Patient description: A 45-year-old woman was referred to the emergency department with abdominal pain lasting about 4 days accompanied by nausea and 2 episodes of vomiting. The pain is localized to the epigastric region and radiates to the right upper quadrant. The pain is worsening after eating fatty food. The patient experienced similar pain twice in the past year. Her past medical history is remarkable for hypercholesterolemia and two C/sections. She has 2 children, and she is menopausal. She doesn't smoke, drink alcohol, or use illicit drugs. She is mildly febrile. Her BP is 150/85, HR 115, RR 15, T 38.2, SpO2 98% on RA. On palpation, she experiences epigastric tenderness and tenderness in the right upper quadrant without rebound. Bowel sounds are normal. Laboratory analysis is remarkable for elevated ESR and leukocytosis with a left shift. The ultrasound revealed several gallstones and biliary sludge. The largest gallstone is 0.7cm. Surgery consultation recommends elective cholecystectomy.

Clinical trial eligibility criteria: eligible ages (years): 18.0-80.0,  Osteoarthritis of the Knee Chronic Lower Back Pain Patient has a primary diagnosis of OA of the index knee with symptoms for at least 6 months prior to screening and patient meets American College of Rheumatology clinical classification for OA of the knee, defined by the following Knee pain and at least 3 of the following 6: 1. Age > 50 years 2. Morning stiffness < 30 minutes 3. Crepitus on active motion 4. Bony tenderness 5. Bony enlargement 6. No palpable warmth of synovium Patient has a radiographic image of the index knee (according to the minimum quality for radiographic image as set by the central radiology reader) showing evidence of OA with a Kellgren-Lawrence grade ≥2 at screening (based on central reading) Patient has moderate to severe index knee pain (pain due to OA of the knee at least 5 days per week for the last 3 months prior to screening, as determined by patient's medical history) Patient is ambulatory and the index knee must not contain any orthopedic and/or prosthetic device WOMAC pain subscale score (with a 48-hour recall period) in the index knee ≥ 4 at baseline (visit 2 predose, mean of all questions on pain subscale) WOMAC physical function subscale score ≥ 4 at baseline (visit 2 predose, mean of all questions on physical function subscale with a 48-hour recall period) Patient is willing to discontinue all current pain medications during the baseline and treatment periods (until day 57) (except for allowed rescue medications). Low dose aspirin for cardioprophylaxis is allowed Patient is compliant with daily pain recording. Compliance with diary completion will be defined as daily average pain ratings on at least 5 days of the baseline period, of which at least 3 days are in the last 4 days prior to visit 2 Male patient and their female spouse/partners who are of childbearing potential must be using a barrier method and 1 form of highly effective birth control starting at screening and continuing throughout the study period and for 90 days after the final study drug administration  Medical History / Clinical Status Patient has a history of suicide attempt or suicidal behavior. Suicidal ideation within the last 12 months (a response of "yes" to questions 4 or 5 on the suicidal ideation portion of the Columbia-Suicide Severity Rating Scale [C-SSRS]), or who are at significant risk to commit suicide, as judged by the investigator at screening and at the time of randomization Patient has current or prior psychosis, major depressive disorder or other clinically significant psychiatric disorder Patient has a current or prior clinically significant neurologic disease, including but not limited to peripheral neuropathy, stroke, cognitive impairment and seizure. Childhood febrile seizures are not exclusionary Patient has any clinically significant uncontrolled musculoskeletal disorder (with the exception of OA), cardiovascular, gastrointestinal, endocrinologic (diabetes mellitus is allowed if controlled [glycated hemoglobin (HbA1c) ≤ 8.0%] and no peripheral neuropathy), hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, dermatologic, renal and/or other major disease Patient has an active malignancy or a history of malignancy (except for treated nonmelanoma skin cancer) within the past 5 years Patient has a history of inflammatory arthritis, (including rheumatoid arthritis or a history of RPOA, osteonecrosis or avascular necrosis of bone and/or joints), or has other diagnoses that may increase the risk of RPOA (e.g., pre-existing atrophic OA, subchondral insufficiency fracture), or severe knee malalignment or any other joint-related condition that makes the patient unsuitable for study participation (e.g., joint pain that is disproportionately severe, or which has atypical features for OA pain, should trigger further medical evaluation to rule out subchondral insufficiency fracture) Patient has findings suggestive of RPOA or increased risk for RPOA on screening radiographs of either index or non-index joints (based on central reading) Patient has a history of shoulder surgery, clinically significant trauma or current symptoms, including pain or impaired range of motion at shoulder joint Patient has a coagulopathy, is receiving anticoagulants or has been diagnosed with thrombocytopenia or a functional platelet disorder