividing the CPM obtained by the number of DPM in the vial. The results of the daily quality control procedure are typically entered in a QC notebook.

When starting on-site analysis, you may wish to send a set of balloons to Halyard Health from the first few (typically three) patients. The samples will be analyzed and results compared to ensure that your results are comparable. The analysis will be done at no charge. When placing your initial order, inform the order entry person that you wish to have a verification package (Order No. 60494). We will be happy to try and answer any questions you may have regarding sample counting.

Which liquid scintillation fluids are compatible with PYtest* Breath Collection Fluid?

Name Manufacturer Phone Number

Halyard Health LSF Halyard Health 844-425-9273

Biosafe II Research Products International 800-323-9814

EconoSafe Research Products International 800-323-9814

EcoLume MP Biomedicals, Inc. 800-854-0530

Optiphase HiSafe 3 PerkinElmer 800-762-4000

Optiphase Supermix PerkinElmer 800-762-4000

Ready Safe Beckman Instruments 800-742-2345

ScintiSafe 30 Fisher Scientific 800-766-7000

ScintiSafe 50 Fisher Scientific 800-766-7000

Universol MP Biomedicals, Inc. 800-854-0530

Which liquid scintillation fluids are not recommended for use with PYtest* Breath Collection Fluid?

The following LSFs have been tested and are not recommended for use with the PYtest*:

Name Manufacturer Phone Number

Biosafe NA Research Products International 800-323-9814

CytoScint MP Biomedicals, Inc 800-854-0530

OptiFluor PerkinElmer 800-762-4000

Optiphase HiSafe II PerkinElmer 800-762-4000

Ultima Gold MV PerkinElmer 800-762-4000

23

INTERPRETATION AND RESULTS

What are the cut-off points for positive and negative results?

<50 DPM = Negative

50-199 DPM = Indeterminate

≥ 200 DPM = Positive

What is the definition of indeterminate?

An indeterminate result is a ten minute background-subtracted DPM result between 50 and 199. This definition also means that the possibility of chemiluminescence has been eliminated. See page 21 regarding chemiluminescence.

What causes an indeterminate result?

The exact cause of an indeterminate result is not known; however, the following is a list of theories about some of the possible causes for indeterminate results.

1. It is possible that the patient may have a confounding factor that they did not report.

2. The patient may have a very mild H. pylori infection that gives a weak response to the 14C-Urea.

3. The sample is obtained less than ten minutes following capsule ingestion.

4. Achlorhydric patients often have bacteria other than H. pylori in their stomach. These bacteria may produce some urease.

5. There are urease-producing bacteria in the mouth. Therefore, there is urease in the mouth that could possibly come in contact with 14C-Urea that has come out of the capsule from a patient who has held the capsule in his/her mouth instead of swallowing immediately, or has cracked the capsule with his/her teeth.

6. The urease in the mouth can also be swallowed with saliva. Normally, the urease swallowed in this fashion is deactivated by the stomach acid. If the patient’s stomach is achlorhydric (without acid) then this urease that is swallowed may react with some of the 14C-Urea and give an indeterminate result.

One of the problems in assessing the cause of these results is that they happen infrequently (approximately 5 percent) so getting useful data on the phenomenon is quite difficult.

What is suggested for retesting a patient with an indeterminate result?

The indeterminate result should be evaluated by repeating the PYtest* or using an alternative diagnostic method. If you repeat the breath test, be sure to obtain a careful history to exclude confounding factors. If confounding factors are present, wait an appropriate time (at least six hours) before repeating the PYtest*. The six hour delay before repeating the PYtest* allows 14CO2 in the breath to be eliminated, and therefore will not interfere with the results of a second test.

Type of Confounding Factor Recommended Time between Confounding Factor and Retesting

Antibiotics One month

Bismuth One month

Proton Pump Inhibitors Two weeks

Sucralfate Two weeks

Non-fasting Six hours

Resective Gastric Surgery None. Not recommended for this population

Does the test result need to be confirmed by serology or other methods of testing?

