Preliminary validity testing of the eHealth Literacy Questionnaire (eHLQ): a Confirmatory Factor Analysis (CFA) in Norwegian hospitalized patients.

AIMS: To perform the first psychometric analysis of the Norwegian version of the eHLQ using confirmative factor analysis (CFA) procedures in a population of patients admitted to hospital using a cross-sectional design. The eHLQ consists of 35 items capturing the 7-dimensional eHealth Literacy Framework (eHLF) which describes users' attributes, user's interaction with technologies and user's experience with digital health systems. METHODS: The 7 independent scales of the eHLQ was translated from Danish and culturally adapted into the Norwegian language following a standardised protocol. Assessment of construct validity of the eHLQ was undertaken using data from a cross-sectional survey of 260 patients hospitalized at a Norwegian University Hospital in the Oslo area during a two-week period in June 2021. The analysis included using correlation analysis (Pearsons R), internal consistency (Cronbach's alpha) and confirmatory factor analysis (CFA). RESULTS: All factor loadings were high to acceptable (i.e. > 0.6), except for five items which had somewhat lower loadings. Regarding internal consistency, alpha ranged from 0.73 to 0.90. For optimal CFA fit for the different scale models, correlated residuals were required for five of the seven scales. Overall our analysis shows an intermediate fit of the orginal construct. Scale intercorrelations were all below 0.8, indicating an overall acceptable discriminant validity between the 7 dimensions. CONCLUSIONS: The results from the CFA analysis indicate that for almost all 7 eHLQ scales, an acceptable model fit was achieved. The 260 hospitalized patients included in this study represented a variety of diagnoses, recruited from a geographically limited area. Further studies on psychometric properties of the Norwegian version of eHLQ in larger samples, diverse settings and by using more comprehensive approaches are warranted.

Health literacy profiling in persons with psoriasis - A cluster analysis.

Objective: To explore health literacy (HL) profiles within a cohort of people with psoriasis. A cluster approach identifies groups of individuals that have similar HL profiles. The method unmasks sub-groups with particular HL strengths, or subgroups with limitations, which require tailored healthcare services to improve. Methods: A cross-sectional sample of 792 patients from the Norwegian Climate Helio Therapy Programme in Gran Canaria participated. The HL questionnaire assessed nine HL dimensions. Using Ward's Hierarchical Clustering Method (Stata version 16), we looked for subgroups of patients across the dimensions. We also explored whether these clusters had specific demographic features and associations to outcomes such as psoriasis knowledge, quality of life and self-management capacity. Result: The analysis revealed four unique clusters identifying clinically meaningful subgroups. Two groups stood out as especially interesting. One cluster representing 26.6% of the sample presented severe HL limitations associated with lower psoriasis knowledge, quality of life, self-management and self-efficacy. HL domains connected to cooperation with healthcare professionals showed deficient scores. The other cluster included a smaller percentage (7.7%) with high HL compared to the total sample. This cluster was associated with higher self-management, quality of life and better self-efficacy. Conclusion: The cluster analysis revealed substantial differences in HL profiles within the sample. These results support the importance of a holistic understanding of the HL needs and the vulnerabilities within a psoriasis cohort. Implementing one size fits all approaches, may not be sufficient in psoriasis context to target HL.

Quality of life from a randomized trial of laparoscopic or open liver resection for colorectal liver metastases.

BACKGROUND: Most treatments for cancer cause a decline in patients' health-related quality of life (HRQoL). Limiting this decline is a universal goal for healthcare providers. Using minimally invasive instead of open surgical techniques might be one way to achieve this. The aim of this study was to compare postoperative HRQoL after open and laparoscopic liver resection. METHODS: This was a predefined substudy of an RCT comparing open with laparoscopic liver resection. Patients with colorectal liver metastases were assigned randomly to open or laparoscopic parenchyma-sparing liver resection. HRQoL was assessed with the Short Form 36 questionnaire at baseline, and 1 and 4 months after surgery. RESULTS: A total of 280 patients were randomized, of whom 273 underwent surgery (129 laparoscopic, 144 open); 682 questionnaires (83.3 per cent) were available for analysis. One month after surgery, patients in the laparoscopic surgery group reported reduced scores in two HRQoL domains (physical functioning and role physical), whereas those in the open surgery group reported reduced scores in five domains (physical functioning, role physical, bodily pain, vitality and social functioning). Four months after surgery, HRQoL scores in the laparoscopic group had returned to preoperative levels, whereas patients in the open group reported reduced scores for two domains (role physical and general health). The between-group difference was statistically significant in favour of laparoscopy for four domains after 1 month (role physical, bodily pain, vitality and social functioning) and for one domain after 4 months (role physical). CONCLUSION: Patients assigned to laparoscopic liver surgery reported better postoperative HRQoL than those assigned to open liver surgery. For role limitations caused by physical health problems, patients in the laparoscopic group reported better scores up to 4 months after surgery. Registration number: NCT01516710 ( http://www.clinicaltrials.gov).

