TASK DEFINITION: Given a passage with a context and an answer, construct a question on the basis of the information present in the passage. Construct the question in such a way that (i) it is unambiguous, (ii) it is answerable from the passage, (iii) its answer is unique (iv) it answer uses text phrases from the passage. Avoid creating questions that (i) can't be answered correctly without actually understanding the passage and (ii) uses the same words or phrases given in the passage.
PROBLEM: Context: To assess the effects of treatment with antitumour necrosis factor (TNF) agents, methotrexate, or other non-biological disease-modifying antirheumatic drugs (DMARDs) on cardiovascular event risks among patients with rheumatoid arthritis (RA).', "We conducted a retrospective study using data from the MarketScan claims database. Patients with RA with 1 prescription for an index drug were included. Each patient's use of an index drug was calculated cumulatively as a time-varying exposure. The incidence of cardiovascular events among patients with RA was determined. Associations between drug exposures and occurrence of cardiovascular events were assessed with Cox proportional hazards models.", 'Of 113677 patients identified, 35.8%, 41.1% and 23.1% received anti-TNF agents, methotrexate and other DMARDs, respectively. Patients were treated for an average of 7.6months; 2138 patients (1.9%) had a cardiovascular event following their index prescription. Each additional 6months of anti-TNF therapy use versus non-use reduced the risk (HR; 95% CI) for any cardiovascular event by 12% (0.88; 0.81 to 0.95, p=0.002). Anti-TNF therapy was associated with a 13% and 12% reduction in cardiovascular events in patients aged 50years (0.87; 0.80 to 0.95, p=0.002) and in those without prior methotrexate use (0.88; 0.78 to 0.99, p=0.04), respectively. Cumulative use of 1, 2 or 3years of anti-TNF therapy versus non-use is expected to reduce cardiovascular event risks by 21%, 38% and 51%, respectively.
Answer: Anti-TNF therapy was associated with a significantly lower risk of cardiovascular events among patients with RA, older patients with RA and patients without prior exposure to methotrexate.

SOLUTION: Are longer durations of antitumour necrosis factor treatment associated with reduced risk of cardiovascular events in patients with rheumatoid arthritis?

PROBLEM: Context: To investigate whether social contact and support received during hospitalization for acute ischemic stroke predict depression and daily life functioning three months later.', 'Prospective observational study using Ecological Momentary Assessments to evaluate the number of social contacts as well as social support received from family, friends and medical staff within 24hours following admission for stroke. Patients also monitored depression symptoms and behavior in real-time and in daily life contexts three months later.', 'A university hospital acute stroke unit.', 'Thirty-four mild ischemic stroke patients.', 'None.', 'One-day Ecological Momentary Assessments immediately following stroke collected information concerning perceived social support, number of social contacts and depression symptoms. Ecological Momentary Assessments was repeated three months later and addressed depression levels as well as activities of daily living, such as working, cooking, shopping and housework.', 'The number of social interactions received at hospitalization did not predict three-month outcomes. However, a better quality of moral support from friends and family immediately after stroke was associated with decreases in later depression levels (p=0.041) and increases in activities of daily living (p=0.011). Material support from friends and family was associated with increases in activities of daily living (p=0.012). No effect was observed for support received from medical staff.
Answer: Patient perceptions of better support quality, and not quantity, immediately following mild stroke, are associated with better behavioral and emotional outcomes three months later.

SOLUTION: Is very early social support following mild stroke associated with emotional and behavioral outcomes three months later?

PROBLEM: Context: AVE9633 is a new immunoconjugate comprising a humanized monoclonal antibody, anti-CD33 antigen, linked through a disulfide bond to the maytansine derivative DM4, a cytotoxic agent and potent tubulin inhibitor. It is undergoing a phase I clinical trial. Chemoresistance to anti-mitotic agents has been shown to be related, in part, to overexpression of ABC proteins. The aim of the present study was to investigate the potential roles of P-gp, MRP1 and BCRP in cytotoxicity in AVE9633-induced acute myeloid leukaemia (AML).', 'This study used AML cell lines expressing different levels of P-gp, MRP1 or BCRP proteins and twenty-five samples from AML patients. Expression and functionality of the transporter protein were analyzed by flow cytometry. The cytotoxicity of the drug was evaluated by MTT and apoptosis assays.', 'P-gp activity, but not MRP1 and BCRP, attenuated AVE9633 and DM4 cytotoxicity in myeloid cell lines. Zosuquidar, a potent specific P-gp inhibitor, restored the sensitivity of cells expressing P-gp to both AVE9633 and DM4. However, the data from AML patients show that 10/25 samples of AML cells (40%) were resistant to AVE9633 or DM4 (IC(50) > 500 nM), and this was not related to P-gp activity (p-Value: 0.7). Zosuquidar also failed to re-establish drug sensitivity. Furthermore, this resistance was not correlated with CD33 expression (p-Value: 0.6) in those cells.
Answer: P-gp activity is not a crucial mechanism of chemoresistance to AVE9633. For patients whose resistance to conventional anthracycline AML regimens is related to ABC protein expression, a combination with AVE9633 could be beneficial. Other mechanisms such as microtubule alteration could play an important role in chemoresistance to AVE9633.

SOLUTION:
Is p-gp activity a critical resistance factor against AVE9633 and DM4 cytotoxicity in leukaemia cell lines , but not a major mechanism of chemoresistance in cells from acute myeloid leukaemia patients?