No.

If I discover a patient has taken a confounding medication, but the result of the test is still positive, is this really a positive test?

Yes, with the exception of resective gastric surgery.

What does it mean if I discover a patient had a confounding factor and the result is negative?

This may be a false negative result. You will need to repeat the test once the patient has been off the confounding factor the appropriate amount of time.

24

RADIATION SAFETY

What is the risk from the 14C?

The PYtest* gives a maximum radiation dose of 0.3 mrem. This dose is the Effective Dose Equivalent (EDE) which takes into account many factors such as the half-life of C-14, the type of emissions, and how quickly the material leaves the body. The PYtest* gives the same radiation dose as 24 hours of normal background radiation.

What is the dose to the people performing the test? Are they at risk?

The Nuclear Regulatory Commission (NRC) has performed an analysis of the radiation dose estimates for personnel working with the PYtest*. The analysis is shown below and is part of the regulatory analysis for the rulemaking, “EXEMPT DISTRIBUTION AND USE OF A RADIOACTIVE DRUG CONTAINING ONE MICROCURIE OF CARBON 14 UREA”. This proposed rule and regulatory analysis may be obtained from the NRC (www.nrc.gov).

Health and Safety Effects

For the purposes of this regulatory analysis, the NRC assumes that the same number of breath tests (i.e., 600,000 tests) will be administered regardless of the level of NRC regulatory control. This view is predicated on the belief that each physician’s primary motivation is to provide the best possible care to his or her patients. In addition, the routine and accidental exposures per Carbon-14 Urea breath test is not expected to be affected by the level of NRC regulatory control. Thus, radiation exposures to the workers and members of the public would be the same regardless of which alternative is adopted.

The NRC has concluded that the human use of these capsules results in insignificant exposures as depicted below:

Scenario Maximum Exposed Individuals

Routine Exposure

Worker administering 14C-Urea breath tests

Full-time workers, 8,000 patients/yr.

Less than 0.7 mrem/yr.

Routine exposure of patients from 14C-Urea breath tests

Patient tests negative

Patient tests positive

0.38 mrem/capsule

0.18 mrem/capsule

Release of 150 µCi of 14C02 into administration facility from fire

Member of public in the administration area

Less than 0.0002 mrem

Rupture of a capsule causing skin contamination of worker or patient

Skin (100 cm2) exposed for one hour prior to washing; 0.075 µCi skin absorption

5.8 mrad skin dose, 0.029 mrem (CEDE)

Furthermore, the NRC concluded that the impacts associated with any releases of 14C to the surrounding environment are expected to be very small and the expected risks are minimal. The earth’s atmosphere contains an inventory of naturally occurring 14C of about 3.8 million curies (equivalent to the activity in 3.8 trillion breath tests), which is in addition to the huge inventory of about 240 million curies in the world’s oceans. The 14C released into the atmosphere from the use of this test would mix with the global inventory and expose the public and other biotic components of the environment to 14C intakes from inhalation, drinking water, and all possible food pathways in the same manner as naturally occurring 14C. The current world inventory of naturally occurring 14C results in an average dose to the public of about 1.25 mrem/year, and the release of 0.6 curies of 14C from the total of 600,000 tests assumed to be administered annually would result in an additional average annual dose of 2 x 10-7 mrem. This is far below the EPA reporting level of 1 mrem/year required under the Clean Air Act for routine exposures to a member of the public, or the 4 mrem/year EPA limit for public drinking water. In a total population of about 260 million people in the U.S., the collective annual dose from the breath tests would be about 0.051 person-rem. In addition, the doses from normal use of breath tests, or from any accidental release of 14C to the environment also are expected to be very small because the concentration of CO2 released is very low and it would mix immediately with the atmosphere.

