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AbstractBackgroundIn‐person cognitive‐behavioral stress‐management interventions are consistently associated with reduced cancer distress. However, face‐to‐face delivery is an access barrier for many patients, and there is a need to develop remote‐delivered interventions. The current study evaluated the preliminary efficacy of an application (app)‐based cancer stress‐management intervention, StressProffen, in a randomized controlled trial.MethodsCancer survivors, maximum 1‐year posttreatment (N = 172), were randomized to StressProffen (n = 84) or a usual care control group (n = 88). Participants received a blended delivery care model: (a) one face‐to‐face introduction session, (b) 10 app‐based cognitive‐behavioral stress‐management modules, and (c) follow‐up phone calls at weeks 2‐3 and 6‐7. Outcome measures included stress (Perceived Stress Scale), anxiety and depression (Hospital Anxiety Depression Scale), and health‐related quality of life (HRQoL; Short‐Form Health Surveys [SF‐36]) at 3‐months post‐intervention, analyzed with change scores as dependent variables in linear regression models.ResultsParticipants were primarily women (82%), aged 20‐78 years (mean 52, SD 11.2), with mixed cancer types (majority breast cancer; 48%). Analysis of 149 participants completing questionnaires at baseline and 3 months revealed significant intervention effects: decreased stress (mean difference [MD] −2.8; 95% confidence interval [CI], [−5.2 to −0.4]; P = .022) and improved HRQoL (Role Physical MD = 17.7, [CI 3.7‐31.3], P = .013; Social Functioning MD = 8.5, [CI 0.7‐16.2], P = .034; Role Emotional MD = 19.5, [CI 3.7‐35.2], P = .016; Mental Health MD = 6.7, [CI 1.7‐11.6], P = .009). No significant changes were observed for anxiety or depression.ConclusionsDigital‐based cancer stress‐management interventions, such as StressProffen, have the potential to provide easily accessible, effective psychosocial support for cancer survivors.

AbstractObjectiveTo test the hypotheses that use of the Head CT Choice decision aid would be similarly effective in all parent/patient dyads but parents with high (vs low) numeracy experience a greater increase in knowledge while those with low (vs high) health literacy experience a greater increase in trust.MethodsThis was a secondary analysis of a cluster randomized trial conducted at seven sites. One hundred seventy‐two clinicians caring for 971 children at intermediate risk for clinically important traumatic brain injuries were randomized to shared decision making facilitated by the DA (n = 493) or to usual care (n = 478). We assessed for subgroup effects based on patient and parent characteristics, including socioeconomic status (health literacy, numeracy and income). We tested for interactions using regression models with indicators for arm assignment and study site.ResultsThe decision aid did not increase knowledge more in parents with high numeracy (P for interaction [Pint] = 0.14) or physician trust more in parents with low health literacy (Pint = 0.34). The decision aid decreased decisional conflict more in non‐white parents (decisional conflict scale, −8.14, 95% CI: −12.33 to −3.95; Pint = 0.05) and increased physician trust more in socioeconomically disadvantaged parents (trust in physician scale, OR: 8.59, 95% CI: 2.35‐14.83; Pint = 0.04).ConclusionsUse of the Head CT Choice decision aid resulted in less decisional conflict in non‐white parents and greater physician trust in socioeconomically disadvantaged parents. Decision aids may be particularly effective in potentially vulnerable parents.

