Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Comparative Effectiveness & Long Term Health Study in Wisconsin Smokers
Brief Summary: The overall purpose of this research is two-fold. First, the two smoking cessation medication treatments with the strongest evidence of effectiveness have never been directly compared. This research will determine how these two treatments compare in effectiveness in a head-to-head trial, and which types of smokers benefit most from each. Second, much of the data on smoking and health come from studies from many years ago. Today's smokers differ from earlier smokers in many ways that could influence the impact of smoking on health (e.g., weight, sex, diet, socio-economic status); the proposed work will determine how smoking cessation affects cardiovascular and pulmonary health in today's smokers.


Options:
A: Inclusion Criteria:

* Age 18-60
* DSM-IV Diagnosis of schizophrenia, schizoaffective disorder, or schizophreniform disorder
* Clinically stable with no change in antipsychotic medications and increase of daily dose for 4 weeks prior to enrollment
* Sufficient understanding of the study and risks (ESC score 10 or above)

Exclusion Criteria:

* Major medical illness history including, but not limited to, history of heart attack, stroke, TIA (transient ischemic attack)
* History of organic brain disorders that may affect neurophysiological measurements, including seizure disorder, brain tumor, head injury with evidence of significant cognitive deterioration
* DSM-IV diagnosis of substance dependence within 6 months except nicotine and marijuana
* On nicotine replacement therapy (nicotine patch, gum, or nasal spray)
* Uncontrolled blood pressure (persistent systolic above 155 or diastolic above 95)
* EKG of second or third degree atrioventricular (AV) block
* Renal insufficiency with estimated creatinine clearance \<40 ml/min
* Women who have positive urine pregnancy tests
* Women who are pregnant, plan to become pregnant, or in breastfeeding
B: Inclusion Criteria:

* are 18 - 70 years of age and seeking treatment of alcohol drinking;
* meet DSM-IV TR Criteria for Alcohol Dependence
* report smoking 100 cigarettes or more in their lifetime and currently smoke at least twice weekly on average in the past 90 days and have a urinary cotinine level of \> 30ng/mL by semi-quantitative urinalysis or equivalent plasma cotinine level (\> 6 ng/mL);
* report heavy drinking on at least 2 days on average per week (i.e., ≥ 4 drinks on an occasion for women and ≥ 5 drinks for men) for the past 90 days and no more than 7 consecutive days of abstinence at intake.

Exclusion Criteria:

* exhibit current, clinically significant physical disease or abnormality based on medical history, physical examination, or routine laboratory evaluation including:

  * any unexplained elevations in liver enzymes (i.e., transaminases, bilirubin)
  * clinically significant, unstable cardiovascular disease/uncontrolled hypertension
  * hepatic or renal impairment
  * severe obstructive pulmonary disease
  * diabetes mellitus requiring insulin or certain oral medications (i.e., sulfonylureas) and an A1C hemoglobin test score of \> 7 for participants not prescribed these medications
  * baseline systolic blood pressure higher than 150 mm Hg or diastolic blood pressure higher than 95 mm Hg
* have a history of cancer (except treated basal cell or squamous cell carcinoma of the skin)
* have a history of serious hypersensitivity reactions or skin reactions to varenicline;
* exhibit serious psychiatric illness (i.e., schizophrenia, bipolar disorder, severe major depression, panic disorder, borderline personality disorder, organic mood or mental disorders by history or psychological examination
* report current suicidal ideation (past 6 months) or lifetime hx of suicidal behavior assessed with the Columbia Suicide Severity Rating Scale 60; or risk for aggression using a cut-off of 15 or more on the Overt Aggression Scale - Modified Aggression Scale or 6 or more on the OAS-M Irritability Subscale 61.
* have used any psychotropic drug in the past month, except individuals who are on a stable dose of a Selective Serotonin Reuptake Inhibitor for at least two months or who report occasional use of prescription sleep aids that they are willing to discontinue;
* have a current DSM-IV diagnosis of drug dependence other than nicotine or alcohol
* are at risk for an alcohol withdrawal syndrome as evidenced by:

  * a history of seizures, delirium, or hallucinations during alcohol withdrawal
  * a Clinical Institute Withdrawal Assessment scale 62 score of \> 8,
  * report drinking to avoid withdrawal symptoms
  * have required medical treatment of alcohol withdrawal within the past 6 months
* have used another investigational drug within 30 days or have used medications to treat alcohol (e.g., naltrexone, topiramate, acamprosate, disulfiram) or nicotine use (e.g., clonidine, varenicline, bupropion, nicotine replacement) in the past 3 months or intend to use these medications;prior use of nicotine replacement in situations where smoking is not permitted (e.g., planes) without the intention to quit smoking is not exclusionary;
* intend to donate blood or blood products during the treatment phase of the study
* have a Body Mass Index (calculated as weight in kilograms divided by the square of height in meters) less than 15 or greater than 39.99 or weight less than 45 kg;
* are a female of childbearing potential who is pregnant, nursing, or not practicing effective contraception (oral, injectable, or implantable contraceptives, intrauterine device, or barrier method with spermicide).
C: Inclusion Criteria:

* daily tobacco smokers
* self-identify as Māori (indigenous New Zealander) or whānau (family) of Māori
* want to stop smoking in the next two weeks
* are at least 18 years of age
* are able to provide verbal consent
* reside in the Lakes District Health Board, Eastern Bay of Plenty or Tokoroa region at the time of enrolment
* have daily access to a mobile phone with text capability and/or email and access to the internet via computer or smartphone
* are eligible for subsidised varenicline under special authority conditions

Exclusion Criteria:

* are pregnant or breastfeeding
* are current users of other smoking cessation therapies (e.g. nicotine replacement therapy \[NRT\], buproprion \[Zyban\], clonidine, nortriptyline, e-cigarettes)
* are enrolled in another smoking cessation programme or another smoking cessation study
* have a contraindication for cytisine or varenicline
* have used varenicline or cytisine in the past 12 months
* have another person in their household involved in the trial
* have moderate or severe renal impairment,
* are being treated for active or latent TB
* have been treated for a heart attack, stroke, or severe angina within the last two weeks
* have uncontrolled high blood pressure (\> 150 mmHg systolic, \> 100 mmHg diastolic)
* have a history of seizures
D: We are only recruiting by invitation only (to members of our past cohort). We will open up enrollment to the public in the Madison, WI and Milwaukee WI areas at the end of 2012.

Inclusion Criteria:

a. To be eligible for the Comparative effectiveness trial, participants must:

* smoke 5 or more cigarettes per day,
* desire to quit smoking but not be currently engaged in cessation treatment,
* be medically eligible to use either combination NRT or varenicline,
* have reliable phone access,
* if female, must not be pregnant and must be willing to use an acceptable birth control method.

Exclusion Criteria:

1. There are no exclusion criteria for participating in the main health outcomes study, other than being unwilling to complete study assessments.
2. All smoking participants from new and original cohorts will be excluded from the cessation trial for the following reasons:

   * end-stage renal disease with hemodialysis;
   * prior suicide attempts within the last 5 years or current suicidal ideation;
   * diagnosis of and/or treatment for schizophrenia;
   * other psychotic disorders or bipolar disorder within the last 10 years;
   * current PHQ-9 score indicative of moderately severe depression;
   * severe untreated hypertension \>200/100 mmHg;
   * currently taking Wellbutrin, Zyban or bupropion;
   * hospitalized for a stroke, heart attack, congestive heart failure or diabetes within the last year;
   * used pipe tobacco, cigars, snuff or chew more than twice in the past week.

It should be noted that if any incidental findings appear in any of the cardiology tests (e.g., ultrasound, tonometry, ECG, or exercise stress test; see forms in Supplemental Information section of application), the study cardiologist (Dr. Stein or his designee) will be assign the participant to the non-randomized treatment arm and they will be given the nicotine patch and the same counseling intervention as CET participants. They will not be included in the CET analyses. This will be done to properly address the cardiovascular risk warning from the FDA regarding varenicline (Chantix).

Answer: D