The small doses from naturally occurring 14C are of little significance to human health and the environment. Potential long-term impacts from widespread releases of the long-lived 14C (5,730-year radiological half-life) from breath tests were concluded to be insignificant. Assuming that the testing in the U.S. would increase over a period of time to an average of a million tests per year for 50 years, the collective annual dose to the U.S. population would be about 5 person-rem over the next 50 years. This dose is very small when compared to the annual collective dose to the U.S. population from naturally occurring 14C of over 300,000 person-rem, and about 78,000,000 person-rem from all naturally occurring radiation. Clearly, an increase of a few person-rem will not significantly change these exposures, and thus there is no expected impact from the widespread use of the breath test on the entire U.S. population.

25

WASTE DISPOSAL

How do I dispose of the vials after they are counted, or how do I dispose of the BCF/LSF?

The vials should be disposed of in accordance with your facility’s regulations. The contents of the vials are flammable containing titrated benzethonium hydroxide, methanol, and liquid scintillation fluid. The pH should be about 9, which is basic but not corrosive (pH >10). Depending on the state you are working in, the material may be disposed without regards to its radioactivity due to the fact that samples are of very low specific activity (<0.05 uCi/g, typically <0.0005 uCi/g). Check your local radioactive materials regulations, looking under “Disposal of Specific Wastes.” There is usually a limit for liquid scintillation media allowing disposal without regard to its radioactivity.

Even though radioactivity is of no concern, the material is still flammable and therefore hazardous. It should be disposed as flammable liquid, with the hazard (assuming you’re using a “safe” or non-hazardous scintillation cocktail) being methanol.

Typically all health care facilities, especially those with clinical labs, must handle solvent waste. It is recommended that you contact your waste disposal group, or clinical lab manager, to help you properly set up PYtest* waste disposal. If you don’t have a clinical lab or someone who deals with solvent waste specifically, it is a good idea to contact the company or person in charge of handling your medical waste (solid waste) since that company likely handles solvent waste. We would like to give you exact procedures on how to deal with the waste, but find it best for you to put this into the framework that may exist at your facility.

The following tips are only for reference and may or may not be applicable for your facility. Consult with local, state and/or Federal regulatory agencies to ensure compliance with those laws. Halyard Health does not take responsibility for users’ compliance with regulations, and the following items serve only as a sensible guide and may not be appropriate for each facility. The following also assumes the use of a “safe” liquid scintillation cocktail such as Halyard Health LSF, EconoSafe, Ready-Safe, etc.

One way to handle the scintillation vials is to collect them in a container (typically a drum) and have them picked up by a chemical waste hauler. They will then crush the vials and separate the glass/lids from the scintillation media. The other method is to pour out the scintillation media into a jug or carboy and throw the empty vials away. This method is more time consuming but is likely cheaper and takes less space. The second method is described in more detail in the following paragraphs.

A good way to deal with the liquid scintillation media is to set up a container clearly labeled “Hazardous Waste – Flammable Liquid (Methanol).” On a periodic basis, pour the contents of the vials in the container. When it becomes 3/4 full, contact your chemical disposal company and/or in-house chemical safety officer. Have the waste disposed of properly and also keep in mind that there are regulations for the amount and time periods for storage of flammable waste.

The empty vials should be disposed in accordance with local policies. Typically they can be disposed in normal trash. The reason for this is that if the scintillation media can be disposed without regards to its radioactivity, then when empty, so can the vials. The worst-case scenario for vials would be that they would need to be washed prior to disposal. To reduce confusion about the vials being empty or not, do not recap the vials when disposing of them.

Do I need a special license to store the waste?

Typically no, since the amount of waste is rather small (13 mL/patient). This qualifies you as an (unlicensed) small-quantity generator of hazardous waste. However, you must check with your local/state facility’s regulations regarding waste collection. Most hospitals already have programs to dispose of solvent waste. Additionally, there are often low-cost programs available for limited or small-quantity generators.