Abstract Background: Secondary CNS involvement (SCNS) is a detrimental complication seen in ~5% of patients with diffuse large B-cell lymphoma (DLBCL) treated with modern immunochemotherapy. Data from older series report short survival following SCNS, typically <6 months. However, data in patients that develop SCNS following primary therapy that contains a rituximab-based-regimen as well as the impact of more intensified treatment for SCNS are limited. Aims: The aims of this study were to i) describe the natural history of SCNS in a large cohort of patients treated with immunochemotherapy, and ii) determine prognostic factors after SCNS. Patients and methods: We performed a retrospective study of patients diagnosed with SCNS during or after frontline immunochemotherapy (R-CHOP or equivalently effective regimens). SCNS was defined as new involvement of the CNS (parenchymal, leptomeningeal, and/or eye) in patients without known CNS involvement at the time of first pathologic diagnosis of DLBCL. Patients were identified from local databases and/or regional/national registries in Denmark, Canada (British Columbia), Australia, Israel, US (University of Iowa/Mayo Clinic SPORE), and England (Guy's and St. Thomas' Hospital, London). Clinico-pathologic and treatment characteristics at the time of SCNS were collected from medical records. Results: In total, 281 patients with SCNS diagnosed between 2001 and 2016 were included. Median age at SCNS was 64 (range 20-93) years and male:female ratio was 1.3. SCNS occurred as part of first relapse in 244 (87%) patients and 112 (40%) had documented concurrent systemic disease at the time of SCNS. The median time from initial DLBCL diagnosis to SCNS was 9 months, which was similar for patients treated with (N=76, 27%) or without upfront CNS prophylaxis (N=205, 73%) (10 vs 9 Mo; P=0.3). The median post-SCNS OS was 4 months (interquartile range 2-13) and the 2yr survival rate was 20% (95% CI 15-25) for the entire cohort. Associations between clinicopathologic features, management strategy, and post-SCNS survival are shown in Table 1, which excludes patients who did not receive any treatment against SCNS, patients treated with steroids alone, and a patient with unavailable treatment information (n=43, 15%). In multivariable analysis, performance status >1, concurrent leptomeningeal and parenchymal involvement, SCNS developing before completion of 1st line treatment, and combined systemic and CNS involvement by DLBCL were associated with inferior outcomes. Upfront CNS prophylaxis did not influence post-SCNS OS. High-dose methotrexate (HDMTX) and/or platinum based treatment regimens (i.e. ICE, DHAP, or GDP [+/- IT treatment and/or radiotherapy], N=163) for SCNS were associated with reduced risk of death (HR 0.45 [0.32-0.62, P<0.01]). The 2yr post-SCNS survival for patients treated with HDMTX and/or platinum-based regimens (N=163) was 29% (95% CI 22-37). For patients with isolated parenchymal SCNS, single modality treatment with radiotherapy resulted in 2-yr OS of 19% (95% CI 8-35). For the subgroup of 49 patients treated with HDMTX- and/or platinum-based regimens for isolated SCNS after 1st line DLBCL treatment and with performance status 0 or 1, the 2yr post-SCNS survival was 46% (95% CI 31-59). Overall, 9% of the patients received HDT with ASCT as part of salvage therapy at the time of SCNS. Amongst 36 SCNS patients without systemic involvement and in CR following intensive treatment (HDMTX and/or platinum-based treatments), 11 patients consolidated with HDT had similar outcomes to 25 patients treated without consolidating HDT (P=0.9, Fig 1) Conclusions: Outcomes for patients with SCNS remain poor in this large international cohort of patients from the immunochemotherapy era. Combined parenchymal and leptomeningeal disease, presence of systemic disease concurrent with SCNS, performance status >1, and SCNS developing during first line treatment were independently associated with inferior OS. However, a significant fraction of patients with isolated SCNS after first line DLBCL treatment and with good performance status may achieve long-term remissions after intensive regimens for SCNS. Disclosures El-Galaly: Roche: Consultancy, Other: travel funding. Cheah:Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Gilead Sciences: Membership on an entity's Board of Directors or advisory committees; Janssen-Cilag: Membership on an entity's Board of Directors or advisory committees, Other: Speaker's Bureau. Kansara:Celgene: Honoraria. Connors:Bristol Myers Squib: Research Funding; NanoString Technologies: Research Funding; F Hoffmann-La Roche: Research Funding; Millennium Takeda: Research Funding; Seattle Genetics: Research Funding. Sehn:roche/genentech: Consultancy, Honoraria; amgen: Consultancy, Honoraria; seattle genetics: Consultancy, Honoraria; abbvie: Consultancy, Honoraria; TG therapeutics: Consultancy, Honoraria; celgene: Consultancy, Honoraria; lundbeck: Consultancy, Honoraria; janssen: Consultancy, Honoraria. Opat:Roche: Consultancy, Honoraria, Other: Provision of subsidised drugs, Research Funding. Seymour:Genentech: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie Inc.: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Villa:Celgene: Honoraria; Lundbeck: Honoraria; Roche: Honoraria, Research Funding.

