Patterns of analgesic use, pain and self-efficacy: a cross-sectional study of patients attending a hospital rheumatology clinic

Background: Many people attending rheumatology clinics use analgesics and non-steroidal anti-inflammatories for persistent musculoskeletal pain. Guidelines for pain management recommend regular and pre-emptive use of analgesics to reduce the impact of pain. Clinical experience indicates that analgesics are often not used in this way. Studies exploring use of analgesics in arthritis have historically measured adherence to such medication. Here we examine patterns of analgesic use and their relationships to pain, self-efficacy and demographic factors. Methods: Consecutive patients were approached in a hospital rheumatology out-patient clinic. Pattern of analgesic use was assessed by response to statements such as 'I always take my tablets every day.' Pain and self-efficacy (SE) were measured using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Arthritis Self-Efficacy Scale (ASES). Influence of factors on pain level and regularity of analgesic use were investigated using linear regression. Differences in pain between those agreeing and disagreeing with statements regarding analgesic use were assessed using t-tests. Results: 218 patients (85% of attendees) completed the study. Six (2.8%) patients reported no current pain, 26 (12.3%) slight, 100 (47.4%) moderate, 62 (29.4%) severe and 17 (8.1%) extreme pain. In multiple linear regression self efficacy and regularity of analgesic use were significant (p < 0.01) with lower self efficacy and more regular use of analgesics associated with more pain. Low SE was associated with greater pain: 40 (41.7%) people with low SE reported severe pain versus 22 (18.3%) people with high SE, p < 0.001. Patients in greater pain were significantly more likely to take analgesics regularly; 13 (77%) of those in extreme pain reported always taking their analgesics every day, versus 9 (35%) in slight pain. Many patients, including 46% of those in severe pain, adjusted analgesic use to current pain level. In simple linear regression, pain was the only variable significantly associated with regularity of analgesic use: higher levels of pain corresponded to more regular analgesic use (p = 0.003). Conclusion: Our study confirms that there is a strong inverse relationship between self-efficacy and pain severity. Analgesics are often used irregularly by people with arthritis, including some reporting severe pain

Model-driven requirements engineering: Synchronising models in an air traffic management case study

Different modelling techniques from different disciplines are needed to model complex socio-technical systems and their requirements. This paper describes the application of RESCUE, a process that integrates 4 modelling techniques to model and analyse stakeholder requirements for DMAN, a system for scheduling and managing the departure of aircraft from major European airports. It describes how human activity, use case and i* modelling were applied and integrated using synchronisation checks to model requirements on DMAN. Synchronisation checks applied at predefined stages in RESCUE revealed omissions and potential inconsistencies in the models and stakeholder requirements that, in turn, led to improvements to the models and resulting specification. The paper ends with implications for requirements model integration, and describes future work to extend and apply RESCUE

Maplirpacept: a CD47 decoy receptor with minimal red blood cell binding and robust anti-tumor efficacy

IntroductionCD47 is highly expressed on cancer cells and triggers an anti-phagocytic “don’t eat me” signal when bound by the inhibitory signal regulatory protein α (SIRPα) expressed on macrophages. While CD47 blockade can mitigate tumor growth, many CD47 blockers also bind to red blood cells (RBCs), leading to anemia. Maplirpacept (TTI-622, PF-07901801) is a CD47 blocking fusion protein consisting of a human SIRPα fused to an IgG4 Fc region and designed to limit binding to RBCs.MethodsTo determine maplirpacept binding to RBCs and interference with blood tests, human blood samples were used. The ability of maplirpacept to promote macrophage-mediated phagocytosis of human tumor cells was assessed using both confocal microscopy and flow cytometry. In vivo antitumor efficacy as a monotherapy and in combination with other therapeutic agents was evaluated in xenograft models.ResultsIn the current study, we demonstrate that maplirpacept has limited binding to RBCs while driving enhanced macrophage-mediated phagocytosis of hematological tumor cells in vitro and reducing tumor burden in human xenograft models. Moreover, phagocytosis of neoplastic cells can be enhanced when maplirpacept is combined with other therapeutic agents, including antibodies or chemotherapeutic agents.ConclusionThese preclinical results establish maplirpacept as an effective CD47 blocker that mitigates the potential for anemia in patients