What do I do with the packaging? (boxes, capsule package, balloon, etc.)

Although the NRC has stated that these packages can be disposed in normal trash, we recommend that you discard waste according to your facility’s regulations, which may likely be to dispose in normal trash based on the NRC exemption. Any references to radioactive material and the radiation symbol should be defaced prior to disposing in the regular trash.

NATIONAL DRUG CODE

What is the NDC # (National Drug Code) for the PYtest*?

Catalog # Description NDC #

60441 One PYtest* Capsule 42536-6044-1

60442 Ten PYtest* Capsules 42536-6044-2

60443 One Hundred PYtest* Capsules 42536-6044-3

60461 One PYtest* Kit 42536-6046-1

60470 One PYtest* Kit 42536-6046-1

60462 One PYtest* Kit 42536-6046-2

60471 One PYtest* Kit 42536-6046-2

26

RADIOACTIVE MATERIAL ISSUES

Do we need to have a CLIA license to perform analysis of this test at our site?

No. This test is not regulated by CLIA. CLIA does not consider breath to be a specimen. Please note that certain states do have their own state regulations. In their state regulations a breath sample may be considered a specimen and therefore regulated under their state licensing procedures. Please check with your individual state offices to determine if a state license is required to analyze the PYtest*.

Do I need a Radioactive Materials License to use the PYtest*?

It is highly unlikely. Please check with your individual state offices to determine if a license is required.

I work in a hospital in an Agreement State that still requires a Materials License. Is there someone in my hospital who might have a license?

Almost all hospitals have a Nuclear Medicine Department or have access to one. It is quite likely that you already have a group within your organization who is licensed to use the PYtest*. In simplest form, you would refer patients to the Radiology/Nuclear Medicine Department for the test just as you would for an X-ray or liver scan. The Nuclear Medicine Department is well-equipped to perform the test. It is possible that their Agreement State license may need to be modified to add 14C to the list of approved radionuclides. You may also want to consult your nuclear medicine physician for details on implementing the test.

I work in private practice in an Agreement State that still requires a Materials License, but have an affiliation with a hospital. Could their license be extended to allow me to use the test?

It depends. If you are working in a private clinic but have an affiliation with a nuclear medicine facility, you may first want to refer patients to that facility. It is also possible for you to obtain authorization to perform the test under the nuclear medicine physician’s license. That physician will need to amend his or her license to include your facility. It is important that you demonstrate a fairly strong link between the two organizations (partnership, being a satellite office of the same institution, etc.). Merely having admitting privileges would not be sufficient in this case.

Can I get my own license?

Yes, to do so, contact the appropriate agency for your state listed at the end of this document. There are some guidelines for applying for these licenses. There will be fees associated with the license application and they are dependent upon the size of your institution and the state in which you are located.

We don’t have a Nuclear Medicine Department, but I’ve heard of mobile nuclear medicine facilities. How does that fit in with the PYtest*?

Mobile nuclear medicine facilities are an option for remote sites and small organizations who do not have resources to staff an entire Nuclear Medicine Department. The authorized user is typically a nuclear medicine physician who stays at a remote site to analyze studies brought in by the mobile unit and the technologist on board who performs the studies. In the case of the PYtest*, you could contact a mobile nuclear medicine facility and they could come to your facility to perform the PYtest*.

Am I in an NRC-regulated state or an Agreement State?

Please check with your individual state office to determine agreement state status.

I have a Radioactive Materials User License. What do I need to do to order the PYtest*?

If you are located in an Agreement State which has not yet adopted the rule change, you will need to send (fax or mail) a copy of your license to (Fax No. 520-664-2804). If you wish to mail your license, the address is Halyard Health Avent, Inc., 6620 S. Memorial Place, Suite 100, Tucson, AZ 85756. Address both fax and mail to: Attn: Customer Service. We will review it to make sure it’s compatible with the PYtest*. We do this to protect both parties, making sure that you are able to receive and use the material, and we are able to legally send the material to you.