Abstract Psychosocial eHealth intervention programs for cancer survivors are still in their infancy, with inconsistent findings so far in the scientific literature. The aim of this study was to explore system use, usefulness, ease of use, and preliminary effects of Stress Proffen, an app-based cognitive-behavioral stress management intervention for patients with cancer. A feasibility pilot project tested the intervention with cancer survivors (N = 25). The intervention contained (a) one face-to-face introduction session, (b) 10 app-based modules with stress management educational material and exercises, and (c) one follow-up phone call. Post-intervention interviews were conducted and user log-data were extracted. Outcome measures—Perceived Stress Scale (PSS), Anxiety and Depression (Hospital Anxiety and Depression Scale [HADS]), Health-Related Quality of Life (HRQoL; SF-36), and Self-Regulatory Fatigue (SRF-18)—were completed at baseline and post-intervention. Participants were primarily women (84%), age 34–71 (mean 48) and represented a variety of cancer diagnoses (majority breast cancer: 40%). Twenty-two participants completed all (pre–post) questionnaires. Sixteen participants (67%) completed at least 7 of 10 modules within the 8-week study period. Post-intervention interviews described StressProffen as providing a new, appreciated, and easily accessible stress management tool for the cancer survivors. Dependent/paired t-tests showed significant pre–post intervention effects with significant decrease in stress (p = .008), anxiety (p = .019), and self-regulatory fatigue (p = .025), and improved HRQoL (Role Physical, General Health, Vitality, and Role Emotional, all p’s &lt;.01). App-based stress management interventions such as StressProffen can provide appreciated support for cancer survivors, should be easy to use, can provide significant stress reduction, and improve emotional well-being. Further testing in a randomized controlled trial is warranted and is in progress. Clinicaltrials.gov: NCT0293961.

Matrix metalloproteinases (MMPs) are secreted as proenzymes, containing propeptides that interact with the catalytic zinc, thereby controlling MMP activation. The MMP‐9 propeptide is unique in the MMP family because of its post‐translational modification with an N‐linked oligosaccharide. ProMMP‐9 activation by MMP‐3 occurs stepwise by cleavage of the propeptide in an aminoterminal (pro‐AT) and carboxyterminal (pro‐CT) peptide. We chemically synthesized aglycosyl pro‐AT and pro‐CT and purified recombinant glycosylated pro‐ATSf−9. First, we report new cleavage sites in the MMP‐9 propeptide by MMP‐3 and neutrophil elastase. Additionally, we demonstrated with the use of western blot analysis a higher resistance of glycosylated versus aglycosyl pro‐AT against proteolysis by MMP‐3, MMP‐9, meprin α, neutrophil elastase and by protease‐rich synovial fluids from rheumatoid arthritis patients. Moreover, we investigated the effect of glycosylation on proteolytic activation of human proMMP‐9 with the use of zymography and dye‐quenched gelatin cleavage analysis. Compared to recombinant Sf‐9 proMMP‐9 glycoforms, larger oligosaccharides of human neutrophil proMMP‐9 increased resistance against proteolytic activation. Additionally, proMMP‐9 from Congenital Disorder of Glycosylation patients, compared to healthy controls, showed a higher activation rate by MMP‐3. Finally, we demonstrated that glycan‐galectin‐3 interactions reduced proMMP‐9 activation. In conclusion, modification of MMP‐9 propeptide glycosylation is a fine‐tuning mechanism and co‐determines the specific activity of MMP‐9 in physiology and pathology.EnzymesMMP‐9 EC 3.4.24.35, MMP‐3 EC 3.4.24.17, meprin α EC 3.4.24.18, neutrophil elastase EC 3.4.21.37, trypsin EC 3.4.21.4 and PNGase F EC 3.5.1.52.

