Background
Rapid genetic counseling and testing (RGCT) in newly diagnosed high‐risk breast cancer (BC) patients may influence surgical treatment decisions. To successfully integrate RGCT in practice, ...knowledge of professionals’, and patients’ attitudes toward RGCT is essential.
Methods
Between 2008 and 2010, we performed a randomized clinical trial evaluating the impact of RGCT. Attitudes toward and experience with RGCT were assessed in 265 patients (at diagnosis, 6‐ and 12‐month follow‐up) and 29 medical professionals (before and after the recruitment period).
Results
At 6‐month follow‐up, more patients who had been offered RGCT felt they had been actively involved in treatment decision‐making than patients who had been offered usual care (67% vs 48%, P = 0.06). Patients who received DNA‐test results before primary surgery reported more often that RGCT influenced treatment decisions than those who received results afterwards (P < 0.01). Eighty‐seven percent felt that genetic counseling and testing (GCT) should preferably take place between diagnosis and surgery. Most professionals (72%) agreed that RGCT should be routinely offered to eligible patients. Most patients (74%) and professionals (85%) considered surgeons the most appropriate source for referral.
Conclusions
RGCT is viewed as helpful for newly diagnosed high‐risk BC patients in choosing their primary surgery and should be offered routinely by surgeons.
Female breast cancer patients carrying a BRCA1/2 mutation have an increased risk of second primary breast cancer. Rapid genetic counseling and testing (RGCT) before surgery may influence choice of ...primary surgical treatment. In this article, we report on the psychosocial impact of RGCT.
Newly diagnosed breast cancer patients at risk for carrying a BRCA1/2 mutation were randomized to an intervention group (offer of RGCT) or a usual care control group (ratio 2:1). Psychosocial impact and quality of life were assessed with the Impact of Events Scale, Hospital Anxiety and Depression Scale, Cancer Worry Scale, and the EORTC QLQ-C30 and QLQ-BR23. Assessments took place at study entry and at 6- and 12-month follow-up visits.
Between 2008 and 2010, 265 patients were recruited into the study. Completeness of follow-up data was more than 90%. Of the 178 women in the intervention group, 177 had genetic counseling, of whom 71 (40%) had rapid DNA testing and 59 (33%) received test results before surgery. Intention-to-treat and per-protocol analyses showed no statistically significant differences between groups over time in any of the psychosocial outcomes.
In this study, RGCT in newly diagnosed breast cancer patients did not have any measurable adverse psychosocial effects.
Abstract
Background:
We compared levels of psychological distress of newly diagnosed breast cancer patients who knew they were at heightened risk of carrying a
BRCA1/2
mutation (HRBC) (eg, because of ...young age at diagnosis and/or a positive family history) with breast cancer patients who were not assessed for their risk (unknown risk breast cancer, or URBC).
Methods:
We administered the Hospital Anxiety and Depression Scale (HADS) to a sample of 238 Dutch HRBC patients and 165 Norwegian URBC patients within 3 weeks of breast cancer diagnosis, prior to primary surgery. We compared HADS scores between these groups, and identified variables associated with those scores.
Results:
The HRBC patients reported significantly more symptoms of depression than URBC patients (
P
< .001, effect size = .40). The percentage of women with a suspected or probable (HADS depression score ≥8) and a probable diagnosis of depression (HADS depression score ≥11) was 29% versus 12% (
P
= .001) and 15% versus 5% (
P
= .01) in the HRBC and URBC groups, respectively. There were no significant group differences in HADS anxiety scores. In the HRBC sample, having children and psychological problems in the year before breast cancer diagnosis were associated significantly with both depression and anxiety following the diagnosis of breast cancer.
Conclusions:
Shortly after diagnosis, high hereditary-risk breast cancer patients report significantly higher levels of clinically relevant depressive symptoms as compared to breast cancer patients not assessed for their risk. Screening for psychological distress among high-risk breast cancer patients could facilitate timely referral to appropriate psychosocial services.
Lymphopenia in coronavirus disease (COVID-19) is associated with increased mortality.
To explore the association between lymphopenia, host response aberrations, and mortality in patients with ...lymphopenic COVID-19.