ANTECEDENTES: La mayoría de los tratamientos para el cáncer causan una disminución de la calidad de vida relacionada con la salud (health-related quality of life, HRQoL) de los pacientes. Limitar este declive es un objetivo universal para los proveedores de atención médica. El uso de técnicas quirúrgicas mínimamente invasivas en lugar de abiertas podría ser una forma de lograrlo. El objetivo de este estudio fue comparar la HRQoL postoperatoria después de la resección hepática abierta y laparoscópica. MÉTODOS: Se trata de un subestudio predefinido de un ensayo aleatorizado y controlado que comparó la resección hepática abierta con la laparoscópica. Los pacientes con metástasis hepáticas colorrectales se asignaron aleatoriamente al grupo de resección hepática con preservación de parénquima por vía abierta o por vía laparoscópica. La HRQoL se evaluó con el cuestionario abreviado SF-36 en el momento basal y al cabo de 1 y 4 meses después de la cirugía. RESULTADOS: Un total de 280 pacientes fueron aleatorizados, de los cuales 273 se sometieron a cirugía (129 = laparoscópica, 144 = abierta) y hubo 682 cuestionarios (83%) disponibles para el análisis. Un mes después de la cirugía, los pacientes del grupo de cirugía laparoscópica presentaron puntuaciones reducidas en dos items de HRQoL (función física y rol físico), mientras que los pacientes del grupo de cirugía abierta presentaron puntuaciones reducidas en cinco items (función física, rol físico, dolor corporal, vitalidad y función social). Cuatro meses después de la cirugía, el grupo de cirugía laparoscópica había vuelto a los niveles preoperatorios de la HRQoL, mientras que los pacientes del grupo de cirugía abierta presentaron puntuaciones reducidas para dos items (función física y salud general). La diferencia entre los grupos fue estadísticamente significativa a favor de la laparoscopia para cuatro items después de un mes de la cirugía (rol físico, dolor corporal, vitalidad y función social) y para un ítem (rol físico) después de cuatro meses. CONCLUSIÓN: Los pacientes asignados a cirugía hepática laparoscópica presentaron mejor HRQoL postoperatoria que los pacientes asignados a cirugía hepática abierta. Para las limitaciones de roles causadas por problemas físicos de salud, los pacientes de cirugía laparoscópica presentaron mejores puntuaciones a los cuatro meses tras la intervención quirúrgica.

A systematic review of quality of life research in medicine and health sciences.

PURPOSE: Quality of life (QOL) is an important concept in the field of health and medicine. QOL is a complex concept that is interpreted and defined differently within and between disciplines, including the fields of health and medicine. The aims of this study were to systematically review the literature on QOL in medicine and health research and to describe the country of origin, target groups, instruments, design, and conceptual issues. METHODS: A systematic review was conducted to identify research studies on QOL and health-related quality of life (HRQOL). The databases Scopus, which includes Embase and MEDLINE, CINAHL, and PsycINFO were searched for articles published during one random week in November 2016. The ten predefined criteria of Gill and Feinstein were used to evaluate the conceptual and methodological rigor. RESULTS: QOL research is international and involves a variety of target groups, research designs, and QOL measures. According to the criteria of Gill and Feinstein, the results show that only 13% provided a definition of QOL, 6% distinguished QOL from HRQOL. The most frequently fulfilled criteria were: (i) stating the domains of QOL to be measured; (ii) giving a reason for choosing the instruments used; and (iii) aggregating the results from multiple items. CONCLUSION: QOL is an important endpoint in medical and health research, and QOL research involves a variety of patient groups and different research designs. Based on the current evaluation of the methodological and conceptual clarity of QOL research, we conclude that the majority QOL studies in health and medicine have conceptual and methodological challenges.