Carbon-14 is not listed on my Radioactive Materials User License. What should I do to use the PYtest*?

If your license is not compatible with the PYtest*, you will need to amend your radioactive materials use and possession license. The amendment requirements will vary from state to state. The amendment process is usually not challenging, but it is strongly recommended that you contact your state licensing agency and discuss the proposed change with them. We recommend that you ask that agency to review your license after explaining what you would like to do, since they may find that no amendment is needed. In many instances a fee for an amendment is required. It is recommended that you contact the other users (especially your Radiation Safety Officer if you have one) in your facility to discuss any other changes you may want to have made to your license.

Agreement States (if they have not adopted the NRC exemption) (exact requirements vary from state to state, so this is general)

1. Contact the licensing agency and ask what is needed to amend your license to include the medical use of 14C-Urea as an uptake, dilution and excretion marker.

2. Follow their instructions to get the amendment established.

Is the 14C for the PYtest* made in an accelerator, natural sources, or a reactor?

The 14C in the PYtest* is byproduct material, meaning it was generated in a reactor as a fission byproduct. The significance of this question is that accelerator-produced materials are state regulated while byproduct materials are NRC-regulated. If the material was accelerator produced or from natural sources, the regulations may be different than specified here. 14C is found in nature, but not in concentrations sufficient to manufacture the PYtest*.

Are we required to check the dose of each PYtest* like we are other radiopharmaceuticals?

No.

Can I contact someone at Halyard Health with questions?

If you are interested in using the PYtest* but still have questions about licensing or other issues, contact Halyard Health at 1-844-425-9273 and ask for a PYtest* technical support representative for assistance. If you have questions regarding test results, please call toll-free 1-844-425-9273.

27

PUBLICATIONS REGARDING THE PYtest*

Abstracts:

Abukhadir BA, Evaluation of a 20 minute 14C-Urea breath test for the diagnosis of Helicobacter pylori infection. Irish Medical Journal 1998; 91(1): 23-25. [abstract]

Agarwal AK, Combs MJ, Teates CD, Feng T, Hoffman SR, Marshall BJ. A Simple and Safe Low-Dose C-14 Urea Breath Test for Detection of H. pylori. JNMT:1996; 24(2). [abstract]

Chey WE, Fey D, Scheiman JM, Nostrant T, DelValle J. The Role of Acid Suppression in the Effects of Lansoprazole and Ranitidine on the 14C-Urea Breath Test. Gastro: 1996; 110 (4). [abstract]

Combs MJ, Stubbs, JB, Buck DA, Marshall BJ. Dosimetry and Reproducibility of a Capsule-Based C-14 Urea Breath Test. J. Nucl. Med.: 1995: 36 (5)98. [abstract]

Combs MJ, Stubbs, JB, Buck DA, Marshall BJ. Safety and Reproducibility of the 14C-Urea Breath Test. Am. J. Gastro: 1995: 108 (4) A74. [abstract]

Corley JH, Raibon SA, Yoder JH, Burke GJ. A Nuclear Medicine Solution to the Diagnosis of Peptic Ulcer: C-14 Urea Breath Test. Soc. Nuclear Med Southeastern Proceedings of the 36th Annual Meeting :1995; Page 2. [abstract]

Duckworth C, Locke C, Peura D. Does the C-14 Urea Breath Test Need to be Done Fasting? American J of Gastro: 1995; 108 (4) A85. [abstract]

Dye KR, PYtest* (C-14 Urea Breath Test) Performs Well in Patients Taking H2 Blockers. American College of Gastroenterology 63rd Annual Scientific Meeting October 12-14, 1998. [abstract]

Dye KR, Active Infection or Serological Scar? H. pylori should not be treated based on whole-blood office serology alone. American College of Gastroenterology 63rd Annual Scientific Meeting October 12-14, 1998. [abstract]

Kroser JA, Faigel DO, Childs M, Furth EE, Alavi A, Metz DC. Quantitative Urea Breath Testing for Helicobacter pylori (Hp): Can it Substitute for Endoscopy with Biopsy. Gastro : 1996; 110 (4). [abstract].

