Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Single-centre, Double-blind, Randomised, Two-stage, Parallel-group Study to Assess the Efficacy and Safety of the Fixed Dose Combination of Ibuprofen 400 mg and Caffeine 100 mg Versus Ibuprofen 400 mg, Caffeine 100 mg and Placebo in Patients With Postoperative Dental Pain
Brief Summary: The primary objective of this study is to compare the efficacy of a combination product containing ibuprofen 400 mg and caffeine 100 mg versus either ingredient alone as well as placebo for the treatment of post-surgical dental pain over an eight-hour period followed by a single dose of study medication (study stage 1). A secondary objective is to evaluate efficacy of multiple doses of the combination in comparison to ibuprofen alone over a 5-day post-surgical period (study stage 2).


Options:
A: Inclusion criteria:

* Males and females 18 to 55 years of age;
* Outpatients scheduled to undergo surgical extraction of 3-4 impacted third molar(s), with a minimum of two mandibular extractions. The two mandibular third molars may be partial bony impactions or full bony impactions (as long as the trauma rating is not severe and the surgeons do not feel the subject will have extreme post-surgical pain) OR there may be a combination of one full bony impaction with the second mandibular being a soft tissue impaction or partial bony impaction. Maxillary third molars (or supernumerary teeth) of any type can be extracted;
* Use of only the following preoperative medication(s)/ anesthetic(s): topical benzocaine, short-acting local anesthetic (mepivacaine or lidocaine) with or without vasoconstrictor and/or nitrous oxide;
* Reliable, cooperative, and of adequate intelligence to record the requested information on the analgesic questionnaire form;
* Examined by the attending oral surgeon or physician and medically cleared to participate in the study;
* Scheduled to undergo a qualifying surgical procedure;
* In good general health, with a BMI of 30 or less, and have no contraindications to any of the study medications or anesthetic drugs;
* Subjects have at least a categorical pain score of moderate and a numerical rating scale (NRS) score of 5 or greater within 4.5 hours from the time of the last suture.

Exclusion criteria:

* Presence of a serious medical condition (e.g., poorly controlled hypertension, poorly controlled diabetes, significantly impaired cardiac, renal or hepatic function, hyper- or hypothyroidism);
* Use of a prescription or non-prescription drug with which the administration of ibuprofen or any other non steroidal anti inflammatory or caffeine is contraindicated;
* Acute local infection at the time of surgery that could confound the post-surgical evaluation;
* Females who are pregnant, lactating, of child-bearing potential, or post-menopausal for less than 2 years and not using a medically approved method of contraception (i.e., oral, transdermal, intravaginal or implanted contraceptives, intrauterine device, diaphragm, condom, abstinence, or surgical sterility), or females who test positive on a urine-based pregnancy test;
* Presence or history (within 2 years of enrollment) of bleeding disorder(s) or peptic ulcer disease;
* History of alcoholism or substance abuse within the last year, or is currently abusing alcohol or other mood-altering drugs (e.g., cannabis). Subjects who are taking central nervous system or other psychotropic drugs (including St. Johns Wort, or any other nutritional supplement known to have psychotropic effects) may be enrolled if they have been on stable doses of medication for at least 2 months, will maintain this dose throughout the study, and their condition is judged by the Principal Investigator to be well-controlled;
* Habituation to analgesic drugs or caffeine (i.e., routine use of oral analgesics 5 or more times per week or ingestion of 4 or more caffeine-containing drinks daily); use of "high energy" drinks more than once per week;
* Use of any type of systemic corticosteroid within the past 30 days or a history of current or previous use of anabolic steroids;
* History of allergic reaction (e.g., asthma, rhinitis, swelling, shock, or hives) to acetaminophen, ibuprofen, naproxen, aspirin, celecoxib, or any other non steroidal anti inflammatory or caffeine;
* Prior use of any type of analgesic or non steroidal anti inflammatory within 5 half-lives of that drug before surgery, except for pre-anesthetic medication and anesthesia for the procedure;
* Ingestion of any caffeine-containing beverages, chocolate, or alcohol 6 hours or less before surgery;
* Has impaired liver function, e.g., serum Alanine transaminase, aspartate aminotransferase, alkaline phosphatase, or Gamma-glutamyltransferase greater than 2.5 times the upper limit of normal, or blood urea nitrogen, creatinine, or bilirubin greater than 1.5 times the upper limit of normal without a known benign explanation;
* Has known history of a positive HIV antibody test or known HIV infection;
* Has a known history of Hepatitis B or C;
* Has a clinically significant abnormal electrocardiogram (ECG) at screening as determined by the Investigator:
* Has taken an investigational product within the past 30 days;
* Has previously been entered into this study;
* The subject is a member of the study site staff either directly involved with the study, an employee of the Sponsor, or a relative of study site personnel directly involved with the study or Sponsor.
B: Inclusion Criteria:

An individual must meet all of the following criteria to be eligible to participate in the study:

* Be able to understand the informed consent.
* Provide signed and dated informed consent form
* Be able to understand all directions for data gathering instruments in English
* Be willing and able to comply with all study procedures and be available for the duration of the study
* Planning to undergo extraction of one or more partial or fully impacted mandibular 3rd molars
* Be 18 years or older
* Be in good general health as evidenced by medical history
* Women must agree to use one of the following methods of contraception while participating in this study:

  * contraceptive pill
  * intra-uterine device
  * condoms
  * abstinence

Exclusion Criteria:

Participants who self-report the following history will be excluded from participating:

* History of gastrointestinal bleeding and/or peptic ulcer
* History of renal disease (excluding kidney stones)
* History of hepatic disease
* History of bleeding disorder
* History of respiratory depression
* Any prior respiratory effect of an opioid or other anesthetic drugs that required respiratory support postoperatively
* Active or untreated asthma
* History of known allegoric reaction to ibuprofen, acetaminophen, hydrocodone, and/or anesthesia
* Currently taking any of the following medications:

  * CYP3A4 inhibitor, such as macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g., ketoconazole), and protease inhibitors (e.g., ritonavir), which may increase plasma concentrations of hydrocodone bitartrate and acetaminophen and prolong opioid adverse reactions, and which may cause potentially fatal respiratory depression
  * CNS depressants.
* Consumes 3 or more alcoholic drinks every day and/or has a history of alcoholism
* History of drug or alcohol abuse
* Family history of drug or alcohol abuse in a first-degree relative
* Has had no more than one opioid prescription filled within the past 12 months
* Currently pregnant or lactating

Participants would also be excluded due to any additional criteria that would place the individual at increased risk or preclude the individual's full compliance with or completion of the study which includes:

* Prior participation in this study
* Inability or refusal to provide informed consent
C: Inclusion Criteria:

* 18 years or older
* English-speaking
* Scheduled to undergo endoscopic sinus surgery for sinusitis (CRSwNP, CRSsNP, or RARS)
* Can commit to follow up for at least one postoperative visit

Exclusion Criteria:

Patients undergoing a septorhinoplasty (septoplasty permissible if patient will also undergo sinus surgery)

* Doyle splints to be used
* Alcohol or opioid use disorder
* History of chronic pain disorders
* Regular use of acetaminophen/NSAIDS (\>4x per week)
* Patients who use narcotics or neuromodulating drugs (e.g. gabapentin, nortriptyline)more than 2x per week on average.
* Gastrointestinal ulcers or bleeding
* Chronic kidney disease/known decreased renal function (estimated glomerular filtration rate \<60)
* Liver cirrhosis or other hepatic impairment
* Prior adverse reaction to opioids or NSAIDS
* Other contraindications to any drug classes in either group.
D: Inclusion Criteria:

* diagnosed with OSAS,
* scheduled for tonsillectomy plus/minus adenoid removal at MUMC,
* between the ages of 1-10years

Exclusion Criteria:

* contraindications to analgesia,
* asthma,
* has had previous adenotonsillectomy, or
* any craniofacial,
* neuromuscular or cardiac conditions

Answer: A