Long-term quality of life after liver transplantation for non-resectable colorectal metastases confined to the liver.

Background: Liver transplantation for patients with non-resectable colorectal liver metastases offers increased survival, with median overall survival of more than 5 years. The aim of this study was to compare quality of life before and up to 3 years after liver transplantation for colorectal liver metastases. Methods: Quality of life was assessed using the European Organisation for Research and Treatment of Cancer QLQ-C30 questionnaire version 3.0. The patients received the questionnaire before and up to 3 years after liver transplantation. Results: Some 23 patients were included in the analysis. Three months after liver transplantation they reported reduced quality of life (global health status scale), physical function and role function, and increased dyspnoea. At 6 months, global health status, physical function and role function had returned to pretransplant values. Three years after liver transplantation all symptom and function scores were comparable to baseline values. Patients with high scores for fatigue, pain and appetite loss at baseline had reduced 3-year overall survival. Conclusion: Patients with non-resectable colorectal liver-only metastases receiving liver transplantation had good long-term quality of life. Patients with high symptom scores before transplantation had reduced 3-year overall survival.

Health literacy: a new piece of the puzzle in psoriasis care? A cross-sectional study.

BACKGROUND: Health literacy (HL) - the ability to seek, understand and utilize health information - is important for good health. Suboptimal HL has been associated with poorer health outcomes in other chronic conditions, although this has not previously been studied in patients with psoriasis. OBJECTIVES: To investigate the HL strengths and weaknesses of a cohort of patients with moderate-to-severe psoriasis. Another aim was to examine possible associations between patients' quality of life, their demographic, clinical and self-management characteristics, and dimensions of HL. METHODS: A cross-sectional study was conducted. Data were collected from a cohort of patients with psoriasis who had received climate helio therapy from 2011 to 2016 (n = 825). HL was assessed by the Health Literacy Questionnaire (HLQ). The association between HL domains, demographic, clinical and self-management variables were analysed using bivariate correlation and a four-step linear multiple regression model. RESULTS: The scores on all HLQ dimensions indicated lower health literacy than other populations. The linear regression models showed a significant association between HL, quality of life and self-management variables, with higher HL predicting higher quality of life, self-efficacy and psoriasis knowledge. Sex, educational attainment, age and disease severity had less influence on health literacy. CONCLUSIONS: Improving HL may be a useful strategy for reducing disparities in self-management skills for patients with psoriasis. Interventions that aim to reduce disease severity and increase psoriasis knowledge, self-efficacy and quality of life may positively increase HL.

The calreticulin (CALR) exon 9 mutations are promising targets for cancer immune therapy.

The calreticulin (CALR) exon 9 mutations are found in ∼30% of patients with essential thrombocythemia and primary myelofibrosis. Recently, we reported spontaneous immune responses against the CALR mutations. Here, we describe that CALR-mutant (CALRmut)-specific T cells are able to specifically recognize CALRmut cells. First, we established a T-cell culture specific for a CALRmut epitope. These specific T cells were able to recognize several epitopes in the CALRmut C terminus. Next, we established a CALRmut-specific CD4+ T-cell clone by limiting dilution. These CD4+ T cells recognized autologous CALRmut monocytes and hematopoietic stem cells, and T-cell recognition of target cells was dependent on the presence of CALR. Furthermore, we showed that the CALRmut response was human leukocyte antigen (HLA)-DR restricted. Finally, we demonstrated that the CALRmut-specific CD4+ T cells, despite their phenotype, were cytotoxic to autologous CALRmut cells, and that the cytotoxicity was mediated by degranulation of the T cells. In conclusion, the CALR exon 9 mutations are targets for specific T cells and thus are promising targets for cancer immune therapy such as peptide vaccination in patients harboring CALR exon 9 mutations.

Induction of Bcl-xL-specific cytotoxic T lymphocytes in mice.