Abstract Background and aims Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is challenging to live with, often accompanied by pervasive fatigue and pain, accompanied by decreased quality of life (QoL) as well as anxiety and/or depression. Associations between higher pain, lower QoL and higher anxiety and depression have been shown in patients with various chronic pain disorders. Few studies have however examined such associations in a sample of patients with ME/CFS. The aims of the current study were to examine the impact of pain levels and compare levels of pain, health related QoL, anxiety and depression between patients with ME/CFS and healthy controls. In addition, the study aimed and to examine these relationships within the patient group only. Methods This is a cross-sectional questionnaire based study comparing 87 well-diagnosed patients with ME/CFS with 94 healthy controls. The De Paul Symptom Questionnaire (DSQ), the Medical Outcomes Study Short-Form Surveys (SF-36) and the Hospital Anxiety and Depression Scale (HADS) were used to examine and compare pain, physical function, QoL, anxiety and depression in patients and healthy controls. Further the pain variables were divided into pain total, pain intensity and a pain frequency score for analyses of the above mentioned variables within the patient group only. Results Significantly higher levels of pain, anxiety and depression, and lower levels of QoL were found in the patient group compared with healthy controls. For the patient group alone, pain was significantly associated with lower QoL in terms of physical functioning, bodily pain, general health functioning, vitality and social functioning capacity. In this patient sample, only frequency of joint pain showed significant difference in psychological variables such as depression and anxiety – depression combined. Conclusions ME/CFS patients differ significantly from healthy controls in pain, health related QoL, anxiety and depression. Pain is significantly associated with reduced QoL and overall a lower level of functioning. The relation between pain and anxiety and depression appears less clear. Implications Pain is for many ME/CFS patients associated with reduced physical functioning and reduced QoL. A thorough pain assessment can therefore be essential for clinicians, and subsequent medical pain treatment combined with good pain coping skills may increase functioning level and QoL for these patients. The link between joint pain and psychological factors should also be focused in clinical practice in terms of mapping and counseling. Pain should be further examined to understand the importance it may have for functioning level as reduced function is a main criteria when diagnosing the patients.

AbstractBackgroundAccurate and reliable clinical and radiological predictors of intracerebral hemorrhage (ICH) outcomes are needed to optimize treatment of ICH. The aim of this study was to investigate functional outcome and identify predictors of severe disability or death following ICH.Materials and methodsRetrospective population‐based study of spontaneous ICH. Clinical and radiological data were obtained from electronic medical records, and functional outcome estimated using the modified Rankin Scale (mRS) before ICH and at 3 and 12 months after ICH.ResultsFour hundred and fifty‐two patients were included (mean age 74.8 years, 45.6% females). Proportion of fatal outcome at 1 week was 22.1%, at 3 months 39.2%, and at 12 months 44.9%. Median mRS score before the ICH was 1 (interquartile range [IQR] 2); for survivors at 3 months, it was 5 (IQR 3); and at 12 months, it was 3 (IQR 2). Independent predictors of severe disability (mRS of 5) or death (mRS of 6) were use of oral antithrombotic drugs (OR 2.2, 95% CI 1.3–3.8, p = 0.04), mRS score before the ICH (OR 1.8, 95% CI 1.4–2.2, p < 0.001), Glasgow Coma Scale (GCS) on admission (OR 8.3, 95% CI 3.5–19.7, p < 0.001), hematoma volume >60 ml (OR 4.5, 05% CI 2.0–10.2, p < 0.001), and intraventricular hematoma extension (OR 1.8, 95% CI 0.8–4.2, p < 0.001).ConclusionIntracerebral hemorrhage is associated with high mortality, and more than one third of survivors end up with severe disability or death 3 months later. Predictors of severe disability or death were use of oral antithrombotic drugs, functional disability prior to ICH, low GCS on admission, larger hematoma volume, and intraventricular hematoma extension.