The association of physician empathy with cancer patient outcomes: A meta-analysis.

In oncology, research remains unclear as to whether physician empathy is associated with patient outcomes. Our goal was to answer this question and explore potential moderators of the association. In this meta-analysis on adult cancer care, we excluded randomised controlled trials, and studies of survivors without active disease or involving analogue patients. Eight databases were searched, in addition to reference lists of relevant articles and grey literature. Two reviewers independently screened citations, extracted data, assessed risk of bias and graded quality of evidence by using the AXIS tool. Effect size correlations (ESr) were chosen and pooled by using a random effect model. Subgroup analyses were performed, and statistically significant variables were introduced in a meta-regression. Several methods were used to explore heterogeneity and publication biases. We included 55 articles, yielding 55 ESr (n = 12,976 patients). Physician empathy was associated with favourable patient outcomes: ESr = 0.23, 95% confidence interval (CI) (0.18 to 0.27), z = 9.58, p < 0.001. However, heterogeneity was high, as reflected by a large prediction interval, 95% (-0.07 to 0.49) and I <sup>2</sup> = 94.5%. The meta-regression explained 53% of variance. Prospective designs and physician empathy assessed by researchers, compared with patient-reported empathy, decreased ESr. Bad-news consultations, compared with all other types of clinical encounters, tended to increase ESr. Patient-reported physician empathy is significantly associated with cancer patient outcomes. However, the high heterogeneity warrants further longitudinal studies to disentangle the conditions under which physician empathy can help patients. Recommendations are proposed for future research

Single-cell quantification of IL-2 response by effector and regulatory T cells reveals critical plasticity in immune response

The sensitivity of T cells to interleukin-2 (IL-2) can vary by three orders of magnitude and is determined by the surface densities of the IL-2 receptor α subunits.Regulatory T cells inflict a double hit on effector T cells by lowering the bulk IL-2 concentration as well as the sensitivity of effector T cells to this crucial cytokine.This double hit deprives weakly activated effector T cells of pSTAT5 survival signals while having only minimal effects on strongly activated effector cells that express increased levels of the IL-2 receptor.Short-term signaling differences lead to a differential functional in terms of proliferation and cell division: regulatory T cell specifically suppress weakly activated effector T cells even at large numbers; small numbers of strongly activated effector T cells overcome the suppression

Exclusive involvement of H-2D(b) or H-2K(d) product in the interaction between T-killer lymphocytes and syngeneic H-2(b) or H-2(d) viral lymphomas

It was demonstrated previously that the cytolysis of murine viral lymphoma cells by anti-murine sarcoma virus (MSV) syngeneic T-killer lymphocytes was restricted by some products of the H-2 complex. The respective role of the products of different regions of the H-2 complex were studied with six H-2(b) and three H-2(d) lymphomas induced by five different type C viruses. They were tested in a classical chromium release test against anti-MSV T-killer cells obtained from different inbred strains of mice, including several H-2 recombinants. Tumors o£ the H-2(b) haplotype were lysed only when effectors and target cells have in common the D(b) region. On the contrary an identity limited to the K end of the H-2 complex is necessary and sufficient in the H-2(d) haplotype. An in vitro restimulation of the spleen cells with concanavalin A strongly increased the activity of in vivo-primed T lymphocytes but did not provide any response for in vivo-primed but nonresponder cells. Preincubation of the tumor cells with anti-H-2 sera abolished the lysis by syngeneic anti-MSV effector lymphocytes. The same results were obtained by preincubating the H-2(b) targets with anti-H-2D(b), or the H-2(d) target with anti-H-2K(d). Preincubation with anti-H-2K(b) or anti- H-2D(d) were ineffective. These results show that the T-killer/target cells interaction in the MSV system involved some products of the H-2 complex which might be different with the various H-2 haplotypes and could possibly vary according to the antigenic specificity. A specific association of a viral product with a normal cellular structure, directed by the H-2 region during the viral budding could explain the observed results

The subjective experience of young women with non-metastatic breast cancer: the Young Women with Breast Cancer Inventory