Marshall BJ, Hoffman SR, Sarosiek J, McCallum RW. A Microdose Capsule-Based 14C-Urea Breath Test for H. pylori. Gastro Supplement : 1991: 100 (5); A118. [abstract].

Noguera EC Helicobacter pylori: 14C-Urea breath test in clinical practice at a general hospital [Spanish]. Medicina 1998; 58(1): 45-50. [abstract].

Smith EM, O’Mara RE, Chey WY. Carbon-14 Urea Breath Test to Detect Helicobacter pylori Infection in Gastritis and Ulcer Disease. J Clin Nuc Med: 1995; 20 (7) 660. [abstract].

Sue M, Peura D, Charles C, Doobay R, Reid H, Morris E, Cambridge S, Green N, Marshall BJ. Comparison of Two Treatment Strategies for the Eradication of H. pylori Utilizing a Screening Antibody Serum Blot Test and Confirmatory C-14 Breath Test. Gastro 1996: 110 (4).[abstract]

Papers:

Chey W, Woods M, Scheiman J, Nostrant T, DelValle J, Lansoprazole and Ranitidine Affect the Accuracy of the 14C-Urea Breath Test by a pH-Dependent Mechanism. American J of Gastro: 1997; 92(3) 446-450.

Combs MJ, Stubbs JB, Sparks R, Teates CD, Feng T, Hoffman SR, Agarwal AK , Marshall BJ. Dose Estimates for a capsule-based 14C-Urea breath test for detection of H. pylori . Proceedings of the 6th International Radiopharmaceutical Dosimetry Symposium, Oak Ridge, TN, 1996. ORISE 99-0164, January 1999, Volume 2, pp.620-630.

Corley J, Yoder J, Raibon S, Burke G. Nuclear Medicines New Role in Peptic Ulcer Disease Management. JNMT 1995: 23 (4) 299-300.

Faigel DO, Childs M, Furth EE, Alavi A, Metz DC. New Noninvasive Tests for Helicobacter pylori Gastritis: Comparison with Tissue- Based Gold Standard. Digestive Diseases and Sciences 1996: 41 (4); 740-748.

Felz MW, Burke GJ, Schuman BM. Breath Test Diagnosis of Helicobacter pylori in Peptic Ulcer Disease: A Noninvasive Primary Care Option. JABFP. 1997; 10(6) 385-389.

Mowat C, Comparison of Helisal Rapid Blood Test and 14C-Urea Breath Test in Determining Helicobacter pylori Status and Predicting Ulcer Disease in Dyspeptic Patients. American Journal of Gastroenterology Vol 93, No. 1, 1998

Peura DA, Pambianco DJ, Dye KR, Lind C, Frierson HF, Hoffman SR, Combs MJ, Guilfoyle E, Marshall BJ. Microdose 14C-Urea Breath Test Offers Diagnosis of Helicobacter pylori in 10 Minutes. American J of Gastro: 1996; 91(2) 233-237.

Sharma BC, 14C-Urea breath test to confirm eradication of Helicobacter pylori. Journal of Gastroenterology and Hepatology (1999) 14: 309-312

Stubbs JB, Marshall BJ. Radiation Dose Estimates for the Carbon 14- Labeled Urea Breath Test. J. Nucl Med. 1993;34: 821-825.

Van de Wouw BAM, Usefulness of the 14C-Urea breath test as a semiquantitative monitor instrument after therapy for Helicobacter pylori infection. Scandinavian Journal of Gastroenterology 1997; 32: 112-116

28

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helicobacter pylori user’s guide · the pytest* user’s guide is intended to provide the user...

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