Relationship between beliefs about medicines and adherence in elderly patients with cardiovascular and respiratory diseases: A cross-sectional study in Romania

ObjectivesThe aim of this study was to explore elderly patients’ beliefs about medicines in general, and specific towards their treatment and the relationship between beliefs and adherence.MethodsA cross-sectional study was performed by administering a questionnaire developed to meet the study’s objectives. Elderly patients were recruited from three different settings.Results167 patients agreed to participate to our study, having a mean age of 73 years. Patients were aware of the necessity for treatment, but they also showed concern over the potential for the adverse outcomes. Only 15% of the patients were completely accepting their treatment having high necessity and low concerns, while 40% were ambivalent, having high necessity beliefs, but also high concerns, with 89% being adherent in this group. Overall, higher adherence was significantly correlated with higher necessity and with higher necessity-concern differential.ConclusionPatients beliefs have an impact on adherence, thus patients’ concerns and necessities should be addressed in order to improve adherence and treatment outcome.Practice implicationsHigher necessity positively influenced adherence to treatment, suggesting the fact that healthcare professionals could improve patients’ adherence by outlining and educating the patients on the necessity of the treatment, while also managing patients’ concerns.     

Specialized Pro-resolving Mediators Reduce Pro-nociceptive Inflammatory Mediator Production in Models of Localized Provoked Vulvodynia

Localized provoked vulvodynia (LPV) is the most common cause of chronic dyspareunia in premenopausal women, characterized by pain with light touch to the vulvar vestibule surrounding the vaginal opening. The devastating impact of LPV includes sexual dysfunction, infertility, depression, and even suicide. Yet, its etiology is unclear. No effective medical therapy exists; surgical removal of the painful vestibule is the last resort. In LPV, the vestibule expresses a unique inflammatory profile with elevated levels of pro-nociceptive proinflammatory mediators prostaglandin E₂ (PGE₂) and interleukin-6 (IL-6), which are linked to lower mechanical sensitivity thresholds. Specialized pro-resolving mediators (SPMs), lipids produced endogenously within the body, hold promise as an LPV treatment by resolving inflammation without impairing host defense. Ten of 13 commercially available SPMs reduced IL-6 and PGE₂ production by vulvar fibroblasts, administered either before or after inflammatory stimulation. Using a murine vulvar pain model, coupling proinflammatory mediator quantification with mechanical sensitivity threshold determination, topical treatment with the SPM, maresin 1, decreased sensitivity and suppressed PGE₂ levels. Docosahexaenoic acid, a precursor of maresin 1, was also effective in reducing PGE₂ in vulvar fibroblasts and rapidly restored mouse sensitivity thresholds. Overall, SPMs and their precursors may be a safe and efficacious for LPV.Perspective: Vulvodynia, like many pain conditions, is difficult to treat because disease origins are incompletely understood. Here, we applied our knowledge of more recently discovered vulvodynia disease mechanisms to screen novel therapeutics. We identified several specialized pro-resolving mediators as likely potent and safe for treating LPV with potential for broader application.     

Sexually Dimorphic Role of Toll-like Receptor 4 (TLR4) in High Molecular Weight Hyaluronan (HMWH)-induced Anti-hyperalgesia

