Phosphorylation of intracellular signalling molecules in peripheral blood cells from patients with psoriasis on originator or biosimilar infliximab.

BACKGROUND: Psoriasis vulgaris is a chronic, inflammatory skin disease characterized by a dysregulated immune response and it is associated with substantial systemic comorbidities. Biological drugs such as tumour necrosis factor (TNF)-α inhibitors can ameliorate the disease but are expensive. Biosimilar drugs have the same amino-acid sequence as the originator, but differences in manufacturing can affect biological activity, efficacy and tolerability. OBJECTIVES: To explore potential differences in intracellular phosphorylation of signalling molecules in peripheral blood cells from patients with psoriasis treated with the TNF-α inhibitor infliximab compared with healthy controls, and to investigate if the phosphorylation pattern was influenced by switching from the originator infliximab to the biosimilar CT-P13. METHODS: By flow cytometry, we measured phosphorylation of nuclear factor kappa B, extracellular signal-regulated kinase 1/2, p38 mitogen-activated protein kinase and signal transducer and activator of transcription 3, before and after TNF-α stimulation in monocytes and T, B, natural killer and CD3+  CD56+ cells from 25 patients with psoriasis treated with infliximab and 19 healthy controls. RESULTS: At inclusion, phosphorylation levels of peripheral blood mononuclear cells (PBMCs) were increased in patients with psoriasis compared with healthy controls, even though clinical remission had already been achieved. Phosphorylation levels declined in patients on both originator infliximab and biosimilar during continued treatment. No significant differences were detected between the two medications after 12 months. CONCLUSIONS: Patients with psoriasis on infliximab have higher activation levels of PBMCs than do healthy controls, possibly reflecting systemic inflammation. Switching from the originator infliximab to biosimilar CT-P13 did not affect phosphorylation levels or clinical parameters, suggesting that CT-P13 is a noninferior treatment alternative to the originator infliximab.

Assays for Infliximab Drug Levels and Antibodies: A Matter of Scales and Categories.

Immunogenicity is a frequent cause of secondary non-response to tumour necrosis factor (TNF) inhibitors. Drug level measurement and detection of antidrug antibodies have been shown to be cost effective and clinically relevant, and a large number of assays are available for these purposes. It is, however, difficult to compare assays and translate results into clinical meaningful information due to different methodological approaches and a lack of assay standardization. We have analysed infliximab drug levels and antidrug antibodies in 107 patient samples using enzyme-linked immunoassays (ELISA), immunofluorometric assays (IFMA) and reporter-gene assays (RGA). The RGA gave the lowest results for drug levels, whereas the IFMA detected the highest number of antidrug antibody positive sera. Applying individualized therapeutic ranges to each assay resulted in agreement among all three assays in 74% of samples for drug levels and 98% of samples for antidrug antibodies. We found that TNF inhibitor monitoring assays measure on different scales and that the agreement between quantitative results is limited. However, interassay differences can partially be overcome by assay-individualized translations of quantities into categories, which also is necessary for a meaningful clinical application. Our data demonstrate that assays should not be used interchangeably and that direct comparison of quantitative drug levels obtained with different assays should be avoided.

Caregiver-infant interaction--comforting post-operative neonates.

Analysis of 40 h of videotaped caregiving to four male infants was conducted using ethology. All infants were full term and had major chest surgery 12 h previously. All incidents of caregiver-infant interaction were examined, and the verbal and tactile comforting behavior of the caregiver was coded for duration, context, infant cue and infant state prior and following the interaction. A total of 191 comforting incidents occurred during the study. Stroking was the most common form of touch used. Most of the comforting (60%) was given in the context of caregiving; sleeping infants were touched often (38%); 25.3% of the touches were given to acutely distressed infants, and wide awake infants relatively little. Most of the infants showed no change in infant state after the relatively brief comforting incidents, but in 15.7% of the incidents the infants 'settled' after comforting. The authors conclude that this is a relatively strong effect considering the short duration of the comforting actions.

Exploring empathy: a conceptual fit for nursing practice?

After three decades, the efficacy of empathy in the clinical setting remains undocumented. Recently, concerns have been raised that the concept may be inappropriate and even harmful to the nurse-patient relationship. An analysis of the concept indicates that empathy consists of moral, emotive, cognitive and behavioral components. By tracing the integration of this concept into nursing, we suggest that empathy was uncritically adopted from psychology and is actually a poor fit for the clinical reality of nursing practice. Other communication strategies presently devalued, such as sympathy, pity, consolation, compassion and commiseration, need to be reexamined and may be more appropriate than empathy during certain phases of the illness experience. Directions for future research are suggested.

Concepts of caring and caring as a concept.

If caring is to be retained as the "essence" of nursing, and if research in this area is to advance, then the various perspectives of caring must be clarified, the strengths and the limitations of these conceptualizations examined, and the applicability of caring as a concept and theory to the practice of nursing identified. Examination of the concept of caring resulted in the identification of five epistemological perspectives: caring as a human state, caring as a moral imperative or ideal, caring as an affect, caring as an interpersonal relationship, and caring as a nursing intervention. Two outcomes of caring were identified: caring as the subjective experience and as the physiologic responses in patients. The authors concluded that knowledge development related to caring in nursing is limited by the lack of refinement of caring theory, the lack of definitions of caring attributes, the neglect to examine caring from the dialectic perspective, and the focus of theorists and researchers on the nurse to the exclusion of the patient.