The induction of active immunity against tumour-associated antigens to prevent relapse of cancer is a promising approach but has so far shown only low efficacy. This low efficacy may in part be due to clonal escape of tumour cell variants by the downregulation of antigen expression or inflammation-induced dedifferentiation. Identification of novel tumour-associated antigens that at the same time are essential for continued tumour cell survival is thus critical for the development of active cancer vaccinations. At the same time, identification of novel endogenous murine tumour antigens will help improve preclinical development of cancer immunotherapy. The anti-apoptotic protein Bcl-xL has been suggested to be such an essential tumour antigen, but the lack of well-defined murine epitopes have delayed preclinical studies of Bcl-xL-targeting cancer vaccines. Here, we report the identification of two novel murine tumour-associated epitopes TAYQSFEQV and AFFSFGGAL derived from mouse Bcl-xL. Dendritic cell (DC)-based vaccination induced CD8(+) T cells capable of producing IFN-γ upon restimulation with these epitopes. Thus, our data may benefit the design of future immunotherapy strategies by providing a preclinical model for cancer vaccination with an endogenous tumour antigen that can be combined with other cancer treatments.

The targeting of immunosuppressive mechanisms in hematological malignancies.

The adaptive immune system has the capacity to recognize and kill leukemic cells. However, immune tolerance mechanisms that normally protect healthy tissues from autoimmune effects prevent the development of effective antitumor immunity. Tumors use several different immunosuppressive mechanisms to evade otherwise effective T-cell responses. A growing number of immune evasion mechanisms have been characterized mainly in solid tumors. In hematological malignancies, less is known about how different immune escape mechanisms influence tumor immune evasion and the extent of their impact on ongoing immune responses. The present review highlights the potential role of three well-defined immunosuppressive mechanisms in hematological malignancies: (i) inhibitory T-cell pathways (especially programmed death ligand 1/programmed death 1 (PD-L1/PD-1)), (ii) regulatory immune cells, and (iii) metabolic enzymes such as indoeamine-2,3-dioxygenase (IDO). The possible therapeutic targeting of these pathways is also discussed. Exciting new strategies that might affect future antileukemia immunotherapy include monoclonal antibodies that block inhibitory T-cell pathways (PD-1/PD-L1) and the prevention of tryptophan depletion by IDO inhibitors. Furthermore, the clinical effect of several chemotherapeutic drugs may arise from the targeting of immunosuppressive cells. Evidence for a new feedback mechanism to suppress the function of regulatory immune cells was recently provided by the identification and characterization of spontaneous cytotoxic T lymphocyte (CTL) responses against regulatory immune cells. Such specific CTLs may be immensely useful in anticancer immunotherapy (for example, by anticancer vaccination). The targeting of one or more immunosuppressive pathways may be especially interesting in combination with antileukemic immunotherapy in cases in which immunosuppressive mechanisms antagonize the desired effects of the therapy.

Functional characterization of Foxp3-specific spontaneous immune responses.

Tumor-infiltrating CD4+CD25+ regulatory T cells (Tregs) are associated with an impaired prognosis in several cancers. The transcription factor forkhead box P3 (Foxp3) is generally expressed in Tregs. Here, we identify and characterize spontaneous cytotoxic immune responses to Foxp3-expressing cells in peripheral blood of healthy volunteers and cancer patients. These immune responses were directed against a HLA-A2-restricted peptide epitope derived from Foxp3. Foxp3-reactive T cells were characterized as cytotoxic CD8+ T cells. These cells recognized dendritic cells incubated with recombinant Foxp3 protein indicating that this protein was indeed internalized, processed and cross-presented in the context of HLA-A2. More importantly, however, Foxp3-specific T cells were able to specifically recognize Tregs. Similarly, Foxp3+ malignant T cells established from a Cutaneous T-cell lymphomas (CTCL) patient were readily killed by the Foxp3-specific cytotoxic T lymphocytes. The spontaneous presence of Foxp3-specific cytotoxic T-cell responses suggest a general role of such T cells in the complex network of immune regulation as such responses may eliminate Tregs, that is, suppression of the suppressors. Consequently, induction of Foxp3-specific cytotoxic T-cell responses appears as an attractive tool to boost spontaneous or therapeutically provoked immune responses, for example, for the therapy of cancer.

Cellular based cancer vaccines: type 1 polarization of dendritic cells.

