Please select the eligibility criteria that correspond to the clinical trial below.
Title: Postoperative Ibuprofen and the Risk of Bleeding After Tonsillectomy With or Without Adenoidectomy
Brief Summary: Tonsillectomy (the surgical removal of the tonsils) is a commonly performed surgery in children. One risk of tonsillectomy is postoperative bleeding, and this can be more dangerous in children because their blood volume is lower than adults. Ibuprofen, a nonsteroidal anti-inflammatory medication (NSAID), is an effective pain medication. Recent guidelines, published by the American Academy of Otolaryngology, advocated use of ibuprofen after tonsillectomy. However, NSAIDs are associated with altered platelet function and a theoretical increased risk of bleeding after surgery. The investigators would like to explore the effect that ibuprofen has on postoperative bleeding, as well as validate previous studies demonstrating it is an effective pain medication after tonsillectomy.


Options:
A: Inclusion Criteria:

1. Is male or female ≥ 18 and ≤ 65 years of age.
2. Is classified by the anesthesiologist as P1 to P2 in the American Society of Anesthesiologists (ASA) Physical Status Classification System.
3. Has undergone primary, unilateral, distal, first metatarsal bunionectomy (osteotomy and internal fixation) with no additional collateral procedures.
4. Experiences a pain intensity rating of ≥ 40 mm on a 100-mm Visual Analogue Scale (VAS) during the 9-hour period after discontinuation of the anesthetic block.
5. Has a body weight ≥ 45 kg and a body mass index (BMI) ≤ 40 kg/m2.
6. If female and of childbearing potential, is nonlactating and nonpregnant (has negative pregnancy test results at Screening \[urine\] and on the day of surgery prior to surgery \[urine\]).
7. If female, is either not of childbearing potential (defined as postmenopausal for at least 1 year or surgically sterile \[bilateral tubal ligation, bilateral oophorectomy, or hysterectomy\]) or practicing 1 of the following medically acceptable methods of birth control:

   Hormonal methods such as oral, implantable, injectable, or transdermal contraceptives for a minimum of 1 full cycle (based on the subject's usual menstrual cycle period) before study drug administration.

   Total abstinence from sexual intercourse since the last menses before study drug administration through completion of final study visit.

   Intrauterine device (IUD). Double-barrier method (condoms, sponge, diaphragm, or vaginal ring with spermicidal jellies or cream).
8. Is able to provide written informed consent to participate in the study and able to understand the procedures and study requirements.
9. Must voluntarily sign and date an informed consent form (ICF) that is approved by an Institutional Review Board (IRB) before the conduct of any study procedure.
10. Is willing and able to comply with study requirements (including diet, alcohol, and smoking restrictions), complete the pain evaluations, remain at the study site for approximately 72 hours, and return for follow-up 7 ± 2 days after surgery.

Exclusion Criteria:

1. Has a known history of allergic reaction or clinically significant intolerance to acetaminophen, aspirin, opioids, or any nonsteroidal anti-inflammatory drugs (NSAIDs, including ibuprofen); history of NSAID-induced bronchospasm (subjects with the triad of asthma, nasal polyps, and chronic rhinitis are at greater risk for bronchospasm and should be considered carefully); or hypersensitivity, allergy, or significant reaction to sulfa (including sulfonamide) medicines, ingredients of the study drug, or any other drugs used in the study including anesthetics and antibiotics that may be required on the day of surgery.
2. Has experienced any surgical complications or other issues that, in the opinion of the investigator, could compromise the safety of the subject if he or she continues into randomized treatment period or could confound the results of the study.
3. Has known or suspected history of alcoholism or drug abuse or misuse within 2 years of screening or evidence of tolerance or physical dependence before dosing with study drug.
4. Has any clinically significant unstable cardiac, respiratory, neurological, immunological, hematological, or renal disease or any other condition that, in the opinion of the investigator, could compromise the subject's welfare, ability to communicate with the study staff, or otherwise contraindicate study participation.
5. Has any ongoing condition, other than a condition associated with the current primary, unilateral, first metatarsal bunionectomy that could generate levels of pain sufficient to confound the results of the study (eg, gout, severe osteoarthritis of the target joint or extremity).
6. Has a history or current diagnosis of a significant psychiatric disorder that, in the opinion of the investigator, would affect the subject's ability to comply with the study requirements.
7. Has tested positive either on the urine drug screen or on the alcohol breathalyzer test. Subjects who test positive at Screening only and can produce a prescription for the medication from their physician may be considered for study enrolment at the discretion of the investigator.
8. Has a history of a clinically significant (investigator opinion) gastrointestinal (GI) event within 6 months before Screening or has any history of peptic or gastric ulcers or GI bleeding.
9. Has a surgical or medical condition of the GI or renal system that might significantly alter the absorption, distribution, or excretion of any drug substance.
10. Is considered by the investigator, for any reason (including, but not limited to, the risks described as precautions, warnings, and contraindications in the current version of the Investigator's Brochure for IV Maxigesic®), to be an unsuitable candidate to receive the study drug.
11. Is receiving systemic chemotherapy, has an active malignancy of any type, or has been diagnosed with cancer within 5 years before Screening (excluding treated squamous or basal cell carcinoma of the skin).
12. Is currently receiving anticoagulants (eg, heparin or warfarin).
13. Has received a course of systemic corticosteroids (either oral or parenteral) within 3 months before Screening (inhaled nasal steroids and regional/limited area application of topical corticosteroids (investigator discretion) are allowed).
14. Has received or will require any analgesic medication within 5 half-lives (or, if half-life is unknown, within 48 hours) before surgery.
15. Has a history of chronic use (defined as daily use for \> 2 weeks) of NSAIDs, opiates, or glucocorticoids (except inhaled nasal steroids and regional/limited topical corticosteroids), for any condition within 6 months before study drug administration. Aspirin at a daily dose of ≤ 325 mg is allowed for cardiovascular prophylaxis if the subject has been on a stable dose regimen for ≥ 30 days before Screening and has not experienced any relevant medical problem.
16. Has been treated with agents that could affect the analgesic response (such as central alpha agents \[clonidine and tizanidine\], neuroleptic agents, and other antipsychotic agents) within 2 weeks before dosing with study drug.
17. Has a significant renal or hepatic disease, as indicated by clinical laboratory assessment (results ≥ 3 times the upper limit of normal \[ULN\] for any liver function test, including aspartate aminotransferase \[AST\], alanine aminotransferase \[ALT\], and lactate dehydrogenase, or creatinine ≥ 1.5 times the ULN).
18. Has any clinically significant laboratory finding at Screening that, in the opinion of the investigator, contraindicates study participation.
19. Has significant difficulties swallowing capsules or is unable to tolerate oral medication.
20. Previously participated in another clinical study of Maxigesic® IV or received any investigational drug or device or investigational therapy within 30 days before Screening.
B: Inclusion Criteria:

* Males and females 16 to 40 years of age
* Moderate to severe post-operative pain following surgical extraction of three or more third molar teeth

Exclusion Criteria:

* Presence of history of significant hepatic, renal, endocrine, cardiovascular, neurological, psychiatric, gastrointestinal, pulmonary, hematologic or metabolic disorder
* Pregnant or breastfeeding females
C: Inclusion Criteria:

* Patients ages 2-18 undergoing tonsillectomy with or without adenoidectomy by electrocautery alone for sleep disordered breathing or infectious tonsillitis will be included.
* Patients with complex medical conditions and craniofacial abnormalities will be included.
* Informed consent and child assent will be required for enrollment

Exclusion Criteria:

* Patients with a known personal or family history of a bleeding disorder will be excluded.
* Patients with a history of asthma, kidney or liver problems will also be excluded.
* Patients with tonsillectomy or adenoidectomy performed using a cold knife technique, microdebrider, coblation or plasma knife.
* Patients on NSAIDs for other medical conditions, or those who have taken NSAIDs within 1 week of surgery will be excluded.
* Patients with allergy to aspirin or other NSAIDs, acetaminophen, Red Dye #40 or Red Dye #33 will also be excluded.
* Pregnancy testing using urine β-subunit of hCG gonadotropin (beta-HCG) will be performed on all children \> 13 years of age, or those younger than 13 who are menstruating; this is the testing protocol used at the Children's Hospital of Boston. Patients found to be pregnant will be excluded from participation.
D: Inclusion Criteria:

* healthy status (ASA class I);
* nonsmoker;
* not pregnant or breastfeeding;
* no medication consumption in the past 21 days;
* good oral hygiene;
* bony impaction of one mandibular third molars;
* the presence of the first and second molars;
* compliance to cooperate with the research protocol.

Exclusion Criteria:

* chronic systemic disease;
* medications with potential interaction to paracetamol-codeine or ibuprofen;
* a history of intolerance or hypersensitivity to the study drugs;
* any pre-existing pain and acute inflammatory or infectious conditions; - inability to understand or perform the study procedure.

Answer: C