International audienceBackground: The subjective experience of young women with breast cancer has some particular features linked to the impact of the disease and its treatment on their age-related issues (e.g. desire for a child, couple relationship, career management). Despite these specific concerns, no questionnaire currently targets the young breast cancer patient's quality of life, subjective experience or common problems when facing cancer. This study presents the psychometric validation of an inventory that aimed to measure the impact of breast cancer on the quality of life of young women (<45 years of age) with non-metastatic disease. Methods: 546 women aged <45 years when diagnosed with a non-metastatic breast cancer were recruited in 27 French cancer research and treatment centers. They answered a self-reported questionnaire created from verbatim collected by non-directive interviews carried out with 69 patients in a first qualitative study. Exploratory and confirmatory analyses were conducted in order to obtain the final structure of the scale. Internal consistency, test-retest reliability and concurrent validity with quality of life questionnaires currently used (QLQ-C30 and the QLQ-BR23 module) were then assessed. Results: The YW-BCI36 contains 36 items and highlights 8 factors: 1) feeling of couple cohesion, 2) negative affectivity and apprehension about the future, 3) management of child(ren) and of everyday life, 4) sharing with close relatives, 5) body image and sexuality, 6) financial difficulties, 7) deterioration of relationships with close relatives, and 8) career management. Psychometric analyses indicated good internal consistency (Cronbach's alpha values ranging from 0.76 to 0.91) and temporal reliability (Bravais-Pearson correlations ranging from 0.66 to 0.85). As expected, there were quite strong correlations between the YW-BCI36 and the QLQ-C30 and QLQ-BR23 scores (r ranging from 0.20 to -0.66), indicating adequate concurrent validity. Conclusions: The YW-BCI36 was confirmed as a valid scale for evaluating the subjective experience of breast cancer in young women. This instrument could help to identify the problems of these women more precisely, in order to respond to them better by an optimal care management. This scale may improve the medical, psychological and social care of breast cancer patients

Novel Human Herpesvirus 8 Subtype D Strains in Vanuatu, Melanesia

We show human herpesvirus 8 with diverse molecular subtype D variants to be highly endemic among the Ni-Vanuatu population. Most K1 genes were nearly identical to Polynesian strains, although a few clustered with Australian or Taiwanese strains. These results suggest diverse origins of the Ni-Vanuatu population and raise questions about the ancient human population movements in Melanesia

The development and psychometric validation of the self-efficacy and performance in self-management support (SEPSS) Instrument

__Aim:__ To develop and psychometrically test the self-efficacy and performance in self-management support (SEPSS) instrument. __Background:__ Facilitating persons with a chronic condition to take an active role in the management of their condition, implicates that nurses acquire new competencies. An instrument that can validly and reliably measure nurses' performance and their perceived capacity to perform self-management support is needed to evaluate current practice and training in self-management support. __Design:__ Instrument development and psychometric testing of the content and construct validity, factor structure and reliability. __Methods:__ A literature review and expert consultation (N = 17) identified the content. The items were structured according to the Five-A's model and an overarching category of 'overall' competencies. The initial instrument was tested in a sample of 472 nurses and 51 nursing students from Belgium and the Netherlands, between June 2014-January 2015. __Results:__ Confirmatory factor analyses revealed satisfactory fit indices for the six-factor structure. Discriminating power was demonstrated for subgroups. The overall internal consistency (Cronbach's alpha) was high both for the self-efficacy and the performance items. The test-retest intra-class correlation coefficients were good. __Conclusion:__ The SEPSS instrument is a 36-item, Likert-scaled self-reporting instrument with good content and construct validity, and good internal consistency reliability and good test-retest reliability. Therefore, it is a promising instrument to measure self-efficacy and performance with regard to self-management support

Markers of Inflammation, Coagulation, and Renal Function Are Elevated in Adults with HIV Infection

(See the article by Kalayjian et al, on pages 1796-1805, and the editorial commentary by Dubé and Sattler, on pages 1783-1785.) Background. Human immunodeficiency virus (HIV) replication and immune activation may increase inflammation and coagulation biomarkers. Limited data exist comparing such biomarkers in persons with and without HIV infection. Methods. For persons 45-76 years of age, levels of high-sensitivity C-reactive protein (hsCRP), interleukin (IL)-6, D-dimer, and cystatin C were compared in 494 HIV-infected individuals in the Strategies for Management of Anti-Retroviral Therapy (SMART) study and 5386 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) study. For persons 33-44 years of age, hsCRP and IL-6 levels were compared in 287 participants in the SMART study and 3231 participants in the Coronary Artery Development in Young Adults (CARDIA) study. Results. hsCRP and IL-6 levels were 55% (P<.001) and 62% (P<.001) higher among HIV-infected participants than among CARDIA study participants. Compared with levels noted in MESA study participants, hsCRP, IL-6, D-dimer, and cystatin C levels were 50%, 152%, 94%, and 27% higher, respectively (P<.001 , for each), among HIV-infected participants. HIV-infected participants receiving antiretroviral therapy who had HIV RNA levels ≤400 copies/mL had levels higher (by 21% to 60%) (P<.001) than those in the general population, for all biomarkers. Conclusions. hsCRP, IL-6, D-dimer, and cystatin C levels are elevated in persons with HIV infection and remain so even after HIV RNA levels are suppressed with antiretroviral therapy. Additional research is needed on the pathophysiology of HIV-induced activation of inflammatory and coagulation pathways, to guide potential intervention