Cancer vaccines designed to re-calibrate the existing host-tumour interaction, tipping the balance from tumor acceptance towards tumor control holds huge potential to complement traditional cancer therapies. In general, limited success has been achieved with vaccines composed of tumor-associated antigens introduced to dendritic cells (DCs) generated in vitro. This may in part result from suboptimal maturation of DCs leading to insufficient production of IL-12, a key driver of cellular immunity. Therefore, tremendous efforts have been put into the design of maturation cocktails that are able to induce IL-12 secreting type 1 polarized DCs mimicing pathogen-derived molecular activation of DCs. Correct timing and potential synergisms of clinical-grade toll-like receptor ligands, interferons (IFN) and CD40L enhance IL-12 production in DCs. However, cytokine exhaustion, predominant expression of tolerogenic molecules and activation-induced dendritic cell death should be avoided. Thus, compounds such as IFN-γ may initially induce immunity but later on tolerance. Maturation with PGE(2) obviously promotes migration via expression of CCR7 but on the down side PGE(2) limits the production of IL-12 especially following encounter with CD40L-expressing cells and furthermore, PGE(2) imprints DCs for preferential interaction with tolerogenic T cells. In addition, type 1 polarized DCs matured without PGE(2) also seem to be capable of migrating in vivo, although concomitant production of CCL19 seems to transiently affect in vitro migration via autocrine receptor-mediated endocytosis of CCR7. In the current review, we discuss optimal design of DC maturation focused on pre-clinical as well as clinical results from standard and polarized dendritic cell based cancer vaccines.

Characterization and comparison of 'standard' and 'young' tumour-infiltrating lymphocytes for adoptive cell therapy at a Danish translational research institution.

Adoptive cell therapy (ACT) with ex vivo expanded tumour-infiltrating lymphocytes (TILs) in combination with IL-2 is an effective treatment for metastatic melanoma. Modified protocols of cell expansion may allow the treatment of most enrolled patients and improve the efficacy of adoptively transferred cells. The aims of this study were to establish and validate the novel 'Young TIL' method at our institution and perform a head-to-head comparison of clinical-grade products generated with this protocol opposed to the conventional 'Standard TIL', which we are currently using in a pilot ACT trial for patients with melanoma. Our results confirm that 'Young TILs' display an earlier differentiation state, with higher CD27 and lower CD56 expression. In addition, CD8(+) TILs expressing CD27 had longer telomeres compared with the CD27(-). A recently described subset of NK cells, endowed with a high expression of CD56 (CD56(bright)), was detected for the first time in both types of cultures but at a higher frequency on Young TILs. Young and Standard TILs' reactivity against autologous tumours was similar, with significant expression of TNF-α/IFN-γ/CD107a by CD8(+) TILs detected in all cultures analysed. However, either slow expansion with high-dose IL-2 only or large numerical expansion with a rapid expansion protocol, which is required for current therapeutic protocols, significantly modified TIL phenotype by reducing the frequency of less differentiated, cancer-specific TILs. These studies further support the adoption of the Young TIL method in our current ACT trial and highlight the importance of continuous quality control of expansion protocols.

Changes in peripheral blood level of regulatory T cells in patients with malignant melanoma during treatment with dendritic cell vaccination and low-dose IL-2.

In this study, changes in peripheral blood regulatory T cell (Treg) levels were evaluated in 46 progressive patients with melanoma treated with a dendritic cell-based vaccine and concomitant low-dose IFN-α and IL-2. The regulatory subset of CD4 T cells, characterized by CD25(high) , was prospectively analysed in fresh blood, and treatment-associated quantitative and qualitative changes were analysed. By the 4th vaccine, patients showed a marked increase in CD4+ CD25(high) T cell subset from 6% to 22% (P<0.001). At the 6th vaccine, a general decline was observed and a significantly (P=0.01) lower level of CD4+ CD25(high) Treg cells was reached in the group of patients who attained disease stabilization (9.5%) compared to patients with continued progressive disease (14.5%). However, when FoxP3 was employed for retrospective analysis of Tregs on frozen blood, this difference did not reach significance (P=0.09). The vast majority of the Treg produced IL-10 and, to a varying extent, TGF-ß. In addition, sorted CD4+ CD25(high) CD127⁻ Tregs were able to suppress proliferation of peripheral blood mononuclear cells in a dose-dependent manner, thus suggesting a regulatory functionality. These findings emphasize the need for strategies to effectively eliminate Treg cells to optimize the clinical effectiveness of cancer immunotherapy.