Please select the eligibility criteria that correspond to the clinical trial below.
Title: Discontinuing NSAIDs in Veterans With Knee Osteoarthritis
Brief Summary: Knee osteoarthritis (OA) is now recognized as a major health problem. It is the number one cause of lower extremity disability and has significant deleterious effects on quality of life. While there are numerous therapies available for knee OA, most have limited efficacy. Of particular concern, is the widespread use of nonsteroidal anti-inflammatory drugs (NSAIDs) for this disorder. Veterans, as a group, are at high risk for both gastrointestinal and cardiovascular NSAID-induced complications. In this study the investigators propose to examine whether replacing NSAIDs with cognitive behavioral therapy delivered by telephone is an effective strategy for Veterans with knee OA. Telephone-administered therapy is particularly appealing since Veterans with knee OA are more likely to have limited mobility. If successful, this program may result in significant cost-savings for both Veterans (decreased co-pays and transportation costs) and the VA (decreased hospitalizations due to NSAID induced toxicity).


Options:
A: Inclusion Criteria:

* Female, having wide spread pain like FMS (IPCS codes CD-10, 79.0 - coded) for at least three months ,\> 18 years, able to understand Norwegian; able to use the webenabled mobile phone.

Exclusion Criteria:

* substantial psychological problems in need of treatment with intensive psychotherapy.
B: Inclusion Criteria:

* female or male
* 18-65 years of age
* chronic low back pain for at least 12 weeks
* if additional back pain is reported, low back pain has to be predominant
* intensity of the average low back pain ≥ 4 on the numeric rating scale (NRS) in the last week
* presence of a smartphone (iphone, Android phone) and willingness to do data entry through a smart phone application (App)
* willingness to be randomized, to apply study intervention according to the protocol, to complete the baseline questionnaire in paper form and electronic questionnaires and diaries provided by an App physical and mental ability to participate in the study
* written and oral informed consent

Exclusion Criteria:

* low back pain caused by a known malignant disease
* neck pain caused by trauma
* known rheumatic disorder
* history or planned surgery of the spinal column of the low back in the next 6 months
* known neurological symptoms e.g radicular symptoms because of prolapsed vertebral disc
* regular intake of analgesics (\>1x per week) because of additional diseases
* intake of centrally acting analgesics
* known severe acute or chronic disorder, that do not allow participation in the therapy
* other known diseases, that do not allow participation in the therapy
* known alcohol or substance abuse
* no sufficient German language skills
* current application for a benefit
* participation in another clinical trial during six months before the study and parallel to the study
* conducting regular relaxation techniques, mindfulness training or meditation six weeks before the study or planned in the next 6 months
C: Inclusion Criteria:

* People with female-assigned reproductive systems aged 18 to 45 years
* Medically confirmed endometriosis diagnosis
* Impairment of quality of life due to endometriosis defined as a value of ≥ 15 points across all scales in the Endometriosis Health Profile 30 + 23 (EHP-30 + 23, (Jones, Kennedy, Barnard, Wong \& Jenkinson, 2001a)
* Adequate German language skills
* Access to a personal computer (PC) / laptop and adequate internet connection

Exclusion Criteria:

* Serious mental disorder: unipolar severe depression (Beck Depression Inventory II: raw value ≥ 29), presuicidal syndrome, bipolar affective disorder, unipolar mania, psychotic disorder, alcohol or substance dependence
* Psychotherapeutic treatment: currently or within the last two years
* Use of benzodiazepines (prevents learning processes that are important for psychotherapy)
* Changes in the intake or use (e.g. start / change of dose / discontinuation) of antidepressants and hormonal contraceptives within the last three months
* Current or planned intrauterine insemination (IUI), in-vitro-fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) treatment with hormonal stimulation within the next eight months
* Suffering from one of the following diseases: malignant tumor, in particular breast, cervical or ovarian cancer, ulcerative colitis, Crohn's disease, a known bacterial or viral infection (e.g. tuberculosis (TBC), hepatitis A virus (HAV), hepatitis B virus (HBV), hepatitis C virus (HCV)
* Current pregnancy or birth of a child within the last six months, breastfeeding within the last six months
D: Inclusion Criteria:

Subjects will include those for whom a discontinuation trial of NSAIDs is most appropriate: 1) Veterans with knee pain despite NSAID use and/or 2) Veterans at relatively higher risk of NSAID toxicity 55-59 as ascertained by meeting 1 or more of the following 4 criteria:

* Answer affirmatively to the question: "Do you have some knee pain on most days over the past 3 months?"
* Have 1 or more risk factors for NSAID-induced nephrotoxicity (age greater than 60 years, atherosclerotic cardiovascular disease, current diuretic use, chronic renal insufficiency, congestive heart failure (New York Heart Association class I-II. Note, Class III and IV are excluded).
* Have 1 or more risk factors for NSAID-induced gastrointestinal toxicity (history of peptic ulcer disease, age \> 65 years, concurrent use of daily ASA or corticosteroids), and are currently on a gastro-protective agent.
* Have 1 or more risk factors for NSAID-induced cardiovascular toxicity (prevalent cardiovascular disease, hypertension, hypercholesterolemia, diabetes, smoking, family history of early heart disease or age greater than 55 years for women).

In addition, subjects must:

* Be age 20 years or older. While the usual cut off for knee OA is approximately 40 years, the investigators chose to lower the age cutoff as younger Veterans have a higher than expected risk of OA (see B.1).
* Have radiographic evidence of knee OA reported in the VistA electronic system.
* Be using an NSAID (other than daily ASA) for knee pain on most days of the month for at least the past 3 months.
* Be able to understand and speak English and have a telephone.
* Be willing to engage in a CBT program, to discontinue (or replace) their NSAID, and to restrict co-therapies to acetaminophen for 14 weeks.

Exclusion Criteria:

* Subjects desiring escalation of analgesics for their current level of knee pain as determined by endorsement of the following statement: "Is your knee pain bad enough that you want to talk to your doctor about taking stronger pain medications?"
* Current use of opioids and/or Celebrex.
* Current use of an NSAID (not including ASA) for a painful condition in addition to knee OA.
* Contraindications to chronic NSAID use: current use of warfarin or antiplatelet agent other than ASA, allergy to any NSAID, active upper gastrointestinal ulceration in the previous 30 days, upper gastrointestinal bleeding in the past year, history of gastroduodenal perforation or obstruction, cardiovascular event within the past 6 months (myocardial infarction, cerebrovascular event, coronary-artery bypass graft, invasive coronary revascularisation, or new-onset angina), severe congestive heart failure (New York Heart Association class III-IV), evidence of serious anemia, hepatic, renal (including nephrotic syndrome), or blood coagulation disorders, and pregnancy.

\*\*\*Though the investigators are proposing a RWT - and thus will not be initiating NSAID therapy - it would not be appropriate to continue NSAIDs (even when prescribed) in high-risk patients. The investigators acknowledge that these exclusion criteria limit generalizability, but the investigators feel justified to ensure subjects' safety.\*\*\*

* Previous hyaluronic acid knee injections (within 6 months) or corticosteroid knee injections (within 3 months).
* Scheduled knee hyaluronic acid or corticosteroid injections, arthroscopy, or knee surgery.
* Co-morbid conditions that include the following: known other causes of arthritis (infectious arthritis, rheumatoid arthritis, connective tissue disease, or psoriatic arthritis), gout or pseudogout attack within the last 12 months, peripheral neuropathy or cardiopulmonary disease that limits walking more than knee pain, bone metastases or Paget's disease involving the lower extremities, and history of drug or alcohol abuse within the past 2 years, bilateral knee replacements or knee pain in the replaced knee only.
* Current involvement in litigation or receiving workmen's compensation.
* Hearing, cognitive impairment or mental illness, as determined by chart review that would preclude participation in a CBT program.
* For Women of Childbearing Age: Must not currently be pregnant, agree to avoid getting pregnant during the course of the study and should inform the study team if pregnancy occurs at any time during study participation.
* Previous meloxicam use discontinued due to lack of effective symptom relief
* Contraindications to prolonged NSAID use, per PI discretion.

Answer: D