High molecular weight hyaluronan (HMWH), a prominent component of the extracellular matrix binds to and signals via multiple receptors, including cluster of differentiation 44 (CD44) and toll-like receptor 4 (TLR4). We tested the hypothesis that, in the setting of inflammation, HMWH acts at TLR4 to attenuate hyperalgesia. We found that the attenuation of prostaglandin E₂ (PGE₂)-induced hyperalgesia by HMWH was attenuated by a TLR4 antagonist (NBP2-26245), but only in male and ovariectomized female rats. In this study we sought to evaluated the role of the TLR4 signaling pathway in anti-hyperalgesia induced by HMWH in male rats. Decreasing expression of TLR4 in nociceptors, by intrathecal administration of an oligodeoxynucleotide (ODN) antisense to TLR4 mRNA, also attenuated HMWH-induced anti-hyperalgesia, in male and ovariectomized female rats. Estrogen replacement in ovariectomized females reconstituted the gonad-intact phenotype. The administration of an inhibitor of myeloid differentiation factor 88 (MyD88), a TLR4 second messenger, attenuated HMWH-induced anti-hyperalgesia, while an inhibitor of the MyD88-independent TLR4 signaling pathway did not. Since it has previously been shown that HMWH-induced anti-hyperalgesia is also mediated, in part by CD44 we evaluated the effect of the combination of ODN antisense to TLR4 and CD44 mRNA. This treatment completely reversed HMWH-induced anti-hyperalgesia in male rats. Our results demonstrate a sex hormone-dependent, sexually dimorphic involvement of TLR4 in HMWH-induced anti-hyperalgesia, that is MyD88 dependent.PerspectiveThe role of TLR4 in anti-hyperalgesia induced by HMWH is a sexually dimorphic, TLR4 dependent inhibition of inflammatory hyperalgesia that provides a novel molecular target for the treatment of inflammatory pain.     

Dynamic changes in myeloid derived suppressor cell subsets following renal transplant: A prospective study

BackgroundMyeloid-derived suppressor cells (MDSC) are powerful suppressors of immune responses. MDSC numbers are increased in some renal transplant recipients (RTR) and there is increasing interest in their potential role in promoting both transplant tolerance and transplant associated malignancy. However the factors influencing MDSC mobilisation are unknown, and the relative temporal changes in the granulocytic (G-MDSC) and monocytic (Mo-MDSC) subsets of MDSC have not been defined.MethodsThe circulating frequencies of MDSC and dendritic cells (DC) were analysed by multicolour flow cytometry in RTR (n = 8) prior to transplant and at regular intervals out to 1 year post-transplant.ResultsIn RTRs, numbers of both G-MDSC and Mo-MDSC increased rapidly following transplant and peaked within 8 days, whilst DC numbers decreased. A second peak in G-MDSC numbers was observed in 7/8 patients within 3 months and 2 patients had a further 3rd peak in G-MDSC numbers which, in one patient, corresponded to a rejection event. Mo-MDSC numbers underwent less fluctuation and a subsequent peak in numbers was observed in only 2/8 patients. Respective kidney donors (n = 5) underwent only small transient increases in MDSC following surgery. Overall, there was little correlation between increases in MDSC and the occurrence of detectable clinical events or treatment changes.ConclusionsIn RTRs, MDSC numbers increase rapidly and peak following commencement of immunosuppression, but then fluctuate in response to as yet undefined stimuli. Further studies are required to identify the factors modulating MDSC mobilisation.     

Dissemination,Implementation, and Improvement Science Research in Population Health: Opportunities for Public Health and CTSAs

Importance

The complex, dynamic nature of health systems requires dissemination, implementation, and improvement (DII) sciences to effectively translate emerging knowledge into practice. Although they hold great promise for informing multisector policies and system‐level changes, these methods are often not strategically used by public health.

Objectives and Methods

More than 120 stakeholders from Southern California, including the community, federal and local government, university, and health services were convened to identify key priorities and opportunities for public health departments and Clinical and Translational Science Awards programs (CTSAs) to advance DII sciences in population health.

Main Outcomes

Participants identified challenges (mismatch of practice realities with narrowly focused research questions; lack of iterative learning) and solutions (using methods that fit the dynamic nature of the real world; aligning theories of change across sectors) for applying DII science research to public health problems. Pragmatic steps that public health and CTSAs can take to facilitate DII science research include: employing appropriate study designs; training scientists and practicing professionals in these methods; securing resources to advance this work; and supporting team science to solve complex‐systems issues.

Conclusions

Public health and CTSAs represent a unique model of practice for advancing DII research in population health. The partnership can inform policy and program development in local communities.