We determined 43 plasma biomarkers reflective of four pathophysiological domains: endothelial cell and coagulation activation, inflammation and organ damage, cytokine release, and chemokine release. We explored if decreased concentrations of lymphocyte-derived proteins in patients with lymphopenia were associated with an increase in mortality. We sought to identify host response phenotypes in patients with lymphopenia by cluster analysis of plasma biomarkers.
A total of 439 general ward patients with COVID-19 were stratified by baseline lymphocyte counts: normal (>1.0 × 10
/L;
= 167), mild lymphopenia (>0.5 to ⩽1.0 × 10
/L;
= 194), and severe lymphopenia (⩽0.5 × 10
/L;
= 78). Lymphopenia was associated with alterations in each host response domain. Lymphopenia was associated with increased mortality. Moreover, in patients with lymphopenia (
= 272), decreased concentrations of several lymphocyte-derived proteins (e.g., CCL5, IL-4, IL-13, IL-17A) were associated with an increase in mortality (at
< 0.01 or stronger significance levels). A cluster analysis revealed three host response phenotypes in patients with lymphopenia: "hyporesponsive" (23.2%), "hypercytokinemic" (36.4%), and "inflammatory-injurious" (40.4%), with substantially differing mortality rates of 9.5%, 5.1%, and 26.4%, respectively. A 10-biomarker model accurately predicted these host response phenotypes in an external cohort with similar mortality distribution. The inflammatory-injurious phenotype showed a remarkable combination of relatively high inflammation and organ damage markers with high antiinflammatory cytokine levels yet low proinflammatory cytokine levels.
Lymphopenia in COVID-19 signifies a heterogenous group of patients with distinct host response features. Specific host responses contribute to lymphopenia-associated mortality in COVID-19, including reduced CCL5 levels.
Coronavirus disease 2019 (COVID-19)-induced mortality occurs predominantly in older patients. Several immunomodulating therapies seem less beneficial in these patients. The biological substrate ...behind these observations is unknown. The aim of this study was to obtain insight into the association between ageing, the host response and mortality in patients with COVID-19.
We determined 43 biomarkers reflective of alterations in four pathophysiological domains: endothelial cell and coagulation activation, inflammation and organ damage, and cytokine and chemokine release. We used mediation analysis to associate ageing-driven alterations in the host response with 30-day mortality. Biomarkers associated with both ageing and mortality were validated in an intensive care unit and external cohort.
464 general ward patients with COVID-19 were stratified according to age decades. Increasing age was an independent risk factor for 30-day mortality. Ageing was associated with alterations in each of the host response domains, characterised by greater activation of the endothelium and coagulation system and stronger elevation of inflammation and organ damage markers, which was independent of an increase in age-related comorbidities. Soluble tumour necrosis factor receptor 1, soluble triggering receptor expressed on myeloid cells 1 and soluble thrombomodulin showed the strongest correlation with ageing and explained part of the ageing-driven increase in 30-day mortality (proportion mediated: 13.0%, 12.9% and 12.6%, respectively).
Ageing is associated with a strong and broad modification of the host response to COVID-19, and specific immune changes likely contribute to increased mortality in older patients. These results may provide insight into potential age-specific immunomodulatory targets in COVID-19.
Introduction
The management of type 1 diabetes (T1DM) has undergone significant advancements with the availability of novel technologies, notably continuous and flash glucose monitoring (CGM and FGM, ...respectively) and hybrid closed loop (HCL) therapy. The dual hormone fully closed loop (DHFCL) approach with insulin and glucagon infusion has shown promising effects in small studies on glycaemic regulation and quality of life in T1DM.
Methods and analysis
The Dual Hormone Fully Closed Loop for Type 1 Diabetes (DARE) study is a non-commercial 12-month open-label, two-arm randomised parallel-group trial. The primary aim of this study is to determine the long-term effects on glycaemic control, patient-reported outcome measurements and cost-effectiveness of the DHFCL compared with usual care, that is, HCL or treatment with multiple daily insulin injections+FGM/CGM. We will include 240 adult patients with T1DM in 14 hospitals in the Netherlands. Individuals will be randomised 1:1 to the DHFCL or continuation of their current care.
Ethics and dissemination
Ethical approval has been obtained from the Medical Research Ethics Committee NedMec, Utrecht, the Netherlands. Findings will be disseminated through peer-reviewed publications and presentations at local, national and international conferences.
Trial registration number
NCT05669547
.
PDF