Necrostatin-1 Analogues: Critical Issues on the Specificity, Activity and In Vivo Use in Experimental Disease Models

Necrostatin-1 (Nec-1) is widely used in disease models to examine the contribution of receptor-interacting protein kinase (RIPK) 1 in cell death and inflammation. We studied three Nec-1 analogs: Nec-1, the active inhibitor of RIPK1, Nec-1 inactive (Nec-1i), its inactive variant, and Nec-1 stable (Nec-1s), its more stable variant. We report that Nec-1 is identical to methyl-thiohydantoin-tryptophan, an inhibitor of the potent immunomodulatory enzyme indoleamine 2,3-dioxygenase (IDO). Both Nec-1 and Nec-1i inhibited human IDO, but Nec-1s did not, as predicted by molecular modeling. Therefore, Nec-1s is a more specific RIPK1 inhibitor lacking the IDO-targeting effect. Next, although Nec-1i was ∼100 × less effective than Nec-1 in inhibiting human RIPK1 kinase activity in vitro, it was only 10 times less potent than Nec-1 and Nec-1s in a mouse necroptosis assay and became even equipotent at high concentrations. Along the same line, in vivo, high doses of Nec-1, Nec-1i and Nec-1s prevented tumor necrosis factor (TNF)-induced mortality equally well, excluding the use of Nec-1i as an inactive control. Paradoxically, low doses of Nec-1 or Nec-1i, but not Nec -1s, even sensitized mice to TNF-induced mortality. Importantly, Nec-1s did not exhibit this low dose toxicity, stressing again the preferred use of Nec-1s in vivo. Our findings have important implications for the interpretation of Nec-1-based data in experimental disease models

Changes in Cardiovascular Disease Risk Factors With Immediate Versus Deferred Antiretroviral Therapy Initiation Among HIV-Positive Participants in the START (Strategic Timing of Antiretroviral Treatment) Trial

Introduction-HIV infection and certain antiretroviral therapy (ART) medications increase atherosclerotic cardiovascular disease risk, mediated, in part, through traditional cardiovascular disease risk factors. Methods and Results-We studied cardiovascular disease risk factor changes in the START (Strategic Timing of Antiretroviral Treatment) trial, a randomized study of immediate versus deferred ART initiation among HIV-positive persons with CD4+ cell counts >500 cells/mm(3). Mean change from baseline in risk factors and the incidence of comorbid conditions were compared between groups. The characteristics among 4685 HIV-positive START trial participants include a median age of 36 years, a CD4 cell count of 651 cells/mm(3), an HIV viral load of 12 759 copies/mL, a current smoking status of 32%, a median systolic/diastolic blood pressure of 120/76 mm Hg, and median levels of total cholesterol of 168 mg/dL, low-density lipoprotein cholesterol of 102 mg/dL, and high-density lipoprotein cholesterol of 41 mg/dL. Mean follow-up was 3.0 years. The immediate and deferred ART groups spent 94% and 28% of follow-up time taking ART, respectively. Compared with patients in the deferral group, patients in the immediate ART group had increased total cholesterol and low-density lipoprotein cholesterol and higher use of lipid-lowering therapy (1.2%;95% CI, 0.1-2.2). Concurrent increases in high-density lipoprotein cholesterol with immediate ART resulted in a 0.1 lower total cholesterol to high-density lipoprotein cholesterol ratio (95% CI, 0.1-0.2). Immediate ART resulted in 2.3% less BP-lowering therapy use (95% CI, 0.9-3.6), but there were no differences in new-onset hypertension or diabetes mellitus. Conclusions-Among HIV-positive persons with preserved immunity, immediate ART led to increases in total cholesterol and lowdensity lipoprotein cholesterol but also concurrent increases in high-density lipoprotein cholesterol and decreased use of blood pressure medications. These opposing effects suggest that, in the short term, the net effect of early ART on traditional cardiovascular disease risk factors may be clinically insignificant.